i
MILITARY DERMATOLOGY

ii
The Coat of Arms
1818
Medical Department of the Army
A 1976 etching by Vassil Ekimov of an
original color print that appeared in
The Military Surgeon, Vol XLI, No 2, 1917

iii
The first line of medical defense in wartime is the combat
medic.  Although in ancient times medics carried the caduceus
into battle to signify the neutral, humanitarian nature of
their tasks, they have never been immune to the perils of
war.  They have made the highest sacrifices to save the lives
of others, and their dedication to the wounded soldier is
the foundation of military medical care.

iv
Textbook of Military Medicine
Published by the
Office of The Surgeon General
Department of the Army, United States of America
Editor in Chief
Brigadier General Russ Zajtchuk, MC, U.S. Army
Director, Borden Institute
Commanding General
U.S. Army Medical Research Development, Acquisition, and Logistics Command
Professor of Surgery
F. Edward Hebért School of Medicine
Uniformed Services University of the Health Sciences
Officer in Charge and Managing Editor
Colonel Ronald F. Bellamy, MC, U.S. Army
Borden Institute
Associate Professor of Military Medicine,
Associate Professor of Surgery,
F. Edward Hebért School of Medicine
Uniformed Services University of the Health Sciences
Scientific Advisor
Donald P. Jenkins, Ph.D.
Deputy Director for Healthcare
Advanced  Research Projects Agency
Department of Defense
Adjunct Associate Professor of Surgery
Georgetown University
Visiting Associate Professor of Anatomy,
F. Edward Hebért School of Medicine
Uniformed Services University of the Health Sciences

v
The TMM Series
Part
I. Warfare, Weaponry, and the Casualty
Medical Consequences of Nuclear Warfare
(1989)
Conventional Warfare: Ballistic, Blast, and Burn
Injuries (1991)
Military Psychiatry: Preparing in Peace for War
(1994)
War Psychiatry
Medical Aspects of Chemical and Biological
Warfare
Military Medical Ethics
Part II. Principles of Medical Command and Support
Medicine and War
Medicine in Low-Intensity Conflict
Part III. Disease and the Environment
Occupational Health: The Soldier and the
Industrial Base (1993)
Military Dermatology (1994)
Mobilization and Deployment
Environmental Hazards and Military Operations
Part IV. Surgical Combat Casualty Care
Anesthesia and Perioperative Care of the
Combat Casualty
Combat Injuries to the Head, Face, and Neck
Combat Injuries to the Trunk
Combat Injuries to the Extremities and Spine
Rehabilitation of the Injured Soldier

vi
This World War II scene painted by Franklin Botts, titled Jungle—Ally of the Enemy, exemplifies Major
General Sir W. G. Macpherson's insight regarding the profound toll that dermatologic problems can take
during wartime:
Diseases of the skin ... are generally regarded as lesser maladies, that is to say, conditions which as a rule neither threaten
life nor seriously impair health. For the individual this is true, but in the case of an army the collective results of such minor
affections may become of high importance because, for military purposes, a man incapacitated for duty is a loss to the
fighting force whatever the extent or cause of his personal disability.1
—Major-General Sir W. G. Macpherson, K.C.M.G., C.B., L.L.D.
1In: Macpherson WG, Horrocks WH, Beveridge WW, eds. Medical Services. Hygiene of the War. In: History of the Great War:  Vol.
1. London, England: His Majesty’s Stationery Office; 1923: 68.
Painting: Courtesy of the U.S. Army Center of Military History, Washington, D.C.

vii
MILITARY DERMATOLOGY
Office of The Surgeon General
U.S. Department of the Army
Falls Church, Virginia
Walter Reed Army Medical Center
Washington, D.C.
Uniformed Services University of the Health Sciences
Bethesda, Maryland
Armed Forces Institute of Pathology
Washington, D.C.
1994
Specialty Editor
COLONEL WILLIAM D. JAMES, MC, U.S. ARMY
Chief
Dermatology Service
Walter Reed Army Medical Center

viii
Editorial Staff:
Lorraine B. Davis
Senior Editor
Colleen Mathews Quick
Associate Editor/Writer
Scott E. Siegel, M.D.
Volume Editor
This volume was prepared for military medical educational use. The focus  of the information
is to foster discussion that may form the basis of doctrine and policy. The volume does not
constitute official policy of the United States Department of Defense.
Dosage Selection:
The authors and publisher have made every effort to ensure the accuracy of dosages cited herein.
However, it is the responsibility of every practitioner to consult appropriate information sources
to ascertain correct dosages for each clinical situation, especially for new or unfamiliar drugs and
procedures. The authors, editors, publisher, and the Department of Defense cannot be held
responsible for any errors found in this book.
Use of Trade or Brand Names:
Use of trade or brand names in this publication is for illustrative purposes only and does not
imply endorsement by the Department of Defense.
Neutral Language:
Unless this publication states otherwise, masculine nouns and pronouns do not refer exclusively
to men.
CERTAIN PARTS OF THIS PUBLICATION PERTAIN TO COPYRIGHT RESTRICTIONS.
ALL RIGHTS RESERVED.
NO COPYRIGHTED PARTS OF THIS PUBLICATION MAY BE REPRODUCED OR
TRANSMITTED IN ANY FORM OR BY ANY MEANS, ELECTRONIC OR MECHANICAL
(INCLUDING PHOTOCOPY, RECORDING, OR ANY INFORMATION STORAGE AND
RETRIEVAL SYSTEM) WITHOUT PERMISSION IN WRITING FROM THE PUBLISHER OR
COPYRIGHT OWNER
Published by the Office of The Surgeon General at TMM Publications
Borden Institute
Walter Reed Army Medical Center
Washington, DC 20307-5001
Library of Congress Cataloging-in-Publication Data
Military dermatology / specialty editor, William D. James.
p. cm. -- (Textbook of military medicine.  Part III, Disease
and the environment)
Includes bibliographical references and index.
1.  Dermatology.   2.  Medicine, Military.    I.  James,  William D.
(William Daniel),  1950-    .  II. Series.
[DNLM:  1.  Skin Diseases.   2.  Military Medicine. 3.  Military
Personnel.      UH  390  T355  Pt.  3  1994]
RL72.M54    1994
616.5'008'80355--dc20
DNLM/DLC
for  Library  of  Congress
94-24682
CIP
PRINTED IN THE UNITED STATES OF AMERICA
03, 02, 01, 00, 99, 98, 97, 96, 95,
5 4 3 2 1

ix
Contents
Foreword by The Surgeon General
xi
Preface
xiii
Patient Flow in a Theater of Operations
xv
1.
Historical Overview and Principles of Diagnosis
1
2.
Cold-Induced Injury
21
3.
Skin Diseases Associated with Excessive Heat,
Humidity, and Sunlight
39
4.
Immersion Foot Syndromes
55
5.
Cutaneous Reactions to Nuclear, Biological, and
Chemical Warfare
69
6.
Allergic and Irritant Contact Dermatitis
111
7.
Cutaneous Trauma and its Treatment
143
8.
Arthropod and Other Animal Bites
157
9.
Arthropod Infestations and Vectors of Disease
183
10.
Viral Hemorrhagic Fevers
197
11.
Rickettsial Diseases
213
12.
Tropical Parasitic Infections
255
13.
Bacterial Skin Diseases
291
14.
Leprosy
319
15.
Cutaneous Tuberculosis
355
16.
Atypical Mycobacterial Diseases
391
17.
Superficial Fungal Skin Diseases
423
18.
Deep Fungal Skin Diseases
453
19.
Sexually Transmitted Diseases
493
20.
Common Skin Diseases
549
Acronyms and Abbreviations
597
Index
599

xi
Foreword
Skin diseases such as infections, infestations, and immersion foot may
devastate the fighting strength of a unit by incapacitating its soldiers.  In
addition, whereas environmental insults such as severe cold will affect an
entire force, the sheer numbers of troops who fall victim to frostbite or
nonfreezing injuries can easily cripple an entire force.  It is important to keep
in mind that incapacity due to skin disease is usually preventable.  When
preventive measures fail, the soldier may be back on the front line relatively
quickly with proper treatment, as opposed to the more dramatic missile
wounds, where evacuation and replacement are often necessary.  The role
that military dermatologists play in educating, implementing preventive mea-
sures, and treating these common disorders is indispensable.
Owing to the historical perspective of the Textbook of Military Medicine
series, this volume contains several lessons to be learned.  First, dermatolo-
gists who can function as consultants, educators, preventive medicine
officers, and healers need to be available for deployments of a division or
greater.  Organization that will provide them mobility so they can provide
on-the-spot advice to unit commanders in the field regarding preventive
strategies will help avoid many days of soldiers’ incapacitation.  Second,
training of nonsurgical medical officers in the diagnosis and treatment of
skin disorders should be firmly established as a portion of the core curricu-
lum.  This volume will provide a useful tool from which such training can
be modeled.  And third, research efforts directed at protective and preven-
tive strategies needs to continue to be supported.
This volume will be useful to active-duty and reservist dermatologists,
family practitioners, general medical officers, internists, nurses, physician
assistants, and medics.  It provides an up-to-date, in-depth, highly visual
resource both for teaching and for providing medical care to our soldiers in
the field.
August 1994
Washington, D.C.
Lieutenant General Alcide M. LaNoue
The Surgeon General
U.S. Army

xiii
Preface
Historically, diseases of the skin have not been accorded the concern they deserve.
This fact may result from the low mortality generally associated with skin disorders.
The high morbidity rates and the noneffectiveness rates, however, demand critical
attention to the skin.... The noneffectiveness rates must be calculated at the
dispensary and sick-call level, where nonduty days caused by dermatologic disor-
ders are a considerable source of manpower loss.1
August 1994
Washington, D.C.
Brigadier General Russ Zajtchuk
Medical Corps, U.S. Army
1In: Allen, AM. Skin Diseases in Vietnam, 1965–72. In: Ognibene AJ, ed. Internal Medicine in
Vietnam. Vol 1. Washington, DC: Medical Department, US Army, Office of The Surgeon
General, and Center of Military 
History; 
1977: 
xi.
The skin is an effective barrier against ordinary environmental intrusions.
In time of war, however, when the soldier is deployed to environments quite
foreign to ordinary peacetime conditions, minor skin insults and irritations
can progress to debilitating illnesses.  During wartime, the knowledge and
application of the principles of simple skin care and routine hygiene are
essential.  Exposure to extremes of temperature and humidity and excessive
sunlight and wetness are only a few of the environmental insults to which the
skin is exposed.  When further compromised by blisters and cuts and
attacked by insects and microorganisms, the skin’s protective barrier is
breached and soldiers are rendered unavailable for duty.
This volume places military dermatology in its historical context and
emphasizes the conditions that specialists and general medical officers in the
field are likely to see (eg, friction blisters, macerated feet, superficial fungal
infections).  Owing to the military’s new peacekeeping role, this volume also
discusses diseases that are uncommon in the United States but prevalent
worldwide in specific geographical locations (eg, cutaneous tuberculosis,
mycobacterial infections).  Chapter 5, Cutaneous Reactions to Nuclear,
Biological, and Chemical Warfare, is unique to a textbook of this type.
As then-Colonel Ognibene understood when he wrote the preface (quoted
above) to Lieutenant Colonel Allen’s masterly treatise on the skin diseases
seen during the Vietnam conflict, combat mortality from dermatologic disor-
ders is low but morbidity from mundane skin conditions can render soldiers
noneffective.  Prevention and treatment of the ordinary dermatologic disor-
ders and recognition of tropical diseases and infections should therefore be
central to the practice of military medicine.  Commanders must continually
be educated that protecting the individual soldier’s skin is integral to con-
serving the fighting strength.
—Andre J. Ognibene
Brigadier General (ret)
Medical Corps, U.S. Army

xiv
The current medical system to support the U.S. Army at war is a
continuum from the forward line of troops through the continen-
tal United States; it serves as a primary source of trained replace-
ments during the early stages of a major conflict.  The system is
designed to optimize the return to duty of the maximum number
of trained combat soldiers at the lowest possible level.  Far-
forward stabilization helps to maintain the physiology of injured
soldiers who are unlikely to return to duty and allows for their
rapid evacuation from the battlefield without needless sacrifice
of life or function.

xv
Medical Force 2000 (MF2K)
PATIENT FLOW IN A THEATER OF OPERATIONS
E:
Echelon
FH:
Field Hospital
FST:
Forward Surgical Team
GH:
General Hospital
MASF:
Mobile Aeromedical Staging Facility,
USAF
Med Co: Medical Company
RTD:
Return to Duty
ASF:
Aeromedical Staging Facility, USAF
ASMB:
Area Support Medical Battalion
ASMC:
Area Support Medical Company
BAS:
Battalion Aid Station
Cbt Medic: Combat Medic
CSH:
Combat Support Hospital
COMMZ:
Communication Zone
CZ:
Combat Zone
Cbt 
Medic
BAS
Med Co
CSH
MASF
GH
FH
Med Co
ASMC/ASMB
ASMC/ASMB
xx
xxx
x
RTD
RTD
RTD
RTD
RTD
RTD
COMMUNICATION 
ZONE
 CORPS
SUPPORT
AREA
 DIVISION
SUPPORT
AREA
 BRIGADE
SUPPORT
AREA
CZ
1st E
2nd E
3rd E
4th E
    CONUS 
FST
 UNIT
SUPPORT
AREA
COMMZ
ASF

Historical Overview and Principles of Diagnosis
1
HISTORICAL OVERVIEW AND
PRINCIPLES OF DIAGNOSIS
Chapter 1
LARRY E. BECKER, M.D.* AND WILLIAM D. JAMES, M.D.†
HISTORICAL OVERVIEW
World War I
World War II
Vietnam Conflict
Lessons Not Learned
Recommendations
PRINCIPLES OF DIAGNOSIS
Anatomy
Physical Examination
Patient History
Differential Diagnostic Considerations
SUMMARY
*Colonel, Medical Corps, U.S. Army; Chief, Dermatology Service, Brooke Army Medical Center, Fort Sam Houston, Texas 78234-6200, and
Consultant in Dermatology to The U.S. Army Surgeon General
†Colonel, Medical Corps, U.S. Army; Chief, Dermatology Service, Walter Reed Army Medical Center, Washington, D.C.  20307-5001

Military Dermatology
2
HISTORICAL OVERVIEW
Skin diseases are of major importance in military
operations.  Although they cause few fatalities, they
are a significant cause of combat ineffectiveness,
troop morbidity, and poor morale.  Widespread
scabetic infestation, as detailed in Chapter 8, Ar-
thropod and Other Animal Bites, is an excellent
example of a skin disease with these repercussions;
successful completion of unit missions has been
compromised repeatedly.  Louse-borne rickettsial
infections have incapacitated entire armies since
the 16th century, as discussed in depth in Chapter
11, Rickettsial Diseases.  The loss of soldiers to the
line commander, whether due to missile injury,
accident, systemic infection, or skin disease, has the
same effect: fewer soldiers available to accomplish
the mission.
Certain skin diseases such as immersion foot
(discussed in Chapter 4, Immersion Foot Syn-
dromes) or tropical acne (Chapter 3, Skin Diseases
Associated with Excessive Heat, Humidity, and
Sunlight) often require extended recovery periods
or evacuation, thus compounding the problem.
While diarrheal illness accounted for the highest
number of admissions during the Vietnam conflict
(skin diseases ranked third), the average hospital
stay for diarrhea was only 3 days, compared to an 8-
day average for dermatologic conditions.1  Because
of poor institutional memory, the history of
dermatology in military operations tends to repeat
itself.  The commentary in Chapter 2, Cold-Induced
Injury, exemplifies this fact.  We must relearn after
every conflict that early diagnosis and treatment of
skin diseases, combined with close supervision,
constant education, preventive measures, and ad-
equate equipment, clearly are vital to preserving
the fighting strength.
World War I
A. N. Tasker wrote, in 1928:
Diseases of the skin, exclusive of dermatological
manifestations of venereal diseases, though ordi-
narily considered to be of minor importance in so
far as danger to life is concerned, are of great
importance to an army operating in the field, by
reason of the noneffectiveness they cause.2(p551)
This assertion is strongly supported by statistics
from World War I.  Although outpatient data are
not available, from 1 April 1917 to 31 December
1919, 126,365 U.S. Army soldiers were hospitalized
for skin disease.2  Recorded diagnostic categories
and case frequencies for these admissions included
scabies, 34,134; other (unclassified), 20,270; fur-
uncle, 19,958; abscess, 16,329; cellulitis, 12,824; ec-
zema, 4,035; ectoparasitism, 3,269; herpes, 3,141;
trichophytosis, 2,813; impetigo, 2,735; carbuncle,
2,330; psoriasis, 1,506; erythema, 1,495; dermatitis,
858; pityriasis, 579; and lichen, 89.2  Over 2 million
days of service are estimated to have been lost by
reason of skin disease alone.3
In World War I, skin diseases became notorious
because of the sickness and lost man-hours they
caused.  In the British army in 1915, in the United
Kingdom, 40.88/1,000 men were admitted for dis-
eases of the skin and areolar tissue.  In France and
Flanders, the rate was 126.13/1,000.4  For one Brit-
ish army in France during the later stages of the
war, the more common diseases were scabies, infec-
tions of the skin, and pyrexia of unknown origin,
and these conditions accounted for 90% of all sick-
ness.5  Because insect bites and infestations are
commonly secondarily infected, pyoderma and
pyrexia often arose as related problems.  Troops
with lice infestations were not admitted to sick call
because disinfection was practiced as a routine
among field forces; nevertheless, the majority of
troops had pediculosis.2
In the U.S. Army in the United States and in the
American Expeditionary Forces in France, derma-
tology was combined with urology.  In The Surgeon
General’s Office, a section of the Division of Infec-
tious Diseases and Laboratories was devoted to
these combined areas.2  Specialists were assigned
to each camp and large hospital in the United
States.  The American Expeditionary Forces’ Divi-
sion of Urology and Diseases of the Skin had a
senior consultant in urology and two consultants in
dermatology.2
In general, both in the United States and in France,
hospitalized patients with skin diseases were
treated on the general wards or on the venereal
disease wards.2  In a few hospitals in the United
States, wards were set aside solely for treating skin
diseases.  During the spring and summer of 1918,
some field hospitals attached to combat divisions of
the American Expeditionary Forces operated as  skin
hospitals.2

Historical Overview and Principles of Diagnosis
3
World War II
During World War II, because many nonderma-
tologic physicians failed to appreciate the impor-
tance of correct early diagnosis and early adequate
care of skin diseases, dermatoses frequently devel-
oped to a stage at which weeks or sometimes
months of duty time were lost before the soldier
could return to duty.6  The correct decision as to the
disposition of a soldier with a cutaneous disease
(evacuation, limited duty, or return to combat duty)
was often difficult to make.  In these circumstances,
a well-qualified dermatologist would have been of
immense value.6
However, prior to mobilization in 1940, not a
single qualified dermatologist served in the U.S.
Army Medical Corps, and army hospitals did not
include a department of dermatology6 or even have
a single medical officer with a cursory knowledge
of dermatology assigned.7  Tables of Organization
of army hospitals had no provision for a derma-
tologist.7  A Consultant in Dermatology to the Of-
fice of The Surgeon General was not appointed until
April 1945, shortly before the end of the war, al-
though many theaters had excellent consultants
who played very important roles in organizing der-
matologic services and outpatient care.7  As the U.S.
Army Medical Corps grew to a total of 48,319
physicians, it included 107 board-certified derma-
tologists, 30 fully trained but not board-certified
dermatologists, and 151 officers with some dermat-
ologic training.6
During the early phases of U.S. involvement in
World War II, Major General James C. Magee stated:
Skin diseases are of greater importance in military
service than in civil life.  Although there are few
fatalities from these diseases they result in a con-
siderable loss of effective manpower and partial
incapacity of a material number of the personnel of
many commands.8(pvi)
Conservative estimates hold that between 15%
and 25% of visits to an outpatient department were
for skin disease in a temperate climate.  This pro-
portion increased to 60% to 75% in a tropical cli-
mate.6
In May 1945, in the southwest Pacific, numerous
dispensaries show as many as three fourths of those
reporting to sick call were suffering from diseases
of the skin.6  From 1 November 1944 to 1 November
1945, approximately 14% to 16% of all patient evacu-
ations to the United States from the southwest Pa-
cific were due to diseases of the skin.6  During all
months, skin disease was a more frequent cause of
evacuation than battle casualties.6  In many general
hospitals located in tropical overseas areas, 15% to
20% of admissions were for skin diseases.6  In one
evacuation hospital in the Pacific, 54.8% of the
evacuations for general medical causes were for
skin diseases.9
Among the Royal Air Force, Royal Australian Air
Force, Royal New Zealand Air Force, and Royal
Canadian Air Force training in Canada during the
war, diseases of the skin and cellular tissue were
among the top six causes of both morbidity and
wastage (time loss).10  In the two New Zealand Expe-
ditionary Forces in the Middle East, skin disease
accounted for 10% of total hospitalizations.11  For
the Royal New Zealand Air Force in the Pacific
Theater, more men were unfit and more time was
lost from skin diseases than from any other type of
disease.  Twenty-eight percent of the medical ad-
missions in the area were on account of skin dis-
ease.11  To put this in perspective, during the first 8
months of 1945, 1,000 cases of skin disease were
reported in a force of 7,800.  Nearly 100 of these
soldiers were hospitalized for more than 3 weeks,
and 79 had to be repatriated to New Zealand.11
Few prevalence figures from World War II are
available.  An excellent prospective study of British
soldiers in Malaya and Hong Kong shortly after the
war revealed that of 1,694 soldiers examined, 79.5%
had dermatoses of the feet; 33.5% had tinea corporis,
tinea cruris, or both; 28% had prickly heat; 13.9%
had acne; and 1.9% had nonbullous impetigo.12
Vietnam Conflict
Statistics for hospital admissions and outpatient
visits are more complete for the Vietnam conflict
than for any other in which the United States has
been involved,1 although many experts believe sub-
stantial underreporting of outpatient information
took place because of political pressures on com-
manders during the war.
Skin diseases were the single greatest cause of
outpatient visits to U.S. Army medical facilities
during the entire Vietnam conflict.1,13  There were
1,412,500 recorded visits for skin diseases, twice as
many as for any other category of disease.1  Skin
disease was probably significantly underreported
because most troops suffering from pyoderma and
fungal infections were placed on light duty and
never appeared in reported statistics.  One of the
greatest medical causes of combat ineffectiveness in
Vietnam was cutaneous disease.1,13,14  In some line

Military Dermatology
4
units in the Mekong Delta, man-days lost from
combat duty secondary to cutaneous disease ex-
ceeded losses from all other causes combined.14
Skin disease had far greater impact on front-line
military units, with relative sparing of troops in
garrison.  Hot, humid conditions and poor hygiene
magnified this disparity.  The U.S. Ninth Infantry
Division operated in the Delta region in southern
South Vietnam and suffered the greatest impact.
Forty-seven percent of the total man-days lost to the
division in a 1-year period (1968–1969) were due to
skin disease.1  This figure includes battle wounds,
nonbattle injuries, and disease.1  More significantly,
in actual infantry battalions, 80% of the man-days
lost in this division were due to skin disease.1
Of all soldiers seeking medical treatment for skin
diseases during the Vietnam conflict, fewer than 1%
were hospitalized.  Cases were selected for hospi-
talization based on the disease severity, refractori-
ness to outpatient treatment, and interest to the
physician.  This procedure was in direct contrast to
such diseases as malaria and hepatitis, for which
hospitalization was routinely practiced.  In this
context, the following hospital statistics are even
more impressive.  By category of disease, skin dis-
ease was the third leading cause for admission,
ranking behind diarrheal disease and respiratory
infections.1  Malaria was the fourth leading cause.1
From 1965 through 1972, 45,815 soldiers were ad-
mitted by all medical officers for skin disease.
Pyoderma, eczema, cystic acne, and tinea led the list
of diagnoses for admission.1  Of soldiers hospital-
ized by dermatologists, 20% to 25% were evacuated
from Vietnam: a total of 4,166 soldiers.1  This figure
represents 9.7% of all evacuations from Vietnam for
disease.1
Lessons Not Learned
Lessons not learned relating to skin disease have
arisen from inadequate organization and training.
The following section contains quotations from the
official histories of warfare in this century that
convey many common themes.  We clearly have not
learned or have not acted on lessons relating to the
dermatologic problems from one conflict to the
next.
Organization
The Table of Organization and Equipment (TOE)
of today’s army hospitals in almost all instances
does not contain a position for a dermatologist, a
situation identical to that at the onset of World War
II.  Furthermore, no positions exist for dermatolo-
gists in division, corps, or army medical staffs.
Outpatient dermatologic care is almost totally ne-
glected at division level and below.  Corps assets
are severely lacking.
In 1947, Pillsbury and Livingood warned, con-
cerning the U.S. Army in World War II, that in any
military organization of greater than 100,000 troop
strength, the surgeon in charge should have an
advisor in dermatology.  They envisioned that the
dermatologist would be assigned to a hospital but
should be called on for advice regarding the overall
policies relating to cutaneous diseases in the com-
mand, and should visit units at intervals to deter-
mine the incidence of dermatologic disease and be
of assistance to the unit medical officers.6
Cautionary advice was not directed solely at the
United States.  In 1953, W. R. Feasby, in commenting
on Canadian forces in World War II, wrote that each
command should have the service of a dermatolo-
gist, as should each large concentration of person-
nel of all three services.  He further stated that each
corps or army should have a senior dermatologist,
with one or two junior specialists available per
division.15  Duncan and Stout,11 in an official history
of New Zealand in World War II, remarked that
each hospital unit in an overseas force should have
a skin specialist on its staff.
The British army was better organized for
dermatologic care than other Allied forces in World
War II.  The British followed their consultant’s
recommendations in organizational structure.
He advised that on the staff of the Director of
Medical Services of each army there should be an
advisor or consultant in dermatology.  A funda-
mental part of the policy adopted in organizing a
dermatologic service was that fully equipped cen-
ters, each under the aegis of a trained dermatolo-
gist, were available, and that evacuation of cases
to these centers was rapidly achieved.  Further, in
each corps a dermatologist was available whose
activity was not entirely confined to work in a skin
clinic.  He had authority to travel about the corps
area and to instruct unit medical officers on the
prevention, diagnosis, and treatment of cutaneous
disease.4
Training
With today’s emphasis on specialization, the ever-
decreasing number of flexible or rotating intern-
ships, and the lack of required rotations in derma-

Historical Overview and Principles of Diagnosis
5
tology in the medical education of a large majority
of physicians and medical students, we remain
poorly trained to care for dermatologic diseases.
Regarding diagnostic skills in the U.S. Army in
World War II, it was noted that many physicians
had so little opportunity for dermatologic training
in medical school and internship that they were
unable to arrive at a diagnosis of even the simplest
conditions of the skin.6
Up-to-date, specialized publications on derma-
tologic diagnosis and care in a field environment
are important to supplementing the knowledge base
of all military physicians and physician assistants.
In Washington, D.C., in 1942, at the instigation of
the U.S. Army and the Committee of Medicine of
the National Research Council, the preparation of a
simple manual dealing with the diagnosis and treat-
ment of cutaneous diseases commonly encountered
was completed.6,8  This small textbook manual was
distributed to nearly all medical corps officers in
the U.S. Army, Army Air Corps, and Navy.  Many
wartime hospital reports carry the statement that
dermatologic disabilities could have been cut in
half if treatment methods had been improved and
patients had been brought into early contact with a
dermatologist.7
R. M. B. MacKenna, writing about the British
army in World War II, remarked that a poorly
trained healthcare provider could do more harm
than good:
It is important to realize that usually the greatest
hazard to which a patient who is suffering from a
cutaneous disease is exposed during the first stages
of his malady is that he is treated by a unit (regimen-
tal) medical officer who, as he has had no specialized
training in dermatology, may be uncertain of the
diagnosis, and therefore may conduct treatment by
a method of trial and error.  This method is success-
ful only in a few cases.  In the majority it leads to
an aggravation of the disability or dermatitis
medicamentosa and eventually to an unneces
sarily prolonged period of hospitalization.4(p159)
Commenting on skin diseases in the U.S. Army in
Vietnam, A. M. Allen observed that the lack of
emphasis on education and training in dermatol-
ogy was undoubtedly responsible for a large por-
tion of the morbidity caused by skin diseases.  This
lack of emphasis was not apparent in other medical
fields of importance in tropical warfare, such as
malaria and enteric diseases, but seemed to be at-
tributable to a general lack of appreciation for the
enormous losses of manpower that can result from
cutaneous diseases.  He concluded that, with the
exception of dermatologists, the medical personnel
who were called upon to diagnose, treat and pre-
vent skin disease in Vietnam had little if any train-
ing in dermatology.1  In Vietnam, until the appear-
ance of a field manual on skin disease in 1969, very
little relevant information was available, and some
of what was available was misleading.  The manual
published in 1942 was long outdated.
Recommendations
To provide first-rate military medical care and to
preserve the fighting strength of our soldiers by
preventing as well as treating skin diseases, we
must address three areas of weakness that have
been important historically: organization, training,
and research.  We must reorganize our TOEs, up-
grade our training efforts to train healthcare pro-
viders adequately about the importance of skin
care in the field, and reestablish significant
research efforts to solve lingering and recurrent
dermatologic problems.
Organization
Working closely with the Combat Developments
Division of the U.S. Army Medical Department
Center and School, we must reexamine TOEs for
medical forces.  A dermatologist should be on the
staff of all larger TOE hospitals.  Corps-level assets
should have a dermatology team with adequate
vehicle support to travel about the corps and divi-
sion areas to evaluate, teach, and treat.  One senior
consultant dermatologist should be assigned to
corps staff and should direct teams that provide
outpatient care to divisional level troops, ensuring
that two dermatologists are available in each corps
team for each division supported.  A theater con-
sultant in dermatology and a dermatology team
should be assigned for all troop deployments greater
than division level, unless deployment is to a tropi-
cal area, in which case a consultant and team should
be assigned for brigade-size and larger deploy-
ments.  Early prevention and outpatient treatment
can prevent many of the medical casualties experi-
enced in prior conflicts.  A change in the Profes-
sional Filler System (PROFIS) approach to desig-
nating dermatology specialists is necessary, in which
dermatologists would be assigned to dermatology
teams or consultant positions.  While this change is
being instituted, consideration should be given to
assigning dermatologists to Division Preventive

Military Dermatology
6
Medicine Officer positions in the PROFIS system.
Sets, kits, and outfits (SKOs) must be updated to
ensure appropriate dermatologic therapeutics and
supplies for all levels, from the company aidman’s
bag through dermatology team sets.
Training
Mandatory rotations in dermatology should be
established for all military nonsurgical interns and
residents to provide a significant base of knowl-
edge for the diagnosis and treatment of common
skin diseases.  Military medical training centers
must ensure that a core curriculum for dermatology
residents and medical students covers the common
skin diseases and does not emphasize only the rare
and unusual diseases.  There should be continued
work with the American Academy of Dermatology
in establishing a core curriculum in dermatology
for nondermatologists.  A manual of dermatology
for physicians patterned after the National Research
Council’s World War II manual8 covering common
dermatologic problems and their treatment should
be published, widely distributed, and periodically
updated.  Universal distribution to military physi-
cians of such a manual should be ensured as is done
for the The Emergency War Surgery NATO Handbook.16
The dermatology consultant’s input into basic medi-
cal training for corpsmen should be ensured.
Research
Since the demise of the Department of Dermatol-
ogy Research at the Letterman Army Institute of
Research,  The Presidio, San Francisco, California,
in 1980, almost no research relating to field prob-
lems and skin disease has been conducted by the
services.  Research efforts should be reestablished
through the U.S. Army Medical Research and De-
velopment Command to address better field diag-
nosis and treatment of common disabling dermato-
logic conditions such as pyoderma, fungal infections,
and miliaria.  An in-depth review of bathing avail-
ability and requirements and their relationship to
skin disease should take place.  A method of fund-
ing should be developed to allow military training
programs in dermatology to send small research
teams to locations such as the Jungle Warfare School
in Panama, where field studies can address real-
time problems.  The military should resurrect, fur-
ther develop, and field better protective and pre-
ventive items of issue such as shower thongs for
wear by troops in base camps to decrease suscepti-
bility to foot problems.1,9
PRINCIPLES OF DIAGNOSIS
The advantage a medical officer has in caring for
the soldier with skin disease is that the abnormali-
ties about which the complaint revolves are usually
visible, and may also be palpable.  In the perfor-
mance of the direct examination, key clues must be
carefully noted by a discerning, educated detective.
Additional observations that can aid in solving the
diagnostic mystery are easily gained by examining
the skin and mucous membrane sites not directly
called into question by the soldier, and through
directed questioning.  Laboratory tests taken as
standard of care in a hospital, such as potassium
hydroxide preparations, Tzanck preparations, cul-
tures, and skin biopsies, may not be readily avail-
able in the field.  Thus, maximum use of informa-
tion gained by close, educated inspection is
necessary.
Anatomy
Knowledge of the normal anatomy is essential
before the healthcare provider can understand der-
matologic terminology and principles of diagnosis.
The skin is composed of three basic layers: the
epidermis, the dermis, and the subcutaneous tissue.
The epidermis is the most superficial and thinnest
of the three; however, it is the principal site avail-
able for inspection.  A key finding in proceeding
through differential diagnostic possibilities will be
based on the pivotal answer to this question: Is
there epidermal involvement?  Normal epidermis is
smooth-surfaced and has skin lines running through
it at regular intervals.  With the notable exception of
the palms and soles, most areas have small, regu-
larly placed openings through which hairs grow.  It
should be appreciated that most cells that compose
the epidermis are keratinocytes, whose primary
role is to provide a physical barrier to external
forces.  A smaller subset of cells is concerned with
pigment production.  These cells—melanocytes—
give the skin its normal color but can be damaged
after inflammation or may proliferate, leading to
the potentially deadly growth, melanoma.  Although
a third group of cells exist, the Langerhans cells,

Historical Overview and Principles of Diagnosis
7
which provide immunological surveillance, these
cells are rarely important in observational diagno-
sis of the conditions discussed in this text.
The dermis is the site of residence of most com-
ponents of the skin.  Within this 1- to 4-mm area lie
blood vessels, nerves, glands, hair follicles, and
structural matrix.  This tough but flexible layer of
tissue provides for temperature regulation, sensa-
tion, and natural lubrication, and gives to the skin
many of the cosmetically important characteristics
valued by all of us.  Abnormalities of the dermis that
will provide clues to the diagnostic dilemmas posed
most commonly in the field environment involve
vascular dilation and inflammation.  A blanchable
redness of the skin implies that one or both of these
changes have occurred.  A nonblanching redness
usually results from extravasation of erythrocytes
into the dermis secondary to vascular damage.
A noninflammatory thickening or growth con-
fined to the dermis (with normal overlying epider-
mis) usually occurs from a benign or malignant
tumor of existing normal structures or from an
infiltrative disease.  In most cases, a biopsy is re-
quired to make a definitive diagnosis.  The impor-
tance of these sporadic conditions to military medi-
cine is minor.  The key diagnostic intervention, the
skin biopsy, is often deferred unless the lesion is
growing rapidly or numerous sites are involved.
Dermal tumors and infiltrative diseases will gener-
ally not be discussed in this textbook.
The third layer of the skin, the subcutaneous
tissue, is composed primarily of fat cells and pro-
vides insulation, cushioning, and a reserve energy
source.  In general, disorders of the fat are of lesser
importance in the field due to their sporadic nature.
Skin biopsy is usually required for definitive diag-
nosis.
Physical Examination
Of the numerous diagnostic clues available to the
physician, the morphologic characteristics of the
lesions are often the most helpful.  They provide
a useful means of categorizing disease states and
allow generation of a meaningful differential
diagnosis.  Once the primary lesion is recognized,
other characteristics obtained by observing second-
ary changes, configuration, regional distribution,
and associated nondermatologic signs as well as
historical information will quickly narrow the
possibilities.  To use this approach, physicians
should employ the basic vocabulary that defines
primary and secondary skin changes as well as
special lesions and configurations, as presented in
Figures 1-1 through 1-19.  It is in these words the
healthcare provider needs to tell the story of skin
disease because, if the end of the diagnostic trail
cannot be successfully reached, consultation
couched in these terms will be most rapidly and
reliably regarded.
Such obvious information as age, sex, race, and
regional distribution (covered vs sun-exposed, flex-
ural vs extensor, truncal vs extremity) needs to be
consciously noted and included for consideration.
Finally, inspection of the skin is not complete unless
details of any alteration in color, consistency, or
growth pattern of hair and nails are noted.  The
mucous membranes are to be viewed as important
sites of ancillary clues to the diagnosis and should
be examined closely in all soldiers who present with
skin disorders.
Patient History
Although the physical characteristics of skin le-
sions provide the most critical information leading
to diagnosis, a historical account of the evolution
of the disease is important not only to understand
the disease process better but, often more vital, to
allow soldiers to express their unique, individual
concerns to the physician.  All soldiers desire a
correct diagnosis and effective medication for their
condition, but equally crucial in most cases is the
individualized education given to them by a sin-
cere, concerned, thoughtful physician.  Only by
allowing soldiers to tell their stories can this be
accomplished.
In nearly every encounter, the duration and evo-
lution of the disorder, as well as any previous
therapy that may have altered the natural course,
need to be elicited.  Skin-related symptoms, par-
ticularly with regard to itching or pain, as well as
associated, concurrent, systemic symptoms; past
medical history (especially as related to oral medi-
cation and allergies); family history; and social his-
tory may be important in individual cases.  The
medical officer needs to understand (a) how the
disease affects the soldier (does it impair function,
alter sleep, or cause cosmetic concern?); (b) the
reason the soldier sought care; (c) suggested causes,
diagnoses, or therapies; and (d) the main concern of
the soldier (eg, “Is it cancer?” “Am I going to give
this to my friends?” “What did I do to cause this?”
“Can I avoid [anything] to make myself better?”).
All of these are of paramount importance in history-
taking.

Military Dermatology
8
Differential Diagnostic Considerations
The algorithms included in this chapter (Figures
1-20 through 1-25) are presented for the nonderma-
tologist in the field who is tasked with the care of
soldiers without laboratory or skin biopsy capabil-
ity.  The algorithms address only some of the most
commonly seen skin diseases.  These diagnostic
road maps make use of classic characteristics of the
disease categories depicted.  Many variations from
the standard presenting physical findings exist;
therefore, these algorithms are not foolproof.  They
depend on the medical officer’s recognition of the
primary or predominant physical findings.  Once a
diagnosis is reached, the appropriate section of this
book can be referred to for further information.
Useful tests or additional information that will help
to confirm the diagnosis have been added next to
the algorithm endpoints; the tests can be obtained
when support is, or becomes, available.
Fig. 1-1. Primary versus secondary lesions. Primary le-
sions are the earliest alterations present. With the pas-
sage of time, changes may occur leading to less diagnos-
tic secondary lesions. Reprinted from the AAD Library of
Teaching Slides with permission from the American Acad-
emy of Dermatology.
Fig. 1-3. Vesicle and bulla. Blisters containing clear fluid.
Vesicles are the smaller of the two, with bullae being
0.5 cm or larger. Reprinted from the AAD Library of
Teaching Slides with permission from the American Acad-
emy of Dermatology.
Fig. 1-2. Macule. A flat change in color of the skin.
Reprinted from the AAD Library of Teaching Slides with
permission from the American Academy of Dermatology.
Fig. 1-4. Pustule. Yellowish cloudy fluid is present. Re-
printed from the AAD Library of Teaching Slides with
permission from the American Academy of Dermatology.
Fig 1-1 is not shown because the copyright permis-
sion granted to the Borden Institute, TMM, does not
allow the Borden Institute to grant permission to
other users and/or does not include usage in
electronic media. The current user must apply to the
publisher named in the figure legend  for permis-
sion to use this illustration in any type of publica-
tion media.
Fig 1-3 is not shown because the copyright permis-
sion granted to the Borden Institute, TMM, does not
allow the Borden Institute to grant permission to
other users and/or does not include usage in
electronic media. The current user must apply to
the publisher named in the figure legend  for
permission to use this illustration in any type of
publication media.
Fig 1-2 is not shown because the copyright
permission granted to the Borden Institute, TMM,
does not allow the Borden Institute to grant
permission to other users and/or does not include
usage in electronic media. The current user must
apply to the publisher named in the figure legend
for permission to use this illustration in any type
of publication media.
Fig 1-4 is not shown because the copyright permis-
sion granted to the Borden Institute, TMM, does
not allow the Borden Institute to grant permission
to other users and/or does not include usage in
electronic media. The current user must apply to
the publisher named in the figure legend  for
permission to use this illustration in any type of
publication media.

Historical Overview and Principles of Diagnosis
9
Fig. 1-7. Wheal. Edema causes a transient papule or
plaque to occur. Reprinted from the AAD Library of
Teaching Slides with permission from the American Acad-
emy of Dermatology.
Fig. 1-5. Papules, nodules, and tumors are palpable skin
lesions of varying size. Papules are less than 0.5 cm in
diameter, nodules larger. Tumors are very large growths.
Reprinted from the AAD Library of Teaching Slides with
permission from the American Academy of Dermatology.
Fig. 1-6. Plaque. An elevated, flat-topped lesion whose
width exceeds its height. Reprinted from the AAD Li-
brary of Teaching Slides with permission from the Ameri-
can Academy of Dermatology.
Fig. 1-8. Scale. Dry, usually whitish flakes on the surface
of the epidermis. Reprinted from the AAD Library of
Teaching Slides with permission from the American Acad-
emy of Dermatology.
Fig 1-5 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does not
include usage in electronic media. The current
user must apply to the publisher named in the
figure legend  for permission to use this illustra-
tion in any type of publication media.
Fig 1-7 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does not
include usage in electronic media. The current
user must apply to the publisher named in the
figure legend  for permission to use this illustra-
tion in any type of publication media.
Fig 1-6 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does not
include usage in electronic media. The current
user must apply to the publisher named in the
figure legend  for permission to use this illustra-
tion in any type of publication media.
Fig 1-8 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does
not include usage in electronic media. The
current user must apply to the publisher
named in the figure legend  for permission to
use this illustration in any type of publication
media.

Military Dermatology
10
Fig. 1-11. Lichenification. A thickening of the epidermis
leading to accentuated skin markings.
Fig. 1-12. Atrophy. A thin, wrinkled, often depressed
area resulting from loss of skin tissue.
Fig. 1-10. Fissure, erosion, ulcer. Fissures are thin linear
tears in the epidermis. An erosion is a wider-based loss of a
portion of the epidermis, while an ulcer is larger and deeper.
Reprinted from the AAD Library of Teaching Slides with
permission from the American Academy of Dermatology.
Fig. 1-9. Oozing and crusts. Oozing consists of tissue fluid,
often with cellular debris, exuding from acutely inflamed
skin. Crusts are usually moist, yellowish debris and appear
when the fluid from vesicles, bullae, pustules, or oozing
dries. Reprinted from the AAD Library of Teaching Slides with
permission from the American Academy of Dermatology.
Fig 1-9 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does
not include usage in electronic media. The
current user must apply to the publisher
named in the figure legend  for permission to
use this illustration in any type of publication
media.
Fig 1-11 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does not
include usage in electronic media. The current
user must apply to the publisher named in the
figure legend  for permission to use this
illustration in any type of publication media.
Fig 1-10 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does
not include usage in electronic media. The
current user must apply to the publisher
named in the figure legend  for permission to
use this illustration in any type of publication
media.
Fig 1-12 is not shown because the copyright
permission granted to the Borden Institute, TMM,
does not allow the Borden Institute to grant
permission to other users and/or does not
include usage in electronic media. The current
user must apply to the publisher named in the
figure legend  for permission to use this illustra-
tion in any type of publication media.

Historical Overview and Principles of Diagnosis
11
Fig. 1-13. Comedo. Commonly called blackheads or
whiteheads, these keratin-filled hair follicles are the ear-
liest lesions of acne. Reprinted from the AAD Library of
Teaching Slides with permission from the American Acad-
emy of Dermatology.
Fig. 1-14. Telangiectasia. Enlarged superficial blood ves-
sels. Reprinted from the AAD Library of Teaching Slides
with permission from the American Academy of Derma-
tology.
Fig. 1-15. Burrow. The scabies mite will leave a linear
track as she moves through the epidermis. Reprinted
from the AAD Library of Teaching Slides with permis-
sion from the American Academy of Dermatology.
Fig. 1-16. Scar. New formation of connective tissue as a
reparative process due to damage to the dermis or deeper
tissues. Reprinted from the AAD Library of Teaching
Slides with permission from the American Academy of
Dermatology.
Fig 1-13 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does
not include usage in electronic media. The
current user must apply to the publisher
named in the figure legend  for permission to
use this illustration in any type of publication
media.
Fig 1-14 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does
not include usage in electronic media. The
current user must apply to the publisher
named in the figure legend  for permission to
use this illustration in any type of publication
media.
Fig 1-15 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does not
include usage in electronic media. The current
user must apply to the publisher named in the
figure legend  for permission to use this
illustration in any type of publication media.
Fig 1-16 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does not
include usage in electronic media. The current
user must apply to the publisher named in the
figure legend  for permission to use this illustra-
tion in any type of publication media.

Military Dermatology
12
OK to put on the Web
OK to put on the Web
OK to put on the Web
Fig. 1-17. Poison ivy will often cause linear lesions due to
brushing of the plant against the skin or spreading of the
allergen by scratching.
Fig. 1-18. Grouped vesicles on an erythematous base
characterize herpes simplex as well as herpes zoster.
Fig. 1-19. An annular arrangement describes a ringlike
lesion that surrounds a central area of more normal-
appearing skin.

Historical Overview and Principles of Diagnosis
13
Yes
No
Acne
Perifollicular?
Yes
No
Location?
Crusts?
Yes
No
Rosacea
Flexural or
Occluded Skin?
Impetigo
G, C
Folliculitis
G, C
Candidiasis
K, C
Beard or
extrafacial
Central face
Yes
C: Culture
G: Gram’s stain
K: Potassium hydroxide preparation (KOH)
Fig. 1-20. Pustular lesions are often a sign of bacterial or fungal infection. Gram’s stain, culture, and potassium
hydroxide analysis will aid in the diagnosis of these conditions.
Comedones?
Pustules

Military Dermatology
14
Vesicles and Bullae
Yes
No
Grouped?
Linear?
No
Yes
Yes
Herpes Simples
T, C
Herpes Zoster
T, C
Allergic Contact Dermatitis
Bx, P
Irritant Contact Dermatitis
Hx
No
Widespread?
Yes
No
Chicken Pox
T, C
Autoimmune Disease
Bx
Bullous Impetigo
G, C
Porphyria Cutanea Tarda
Bx
Dermatomal
Distribution?
C: Culture
Bx: Biopsy
G: Gram’s stain
Hx: History
P: Patch test
T:
Tzanck smear
Fig. 1-21. Blisters may be a sign of infection; however, in a field environment they are likely to be secondary to irritant
or allergic contact dermatitis.

Historical Overview and Principles of Diagnosis
15
No
Melanoma:
Bx soon
No
Yes
Epidermal
Involvement?
Dermal Tumor
or Cyst:
 Bx Usually Elective
No
Yes
Translucent
Surface?
Multiple Small
Lesions?
Warty Surface?
Yes
Yes
No
No
Wart Bx
Squamous Cell Carcinoma
(Look for crusted or
ulcerated surface on
hard nodule)
Bx
Basal Cell
Carcinoma
Bx
Molluscum
Contagiosum
CP, Bx
Pigmented?
Fig. 1-22. New or changing growths do not often require immediate attention in the field, as they are usually slow in
their development.
New or Changing Growth
Yes
Bx: Biopsy
CP: Crush preparation with microscopy

Military Dermatology
16
Widespread?
Scalp, Retroauricular,
Eyebrows, Nasolabial
Folds?
No
Herald Patch?
Pityriasis
Rosea
Bx
Seborrheic
Dermatitis
Superficial Fungal
Infection:
Tinea Pedis
Tinea Cruris
Tinea Manum
Tinea Corporus
Tinea Faciale
K, C
Syphilis
(Look at palms,
soles, and oral
mucosa)
Bx, VDRL, Hx
Reddish-brown
papules
Silvery scales on
pink base
Whitish macules
Psoriasis
(Look at scalp,
elbows, knees,
and nails)
 Bx, Hx
Tinea
Versicolor
K
Color?
Fig. 1-23. A number of disorders exhibit scaling papules, plaques, and patches. Superficial fungal infections are
extremely common in tropical environments. Syphilis is important to recognize because treatment will prevent long-
term sequelae and spread of disease.
No
Yes
Yes
No
Yes
Scaling Papules, Plaques, and Patches
Bx: Biopsy
C:
Culture
Hx: History
K:
Potassium hydroxide preparation (KOH)
VDRL:
Veneral disease research laboratory test (Syphilis serology)

Historical Overview and Principles of Diagnosis
17
Widespread?
Primarily
Sun Exposed?
Fever?
Viral Exanthem
(Look at oral
mucosa)
Hx, SS
Drug Eruption
Hx, Bx
Lupus
Erythematosus
Bx, ANA, SS
Cellulitis
(Look for warmth,
tenderness, fever)
C
ANA:
Antinuclear antibody
Bx: Biopsy
C:
Culture
Hx: History
SS:
Systemic symptoms
Fig. 1-24. Macular erythema is a usually acute event that may worsen and even cause death if not recognized. A papular
component may sometimes be present.
No
Yes
No
Yes
No
Yes
Macular Erythema

Military Dermatology
18
Lichen Planus
(Look at oral mucosa,
lavender color)
Bx
Predominantly on
Genitals, Fingers,
Waist, and Buttocks?
Scabies
S
Randomly Distributed
and
Asymmetrical?
Insect Bites
(Look for grouping
and central puncta)
Hx, Bx
Primarily Truncal?
Yes
Milaria Rubra
Hx
Bx: Biopsy
Hx: History
S:
Scraping with microscopy
Fig. 1-25. Pruritic, inflamed papules are among the most common types of skin lesions. Itching is intense, and the
lesions commonly show secondary changes such as excoriations and crusts.
Pruritic, Inflamed Papules
No
Yes
No
Yes
No

Historical Overview and Principles of Diagnosis
19
SUMMARY
Skin diseases are a significant cause of combat
ineffectiveness, morbidity to soldiers, and poor
morale.  Their importance to military operations is
most pronounced in tropical and subtropical cli-
mates, where over half the man-days lost to front-
line troops are directly related to skin disease.  Al-
though these facts have been repeatedly observed
and recorded in official histories from World War I,
World War II, and the Vietnam conflict, the U.S.
Army today remains largely unprepared to prevent
skin disease or provide expert dermatologic medi-
cal care in tropical operations.
Reevaluation of Tables of Organization and
Equipment and Professional Filler System policies
is highly recommended.  Increased research on
the prevention and early treatment of skin dis-
eases is sorely needed.  Finally, training of non-
dermatologists in the basics of skin care, preventive
policies, and dermatologic diagnosis needs to be
accomplished.
REFERENCES
1.
Allen, AM. Skin Diseases in Vietnam, 1965–72. In: Ognibene AJ, ed. Internal Medicine in Vietnam. Vol 1.
Washington, DC: Medical Department, US Army, Office of The Surgeon General and Center of Military History;
1977: 2, 29–30, 34–35, 42.
2.
Tasker AN. Diseases of the skin. In: Siler JF, ed. Communicable and Other Diseases. In: The Medical Department of
the United States Army in the World War. Vol 9. Washington, DC: Medical Department, US Army, Office of The
Surgeon General; 1928:551–557.
3.
Lane CG. Medical progress, military dermatology. N Engl J Med. 1942;227:293–299.
4.
MacKenna RMB. Special contributions on military dermatology. British Med Bull. 1945;3:158–161.
5.
MacPherson WG, Horrocks WH, Beveridge WWO, eds. History of the Great War, Medical Services, Hygiene of the
War. London, England: His Majesty’s Stationery Office; 1923: 68–111.
6.
Pillsbury DM, Livingood CS. Experiences in military dermatology: Their interpretation in plans for improved
general medical care. Arch Dermatol and Syph. 1947;55:441–462.
7.
Pillsbury DM, Livingood CS. Dermatology. In: Havens WP, ed. Infectious Diseases and General Medicine. In:
Havens WP, Anderson RS, eds. Internal Medicine in World War II. Vol 3. Washington, DC: Medical Department,
US Army, Office of The Surgeon General; 1968: 543–588.
8.
Pillsbury DM, Sulzberger MB, Livingood CS. Manual of Dermatology. Philadelphia, Pa: WB Saunders Company;
1942: vi.
9.
Grauer FH, Helms ST, Ingalls TH. Skin infections. In: Hoff EC, ed. Communicable Diseases Transmitted Through
Contact or by Unknown Means. In: Coates JB Jr, ed. Preventive Medicine in World War II. Vol 5. Washington, DC:
Medical Department, US Army, Office of The Surgeon General; 1960: 83–137.
10.
Feasby WR, ed. Organization and campaigns. In: Official History of the Canadian Medical Services, 1939–1945. Vol
1. Ottawa, Canada: Queen’s Printer and Controller of Stationery; 1956: 391–427.
11.
Duncan T, Stout M. War Surgery and Medicine, Official History of New Zealand in the Second World War, 1939–45.
Wellington, New Zealand: War History Branch; 1954: 688–703.
12.
Sanderson PH, Sloper SC. Skin disease in the British army in S.E. Asia. Part 1. Influence of the environment on
skin disease. Brit J Dermatol. 1953;65:252–264.
13.
Blank H, Taplin D, Zaias N. Cutaneous Trichophyton mentagrophytes infections in Vietnam. Arch Dermatol.
1969;99:135–142.

Military Dermatology
20
14.
Allen AM, Taplin D, Lowy JA, Twigg L. Skin infections in Vietnam. Milit Med. 1972;137:295–301.
15.
Feasby WR. Clinical subjects. In: Official History of the Canadian Medical Services, 1939–1945. Vol 2. Ottawa,
Canada: Queen’s Printer and Controller of Stationery. 1953; 123–132.
16.
US Department of Defense. Bowen TE, Bellamy RF, eds. The Emergency War Surgery NATO Handbook. 2nd rev.
Washington, DC: GPO; 1988.

Cold-Induced Injury
21
Chapter 2
COLD-INDUCED INJURY
DAVE CORBETT, D.O.* AND PAUL BENSON, M.D.†
INTRODUCTION
MECHANISMS OF HEAT LOSS
Conduction
Convection
Radiation
Evaporation
Respiration
FACTORS INFLUENCING HEAT LOSS
Weather and Duration of Exposure
Type of Combat Action
Clothing
Other Factors
PATHOGENESIS OF COLD INJURY
DIRECT COLD INJURY
Asteatotic Eczema
Frostbite
INDIRECT COLD INJURY
Pernio
Livedo Reticularis
Acrocyanosis
Erythrocyanosis
Trench Foot
Cold Panniculitis
Raynaud’s Disease and Phenomenon
SUMMARY
*Captain, Medical Corps, U.S. Navy; Dermatology Branch, National Naval Medical Center, Bethesda, Maryland  20814
†Lieutenant Colonel, Medical Corps, U.S. Army; Dermatology Service, Walter Reed Army Medical Center, Washington, D.C.  20307-5001

Military Dermatology
22
INTRODUCTION
Cold injuries have played an important role in
the loss of combat effectiveness for armies since
early recorded history.  References to frostbite have
been found in the writings of Hippocrates, Aristotle,
and Galen.  Other historical entries have docu-
mented significant problems with cold injuries
among the Greek armies of the late fourth and early
third centuries BC.1
During the American Revolution, James Thatcher
described serious losses from cold injury in 1777; an
army of 10,000 men lost 2,900 to combat operations.
Even in 1777, there was some understanding of the
pathogenesis of cold injury.  A physician general to
the military hospitals, Benjamin Rush, wrote in a
small pamphlet with directions for preserving the
health of soldiers:
The commanding officer should take the utmost
care never to suffer a soldier to sleep, or even to sit
down in his tent with wet clothes, nor to lie down
in a wet blanket or upon damp straw.  The utmost
vigilance will be necessary to guard against this
fruitful source of diseases among soldiers.1(pp29–30)
Baron Larrey, surgeon to the French armies in
the Napoleonic Wars, described frostbite and
“congelation” as important reasons for the defeat of
the army in Poland in 1812.  He also noted that
“general remedies should always precede surgery”1
and described the detrimental effects of sudden rapid
warming of frozen body parts by the camp fire.
The Crimean War (1854–1856) revealed the im-
pact of proper training and equipment on the num-
ber of casualties caused by cold.  During the first
winter (1854–1855), British troops fought trench
warfare, with static defensive positions.  Soldiers
were inexperienced and unfamiliar with the poten-
tial hazards of cold weather.  They were also ham-
pered by a lack of adequate food and clothing, and
the debilitating effects of diarrhea and dysentery.
In a force of slightly less than 50,000 soldiers, 1,924
cases of cold injury were reported, with 457 fatali-
ties—23.8% of the total cold injuries.  During the
winter of 1855 to 1856, there were only 474 cases of
cold injury and 6 fatalities (1.3%).  Weather condi-
tions and precipitation were essentially the same in
both years.  But during the second year the troops
had far better living conditions along with improved
winter clothing and ample food.  The average sol-
dier was hardened and knew better how to care for
himself and prevent cold injury.1
In the Franco-Prussian War of 1870, 1,450 cases of
severe frostbite occurred among 92,067 Prussian
troops.  During the Russo-Turkish War (1877–1878),
4,500 frostbite casualties were reported, represent-
ing 1.5% of the 300,000-man force in Bulgaria and
5.1% of the 87,989 casualties evacuated.1
British medical observers with the Japanese Army
made detailed reports from 25–29 January 1905
during the Russo-Japanese War.  Of 7,742 total
casualties, 505 soldiers were hospitalized for frost-
bite, approximately a 1:15 ratio of frostbite to battle
wounds.  The toes were affected in 67% of the cold
injury cases and the fingers in 28%.  Injuries were
mild and amputation was seldom required.  In a
subsequent engagement, the British observers noted
that the Japanese troops were given extra socks and
rations.  Halts were called during marches to re-
move boots and replace them with Chinese felt or
straw shoes.  The number of frostbite casualties
dropped dramatically to only 70 soldiers hospital-
ized for cold injury.1
The most detailed history of cold injuries among
combat soldiers can be gleaned from World War I.
The British experience is the most extensive, and
U.S. casualties were lower as a result of lessons
learned before our involvement.  Additionally, most
of the trench warfare for U.S. forces occurred dur-
ing times of the year when exposure to cold and wet
was not great.  The British, however, did not seem to
profit from their experience in the Crimean War
and, as a result, their expeditionary force suffered a
high rate of cold injury during the first winter of
World War I.1  Injuries were reported as frostbite,
water bite, footbite, cold bite, puttee bite, trench
bite, chilled feet, or only as “feet cases.”1  Not until
after the first winter did the term “trench foot”
come into general usage.  Medical and nonmedical
officers promptly realized the significance of this
affliction, which is caused by prolonged exposure
to cold and dampness at temperatures above freez-
ing.  Forces suffered not only loss of manpower but
the additional financial consideration of casualties
that were entitled to disability pensions.1
Cold injury began insidiously among British
troops with one case of frostbite in August 1914, one
in September, 11 in October, 1,555 in November,
and 4,823 in December, when the term “trench foot”
first appeared in medical records.  The highest
incidence of cold injury was in the infantry, with
officers affected slightly less severely than enlisted

Cold-Induced Injury
23
soldiers.  The total number of cold injuries in all
theaters of operations and bases including the United
Kingdom was 115,361 cases.  During 1915, the cases
of frostbite and trench foot were separated (they
were not thereafter), with 30,691 admissions for
frostbite and 29,172 for trench foot.  Total cold
injuries for 1914 to 1915 numbered 97,414 cases.
Only 443 cases were noted in the hospital records of
1916 to 1918.1
The American records for World War I reveal a
total of 2,061 admissions for trench foot, which includ-
ed 27 officers.  The total number of man-days lost was
92,249, an average of 45 days per case.  Preventive
measures included regular inspections of the feet
by officers, as well as changing socks once daily,
foot exercises, dry clothing, and a nutritious diet.1
The lessons from World War I were forgotten
and the United States sustained many casualties in
World War II before the problem was again taken
seriously.  Cold injuries ranged from high-altitude
frostbite injuries to trench foot and immersion foot
injuries suffered by ground troops from the
Mediterranean and European theaters to the Aleu-
tian Islands.  Lessons learned in one theater or
service were not used to full advantage in other
theaters.1
The Eighth Air Force could attribute varying
proportions of the total number of casualties in
airborne personnel to high altitude frostbite from
the beginning of their operations in 1942 to the end
of conflict in May 1945.  During fiscal year 1943 to
1944, more crew members sustained wounds from
cold than from enemy fire.  These losses were even
more significant in that one third required hospital-
ization, with an average loss of 4 to 14 days of duty
even for mild injuries.  Of these, many required
months of recuperation and many were unable ever
to return to duty.1  For one 14-month period ending
in December 1943, 1,634 men were removed from
flying status as a result of cold injuries.  During this
same period, 1,207 men were removed from flying
status because of injuries sustained from enemy
action.  In 1944 the number of casualties increased
because of increased combat operations, but the
percentage of losses from cold injuries decreased
presumably because of lessons learned as well as
improved equipment and training.1
In the Mediterranean theater, during the winter
of 1943 to 1944, combat ground losses from cold
injuries, mainly trench foot, were significant.  For
the 6-month period ending 30 April 1944, there
were 5,700 cold casualties of 27,602 wounded in
action, or an approximate 1:5 ratio of cold-to-com-
bat loss, for the Fifth U.S. Army alone.1  These losses
become even more significant when we realize that
almost all these injuries occurred among combat
troops, the most difficult to replace.  Many of these
troops were never able to return to full duty.  Of
those who did return to duty, about 60% were
casualties the following winter, as recurrent trench
foot was a significant problem.  Improved clothing
and education and changes in the daily routine
(such as changing socks at least daily and providing
laundry and exchange of dirty socks for clean socks)
were instrumental in reducing these numbers the
following winter.  The British had much lower cold
casualty rates yet they fought in the same weather
conditions and intensity of combat as the American
forces.  The British had troop rotation, much stricter
enforcement of foot care, and better clothing than
the Americans.  Their cold-to-combat loss ratio was
1:45, compared to a 1:4 ratio for the Americans
during the same period.1
The bitter lessons learned by the Fifth U.S. Army
in Italy during 1943 to 1944 unfortunately did not
reduce cold injuries in the European theater.  Records
show 46,000 cold injuries in the European theater
from autumn 1944 to spring 1945, or about 5% of all
hospital admissions for medical treatment.  In the
Mediterranean theater, the rate had dropped to
1.3% of admissions from 4% the previous winter.
Cases peaked the week ending 17 November 1944
with 5,386 cases, with another smaller peak of 3,213
cases appearing during the week ending 29 Decem-
ber 1944, the Battle of the Bulge.  The incidence of
frostbite was much higher during December, with
more cases of trench foot in November.  After the
spring thaw began 1 February 1945, the character of
the epidemic returned to increasing numbers of
trench foot cases.  During November and December
1944, there were an astonishing 23,000 cases of cold
injury on the Western Front.  In terms of combat
riflemen (4,000 to a division), the loss amounted to
about 5.5 divisions.1
Changes in clothing types and design had oc-
curred because of U.S. experiences in Italy during
the winter of 1943 to 1944, but requisitions were
made too late and clothing did not arrive in theater
until after the worst of winter was over.  Poorly
fitting and poorly insulated shoes, a lack of ad-
equate socks, and poorly fitting outer garments all
played a role in producing the large number of cold
casualties sustained in the European theater.  The
mistaken belief that the war would end before win-
ter arrived in 1944 was a factor in not requisitioning
the necessary cold weather clothing.1
During the Korean conflict, experiences of previ-
ous wars were once again forgotten, and 9,000 cold

Military Dermatology
24
injuries were reported, mostly frostbite.2  Of these
injuries, 8,000 occurred in the winter of 1950 to
1951.2  Inactivity such as often occurs in heavy com-
bat seemed to be a prime factor in developing cold
injuries.  In one study of over 1,000 cases, 67% of
cold-injured individuals had been pinned down by
enemy fire, sleeping in a foxhole, or riding in a
truck.3  Comparing injuries from the winters of 1950
to 1951 and 1951 to 1952 shows a decrease not only
in numbers, but in severity as well.  Nearly 50% of
frostbite injuries were third and fourth degree dur-
ing 1950 to 1951 compared to only 25% during 1951
to 1952.3  This lessened severity seems best related
to the change in U.S. military position during the
second winter from more active combat to a more
static defensive position.3  One third of the cold
injuries during the winter of 1951 to 1952 occurred
during the period 22 to 26 November during an en-
emy attack.  American troops were changing posi-
tions previously held by Republic of Korea person-
nel and were pinned down.3  To show the importance
of combat tempo on the cold casualty rate, Orr4
noted the following statistics from the winter of
1950 to 1951, based on 320 soldiers from one unit
admitted to Osaka Army Hospital over a 90-day
period: days with no enemy contact had an average
of 0.7 admissions per day; light contact, 1.2 admis-
sions per day; moderate contact, 6.4 admissions per
day; and heavy action, 9.3 admissions per day.
History has repeatedly demonstrated the devas-
tating effects of underestimating the impact of cold
weather and of failing to plan for cold weather
EXHIBIT 2-1
PREVENTION OF COLD INJURIES
Leadership
Buddy system
Instruction and training
Appropriate clothing
Protection of skin from contact with metals or liquids
Advance meteorologic data
Frequent troop rotation
Adequate diet and hydration
Adequate rest
Data source: Corbett D. Cold injuries. Journal of the Assoc-
iation of Military Dermatologists. Fall 1982:8(2):34–40.
injuries.  The British may have had fewer casualties
because of the way they approached the prevention
of cold injuries.  Their view was that cold injuries
were a result of poor leadership rather than a need
for better medical care.  Cold injuries, like heat
injuries, are avoidable in all but the most intense
combat situations.  Close supervision, constant
education, and adequate equipment are essential
to avoiding cold injuries (Exhibit 2-1).  As medical
professionals, our duties and obligations are to
provide the best educational support to the line
unit commanders as well as to provide the best
treatment for injuries.
MECHANISMS OF HEAT LOSS
Cold injury is the damage to tissue produced by
heat loss, resulting from exposure to cold.  This loss
can occur by several mechanisms: conduction, con-
vection, radiation, evaporation, and respiration.
Conduction
Conduction loss is heat loss by direct contact
with a cold object.  This loss is infrequent but can be
a severe source of injury.  Contact with cold metal is
a common injury.  Liquids such as gasoline and other
solvents cause rapid evaporative cooling because of
their low freezing points, which can result in instant
frostbite on contact in subfreezing temperatures.
Heat loss by conduction may occur up to 32-fold fast-
er in water than in air.5  The source of the moisture can
be perspiration, water, or other liquids.
Convection
Convection loss occurs when air currents dissi-
pate the thin warm air layer that surrounds us.  Body
hair and clothing help to maintain this warm air layer.
Wind chill is important in that the faster the wind
blows, to a maximum of 40 mph, the faster the pro-
tective layer of warm air is removed (Figure 2-1).
Radiation
Radiation of heat occurs from exposed body sur-
faces.  The hands, face, head, and neck are the most
commonly exposed sites.  At 4°C approximately
50% of body heat can be lost from an uncovered
head and at –15°C this loss may increase to 75%.5
Proper headgear can help elevate body tempera-

Cold-Induced Injury
25
Fig. 2-1. Potential heat loss, skin cooling, and lower internal temperature can be increased by air movement. The wind-
chill index integrates windspeed and air temperature to estimate associated risk of cold injury. The wind-chill
temperature index is the equivalent still-air (no wind) temperature that would produce the same heat loss on bare skin.
A full description of the medical aspects of military operations in the cold is the subject of US Army Research Institute
of Environmental Medicine (USARIEM) Technical Note 92-2, Sustaining Health and Performance in the Cold.  Source of
chart: US Army Research Institute of Environmental Medicine Technical Note 92-2. Sustaining Health and Performance
in the Cold: Environmental Medicine Guidance for Cold-Weather Operations. Natick, Mass: USARIEM; July 1992: 37.
keeps us alive in hot climates, but is detrimental in
a cold environment.
Respiration
Respiration is an additional source of heat loss
and results from breathing out humidified, warm
air.  Heavy exercise results in rapid breathing and
significant loss of heat and water.  Covering the
mouth with a mask (eg, wool) can retain some of the
exhaled heat and prewarm the incoming air.3
ture by reducing heat loss; by removing headgear
during heavy exercise, soldiers can increase heat
loss.
Evaporation
Evaporation that occurs when water vapor is
released from the skin is an important form of heat
loss.  Clothing that allows water vapor to escape
helps to conserve heat because wet skin requires
increased heat loss to dry the skin.  This loss of heat
FACTORS INFLUENCING HEAT LOSS
Multiple factors can contribute to heat loss and the
risk of cold injury.  These factors include the degree of
cold encountered, intensity of combat, protective cloth-
ing available, and others.  Combat conditions often
involve several of these factors and leave military and
involved civilians at high risk for cold injuries.
Actual Temperature (°F)
Equivalent Chill Temperature (°F)
50
40
30
20
10
0
–10
–20
–30
–40
–50
–60
50
40
30
20
10
0
–10
–20
–30
–40
–50
–60
48
37
27
16
6
–5
–15
–26
–36
–47
–57
–68
40
28
16
3
–9
–21
–33
–46
–58
–70
–83
–95
36
22
9
–5
–18
–32
–45
–58
–72
–85
–99
–112
32
18
4
–10
–25
–39
–53
–67
–82
–96
–110
–124
30
15
0
–15
–29
–44
–59
–74
–89
–104
–118
–133
28
13
–2
–18
–33
–48
–63
–79
–94
–109
–125
–140
27
11
–4
–20
–35
–51
–67
–82
–98
–113
–129
–145
26
10
–6
–22
–37
–53
–69
–85
–101
–117
–132
–148
Calm
5
10
15
20
25
30
35
40
Wind Speed 
(mph)
Increasing Danger
Great Danger
Little Danger
(in < 5 h with dry skin; 
greatest hazard is from 
false sense of security)
Wind speeds > 40 mph have 
little additional effect 
(exposed flesh may freeze 
within 1 min)
(exposed flesh may freeze 
within 30 sec)
Wind Speed (mph)
Wind speeds > 40 mph
have little additional effect
Little Danger
(in < 5 h with dry skin;
greatest hazard is from
false sense of security)
Increasing Danger
(exposed flesh may
freeze within 1 min)
Great Danger
(exposed flesh may
freeze within 30 sec)
Calm

Military Dermatology
26
Weather and Duration of Exposure
Short exposure (ie, only a few minutes) to intense
cold, especially with high winds, moisture, or skin
contact with metal or volatile solvents, can lead to
frostbite, whereas prolonged exposure to higher
temperatures contributes to trench foot, immersion
foot, and pernio.  The average duration of exposure
resulting in frostbite is 10 hours.  During the Korean
conflict, 80% of the cases in 1950 to 1951 reported a
duration of exposure of 12 hours or less, with a
range of 2 to 72 hours.4  Trench foot and immersion
foot occurred in as little as a few hours or as long as
14 days, with an average of 3 days.2
Type of Combat Action
Units on active defense, under attack, or on the
attack are at the greatest risk of cold injury.  Static
situations do not allow for movement and lead to
prolonged exposure.  Active combat and defense
increase fatigue, and often do not allow for re-
warming, clothing changes, or proper nutrition.
Clothing
Modern cold weather clothing is based on the
“layering” principle and employs a wind- and wa-
ter-resistant outer layer.  Multiple layers of loosely
fitting clothing make use of the insulating proper-
ties of dead air spaces.  This looseness extends to the
boots as well.  Footgear must be loose enough to
allow for thick socks and not constrict the circula-
tion and yet must be water-resistant.  As exercise
increases, clothing layers must be removable to
allow for heat loss equal to the increased output.
Wearing or not wearing a hat, as previously noted,
can make a significant difference.  Newer water-
vapor–permeable outer garments permit the escape
of moisture, which helps preserve the garment’s
insulating capability.  Finally, mittens are more
protective than gloves; the individual finger slots in
gloves increase surface-area heat loss.
Other Factors
Several other factors can significantly increase
the risk of suffering cold injuries:
• Young children and the elderly have greater
susceptibility to cold injuries.
EXHIBIT 2-2
COLD INJURY RISK FACTORS
Inadequate clothing
Harsh weather (low temperatures, high winds,
moisture)
Active combat or defense
Lack of troop rotation
Decreased blood flow from combat injuries
Age (children and elderly)
Low military rank
Previous cold injury
Fatigue
Discipline and training
Psychosocial factors (eg, homeless or mentally ill
out in the cold)
Race
Geographic origin
Poor nutrition
Erratic physical activity
Vasoconstricting medications
Use of alcohol
Data source: Corbett D. Cold injuries. Journal of the Asso-
ciation of Military Dermatologists. Fall 1982;8:34–40.
• Junior enlisted ranks are more susceptible to
cold injury than senior enlisted ranks and
officers because of their inexperience and
increased exposure to cold.  They may also
be less receptive to preventive training.
• Previous cold injury predisposes to reinjury.
• Fatigue leads to apathy, improper wearing
of clothing, and neglect of hygiene (eg, keep-
ing feet dry).
• Lack of adequate troop rotation can increase
the risk of cold injury.
• Combat injuries can be complicated by shock
and decreased blood flow, further increas-
ing the risk of cold injury.
• Race is an important risk factor, with blacks
being 2- to 6-fold more vulnerable to frost-
bite than whites.6,7
• Overactivity leads to excessive perspiration
and wetting of clothing, resulting in its loss
of insulating capacity.  However, underac-
tivity is equally detrimental, causing stasis
and lack of heat generation (Exhibit 2-2).

Cold-Induced Injury
27
PATHOGENESIS OF COLD INJURY
Several mechanisms are responsible for cold in-
jury with its subsequent tissue damage and loss.
Cellular damage can occur from intracellular ice
crystal formation as tissue freezes.  Other mecha-
nisms of injury are believed to be secondary to
vascular damage with resulting microcirculatory
failure and tissue hypoxia.  This leads to clumping
of erythrocytes and capillary stasis.  Irreversible
occlusion of small vessels by aggregates of cells
with thrombus formation has been demonstrated in
rewarmed tissue after freezing.  In addition, as a
result of tissue hypoxia and possibly the direct
effect of cold, there is an increase in capillary per-
meability with loss of plasma into the extravascular
space.  These events lead to further hemoconcentra-
tion, increased viscosity, and stasis.8
Cold causes direct metabolic impairment, affecting
sensitive cellular enzyme systems adversely and im-
pairing cellular function.  Injuries resulting from cold
exposure can be classified as direct and indirect.
DIRECT COLD INJURY
Treatment
Lubrication is the mainstay of therapy for the dry
skin associated with asteatotic eczema.  Any mois-
turizer is acceptable, and common petrolatum is
excellent and usually readily available.  Applying
after a shower will help seal water in the skin.
OK to put on the Web
Direct cold injuries are caused by exposure to
low temperatures and are not associated with exac-
erbation of an underlying disease.  Examples of
direct cold injury include asteatotic eczema and
frostbite.
Asteatotic Eczema
Asteatotic eczema is a pattern of skin that is dry,
scaly, rough, and less flexible than normal, often
with a cracked appearance.  The dermatosis is more
frequently seen in the elderly, though quite com-
mon in young adults, and is aggravated by cold.
Dry pruritic skin leads to scratching, excoriations,
and often secondary infection.  The most common
site is the anterior lower legs (Figure 2-2).
Etiology
The dry skin of asteatotic eczema is due to de-
creased hydration of the stratum corneum.  De-
creasing sebaceous secretion, which occurs with
aging, results in insufficient lipid to maintain water
within the stratum corneum.  Atmospheric condi-
tions, cold, and low humidity play definite roles in
developing dry skin.  Poor nutrition is also a factor.9
Clinical Manifestations
Scaling and pruritus is prominent in asteatotic
eczema, particularly on the lower legs, but any
body area can be involved.  With increasing sever-
ity, fissuring in a lacework pattern and follicular
hyperkeratosis eventually occur.  Rubbing and scratch-
ing can lead to lichenification of affected areas.
Fig. 2-2. An example of typical asteatotic eczema on a
lower extremity. Note the almost fish-scale appearance
and mild lichenification secondary to scratching.

Military Dermatology
28
Frostbite
Frostbite is destruction of local tissue induced by
temperatures below freezing.  All the predisposing
factors mentioned in Exhibit 2-2 may interact and
lead to injury.
Etiology
Frostbite is caused by both the actual freezing of
tissue and the subsequent vascular changes that
occur.  The human body’s initial response to cold
exposure is vasoconstriction of skin vessels to re-
duce heat loss and conserve core temperature.  The
vasoconstriction persists with continued cold expo-
sure.  Blood vessel walls and endothelial cells10 are
altered with increased permeability and sludging
of blood.  Arteriovenous shunting eventually oc-
curs and areas of tissue are bypassed and devital-
ized.  Rapid freezing leads to the formation of
intracellular ice crystals and consequent cell dam-
age.  Proteins are denatured and enzyme systems
impaired.  Cells dehydrate when they are damaged
by cold, and water moves into the extracellular
spaces.8
Clinical Manifestations
Frostbite is separated into four categories, which
will be discussed in increasing order of severity:
first-degree frostbite, or frostnip; second-degree or
superficial frostbite; and third- and fourth-degree
or deep frostbite.
First-Degree Frostbite (Frostnip).  Frostnip is the
superficial freezing of skin, often facial skin or fin-
gertips, which becomes blanched and numb.  If no
further cold exposure occurs and the area is re-
warmed, no permanent damage or tissue changes
ensue.  There can be redness, itching, and mild
edema beginning within 3 hours after thawing and
lasting up to 10 days.2,8,11
Second-Degree Frostbite (Superficial Frostbite).
Superficial frostbite freezes the skin and subcutane-
ous tissues but spares the deeper structures, which
are still soft to deep palpation.  Blanching and
numbness are present.  As the tissue thaws, the
patient develops pain, erythema, and swelling of
the affected sites.  The skin can take on a mottled
cyanotic appearance (Figure 2-3).  Blisters may form
(Figure 2-4), usually within 24 to 48 hours but some-
times as soon as 6 hours after thawing.  These
blisters are clear and often extend to the tips of
digits, which is considered a good prognostic sign
(Exhibit 2-3).  Only ruptured blisters should be
debrided.  Over the next several weeks, the tissue
may mummify, turn black, and slough, revealing
red, atrophic new skin (Figures 2-5 and 2-6).
Hyperhidrosis often occurs by the second to third
week, and long-term cold sensitivity can also arise.
Third- and Fourth-Degree Frostbite (Deep Frost-
bite).  Both third- and fourth-degree frostbite in-
volve loss of deep tissue.  Third degree frostbite
involves freezing of skin and subcutaneous tissue
with tissue loss and ulceration.  With thawing,
vesicles may form, but they are often smaller and
hemorrhagic and do not extend to the tips of digits.
After early anesthesia, severe pain can begin within
a few days.  Hard black eschars form and separate
over several weeks, leaving a granulation base (Fig-
ure 2-7).  Healing time averages 68 days, and
OK to put on the Web
OK to put on the Web
Fig. 2-4. Superficial frostbite with large blebs extending
to the fingertips.
Fig. 2-3. Early appearance of either superficial or deep frost-
bite. Note the mild edema and cyanotic appearance of the toes.

Cold-Induced Injury
29
OK to put on the Web
EXHIBIT 2-3
PROGNOSTIC SIGNS OF FROSTBITE
Favorable Indicators
Large, clear blebs extending to the tips of the
digits
Rapid return of sensation
Rapid return of normal (warm) temperature to
the injured area
Rapid capillary filling time after pressure
blanching
Pink skin after rewarming
Unfavorable Indicators
Hard, white, cold, insensitive skin
Cold and cyanotic skin without blebs after
rewarming
Dark, hemorrhagic blebs
Early evidence of mummification
Constitutional signs of tissue necrosis, such as
fever and tachycardia
Cyanotic or dark red skin persisting after
pressure
Freeze-thaw-refreeze injury
Data source: US Department of the Navy. Cold Injury. Wash-
ington, DC: DOD; NAVMED P-5052-29. March 1970: 1–14.
hyperhidrosis, which can appear at 4 to 10 weeks,
may persist for months.2
Fourth-degree frostbite involves complete ne-
crosis and loss of deep tissue including bone (Fig-
ure 2-8).  The deeper tissues are solid to deep palpa-
tion.  With rewarming, the skin can become purple
to red and anesthetic.  Edema is usually found
proximal to the area of fourth-degree injury, reach-
ing a peak by 6 to12 hours.2  The area may then
rapidly progress to a dry type of gangrene with
lines of demarcation noted as early as 72 hours post-
thaw.11  A slower progression also can occur, with
eschar and gangrene formation not evident until 2
to 3 weeks after thawing.  Severe pain and intense
burning will occur with thawing, and large amounts
of analgesics may be needed.9  Paresthesias appear 3
to 13 days after rewarming, lasting for at least 6
months in more than 50% of frostbite victims.12  The
line of demarcation becomes apparent in an average
of 36 days and extends to bone 60 to 80 days after
injury.2  Long-term frostbite sequelae consist of cold
sensitivity, paresthesia, numbness, pain, and
hyperesthesia.12  Other problems include frostbite
arthritis, which occurs weeks to years later and
resembles osteoarthritis,13 and hyperhidrosis.9
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Fig. 2-5. Same patient seen in Figure 2-3, approximately
6 weeks later, showing demarcation.
Fig. 2-6. Early presentation of superficial frostbite. No
loss of digits took place. Note shallow ulcerations on
plantar aspect of feet.

Military Dermatology
30
OK to put on the Web
OK to put on the Web
Treatment
Prevention of frostbite is the best form of therapy.
Frostnip can be treated immediately in the field.
Rewarming can be accomplished by placing fingers
in the axilla, blowing warm air over the frozen
surfaces, or placing a warm hand on the area.  Re-
covery is usually prompt and no long-term therapy
is necessary.
Frozen parts should not be thawed until defini-
tive care is available (ie, no possibility of refreez-
ing).  Once thawed, the part is painful, and if the feet
are involved, the individual will be unable to walk.
Freeze-thaw-refreeze cycles are also very damag-
ing and must be avoided.  When treating military
personnel, one must consider the availability of
definitive care.  If transportation is not available,
the soldier with frostbite may have to continue to
fight or walk out of the combat area.  Neither action
would be possible if frostbitten feet were permitted
to thaw.
The more serious types of frostbite are treated by
rapid rewarming of the affected areas in a warm-
water bath at 40°C to 42°C until the most distal part
is flushed.4  Rewarming is painful and analgesia is
required.  Bed rest, elevation of the affected extrem-
ity, and protection of the injured area with twice
daily antiseptic whirlpool baths for gentle
debridement are essential.  Tetanus toxoid should
be given to all victims.  Secondary infection is com-
mon, but not all sources recommend prophylactic
antibiotics.  Smoking is not permitted.  Early
heparinization, begun within 36 hours2 and stopped
in 2 to 3 days,11 has been shown to be of help, but
anticoagulation of individuals in a field setting may
be impossible and there may be other trauma to
consider.2  Low molecular weight dextran, 1.5 gm/
kg intravenously on the first day, then 0.75 mg/kg
intravenously daily for 5 days, has been shown
to decrease blood viscosity and increase tissue
perfusion in limited trials.14  Intraarterial reserpine,
0.25 to 0.5 mg, can be used if vascular spasm is
noted on angiogram at about the 10-day point, with
repeat angiogram in 2 days.11  Surgical sympa-
thectomy has been used late in the healing process
for severe cases8 but its use is not universally recom-
mended.6  Both extensive surgical debridement and
amputation are to be avoided until devitalized tis-
sue is clearly demarcated and spontaneous slough-
ing has occurred, which may take months.9  Moist
gangrene with infection is, of course, an exception
to this rule.
Fig. 2-7. Hands with deep frostbite and well-demarcated
areas of eventual tissue loss. These will autoamputate if
left alone, allowing for the preservation of maximal tissue.
Fig. 2-8. This hobo suffers from deep frostbite. He was
locked in a freezer car for approximately 18–24 hours,
with these unfortunate results.

Cold-Induced Injury
31
INDIRECT COLD INJURY
Indirect cold injury is associated with exposure
to low temperatures as well as other factors, and is
often linked to disease processes that are exacer-
bated by cold.  Finding skin lesions after cold expo-
sure can lead to the discovery of underlying disease.
Pernio
Pernio, or chilblain, refers to the development of
bluish red patches on arms and legs that are chroni-
cally exposed to cold, damp climates.  A mild form
of cold injury, pernio was described as early as
1680.8  This condition is prevalent in England and is
less commonly seen in very cold climates where
heating is usually more adequate and protective
clothing is worn on a regular basis.9
Etiology
Vasospasm is the primary mechanism causing
pernio in predisposed individuals who appear to
have an inherently high peripheral vascular tone.
The nonfreezing cold is amplified by high humid-
ity.  The vasospasm produces local tissue hypoxia,
which leads to the initial cyanotic and erythematous
skin lesions.8
Histological evaluation of pernio reveals edema
of the papillary dermis and a superficial or both
superficial and deep perivascular lymphocytic in-
filtrate.  Necrotic keratinocytes and lymphocytic
vasculitis have also been reported.9
Clinical Manifestations
Pernio is divided into acute and chronic disease.
The acute form is seen primarily in children and
young adults.  The chronic form is seen most com-
monly in adults.  Acute pernio presents with bluish
red, slightly edematous patches, most commonly
on the lower extremities.  Prolonged exposure to
damp cold with inadequate protection precedes the
development of lesions.  The skin findings persist
for 7 to 10 days or less, and resolve spontaneously
with a residual brownish red hyperpigmentation in
many cases.8
Chronic pernio—edematous, cyanotic lesions
with secondary ulceration and hemorrhage—is seen
after repeated episodes of acute pernio.  Patients
can present with subcutaneous nodules accompa-
nied by a burning sensation, pruritus, or both.  Acute
pernio is more common in winter, but with re-
peated episodes lesions may become persistent,
with the atrophy and ulcerations lasting through-
out the year.  The differential diagnosis includes
nodular vasculitis, erythema induratum, erythema
nodosum, and livedo vasculitis with ulcerations.8
Treatment
Protective clothing and warmth are the mainstay
of therapy for pernio.  Emollient creams can be of
benefit.  Antibiotics and topical care may be needed
if ulcerations or secondary infection is present.
Vasodilating drugs can be useful in some patients.
Nifedipine has been effective at a dose of 20 mg
three times daily.9  Sympathectomy has been uti-
lized in extreme cases only, but does not prevent
recurrences.8
Livedo Reticularis
Livedo reticularis is a persistent reticulated pattern
of red to bluish coloration of the skin (Figure 2-9).  The
skin mottling can be transient as seen with infants
exposed to cold and is known as cutis marmorata.  If
the pattern persists after rewarming then the
term livedo reticularis is used.  Congenital livedo
reticularis (cutis marmorata telangiectatica
congenita)15 results from several inherited syn-
dromes, such as Down’s syndrome, Cornelia de
Lange syndrome, homocystinuria, and neonatal
Fig. 2-9. Livedo reticularis. The netlike vascular pattern
is typical of the disease.
OK to put on the Web

Military Dermatology
32
lupus erythematosus.  These disorders display per-
sistent forms of livedo that are not related to cold
exposure.  The causes of acquired livedo reticularis
are numerous (Exhibit 2-4).  It can be benign, as with
cold, or may be a sign of serious underlying disease
such as vasculitis, connective tissue disease, or
malignancy.  Livedo derives from the Latin liveo,
meaning “blue, black, or livid.”  The term was first
used by Hebra in 1868.8
Etiology
Similar physiological explanations for the livedo
pattern were given by Renault (1883), Unna (1896),
and Spalteholz (1927).16  It was postulated by all
three authors that the cutaneous circulation is ar-
ranged in “cones,” 1 to 3 cm in diameter, with the
apex deep in the dermis and a central ascending
arteriole.  They proposed that the density of the
EXHIBIT 2-4
CAUSES OF ACQUIRED LIVEDO RETICULARIS
Adapted with permission from Fleischer A, Resnick S. Livedo reticularis. Dermatol Clin. 1990;8(2):347–354.
Ex 2-4 is not shown because the copyright permission granted to the Borden Institute, TMM, does not
allow the Borden Institute to grant permission to other users and/or does not include usage in electronic
media. The current user must apply to the publisher named in the figure legend  for permission to use
this illustration in any type of publication media.

Cold-Induced Injury
33
arterial bed is decreased at the margins, but that the
superficial venous plexus is more prominent at the
periphery.16  If this theory were valid, any process
that impedes blood flow would result in a larger
proportion of deoxygenated hemoglobin.  There
would then be a more livid color at the margins of
the cones, and the reticulated pattern would be
prominent.8  This hypothesis does help to explain
the clinical findings.  However, anatomical studies
using serial thick sections have failed to demon-
strate the proposed pattern.16
Clinical Manifestations
The congenital form of livedo reticularis can be
regional or widespread, and is associated with su-
perficial ulcerations.  Other anomalies are found in
up to 50% of these cases.16  The acquired form can be
seen in many conditions (see Exhibit 2-4).  These
conditions are exacerbated by exposure to cold, but
rewarming does not cause resolution of the livedo
pattern.  The red-blue net pattern is usually
asymptomatic unless ulceration has occurred, and
is seen most commonly on the lower legs.  The pat-
tern can be seen on other body areas as well, includ-
ing upper legs, buttocks, lower trunk, and arms.8
Finding the underlying cause for livedo is impor-
tant, and cold exposure may make the disease
more evident and lead to a definitive diagnosis and
treatment.
Treatment
No specific therapy for livedo reticularis exists.
Underlying treatable causes must be addressed.
Acrocyanosis
Acrocyanosis is characterized by symmetrical
bluish discoloration and coolness of the extremities
and is often associated with hyperhidrosis of the
palms and soles.  The disorder is usually seen in
colder climates.
Etiology
The exact cause of acrocyanosis is unknown but
there are several theories.  Nailfold biomicroscopy
reveals decreased blood velocity and dilated capil-
laries and venules in patients with acrocyanosis.
Various investigators have localized initiating
events to arterioles, capillaries, and the venous sys-
tem.  It has also been proposed that the initial
change is an alteration in blood viscosity that is
enhanced by cooling and leads to damage of the
capillaries in the papillary dermis.8
There have been various reports of acrocyanosis
associated with conditions such as mental defi-
ciency,17 but these have not been independently
confirmed.8  A familial predisposition has been
noted.17
Clinical Manifestations
Persistent symmetrical cyanosis and coolness of
the hands and feet are the most common findings of
acrocyanosis, with occasional involvement of the
chin, lips, and nose.  Hyperhidrosis and edema of
the palms and soles are also commonly noted.
Cyanosis increases as the temperature decreases
and changes to erythema with elevation of the de-
pendent part.  Peripheral pulses are usually intact,
and the symptoms may persist for years after typi-
cally beginning in the second or third decade.  Vas-
cular disease and ulceration are absent, which dis-
tinguishes acrocyanosis from other diseases such as
Raynaud’s (Figure 2-10).8
Treatment
The mainstay of therapy for acrocyanosis is pro-
tection from the cold.  Other forms of treatment
have included α-adrenergic blocking agents, which
may provide temporary relief.8
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Fig. 2-10. Acrocyanosis. Note that the cyanotic appear-
ance stops at the palmar crease, which is common in this
disorder.

Military Dermatology
34
Erythrocyanosis
Erythrocyanosis consists of cyanotic discolora-
tion occurring over areas of thick, subcutaneous fat
such as the thighs, and is seen most commonly in
winter.  The lesions may be nodular and similar to
pernio.  Discussions of this disorder are usually
found in older British literature.  Erythrocyanosis is
rarely encountered now.9,17
Etiology
Erythrocyanosis may be a form of cold panni-
culitis; however, the exact etiology is unknown.9,17
Clinical Manifestations
Erythrocyanosis is usually seen in women on the
legs and thighs and is often found in horseback
riders.  The skin is at times tender.
Treatment
Warm clothing and reduction of the insulating
fat layer are the only effective treatments for
erythrocyanosis.
Trench Foot
Trench foot, or immersion foot, is seen after pro-
longed exposure to cold and dampness at tempera-
tures above freezing (0°C–10°C).8  This subject is
discussed in detail in Chapter 4, Immersion Foot
Syndromes.
Cold Panniculitis
Cold panniculitis consists of tender subcutane-
ous nodules occurring with cold exposure on un-
covered areas.  Cheeks and legs are the most com-
mon sites, and children are more often affected than
adults.
Etiology
Because the nodules of cold panniculitis are usu-
ally seen in children, it has been postulated that the
more highly saturated fat seen in newborns solidi-
fies at a higher temperature than the adult’s less
saturated fat.17  Excessive fibrinolytic activity and
cryofibrinogens have been detected in the serum of
affected individuals.8  It has also been thought to be
a hypersensitivity reaction.8,17
Clinical Manifestations
Tender nodules develop several hours after cold
exposure of unprotected areas.  The legs and cheeks
are common sites, as previously mentioned.  The
nodules may enlarge and become plaques, which
then spontaneously resolve over 2 to 3 weeks.
Treatment
No specific therapy exists for cold panniculitis.
Proper clothing and avoidance of cold will prevent
most cases.
Raynaud’s Disease and Phenomenon
Raynaud’s disease is a paroxysmal constriction
of small arteries and arterioles of the extremities,
usually precipitated by cold.  However, it can be
induced by other stimuli including emotions.  The
etiology of Raynaud’s disease is unknown.  By
definition, Raynaud’s phenomenon (syndrome)
occurs secondary to an underlying systemic disease
or occupational trauma (Exhibit 2-5).8,17,18
Raynaud’s disease was first described by Raynaud
in 1862.  Hutchinson noted in 1901 that the clinic-
al manifestations of Raynaud could be seen in
association with several different conditions.  He
EXHIBIT 2-5
CAUSES OF RAYNAUD’S PHENOMENON
Cold injury sequelae (frostbite and trench foot)
Arterial occlusive disease (arteriosclerosis)
Collagen vascular diseases (systemic lupus,
dermatomyositis)
Occupational trauma (jackhammer, typist,
mechanic, etc.)
Cold agglutinins (atypical pneumonia,
lymphoma, etc.)
Cryoglobulins (neoplastic, collagen vascular,
chronic disease)
Neurologic disorders (central and peripheral)

Cold-Induced Injury
35
suggested that when an underlying disease process
could be identified, the condition should be
called Raynaud’s phenomenon.  When the condi-
tion is idiopathic, it is referred to as Raynaud’s
disease.8
Raynaud’s is seen in females 5-fold more often
than in males, with an average age of onset of 31
years and a range of 4 to 68 years of age.  In males,
73% of patients were less than 40 years of age.  After
long-term follow-up in two studies, 60% to 70% of
the patients with Raynaud’s could be described as
having primary Raynaud’s disease.8
Etiology
The pathophysiology of the vasospastic attacks
in primary Raynaud’s disease is unknown.  In sec-
ondary Raynaud’s phenomenon, the vasospasm can
be caused by sympathetic stimuli, external physical
pressure (seen in farmers, typists, pianists, and
individuals who use vibrating tools, eg, hard-rock
miners), and decreased blood flow secondary to
increased blood viscosity or arterial disease.  A
study on Raynaud’s disease and phenomenon
showed that vasospasm could be induced in fingers
even with a lidocaine digital nerve block in place,
arguing against the widely believed etiologic role of
sympathetic hyperactivity.19
Histological evaluation of vessels in Raynaud’s
patients has revealed intimal thickening, thrombus
formation, and recanalization in the digital arteries
of patients with severe disease, especially those
with secondary disease.
Clinical Manifestations
With Raynaud’s disease and phenomenon, the
skin classically undergoes a triple response with
initial blanching or pallor proceeding to cyanosis
indicative of vasospasm.  The third (recovery) stage
is erythema, probably secondary to an end-stage
hyperemia.8  Typically the problem is noted distally
in a bilateral digital distribution, and eventually the
entire digit becomes involved.  Involvement of the
hands, feet, and thumbs is less common.  Unilateral
involvement has been reported.  The lips, tip of the
nose, ears, and, less commonly, even the tongue can
be involved.8,17  Numbness is common, and pain
may be mild or absent; paresthesia can occur during
the recovery phase.  Nails may show longitudinal
ridging, increased brittleness, onycholysis, koi-
lonychia, and thinning of the plate.8,17  Ulcerations
and stellate scars occur on the tips of fingers and
toes.  In severe cases gangrene develops, and ampu-
tation of the gangrenous tips of digits has been
necessary on rare occasions (0.4% of cases).8
Treatment
The goal of treatment for Raynaud’s is vasodila-
tion of the involved vessels with minimal side ef-
fects.  Prevention of episodes is of primary impor-
tance.  Protective warm clothing, especially for the
hands and feet, is important to avoid localized and
generalized cooling.  Sudden cooling of the skin,
such as occurs when reaching into refrigerators and
freezers, entering air-conditioned buildings, and
handling cold objects, is to be avoided.  Patients
with underlying disease that causes the vessels to
have limited capacity to dilate are the most difficult
to manage.
Vasodilating agents typically have too many side
effects to be of extensive use in treating Raynaud’s.
These sympatholytic agents, which include
methyldopa, phenoxybenzamine, tolazoline,
guanethidine, and oral or intraarterial reserpine,
have generally been abandoned.  However, prazosin
hydrochloride has been shown to be effective and
has acceptable side-effect levels.  In one 8-week
study,20 the drug was effective when given in doses
of 1 to 2 mg orally three times daily.  Doses up to a
maximum of 20 mg per day are used to treat hyper-
tension.20  Postural hypotension can occur suddenly,
and the initial doses should be given cautiously and
while the soldier is supine.8
Biofeedback has been shown to increase digital
blood flow but time and expense can be prohibitive.
Surgical sympathectomy, once popular, has been
shown to be less useful, and now conservative
therapy is usually advocated.  Sympathetic stellate
ganglion block can be useful in acute cases of severe
digital infarction and can be given daily by an
experienced anesthesiologist.8
Direct vasodilating agents, such as the calcium
channel–blocking agent nifedipine, have been use-
ful in treating Raynaud’s.  In a 7-week study,21
effective doses were begun at 10 mg three times
daily and, if well tolerated, were increased to 20 mg
three times daily.  Again, Raynaud’s patients with
fixed vascular disease benefit the least.8  Topical
nitrates appear to improve digital blood flow and
temperature and can be useful in conjunction with

Military Dermatology
36
other therapies.  Two percent glyceryl trinitrate in
lanolin applied for 3 minutes and allowed to remain
on for 20 minutes before removal may provide
temporary improvement in digital blood flow and
skin temperature.22
Patients must not smoke under any circumstance.
SUMMARY
History has demonstrated that cold injuries may
cause a loss of combat troops that can exceed battle
casualties.  Proper training of our combat forces,
combined with proper supplies and planning, can
minimize losses to cold injury.  Good planning
requires that a number of questions be posed: What
weather conditions and intensity of combat will be
encountered?  Are sufficient supplies such as food
and clothing available?  Have the officers and en-
listed soldiers been trained in prevention?  Do com-
manders have sufficient troops for frequent rota-
tions to the line?
Cold injuries most often involve front-line infantry,
a commander’s most valuable commodity.  These
injuries often require months of rehabilitation or
cause permanent disability.  Because large numbers
of cold injuries usually occur only during times of
war, exact treatment protocols have not been devel-
oped, and further research needs to be done.  Early
recognition of signs and symptoms and immediate
institution of therapy are critical.  Training of medical
officers in recognition and treatment of diseases
caused or exacerbated by cold must be a priority.  Line
officers also need our help as their medical advisors
in establishing adequate preventive measures and
enabling the swift return of troops to duty.
REFERENCES
1.
Whayne TF, DeBakey ME. Cold Injury, Ground Type, in World War II. Washington, DC: Medical Department, US
Army, Office of The Surgeon General; 1958.
2.
US Departments of the Army, Navy, and Air Force. Cold Injury. Washington, DC: DOD; TB MED 81, NAVMED
P-5052-29, AFP 161-11. 30 September 1976: 1–15.
3.
Hanson H, Goldman R. Cold injury in man: A review of its etiology and discussion of its prediction. Milit Med.
October 1969;134(11):1307–1316.
4.
Orr K, Fainer D. Cold injuries in Korea during winter of 1950–1951. Medicine. 1952;39:177–220.
5.
Reuler J. Hypothermia: Pathophysiology, clinical settings, and management. Ann Intern Med. 1978;89:519–527.
6.
Vaughn B. Local cold injury—menace to military operations: A review. Milit Med. 1980;145(5):305–310.
7.
Sumner D, Criblez T, Doolittle W. Host factors in human frostbite. Milit Med. 1974;139:454–461.
8.
Demis DJ. Clinical Dermatology. 17th ed. Philadelphia: JB Lippincott, 1990.
9.
Page E, Shear N. Temperature-dependent skin disorders. J Am Acad Dermatol. 1988;18(5):1003–1019.
10.
Marzella L, Jesudass R, Manson P, Myers R, Bulkley G. Morphologic characterization of acute injury to vascular
endothelium of skin after frostbite. Plast Reconstr Surg. 1989;83(1):67–75.
11.
Leecost T. Frostbite, diagnosis and treatment. Journal of the American Podiatry Association. November
1981;71(11):599–603.
12.
Taylor M, Kulungowski M. Frostbite injuries during winter maneuvers: A long-term disability. Milit Med.
1989;154(8):411–412.
13.
Glick R, Parnami N. Frostbite arthritis. J Rheumatol. 1979;6(4):456–460.

Cold-Induced Injury
37
14.
Bangs C, Boswick J, Hamlet M, Sumner D, Weatherley-White RCA. Winter problems: When your patient suffers
frostbite. Patient Care. 1 Feb 1977:132–157.
15.
Cohen P. Cutis marmorata telangiectatica congenita: Clinicopathologic characteristics and differential diagno-
sis. Cutis. 1988;42:518–522.
16.
Fleischer A, Resnick S. Livedo reticularis. Dermatol Clin. 1990;8(2):347–354.
17.
Corbett D. Cold injuries. J Assoc Military Dermatologists. Fall 1982;8:34–40.
18.
Coffman J. The enigma of primary Raynaud’s disease. Circulation. 1989;80(4):1089–1090.
19.
Freedman R, Mayes M, Sabharwal S. Induction of vasospastic attacks despite digital nerve block in Raynaud’s
disease and phenomenon. Circulation. 1989; 80(4): 859–862.
20.
Surwit R, Gilgor R, Allen L, Duvic M. Double-blind study of prazosin in the treatment of Raynaud’s phenom-
enon in scleroderma. Arch Dermatol. March 1984;120:329–331.
21.
Rodeheffer R, Rommer J, Wigley F, Smith C. Controlled double-blind trial of nifedipine in the treatment of
Raynaud’s phenomenon. N Engl J Med. 1983;308(15):880–883.
22.
Kleckner M, Allen E, Wakim K. The effect of local application of glyceryl trinitrate (nitroglycerine) on Raynaud’s
disease and Raynaud’s phenomenon, studies on blood flow and clinical manifestations. Circulation. May
1951;3:681–689.

39
Skin Diseases Associated with Excessive Heat, Humidity, and Sunlight
Chapter 3
*Lieutenant Colonel, Medical Corps, U.S. Army; Dermatology Service, Walter Reed Army Medical Center, Washington, D.C.  20307-5001
SKIN DISEASES ASSOCIATED WITH
EXCESSIVE HEAT, HUMIDITY,
AND SUNLIGHT
LEONARD SPERLING, M.D.*
INTRODUCTION
CLASSIC FORMS OF HEAT INJURY
Heat Cramps
Heat Exhaustion
Heatstroke
DERMATOSES CAUSED BY EXCESSIVE ENVIRONMENTAL HEAT
Miliaria
Hypohidrosis Syndrome
Tropical Acne
Cholinergic Urticaria
DERMATOSES EXACERBATED BY HEAT AND HUMIDITY
Dyshidrotic Eczema
Bacterial Infections of the Skin
Fungal Infections of the Skin
Friction Blisters
Erythermalgia
DERMATOSES CAUSED BY EXCESSIVE SUN EXPOSURE OR
ALLERGY TO SUNLIGHT
Sunburn
Phototoxicity and Photoallergy
Polymorphous Light Eruption
Solar Urticaria
DERMATOSES EXACERBATED BY SUNLIGHT
Porphyria Cutanea Tarda
Erythropoietic Protoporphyria
Others
SUMMARY

Military Dermatology
40
INTRODUCTION
Whenever the armed forces of the United States
have first entered extremely hot climates, a large
number of heat-related casualties have been en-
countered.1  In all 20th-century wars, however, sol-
diers have quickly adjusted and were able to func-
tion successfully.  Operations Desert Shield and
Desert Storm (1990–1991) were no exceptions.  In
the Saudi Arabian desert, troops relearned the les-
sons of North Africa and the Pacific islands of
World War II, where the casualties included numer-
ous heat-related deaths.  The same lessons were
relearned during the summer months in Korea and
in the jungles of Vietnam.
Heat injury is generally defined as a fairly acute
physiological stress manifested by such conditions
as heat cramps, heat exhaustion, and heatstroke.2
Heat also has many deleterious effects on the skin,
and several disorders are caused by, or are severely
exacerbated by, high ambient temperatures.  This is
particularly important because the skin is largely
responsible for thermoregulation in humans.  Skin
acts as a radiator and, in concert with fluids and
electrolytes, can allow soldiers to withstand re-
markably hot climates for indefinite periods.  Cer-
tain skin diseases impair this critical thermoregula-
tory function, predisposing the affected soldier to
the various types of acute heat injury.
The various skin diseases related to heat have
another important impact: their disabling effects on
troops.  Skin diseases accounted for over 12% of
total outpatient visits during the Vietnam conflict.3
The three most common ailments in this group
were miliaria, pyoderma (bacterial infections of the
skin), and tinea (fungal infections of the skin), all of
which are intimately related to heat and humidity.
Over one half the patients who were evacuated
from Vietnam for dermatological ailments suffered
from tropical acne, eczematous dermatitis,
dyshidrosis, and fungal infections.3  The tropical
environment of Southeast Asia clearly played an
important role in the pathogenesis of all of these
conditions.
Warm climates present another danger to troops:
sun exposure.  A variety of dermatoses are caused
or severely exacerbated by solar radiation.  Tropical
climates are notorious for their long hours of in-
tense sunshine.  Most desert climates share this
abundance of radiation, with an additional ingredi-
ent—lack of shelter from the sun.
Although problems due to heat will be discussed
separately from those due to sunlight (visible and
ultraviolet [UV]), in many cases these factors are
related.  Perspiring soldiers are apt to remove as
much clothing as possible, thus predisposing them-
selves to burns from UV light.  The injury of sun-
burn can impair the sweating mechanism, and by so
doing impair the thermoregulatory mechanisms
that allow soldiers to function in the heat.
CLASSIC FORMS OF HEAT INJURY
A discussion of heat-related dermatoses would
not be complete without a review of heat injury in
general.  The subject is covered in detail in Techni-
cal Bulletin MED 507, Prevention, Treatment and Con-
trol of Heat Injury.2  The resting human eliminates
about one fourth of the basal metabolic heat pro-
duction via the lungs and skin.2  If body tempera-
ture starts to increase above its normal set point, the
first physiological responses are vasodilation of the
skin and an increase in the heart rate.  These allow
the skin to function more efficiently as a radiator of
excess heat.  When the body no longer can lose
sufficient heat by simple radiation, and the skin
temperature reaches or exceeds a critical level, the
activity of the sweat glands increases.  The heat loss
that can be achieved by sweating becomes the most
important, and sometimes the only, means of maintain-
ing a normal core body temperature.2  As environmen-
tal humidity increases, the ability of the air to
evaporate the sweat decreases, thus reducing cool-
ing.  Inadequate cooling results in continued sweat-
ing, which results in a loss of body water and salt.
Initially, the lost water is drawn from the circulat-
ing blood volume.  If this fluid is not replaced, the
resulting dehydration adds strain to the circulatory
system, which has already resorted to an increased
heart rate in its efforts to radiate heat from the skin.
Hyperventilation (panting) will increase heat loss
from the lungs, but creates a respiratory alkalosis
that contributes to the signs and symptoms of heat-
exhaustion syndromes.
Air motion (convection), in the forms of natural
breezes and artificial wind produced by fans, is an
important factor in cooling.  It replaces the layer of

41
Skin Diseases Associated with Excessive Heat, Humidity, and Sunlight
air next to the skin with cooler and dryer air, im-
proving heat loss by conduction and accelerating
the evaporation of sweat.  The efficacy of air motion
diminishes progressively as humidity and air tem-
perature increase.  If air temperature becomes
higher than skin temperature, heat transfer by
conduction will proceed from the air into the skin.
Other factors in the production of heat injury
include the physical work being performed and the
physical condition of the individual.  Intense work
obviously increases body heat and the burden on
homeostatic mechanisms such as sweating and heart
rate.  Lack of acclimatization, obesity, dehydration,
excessive intake of alcohol, lack of sleep, increasing
age, poor general health, and fatigue of the homeo-
static mechanisms over time all decrease a person’s
ability to withstand high temperatures.  The follow-
ing discussions of heat cramps, heat exhaustion,
and heatstroke summarize the various forms of
heat injury.2
Heat Cramps
Heat cramps result primarily from the excessive
loss of salt relative to water from the body.  The
muscles of the extremities and the abdominal wall
are subject to these painful cramps.  Body tempera-
ture remains normal unless heat exhaustion has set
in.  Treatment is simply the intravenous adminis-
tration of normal (0.9%) saline solution in adequate
quantities.
Heat Exhaustion
Heat exhaustion results from peripheral vascu-
lar collapse due to excessive salt depletion and
dehydration.  It is characterized by profuse sweat-
ing, headache, tingling in the extremities, pallor,
shortness of breath, palpitations, and gastrointesti-
nal symptoms.  Neuromuscular disturbance (inco-
ordination) and cerebral dysfunction (clouded sen-
sorium) may be present in varying degrees.  Rectal
temperature is often elevated.  The signs and symp-
toms are basically those of shock; normal saline
must be administered, and the soldier should rest.
Any physical factor that promotes the return of
blood to the heart is indicated, as is true for other
forms of shock.
Heatstroke
Heatstroke is a medical emergency with a high
mortality rate.  It results when the normal ther-
moregulatory mechanisms become nonfunctional,
and the main source of heat loss (sweating) is
blocked.  Heat exhaustion can act as a prodrome, but
the onset of heat shock is abrupt, with loss of con-
sciousness, seizures, or delirium.  Core body tem-
perature rises rapidly to 106°F to 108°F or higher.
Signs and symptoms of obvious shock are evident,
and if elevated body temperatures persist, organ fail-
ure (eg, kidney, brain, or heart) occurs.  The first goals
of treatment are to lower the body temperature and
simultaneously to replace fluids and electrolytes.
These forms of heat injury become less likely
with proper acclimatization.  If troops are exposed
to a hot climate and gradual incremental physical
activity over a 2-week period, substantial tolerance
to the ill effects of heat can be acquired.  This
process includes improvement in cardiovascular
performance, sweating, and probably other factors
as well.  Even though acclimatization to a hot, dry,
desert climate is an effective way to prepare for hot,
humid, tropical climates, adjustment to tropical
conditions still requires several weeks of increasing
exercise at the actual site to be fully effective.
DERMATOSES CAUSED BY EXCESSIVE ENVIRONMENTAL HEAT
to the effects of heat and humidity.4  Miliaria
crystallina (sudamina), miliaria rubra, miliaria
profunda, and miliaria pustulosa are clinical sub-
types.5  This disorder of sweating was one of the
most common diseases affecting soldiers stationed
in tropical climates during World War II.6  Not only
was miliaria a very common problem in areas such
as the Southwest Pacific and the China-Burma-In-
dia theater, it was also common within warmer
regions of the United States.  Sixty-six percent of the
naval personnel studied on Guam in 1945 exhibited
miliaria rubra at some time during their first 7
Overexposure to environmental heat can cause a
number of skin disorders including miliaria,
hypohidrosis syndrome, tropical acne, and cholin-
ergic urticaria.  The pathogenesis and treatment of
these disorders are not militarily unique but are
among the most prevalent among soldiers newly
introduced to hot climates.
Miliaria
Miliaria is probably the simplest and purest ex-
ample of a skin disease attributable almost entirely

Military Dermatology
42
months of duty.7  In Vietnam, miliaria was very
common but was almost never a direct cause of
disability in troops.  However, some physicians
thought that it predisposed soldiers to fatigue and
heat exhaustion.  Miliaria was a major cause of
outpatient visits and referrals to dermatologists.3
In Vietnam, where the ambient temperature had
marked seasonal changes, the incidence of clini-
cally significant miliaria in soldiers rose sharply
after the temperature exceeded 38°C.  Cooks were
especially vulnerable to the disorder because they
worked in small, poorly ventilated rooms where
both temperature and humidity were especially
high.  Some soldiers in Vietnam were clearly more
susceptible to the condition than others, an obser-
vation that was never explained; the condition oc-
curred among those who were heat-acclimatized as
well as among those who were not.3
Miliaria Crystallina
Miliaria crystallina is characterized by clear, su-
perficial vesicles without any evidence of inflam-
mation (Figure 3-1).  It is typically asymptomatic
and short-lived.  No treatment is necessary, and the
condition usually resolves spontaneously in a few
hours to a few days.
Miliaria Rubra
The most common form of miliaria is miliaria
rubra, more commonly known as prickly heat.
Miliaria rubra usually begins in the flexural folds
and intertriginous parts of the body.  It appears as
a deeply erythematous, follicular, papulovesicular
eruption.  Typically it flares during the day and
subsides to some extent at night.  Untreated, the
rash often becomes increasingly widespread and
severe, and eventually persists even during the
night.  Its character also changes with time, becom-
ing more inflammatory and fixed.  If perspiration is
excessive, the erythematous papules become capped
by small, firm vesicles.6  Miliaria rubra causes con-
siderable discomfort but is seldom disabling.  The
condition does not seem to be influenced by race,
obesity, complexion, place of former habitat, gen-
der, or tanning.7
Miliaria Profunda
A more serious form of miliaria—miliaria
profunda—was seen much less frequently than
miliaria rubra during the Vietnam conflict.  It typi-
cally develops from severe and prolonged miliaria
rubra.  Patients with miliaria profunda present with
noninflamed nodules on the trunk and extremities;
in most cases, these nodules are nonpruritic and not
readily apparent on examination.  The disease can
be truly debilitating and is the cause of hypohidrosis
syndrome (discussed below), also called tropical
anhidrotic asthenia, a potentially fatal disorder.
Miliaria Pustulosa
Miliaria pustulosa is always preceded by some
other dermatitis that has produced injury, destruc-
tion, or blocking of the sweat ducts.5  Examples of
predisposing dermatoses include contact and atopic
dermatitis and lichen simplex chronicus.  The pus-
tules are discrete, superficial, sterile, and are not
associated with the hair follicle; lesions can thus be
distinguished from a bacterial folliculitis (Figure 3-
2).  These pruritic lesions occur most frequently on
the intertriginous areas, on the flexure surfaces of
the extremities, and on the scrotum.
Pathogenesis and Treatment
The pathogenesis and treatment of miliaria, and
the anhidrosis that is its sequela, have been subjects
of considerable investigation and debate.4,8–10  One
researcher found that miliaria could be reliably
reproduced by applying occlusive plastic film to
the skin.9  After 48 to 72 hours of such occlusion,
clinically and histologically typical miliaria was
produced.  When more than 30% of the total skin
OK to put on the Web
Fig. 3-1. Miliaria crystallina exhibits clear, superficial
vesicles with no signs of inflammation. It is usually
asymptomatic and short-lived, and no treatment is
needed.

43
Skin Diseases Associated with Excessive Heat, Humidity, and Sunlight
b
a
Fig. 3-2. (a) These discrete, superficial pustules are typical of miliaria pustulosa. Unlike bacterial folliculitis, the lesions
are sterile and are not associated with a hair follicle. (b) Miliaria pustulosa—magnified view of sterile, pustular lesions.
surface was wrapped and occluded, the ensuing
widespread hypohidrosis produced an increased
susceptibility to heat-retention disease.4  This sus-
ceptibility persisted even when the skin appeared
normal on casual inspection.  Substantial hypohi-
drosis or even anhidrosis was a typical sequela of
experimentally induced miliaria, just as it is in the
naturally occurring disease.  Experimental hypo-
hidrosis lasted as long as 3 weeks in some volun-
teers, usually those most severely affected.10  These
volunteers, whose work performance was tested 1
and 2 weeks after suffering from miliaria, were
found to have markedly impaired tolerance for
working in the heat.  After approximately 60%
of the body was wrapped, the postmiliarial
hypohidrosis caused incapacitating and potentially
dangerous heat exhaustion, even in heat-acclima-
tized volunteers who worked in a hot environ-
ment.10
The pathogeneses of both miliaria and its conse-
quent hypohidrosis are associated with alterations
in the orifices or ducts of the sweat glands.  These
changes are related to the suppression of normal
delivery of sweat to the skin’s surface.4  However, it
remains unclear whether any of the observable ana-
tomical alterations cause hypohidrosis or merely
result from sweat retention.  Inflammation is almost
certainly a secondary event because it does not
occur until 24 hours after sweat blockade has en-
sued.  One group of researchers8 found that they
could relieve experimental anhidrosis with stratum
corneum stripping, which implies a sweat blockage
in or just below the horny layer.
Other researchers5 studied the role of resident
bacteria in the etiology of miliaria.  They found that
the degree of miliaria and hypohidrosis after ex-
perimentally induced disease was directly propor-
tional to the increase in the density of resident
aerobic bacteria, notably cocci.  No anhidrosis re-
sulted when antibacterial substances were used to
prevent the proliferation of the microflora.  The
investigators postulated that cocci secrete a toxin
that injures sweat-duct luminal cells and precipi-
tates a cast within the lumen.  Infiltration by inflam-
OK to put on the Web
OK to put on the Web

Military Dermatology
44
matory cells might create an impaction that com-
pletely obstructs the passage of sweat for several
weeks.  This hypothesis has never been established
with certainty; the antecedent to the histological
changes of sweat-duct leakage or rupture and the
clinical picture of miliaria remain elusive.4
Miliaria crystallina requires no treatment.  The
other, deeper forms of miliaria are best treated by
removing the soldier from the hot, humid environ-
ment.
Hypohidrosis Syndrome
Hypohidrosis syndrome (also known as tropical
anhidrotic asthenia) is a curious and unusual disor-
der that was first described in American and British
troops during World War II.1  Some of these soldiers
were stationed in the desert in the southwestern
United States at the time, and others were in south-
ern Iraq.  Cases that occurred in Louisiana and the
Southwest Pacific were also described.
The syndrome, which can either appear sud-
denly or have a gradual onset, is characterized by
• absence of sweating over most or all of the
cutaneous surface;
• ability to sweat in profuse amounts in a very
limited area (usually the face);
• relatively mild symptoms of overheating,
weakness, dizziness and headache;
• diuresis; and
• cutaneous changes ranging from prickly heat
and transient papules to xerotic skin with a
fine scale.1
Most patients had already been in a hot climate for
some time and had had no previous difficulty sweat-
ing.  Often the hottest season was drawing to a close
when the symptoms emerged.1
Most patients suffering from hypohidrosis were
not severely ill and did not suffer from hyperpyrexia.
Many had been mildly uncomfortable for several
days before seeking medical attention.  Blood elec-
trolyte studies and skin biopsies, when performed,
were normal.  Treatment consisted of rest in a rela-
tively cool place, and subjective recovery was usu-
ally rapid.  However, several weeks to as long as 4
months elapsed until sweating returned to normal.
No satisfactory explanation for the cessation of
sweating was ever found.  Some speculated that a
functional fatigue or exhaustion of the sweat mecha-
nism was responsible.1  Miliaria profunda may be
the underlying mechanism in some cases of
hypohidrosis.3
Tropical Acne
Tropical acne is a severe, disabling condition that
is peculiar to hot and humid environments.  Al-
though many of the victims have a history of mild
acne during adolescence, the skin is often quiescent
when the problem erupts.  Most young people with
a history of acne do not develop tropical acne, and
there is no way to predict which individuals will
develop the condition.11  Tropical acne has an explo-
sive onset that begins, on the average, 3 to 6 months
after the patient is exposed to tropical climatic con-
ditions.  Patients are usually about 25 years old
when affected, but susceptibility ranges from teen-
agers through 30-year-olds.  Those who are de-
prived of proper bathing facilities and are subjected
to extreme heat and poor hygienic conditions for
great lengths of time are most susceptible.  Garrison
troops with access to adequate facilities are not
affected nearly so severely.6
The lesions in tropical acne are typical of those
found in conglobate acne: pustules, papules, nod-
ules, and draining sinuses.11  Each lesion tends to be
highly inflamed and juicy, with a purulent or
sanguinous discharge.  In soldiers, the first mani-
festation is of cystic lesions on the back, making it
impossible to carry a pack.6  Confluence of lesions
covering broad expanses of skin is often seen (Fig-
ure 3-3).  The face tends to be spared, but elsewhere
the lesions are more extensive even than those seen
in conglobate acne.  The neck, arms (even forearms),
and entire torso are often involved.  Characteristi-
cally, the buttocks and upper thighs are affected.
OK to put on the Web
Fig. 3-3. Tropical acne first manifests itself as cystic
lesions on the back, making it impossible for a soldier to
carry a pack. Therapy is futile unless the soldier is moved
out of the hot, humid climate.

45
Skin Diseases Associated with Excessive Heat, Humidity, and Sunlight
As is typical of other highly inflammatory dis-
eases, the sedimentation rate is often elevated and a
leukocytosis is present.  The patient with tropical
acne often feels ill and can no longer function suc-
cessfully as a soldier.  The bacterial organisms
recovered from cultures usually show normal skin
flora or occasional colonies of Staphylococcus aureus
and Gram-negative rods.  However, bacterial in-
fection is not believed to play an important role,
and antimicrobials are ineffective as a form of
therapy.11
Tropical acne persists undiminished in intensity
until the patient is moved to a cooler, dryer climate.
The patient is usually treated for weeks or months
before the medical officer makes the inevitable de-
cision to evacuate the patient to a more favorable
locale.6  Once the patient is removed from the tropi-
cal environment, the condition promptly begins to
clear.  Before the advent of systemic retinoids, no
treatment, including hospitalization, was effective.
Few data are available concerning the efficacy of
isotretinoin in treating tropical acne, but even this
drug would not be practical.  Under the best of
conditions, the drug takes several months to re-
verse the changes of severe, inflammatory acne.
Frequent monitoring of laboratory parameters
would be required during this period, and success
is by no means guaranteed.  The simplest, most
effective, and essential therapy for this devastating
disease is removal of the patient from the tropics.
Cholinergic Urticaria
Cholinergic urticaria is a fairly common disor-
der, and is seen most often in young adults.12  The
condition can be triggered by a variety of factors,
including heat, exercise, and emotional stress.  The
patient first notes a sensation of warmth, which is
then followed by an eruption of 1- to 3-mm wheals,
which are surrounded by an erythematous flare
(Figure 3-4).  Usually the torso is affected, but in
severe cases the rash is generalized.  Wheezing and
systemic symptoms (nausea, headache, and ab-
dominal pain) are unusual but have been report-
ed.13  Angioedema has also been reported.14
Avoiding the predisposing factors is the most
OK to put on the Web
Fig. 3-4. In cholinergic urticaria, multiple small (1- to 3-
mm) wheals are surrounded by an erythematous flare.
Lesions are induced by exercise and resolve completely
in a few hours.
important aspect of treatment.  This is understand-
ably difficult in a hot environment, especially when
coupled with the rigorous exercise and stressful
training expected of a soldier.  Regular exercise can
induce tolerance, but could be dangerous in a pa-
tient who develops systemic symptoms.12  H1-block-
ing antihistamines such as hydroxyzine (10–25 mg
four times daily)15 can be helpful.  Aspirin should be
avoided because it often will worsen the eruption.16
These patients should never exercise alone when
their disease is active.12
Dyshidrotic Eczema
Dyshidrotic eczema (also known as dyshidrosis
or pompholyx) is a vesicular eruption of the palms
and soles.  Lesions are spongiotic intraepidermal
Hot, humid conditions can worsen a variety of
dermatoses, among which are dyshidrotic eczema,
bacterial and fungal infections, friction blisters,
and erythermalgia.  Frequently, wet clothing and
boots are also contributing factors.
DERMATOSES EXACERBATED BY HEAT AND HUMIDITY

Military Dermatology
46
vesicles that often burn or itch.  The characteristic
vesicles are usually bilateral and roughly symmetri-
cal in distribution.  Sometimes the lesions are ar-
ranged in groups and can become confluent to form
bullae (Figures 3-5 and 3-6).  The vesicle fluid is at
first clear and colorless but may eventually become
straw colored or purulent.  Hyperhidrosis is often
present in affected individuals.
The exact etiology of dyshidrotic eczema is un-
known.  Some investigators believe that hyper-
hidrosis is not one of the causative factors but that
emotional stress is a more important prerequisite.5
However, combat troops in tropical environments
are subjected to both considerable stress and pro-
fuse sweating; regardless of the exact etiology, they
are prime candidates for the condition.  The combi-
nation of extreme heat and nervous tension was
believed to be largely responsible for the large num-
ber of cases seen in Vietnam.3  Treatment is often
difficult.  Potent topical corticosteroids and cool
soaks (eg, with Burow’s solution or just cool tap
water) may suffice for milder cases.  Severe involve-
ment can require oral or intramuscular corticoster-
oids.  Extensive lesions on palms, soles, or both can
be disabling and may require evacuation for the
problem to remit.
Bacterial Infections of the Skin
Heat and humidity predispose soldiers to a vari-
ety of bacterial infections.  The combination of heat,
humidity, wet clothing, poor hygiene, and minor
OK to put on the Web
Fig. 3-6. Lesions on the sides of the fingers are common in
dyshidrotic eczema. Other frequently affected sites in-
clude the palms and the soles.
skin trauma was believed to be the most important
factor contributing to the high rates of cutaneous
infections seen in Vietnam.3  These infections were
especially common in combat troops (as opposed to
support personnel).  Adverse climatic conditions,
when coupled with the poor personal hygiene often
found in combat troops, can lead to frequent and
severe infections.  Staphylococcal skin infections
(superficial pustular impetigo, furunculosis,
pyogenic paronychia, and staphylococcal impetigo),
streptococcal infections (impetigo, ecthyma,
erysipelas, and cellulitis), and a host of less com-
mon infections are found among soldiers in tropical
climates.  A detailed account of bacterial infections
and their treatment may be found in Chapter 13,
Bacterial Skin Diseases.
Fungal Infections of the Skin
The various forms of tinea (ringworm) are more
frequent and more severe among soldiers who are
stationed in hot and humid environments.  Superfi-
cial fungal infections were the most common and
troublesome of all the dermatologic  conditions that
occurred among United States forces in Vietnam.3
Just as in bacterial infections, the combination of
heat, humidity, wet clothing and boots, and poor
hygiene contributed significantly to the severity
and frequency of fungal infections (Figure 3-7).  A
detailed discussion of these superficial fungal in-
fections may be found in Chapter 17, Superficial
Fungal Skin Diseases.
OK to put on the Web
Fig. 3-5. Vesicles characteristic of dyshidrotic eczema
are seen here on the palm. The lesions can be intensely
pruritic.

47
Skin Diseases Associated with Excessive Heat, Humidity, and Sunlight
Erythermalgia
Erythermalgia is a condition in which the hands,
legs, or feet develop intense erythema and pain
resulting from environmental heat.  A particularly
warm climate is not necessary to precipitate attacks.
Simply an increase in local skin temperature may be
sufficient to precipitate a prolonged and painful
attack.  Symptoms usually involve the lower ex-
tremities and are almost always bilateral.17  Men are
more often affected than women.  Patients try to
relieve the discomfort by cooling their affected limbs
using fans, cold water soaks, ice packs, and so forth.
Cases can either be primary (with no underlying
disorder) or secondary, in which case an under-
lying condition such as polycythemia vera exists.
Other associations seen with secondary ery-
thermalgia include venous insufficiency, diabetes
mellitus, hypertension, systemic lupus ery-
thematosus, and rheumatoid arthritis.12  The path-
ogenesis is unknown and no treatment is univer-
sally effective.  Aspirin (650 mg every 4 hours) is
the most dependable therapy.12  In cases of second-
ary erythermalgia, treatment of the underlying
or associated disorder may relieve this painful
 condition.
Fig. 3-7. Superinfected tinea pedis. Gram-negative or-
ganisms are often found in these mixed infections.
OK to put on the Web
Friction Blisters
Friction blisters are common in all climates but
can be significantly more frequent and severe in
hot, humid environments.  For a detailed discus-
sion of friction blisters, see Chapter 7, Cutaneous
Trauma and Its Treatment.
DERMATOSES CAUSED BY EXCESSIVE SUN EXPOSURE OR ALLERGY TO SUNLIGHT
Several skin disorders can arise either directly
from exposure to the sun’s rays or from sunlight’s
interaction with drugs.  With all of these conditions,
preventive measures are critical.
Sunburn
Sunburn is a cutaneous photosensitivity reaction
that can occur in all humans, although its severity
diminishes as melanin pigmentation increases.18  It
seldom occurs in black-skinned individuals.  A single
instance of severe sunburn can be disabling, and
repeated episodes put the person at much greater
risk for the development of nonmelanoma skin can-
cer (usually basal cell and squamous cell carcino-
mas).  Additionally, there is evidence to suggest
that several episodes of sunburn or even one severe
sunburn substantially increases the risk of develop-
ing malignant melanoma.19  For all these reasons,
prevention of sunburn is important to improving
not only fighting capability but also the long-term
general health of the soldier.
UV-B radiation, with the shortest wavelengths
of light (290–320 nm) to reach the earth’s surface,
is responsible for most if not all of the short-term
effects of sunburn.  The common name for UV-B
radiation is therefore “sunburn rays.”  UV-A radia-
tion (320–400 nm) and visible light (400–800 nm)
have longer wavelengths, and are not associated
with sunburn.
UV-B erythema (sunburn) becomes visible with-
in 2 to 6 hours of sun exposure and peaks at 24 to
36 hours.18  The erythema fades in 3 to 5 days, and in
all but the fairest-skinned individuals, is followed
by an increase in skin pigmentation (tanning).  Se-
vere sunburn is as injurious to the skin as a thermal
burn, and severe cases can actually require hospi-
talization in a burn unit.  Because UV-B radiation
does not penetrate beneath the epidermis to any
significant degree, the actual injury is primarily
epidermal.  This injury is manifested histologic-
ally by dyskeratotic “sunburn cells” and clinically
by erythema, edema, and in more severe cases,
blistering.  Various mediators of inflammation are

Military Dermatology
48
activated by the sunburn phenomenon, and the
dermis also becomes secondarily involved.  These
consequences are evident from the vasodilation,
dermal edema, and leukocyte infiltration that occur
in sunburned dermis.  The exact mechanism by
which UV radiation causes skin inflammation re-
mains poorly understood.18  For practical purposes,
it is enough to remember that sunburn acts like a
true burn, although third-degree injury (dermal
necrosis) does not occur.
Once the erythema of a sunburn is well estab-
lished, its treatment is similar to a thermal burn of
equivalent severity.  Severe sunburn with extensive
blistering may require hospitalization and the kind of
management that is utilized in a thermal burn unit.
Oral or parenteral administration of high doses of
corticosteroids can be of symptomatic benefit, but
they must be tapered rapidly to reduce the chance
of secondary infection.18  Most sunburn cases are
much milder and can be managed with cool-water
soaks, topically applied corticosteroid creams, and
oral aspirin (650 mg every 4 hours, as needed) or
indomethacin (25 mg three times a day, as needed).
If an anticipated case of sunburn is treated early,
before erythema has appeared or peaked, topical or
oral indomethacin may delay the onset and dimin-
ish the intensity of UV-B erythema.20,21  Although
indomethacin might afford some symptomatic re-
lief, there is no evidence to suggest that these drugs
prevent the actual epidermal injury that accompa-
nies sunburn.  The delayed, post–24-hour erythema
appears to be uninhibited by such treatment.21
Clearly the most helpful tactic is to avoid sun-
burn in the first place.  The largest amounts of UV-
B radiation penetrate the atmosphere at midday,
when the sun casts no shadow.  Avoiding outdoor
work during the hours of 1000 to 1400 will reduce
the chance of overexposure.  Another rule of thumb
is for soldiers to avoid outdoor work when their
shadows are shorter than their height, which al-
ways corresponds to the time of day when UV-B
radiation is most intense.
EXHIBIT 3-1
PHOTOTOXIC AND PHOTOALLERGIC CHEMICALS
Phototoxic chemicals
Dyes
Eosin
Coal-tar derivatives
Acridine
Anthracene
Furocoumarins
Psoralen
8-methoxypsoralen
4,5,8-trimethylpsoralen
Drugs
Thiazides
Chlorothiazides
Doxycycline and other tetracycline-like
derivatives
Furosemide
Nalidixic acid
Naproxen
Benoxaprofen
Phenothiazines such as chlorpromazine
Piroxicam
Quinidine
Amiodarone
Sulfonamides
Photoallergic chemicals
Halogenated salicylanilides
Tetrachlorosalicylanilide
Antifungal drugs
Multifungin
Fentichlor
Jadit
Phenothiazines
Chlorpromazine
Promethazine
Sulfanilamides
Sunscreens
PABA esters
Digalloyltrioleate
Whiteners
Stilbene
Fragrances
Musk ambrette
6-methylcoumarin
Chemicals that are both phototoxic and photoallergic
Phenothiazines
Sulfonamides
Source: Harber LC, Bickers DR, eds. Photosensitivity Diseases: Principles of Diagnosis and Treatment. Philadelphia, Pa: BC
Decker, Inc; 1989.

49
Skin Diseases Associated with Excessive Heat, Humidity, and Sunlight
Protective clothing should be worn whenever
possible.  A broad-brimmed hat is appropriate for
any climate, and will reduce UV radiation exposure
to the head and neck.  Long-sleeved shirts and full-
length trousers should be worn whenever possible.
A significant amount of light can penetrate loosely
woven or soaking-wet clothing, and a tightly wo-
ven, heavier fabric is always preferable.  Gloves will
protect the hands.
When protective clothing is impractical, such as
in an extremely hot and humid climate, a chemical
sunscreen should be applied.  Numerous types are
available, but for field conditions a sunscreen with
a sun protection factor (SPF) of at least 15 should be
used.  It is especially important to treat the face,
ears, neck, and hands, because it is often impossible
to cover these areas with protective clothing (a hat
is not protective from reflected light off sand, snow,
water, and so forth).  Most chemical sunscreens
contain p-aminobenzoic acid (PABA) or its deriva-
tives.  Soldiers who are sensitive to PABA can use
equally effective sunscreens based on salicylates,
cinnamates, benzophenones, and dibenzoyl-
methanes.
Individuals with deep tans or naturally dark skin
have considerable protection from UV-B radiation
but are still susceptible to UV radiation–induced
photodamage.21  However, tanning as a protective
measure is both impractical and injurious.  Some
individuals can never achieve a truly protective tan;
rapid deployment to sunny climates eliminates the
possibility of achieving a tan without the morbidity
of burning.  Tanning itself is an indication that UV
radiation–induced epidermal injury has occurred,
which predisposes an individual to all the long-
term adverse sequelae such as skin cancer and pre-
mature aging.
Phototoxicity and Photoallergy
Both phototoxicity and photoallergy are due to
the combined effects of drugs (or other chemicals)
and sunlight.  Neither drug nor light is alone suffi-
cient to cause the reaction.  In theory, phototoxic
drugs are capable of causing an adverse reaction in
all individuals if administered in high enough
doses.  Photoallergic drugs cause idiosyncratic re-
sponses (only certain predisposed patients will de-
velop the allergy).  Some photoallergic and photo-
toxic reactions occur when the responsible drug or
chemical is taken internally and carried to the skin
via the bloodstream.  Other chemicals are capable of
causing photocontact allergy (the reaction between
light and drug occurs when the offending chemical
is applied to the surface of the skin and then irradi-
ated) (Exhibit 3-1).
In general, phototoxic reactions are confined to
areas of the skin exposed to light, such as the face,
the pinnae of the ears, the “V” of the neck, the
nuchal area, and the extensor and dorsal surfaces of
the arms (Figure 3-8).  Phototoxicity from many
systemically administered drugs, such as the tetra-
cycline derivatives, can appear as mild erythema
resembling severe sunburn.  However, the full spec-
trum of sunburnlike reactions may occur, including
extensive blistering.  Reactions to some agents such
as the psoralens can cause eventual hyperpigmen-
tation of the involved areas.  Certain systemically
administered phototoxic drugs such as demeclo-
OK to put on the Web
Fig. 3-8. Phototoxic reactions such as this one caused by
Tegretol (carbamazepine, manufactured by Basel Phar-
maceuticals, Summit, N.J.) are generally confined to re-
gions of the skin exposed to light. A photoallergic erup-
tion might assume a similar appearance.

Military Dermatology
50
cycline can also cause photoonycholysis, in which
separation of the nail from the nail bed occurs.
Photoallergy is much less common than photo-
toxicity.18  It involves an immunological response of
the skin to the combination of a specific chemical
and light.  The general mechanism of action is
believed to be the conversion of the offending chemi-
cal by light into a photoproduct.  The photoproduct
then binds to a soluble or membrane-bound protein
to form the antigen that precipitates a delayed–
hypersensitivity immune response.  Once the pa-
tient has been sensitized to the chemical, subse-
quent reexposures will elicit a cutaneous reaction.22
The most common groups of chemicals causing
photoallergy are topically applied fragrances and
antibiotics.  Typically, the reactions caused by these
agents resemble acute contact dermatitis such as
that seen with poison ivy.  The eruption is
papulovesicular or vesicular and frankly eczema-
tous.  Light-exposed areas of the body are the sites
of involvement, just as is the case with phototoxic
reactions.  Postinflammatory hyperpigmentation,
however, is less often encountered in photoallergy.
Establishing the diagnosis of photoallergy or
phototoxicity requires phototesting (and photopatch
testing in cases of photoallergic contact dermatitis).
The technique of phototesting, which may require
specialized equipment, is beyond the scope of this
chapter.  Treatment involves avoiding the contrib-
uting factors—certain wavelengths of light and the
responsible chemical.  In theory, avoiding the chemi-
cal or drug alone should be sufficient.  However,
certain drugs such as hematoporphyrin bind avidly
to dermal proteins and are only slowly eliminated
from the skin, which can take months.  Phototoxic-
ity from this drug can therefore be prolonged.
Polymorphous Light Eruption
Polymorphous light eruption (PMLE), a condi-
tion of unknown etiology, is one of the most com-
mon disorders of photosensitivity.18  Several other
names have been applied to the condition, some of
which are either synonymous with or variants of
PMLE.  These names include solar eczema, summer
prurigo, solar dermatitis, and perhaps hydroa
aestivale.  A photosensitivity disease called actinic
prurigo is often included as a clinical subset of
PMLE, although some authorities consider it to be a
separate condition.23  The entire group of conditions
designated as PMLE may represent a clinical spec-
trum of severity for a single disease or, alterna-
tively, may actually represent a diverse group of
photosensitivity disorders with different patho-
geneses.  For purposes of this chapter, the entire
group will be referred to as PMLE.
PMLE occurs in all ethnic groups, but Native
Americans appear to be genetically predisposed to
the subset called actinic prurigo.  All age groups can
be affected, and there does not seem to be a clear-cut
difference in incidence between males and females.
The lesions of PMLE can assume a variety of
appearances (hence the name polymorphous) in-
cluding erythema, eczema, vesicles, papules, nod-
ules, plaques, and areas that are excoriated,
lichenified, or both (Figures 3-9 and 3-10).  The
lesions are most common on the face, but relatively
sun-protected areas such as the submental region
are spared.  The eruption is usually confined to sun-
exposed areas, but because the lesions of PMLE are
usually patchy and irregular, a sharp border is
seldom as evident as that seen in phototoxic or
photoallergic reactions.
Typically, PMLE begins or recurs in the spring as
the amount of UV light and opportunities for expo-
sure increase.  Lesions usually erupt several hours
after sun exposure has occurred.  They begin as
papules or plaques in light-exposed areas, and are
moderately to severely pruritic.  The pruritus is
often described as “stinging.”18  Subsequent expo-
sures to sunlight will cause new lesions, again after
a lag of several hours.  However, as spring and
summer progress, many patients experience a less-
ening of disease severity, as if “hardening” is occur-
ring.  Lesions persist for several days.  With repeat-
ed outbreaks at close intervals, large eczematous or
lichenified plaques may form.
The histopathological findings are often helpful
Fig. 3-9. Polymorphous light eruption: papular lesions.
OK to put on the Web

51
Skin Diseases Associated with Excessive Heat, Humidity, and Sunlight
OK to put on the Web
Antimalarial drugs taken systemically are the
mainstay of therapy for incapacitating disease that
is not adequately controlled by the above methods.
Plaquenil (Hydroxychloroquine, manufactured by
Sanofi Winthrop Pharmaceuticals, New York, N.Y.)
is used most often, and can be effective in low doses
(250–500 mg daily).  It may only be required during
the spring and early summer, when disease activity
is at its peak.  The major drawback to the antimalarial
drugs is the retinal toxicity that they can cause.
Patients need to be monitored every 3 months to
assure that irreversible ocular changes are not in
progress.  These drugs also may produce some less
serious side effects such as headaches, gastrointes-
tinal upset, blurred vision, and pruritus.  Clearly
the antimalarial drugs are far from ideal as a treat-
ment for a relatively benign, although potentially
incapacitating, disease.
For severe flare-ups of PMLE, systemic cortico-
steroids are effective.  Serious long-term side effects
make this class of drugs undesirable for chronic
therapy.
Solar Urticaria
Solar urticaria manifests itself by the onset of
erythema and pruritus a few minutes after sun
exposure; these areas then become edematous or
frankly urticarial.  The eruption is limited to sun-
exposed skin, and in the absence of reexposure, the
lesions disappear after several hours.  This stage is
followed by a period of 12 to 24 hours in which the
skin is refractory to new lesions, even if sun expo-
sure occurs.  Like typical urticaria, an extensive
outbreak can be associated with an anaphylaxis-
like reaction.18
Solar urticaria can occur at any age, but most
reported cases have been in the 30- to 40-year-old
age group.  Women are more often affected than
men.  The condition may spontaneously remit within
a few months (which occurs in about one fourth of
patients), but usually persists for years.
All wavelengths of sunlight have been impli-
cated in causing one or more of the various subsets
of solar urticaria.  Eruptions caused by visible light
seem to have the best prognosis.18  Phototesting may
reveal the culprit wavelengths, which is of obvious
practical value in preventing outbreaks.  However,
because such testing requires special equipment
that is usually only available in medical centers, it
has little use in field medicine.
No specific therapy exists for solar urticaria.
Avoiding sun exposure is the most successful pre-
Fig. 3-10. Polymorphous light eruption: diffuse erythema
and swelling.
in making a diagnosis.  Characteristically, dense
aggregates of mononuclear cells are seen in a
perivascular distribution in the mid- and upper der-
mis.  Epidermal changes are nonspecific and include
edema, spongiosis, parakeratosis, acanthosis, and
mild vacuolar degeneration of the basal cell layer.18
PMLE can be caused by UV-B or UV-A radiation,
visible light, or a combination of these.  Different
patients seem sensitive to different wavelengths of
light.  This phenomenon may be a true difference in
reactivity between individuals, or may simply indi-
cate that the term PMLE represents a variety of
diseases with differing etiologies.  Phototesting may
pinpoint the offending wavelengths of light, but
such an evaluation is relatively complex and is
often unrewarding.
The best treatments for PMLE are avoiding sun-
light and wearing protective clothing.  However,
avoidance is often impractical, especially in sol-
diers whose duties require outdoor work.  Sun-
screens are usually somewhat helpful, although
they seldom achieve complete control.  Because
many cases of PMLE are caused by UV-B radiation,
suncreens containing PABA or other UV-B blockers
can be useful.  Suncreens that are protective in the
UV-A range (eg, Photoplex, consisting of avo-
benzone and padimate O, manufactured by Allergan
Herbert, Irvine, Calif.) are less effective because
they screen relatively little UV-A radiation (com-
pared to the excellent blockade achieved by many
UV-B sunscreens).  Opaque sunscreens such as tita-
nium dioxide are effective against all damaging
wavelengths but are also messy and cosmetically
unacceptable.

Military Dermatology
52
ventive measure, but this is usually impractical.
Antihistamines are often not effective until sedat-
ing doses are used.  Antimalarials have been found
useful in a few cases.  Desensitization has proven
effective in several cases.18  This method involves
frequent exposure of a small area of the skin to the
offending wavelengths of light until no reaction
occurs.  Then the size of the treated area is gradually
increased until the entire body can be exposed with-
out a reaction.  Daily or every-other-day exposures
of 10 to 20 minutes often keep the patient lesion-free
despite normal sunlight exposure.
DERMATOSES EXACERBATED BY SUNLIGHT
Several skin diseases can be markedly worsened
by exposure to sunlight, making it extremely diffi-
cult for the soldier to function effectively.  Fortu-
nately, most of these disorders are uncommon.
Porphyria Cutanea Tarda
Porphyria cutanea tarda (PCT) actually is an
example of phototoxicity, but in affected patients
the phototoxic drugs are endogenous porphyrins.
PCT patients present with blisters and erosions in
sun-exposed areas.  The disease is caused by a
metabolic defect in the production or metabolism
of porphyrins.  Visible light in the 400 to 410 nm
range is the part of the spectrum most responsible
for the reaction.  Therapy consists of phlebotomy
(to reduce hepatic iron stores), antimalarial drugs,
or both.
Erythropoietic Protoporphyria
Patients with erythropoietic protoporphyria, a
much less common defect in porphyrin metabo-
lism, present acutely with areas of sun-exposed
skin that become painful shortly after sun exposure.
Erythema and edema then develops in those sites
where stinging pain has occurred.  Pain is usually
more prominent than the visible skin lesions, but
small, pitted scars can develop over time.  Oral beta
carotene has been found to be useful in reducing
the severity of the disease.  Erythropoietic proto-
porphyria is an autosomal dominant inherited con-
dition that usually manifests itself in childhood,
and is therefore very unlikely to be encountered in
active-duty military personnel.
Others
The skin lesions of both discoid lupus erythe-
matosus and systemic lupus erythematosus can be
induced or significantly worsened by sunlight.
Recurrent herpes simplex viral outbreaks can be
precipitated by sun exposure.
The rash of pellagra is clearly a photosensitive
disorder.  Except in maltreated prisoners of war and
soldiers who are taking the drug isoniazid, this
deficiency of tryptophan and niacin is very unlikely
to occur.
SUMMARY
Soldiers entering hot or sunny climates are at risk
for heat-related skin injury or disease, which can
often be debilitating.  Even the classic forms of heat
injury such as heatstroke are influenced by the skin
because sweating is so important for temperature
homeostasis.
Excessive environmental heat is directly respon-
sible for miliaria, the best known form of which is
prickly heat.  Tropical acne, cholinergic urticaria,
and the hypohidrosis syndrome can also be prob-
lems in hot climates.
Some skin conditions may be exacerbated by
heat and humidity, turning a mild dermatosis into
a disabling disease.  Bacterial and fungal infections
of the skin are always problems in hot and humid
settings, and friction blisters and dyshidrotic ec-
zema are far more commonly seen in those condi-
tions.
The intense UV light found in sunny climates is
responsible for sunburn, which can be just as incapaci-
tating as a thermal burn.  A higher incidence of pho-
totoxic and photoallergic reactions to drugs is ex-
pected with increased sun exposure.  Allergy to certain
wavelengths of sunlight (polymorphous light erup-
tion) can be especially problematic.
Certain skin conditions such as the porphyrias
and cutaneous lupus erythematosus can be signifi-
cantly worsened by exposure to sunlight.  It is
unlikely that a soldier with either condition could
function effectively in a sunny environment.

53
Skin Diseases Associated with Excessive Heat, Humidity, and Sunlight
REFERENCES
1.
Eichna LM. Heat casualty. In: Infectious Diseases and General Medicine. Vol 3. In: Havens WP, Anderson RS, eds.
Internal Medicine in World War II. Washington, DC: Medical Department, US Army, Office of The Surgeon
General; 1968: 195–330.
2.
US Departments of the Army, Navy, and Air Force. Prevention, Treatment and Control of Heat Injury. Washington,
DC: 1980. Technical Bulletin MED 507.
3.
Allen AM. Skin Diseases in Vietnam, 1965–72. In: Ognibene AJ, ed. Internal Medicine in Vietnam. Vol 1. Washing-
ton, DC: Medical Department, US Army, Office of The Surgeon General, and Center of Military History; 1977:
29–52.
4.
Sulzberger MB, Harris DR. Miliaria and anhidrosis. Arch Dermatol. 1972;105:845–850.
5.
Arnold HL, Odom RB, James WD. Andrews’ Diseases of the Skin. Philadelphia: WB Saunders Co; 1990: 4.
6.
Pillsbury DM, Livingood CS. Dermatology. In: Infectious Diseases and General Medicine. Vol 3. In: Havens WP,
Anderson RS, eds. Internal Medicine in World War II. Washington, DC: Medical Department, US Army, Office of
The Surgeon General; 1968: 543–674.
7.
Sulzberger MB, Emik LO. Miliaria: Clinical and statistical findings. J Invest Dermatol. 1946;7:53–59.
8.
Papa CM, Kligman AM. Mechanisms of eccrine anhidrosis. Part 1: High level blockade. J Invest Dermatol.
1966;47:1–9.
9.
Stoughton, RB. Suppression of miliaria rubra (prickly heat) by a topical anticholinergic agent. J Invest Dermatol.
1964;42:228.
10.
Sulzberger MB, Griffin TB. Induced miliaria, post-miliarial hypohidrosis and some potential sequelae. Arch
Dermatol. 1969;99:145–151.
11.
Plewig G, Kligman AM. Acne: Morphogenesis and Treatment. New York: Springer-Verlag; 1975; 194–196.
12.
Page EH, Shear NH. Temperature-dependent skin disorders. J Amer Acad Dermatol. 1988;18:1003–1019.
13.
Kounis NG, MacMahon RG. Cholinergic urticaria with systemic manifestations. Ann Allergy. 1975;35:243–245.
14.
Lawrence CM, Jorizzo JL, Kobza-Black A, Coutts A, Greaves MW. Cholinergic urticaria with associated
angioedema. Br J Dermatol. 1981;105:543–550.
15.
Lookingbill DP, Marks JG Jr. Principles of Dermatology. Philadelphia: WB Saunders Co; 1986: 198.
16.
Douglas HMG. Reactions to aspirin and food additives in patients with chronic urticaria, including the physical
urticaria. Br J Dermatol. 1975;93:135–144.
17.
Babb RR, Alarcon-Segovia D, Fairbairn JF II. Erythermalgia, review of 51 cases. Circulation. 1964;29:136–141.
18.
Harber LC and Bickers DR, eds. Photosensitivity Diseases: Principles of Diagnosis and Treatment. Philadelphia: BC
Decker, Inc; 1989.
19.
Lew RA, Sober AJ, Cook N, Marvell R, Fitzpatrick TB. Sun exposure habits in patients with cutaneous melanoma.
J Dermatol Surg Oncol. 1983;9:981.
20.
Eaglstein WH, Marsico AR. Dichotomy in response to indomethacin in UV-C and UV-B induced ultraviolet light
inflammation. J Invest Dermatol. 1975;65:238–240.

Military Dermatology
54
21.
Consensus Development Panel. National Institutes of Health Summary of the Consensus Development Confer-
ence on sunlight, ultraviolet radiation, and the skin. J Am Acad Dermatol. 1991;24:608–612.
22.
Epstein JH. Phototoxicity and photoallergy in man. J Am Acad Dermatol. 1983;8:141–147.
23.
Lane PR, Sheridan DP, Hogan DJ, Moreland A. HLA typing in polymorphous light eruption. J Amer Acad
Dermatol. 1991;24:570–573.

Immersion Foot Syndromes
55
IMMERSION FOOT SYNDROMES
Chapter 4
*Private Practice of Dermatology, Overton Park Building, 4200 S. Hulen Drive, Fort Worth, Texas 76109; formerly, Dermatology Service,
Fitzsimons Army Medical Center, Aurora, Colorado 80045
†Private Practice of Dermatology, Dermatology Clinic, Regenstrief Health Center, 1050 Walnut Street, RG524, Indianapolis, Indiana
46202; formerly, Chief, Dermatology Service, Brooke Army Medical Center, Fort Sam Houston, Texas 78234
JOHN ADNOT, M.D.* AND CHARLES W. LEWIS, M.D.†
INTRODUCTION
OVERVIEW
INJURIES IN COOL OR COLD CLIMATES
Trench Foot
Immersion Foot
Management
INJURIES IN WARMER CLIMATES
Tropical Immersion Foot
Warm Water Immersion Foot
SUMMARY

Military Dermatology
56
INTRODUCTION
Since the founding of this country, American
soldiers have been fighting wars wearing a wide
variety of shoes and boots to protect their feet from
the environment.  Soldiers of the Continental Army,
1775 to 1781, wore simple low-cut leather shoes
with the rough side out and cloth leggings laced
over the lower leg.1  Joseph Lovell, a surgeon gen-
eral in the 1800s, noted the importance of enabling
soldiers to keep their feet warm and dry with wool
socks and laced shoes reaching at least to the ankle.
He also observed that letting the feet remain wet
and cold for any length of time led to constitutional
illnesses.2
In 1861, Union and Confederate soldiers wore
any type of personally owned boot or shoe, but
most used a simple, laced, ankle-high brogan.  Dur-
ing the Civil War, Union troops were issued the
first mass-produced shoes that distinguished be-
tween the left and right foot.  Up to this time, most
shoes were made to be worn on either foot.  Many
Confederate troops were barefoot or used can-
vas and wood to fashion crude walking shoes.  Of-
ficers and mounted troops typically wore leather
boots.2
Ankle-high, heavy leather shoes continued to be
manufactured and were issued to soldiers during
World War I.  Wool wraps called puttees were
wound around the lower leg from the knee to the
ankle to protect the leg.  It was not until the spring
of 1918, however, that the Pershing boot, a heavier
shoe with more waterproof construction, was de-
veloped.3  It was effectively designed for the de-
mands of trench warfare.  After the war, modifica-
tions on footwear reflected garrison life and the
need for economy.3
Ankle-high shoes and canvas leggings were ini-
tially worn in World War II.  Because of material
shortages and lack of preparedness for the footwear
needs of wartime, despite the experience available
from World War I, it was not until the end of 1943
that the first combat boot appeared.3  It was a brown
laced boot with a leather flap on the upper.  Because
leather is a permeable material, all leather boots
leak to some extent.  It was not until 1944 that the M-
1944 Shoepac, with a moccasin-type rubber boot,
was approved for distribution.  It was the best
available modification for the cold, wet conditions
of trench warfare in Europe.3  The first jungle boots
made of canvas and rubber were used in the
South Pacific.3  A modified jungle boot, the tropical
combat boot, was designed and tested during the
latter part of World War II.  It consisted of spun
nylon, a leather midsole, and a full-length rubber
outer sole.  Production was not started until the sum-
mer of 1945.3
During the Korean conflict, a special brown
leather jump boot that laced all the way up the front
was issued to paratroopers and became popular
throughout the army.  Except for switching to a
black color, these boots remained mostly un-
changed through the Korean and Vietnam conflicts.
In the mid-1960s a black leather and olive drab
nylon-webbing jungle boot with a cleated sole be-
came the favorite footwear of the American soldier.4
The type of footwear worn by the soldier in
combat, along with environmental conditions and
preventive hygiene measures, has played a crucial
role in producing a variety of cutaneous disorders
of the feet.  These “disease, nonbattle injuries” range
from minor inconveniences to very significant con-
ditions that may result in hospitalization.
Based on methods of clinical diagnosis and labo-
ratory confirmation of soldiers evacuated from war
zones with inflammatory conditions of the feet, the
following list was presented by Pillsbury and
Livingood:
At Fitzsimons General Hospital, after classification
and appropriate studies, patients referred with this
diagnosis were divided into the following catego-
ries and proportions:
1.
The hyperhidrosis (dyshidrosis) syndrome,
51 percent.
2.
Pyoderma secondary to trauma, maceration,
or hyperhidrosis (dyshidrosis) syndrome,
14 percent.
3.
Dermatophytosis, 20 percent.
4.
Dermatitis venenata produced by medica-
tion (which had usually been prescribed for
the treatment of the presumed fungal infec-
tions), 11 percent.
5.
Other dermatitis venenata, 2 percent.
6.
Resistant pustular eruptions (the so-called
bacterid of Andrews), 1 percent.
7.
Pustular psoriasis, 0.5 percent.
8.
Acrodermatitis continua of Hallopeau, 0.5
percent.5(p593)
Controlled studies demonstrating effective meth-
ods for preventing foot diseases in military popula-

Immersion Foot Syndromes
57
tions are rare.  However, two studies are well docu-
mented:
A convincing controlled study along these lines
was conducted by Maj. (later Lt. Col.) Laurence
Irving, Chief, Physiology Section, Headquarters,
Eglin Field, Fla.  Sandals were issued to approxi-
mately 1,000 men, who were permitted to wear
them on the post as much as they wished; most of
them practically gave up wearing shoes.  A similar
number of men wore shoes as usual.  Within a
month, the proportion of severe dermatophytoses
in men wearing sandals fell from 30 to 3 percent,
while in the control group, the disease remained as
troublesome as usual.
A similar study was conducted in New Guinea,
while the 43d Infantry Division was in a rest area.
Some 300 men with unclassified skin diseases, many
of whom undoubtedly had dermatophytosis of the
feet, were kept on the beach for 4 hours daily,
without clothing or shoes.  They bathed, exercised,
or just lay in the sun as they wished.  Within a
month, the majority of infections had cleared with-
out any other treatment.5(pp602–603)
During the conflict in Vietnam, one of the au-
thors (CWL) convinced the Commander of the Sec-
ond Brigade, First Infantry Division, to direct the
purchase of 5,000 pairs of rubber shower thongs for
use after combat operations in the rice paddies.  By
allowing soldiers to use these open rubber thongs
upon return to base camp, and limiting the continu-
ous wet exposure to not more than 72 hours, the rate
of tropical immersion foot problems was generally
kept to a level of 10% or less.  Prior to institution of
these policies, a combat unit could experience 70%
to 75% loss of personnel due entirely to inflammatory
skin diseases of feet that had been continuously wet
more than 72 hours (Exhibits 4-1 through 4-3).
While it is often impossible to determine the
exact role of diseases limited to the feet in overall
effectiveness of a combat unit, rates of sick call and
hospitalization always increased during periods of
combat operations in the rainy seasons and de-
creased in dry seasons.4  However, the fact that
many combat units lost hundreds to thousands of
man-days due to large numbers of individuals
placed either on quarters or on light, noncombat
status because of their skin diseases, was rarely
included in statistical reports.
OVERVIEW
Injuries to the feet from prolonged immersion in
water or contact with dampness, in a range of envi-
ronmental temperatures, may be collectively re-
ferred to as “immersion foot syndromes.”  These
syndromes have been referred to as trench foot,
swamp foot, tropical jungle foot, paddy-field foot,
jungle rot, sea boot foot, bridge foot, and foxhole
foot.  Although most common during wartime, they
also appear with occupational and recreational ac-
tivities.
Injuries related to simultaneous exposure to cold
temperatures and a wet environment are subdi-
vided into trench foot and immersion foot.  Those
involving warmer temperatures include tropical
immersion foot and warm water immersion foot.
This review describes each condition to alleviate
confusion over nomenclature and to aid in recogni-
tion and treatment (Table 4-1).  To keep the focus
narrow, the extremes of the temperature injury spec-
trum (ie, true frostbite and burns) are not specifi-
cally addressed, but referred to as necessary for
clarification.
INJURIES IN COOL OR COLD CLIMATES
All four of the immersion foot syndromes dis-
cussed in the next two sections are characterized by
pain that is continuous over several days to weeks.
They may incapacitate large numbers of troops in a
unit simultaneously because of common exposure
to the harsh environment.  Commanders may prevent
these injuries by being aware of the hazards and
preventing long-term exposure to the predisposing
conditions.  In this section the two syndromes result-
ing from cold, wet conditions will be discussed.
Trench Foot
“Trench foot” refers to injury resulting from pro-
longed exposure to wet conditions, without immer-
sion, in cold weather.  The term probably originated
in World War I, when many men were confined to
trenches in cold, damp weather for prolonged peri-
ods.  The condition was recognized as a cause of
considerable loss of manpower as far back as the
Greek Campaigns6 and the Napoleonic and Crimean

Military Dermatology
58
EXHIBIT 4-1
ARMY REGULATION 40-29: PREVENTION OF SKIN DISEASE AMONG TROOPS OPERATING
IN INUNDATED AREAS
HEADQUARTERS
UNITED STATES ARMY VIETNAM
APO SAN FRANCISCO 96375
REGULATION NUMBER 40-29
10 January 1968
MEDICAL SERVICE
Prevention of Skin Disease Among Troops
Operating in Inundated Areas
1.
PURPOSE:  To outline policy and procedures for the prevention of disabling skin conditions, which may occur when
troops are required to conduct field operations in flooded rice paddies and other inundated areas.
2.
SCOPE:  This regulation is applicable to all units assigned or attached to this command.
3.
GENERAL:  Fungus infection of the foot is probably the most common skin disease causing disability among troops
in RVN.  The common athlete’s foot with involvement of the toe webs and soles of the feet does not occur frequently
in Vietnam; or if it does, it is relatively mild.  The most severely affected areas have been the top of the feet and legs
under the boots, the groin, and the buttocks.  The lesions often spread to produce bright red rings which may run
together.  Although not so common, immersion foot is also a potential hazard.
4.
RESPONSIBILITIES: Commanders are responsible for implementing measures outlined below when, in their opinion
and upon the advice of their surgeon, they are considered necessary and practical.
5.
PREVENTIVE MEASURES:
a. Limiting the duration of operations in watery terrain.  The tactical situation permitting, a 48 hour limit (2 days
and 2 nights) should be placed on operations involving continuous exposure to water.  If this is not possible,
casualties from fungus infection may be disabled for 2 or more days after a five-day operation.
b. Proper care of the feet.
(1) One of the most important measures is to insist that troops wear boots and socks only when necessary while
in base camps.  Shower clogs or thongs are recommended as substitutes.
(2) During operations, commanders should have a few men at a time remove their footgear and allow their feet
to dry as the tactical situation permits.
(3) Dry socks should be included in resupply missions in the field whenever possible.  Mesh socks are preferred.
c. Exposure of the skin to the sun.
(1) Where possible, exposure of as much of the body as possible to the sun for 30 minutes every day is recom-
mended.  To avoid sunburn, new arrivals should be gradually exposed for short periods of time until a
protective tan develops.
(2) In base camps, during daylight hours when mosquitoes are not a problem, troops should be allowed to wear
abbreviated clothing such as shorts.  This should be limited to those troops whose operations mission
predisposes them to skin disease.
d. Cleansing of the skin.
(1) As soon as troops return from an operation, they should remove dirty clothing and shower immediately.  It
appears that showering in potable water will reduce the incidence of skin diseases.  However, showers using
nonpotable water are preferable to no showers.
(2) The use of antibacterial (germicidal) soaps should be encouraged.  Any of the nationally advertised brands
are acceptable.
e. Laundering field clothing.  Field clothing should be washed in potable water.  Quartermaster or modern contract
laundries are preferred.  Starching of field clothing reduces ventilation, and is not recommended for troops in
active combat operations or other strenuous physical activities.
f.
Underclothing.  Troops should be discouraged, but not prohibited, from wearing underclothes while on opera-
tions in the field.  Underclothes reduce ventilation of the skin.
(AVHSU-PM)
FOR THE COMMANDER:
ROBERT C. TABER
Brigadier General, US Army
Chief of Staff
WILLIAM H. JAMES
Colonel, AGC
Adjutant  General
This Regulation supersedes USARV Reg 40-20, 25 Jan 66

Immersion Foot Syndromes
59
EXHIBIT 4-2
MEMORANDUM ON PREVENTION OF SKIN DISEASE IN NINTH INFANTRY DIVISION
DEPARTMENT OF THE ARMY
HEADQUARTERS 9th INFANTRY DIVISION
APO SAN FRANCISCO 96370
AVDE-MD
28 October 1968
SUBJECT: Prevention of Skin Disease SEE DISTRIBUTION
1.
The maintenance of the health of a unit is a command responsibility.  Tropical skin diseases are the most common
cause of non-effectiveness within the 9th Infantry Division Area.  Commanders have adequate medical personnel,
effective medications and proven techniques to reduce this very serious problem
2.
Diseases of the foot and boot area developed rapidly after 48 hours of continuous exposure to the rice paddies and
swamps, and may affect 35% to 50% of the combat strength of an infantry unit after 72 hours.  With each succeeding
exposure, skin infections are more severe and require over three weeks of intensive treatments.
3.
Consequently, commanders will limit operations to 48 hours in the paddy followed by a minimum of 24 hours
utilization in a dry area.  This limitation will be exceeded only in situations which override the inevitable loss of
combat strength from skin disease.
4.
Additionally, to reduce the non-effectiveness rate caused by skin disease, commanders will conduct foot inspections
and require their men to put on dry socks daily.  Men should remove their boots and socks whenever possible (up to
four hours daily), to let their feet dry out.  After an operation all personnel will be examined by medical personnel.
JULIAN J. EWELL
Major General, USA
Commanding
DISTRIBUTION:
A
EXHIBIT 4-3
MEMORANDUM ON PROPER FOOT CARE FOR SOLDIERS AT FORT GORDON, GEORGIA
DEPARTMENT OF THE ARMY
HEADQUARTERS U.S. ARMY SIGNAL CENTER AND FORT GORDON
FORT GORDON, GEORGIA  30805-5000
AZTH-CG
20 November  1990
MEMORANDUM FOR Commander, U.S. Army Training and Doctrine Command
ATTN:  ATCD-SE (COL Charles Ball), Fort Monroe, Virginia  23651-5000
SUBJECT:  Proper Foot Care for Soldiers at Fort Gordon
1.
Every summer an unnecessarily large number of soldiers at Fort Gordon require treatment in the Dermatology Clinic
for severe eczema of the feet, usually with secondary infection which results from excessive heat and humidity.  It is
aggravated by the wearing of wool winter socks and combat boots during periods of high heat and humidity.
Soldiers suffering from this problem lose many hours of training and are restricted from physical training until the
skin of the feet can heal.  After a severe episode of foot eczema, the skin is easily broken down for many weeks
following recovery and relapses are common.
2.
Standard treatments for this condition include topical and internal medications.  An integral part of treatment,
however, is evaporation of perspiration through the wearing of adequately ventilated foot wear and cotton or cotton
blend socks.
3.
Therefore, recommend that OD cotton socks be added as an additional issue item primarily to those soldiers
participating in basic and advanced individual training in the summer months where excessive heat and humid
climate exists.  With the addition of cotton socks, daily rotation of boots and normal foot care during the summer
months, many cases of foot eczema can be prevented and excessive lost training time and physical training restric-
tions can be minimized.
4.
Point of contact at Fort Gordon is Ms. Ree Hill, Chief, Supply Brand, Installation Supply and Services Division,
Directorate of Installation Support, AUTOVON 780-5186/4507.
PETER A. KIND
Major General, USA
Commanding
JAMES E. HASTINGS
Brigadier General, MC
Director, Health Services

Military Dermatology
60
TABLE 4-1
COMPARISON OF IMMERSION FOOT SYNDROMES
Systemic
Healing
Pathological
Syndrome
Site
Symptoms
Signs
Involvement
Time
Changes
Trench foot
Foot
Prehyperemic:
Prehyperemic:
None
Visible
Prehyperemic:
Early:
pale, swollen,
changes in
thrombosis,
numbness,
vesiculobullous
4 wk–6 mo;
edema,
pain, paresthesia
lesions, distal
neurological
vasoconstriction
Late: anesthesia,
cyanosis
and structural
Hyperemic:
“walking on
Hyperemic:
changes in
thrombosis,
blocks of wood”
increased edema,
months (may
capillary rupture,
Hyperemic:
warm, dry,
be permanent)
hemorrhage,
tingling,
erythematous,
vasodilation,
progressing to
bounding pulses,
edema,
throbbing, burning
vesicles, bullae,
subepidermal
pain, and
ecchymosis
vesiculation
hyperesthesia;
Posthyperemic:
Posthyperemic:
distal anesthesia
Early: cool, moist,
fibrin deposition
may persist
patchily or entirely
in vessels and
Posthyperemic:
cyanotic, normal to
muscles, edema of
deep ache joint pain,
decreased pulses
nerve axons,
prolonged
Late: skin and
variable lymphatic
anesthetic changes
muscular atrophy,
damage
osteoporosis,
deformity
Immersion
Usually
Same as trench foot
Same as trench foot
None
Same as
Same as trench foot
foot
foot,
trench foot
occasionally
knee, thigh,
or buttocks
Tropical
Dorsum
Early:
Early:
Fever
3–7 d
Parakeratosis,
immersion
of foot,
burning pain
erythema,
(38°C–39°C),
acanthosis,
foot
ankles
(aggravated by
edema, macu-
femoral
lymphocytic
pressure from
lopapular rash,
adenopathy
perivascular
footwear, walking,
vesicles or bullae,
infiltrate, edema,
or both) and itching
and tenderness,
telangiectasia,
delineatedby top
extravasation of
of boot
erythrocytes
Late:
Recovery:
paresthesia,
decreased fever,
hyperesthesia,
adenopathy,
anesthesia
tenderness, and pain
by 72 h; erythema
and edema subside in
5–7 d followed by
fine branny
desquamation of all
affected areas
Warm water
Plantar
Pain on weight-
Early:
None
1–3 d
Thickening of
immersion
surfaces
bearing, tingling,
swelling, wrinkling,
(symptoms);
stratum
foot
of feet
“walking on rope”
and pallor of plantar
7–14 d
corneum
sensation
surfaces
(fully
Recovery:
functional)
resolution of changes
in 24 h; shedding
of stratum corneum
starts in 4–6 d,
lasts 7–14 d; feet
remain tender until
new callus develops

Immersion Foot Syndromes
61
Water
Water
Relation to
Susceptibility
Pathogenesis
Exposure
Temp.
Water Temp.
Treatment
Prophylaxis
Factors
Direct
2–14 d
15°C
Lower temp-
Removal from wet
Individual education
Dependency,
vascular
continuously
erature
environment, avoid-
in first aid and
immobility,
injury by
wet (but not
hastens
ance of weight-
recognition;
trauma, anoxia,
cold
necessarily
injury
bearing, rewarming
frequent rotation
poor nutrition,
immersed)
of body, elevation
out of wet, cold areas;
improper
and cooling of feet,
maintenance of
warming
nutritious diet, asepsis,
nutritional status;
tetanus prophylaxis,
informed command
prophylactic antibiotics,
elements
conservative surgical
approach, avoidance of
smoking
Same as trench
1 d or more of
15°C
Same as trench
Same as trench foot
Enclosed survival
Same as trench foot
foot
continuous
foot
craft, individual
immersion
protective suits
Passage of water
3–10 d of
22°C–32°C
None
Allowing feet to dry
24 h of drying for
Previous episodes
through
continuous
until asymptomatic
each 48 h of
may increase
epidermis,
immersion
exposure
susceptibility
with secondary
to repeated
subacute
episodes
dermatitis
Hyperhydration
1–5 d of
22°C–32°C
Increased
Allowing feet to dry
Daily drying
Thicker stratum
of stratum
intermittent
temperature
until asymptomatic
(overnight),
corneum
corneum
immersion
hastens
silicone barrier
predisposes to
injury
greases
injury

Military Dermatology
62
Wars.7,8  Yet these lessons seem to have been lost on
modern armies.  In Europe during World War II,
American forces sustained 11,000 cases of trench
foot in November 1944 with more than 6,000 in the
Third U.S. Army alone.9
Trench foot is nearly identical to gradual-onset
frostbite, but the maximum temperature at which
trench foot can occur has not been established.  Ice
crystals will not form in tissue above 0°C, but from
0°C to 10°C to 15°C clinical trench foot will develop
if exposure lasts 48 hours or longer.8  Other contrib-
uting factors include nutritional deficiency; trauma
(rubbing or walking on affected feet); wind; im-
proper clothing type and integrity; circulatory stag-
nation and tissue anoxia from dependency, inactiv-
ity, hemorrhage, or shock; and improper technique
used to rewarm an injured limb.7
Clinically, trench foot is insidious in onset, the
soldier first noting a cold sensation giving way to
numbness.  Paresthesia and pain may be noted with
weight bearing.8,10  With continued exposure, complete
anesthesia to touch, pain, and temperature occurs: a
feeling described as “walking on blocks of wood.”9
The feet appear pale and swollen and may ex-
hibit vesiculobullous lesions.6–8  The degree of edema
during this ischemic or prehyperemic stage de-
pends on whether the feet are intermittently re-
warmed during the course of exposure (which re-
sults in less edema).9  The feet may appear mottled
or purple, suggesting impending gangrene, yet such
permanent damage is usually minimal with proper
care (Figure 4-1).9–10
The hyperemic6 or inflammatory9 stage occurs
several hours after removal of footgear and re-
warming of the extremity.  Sensation returns proxi-
mally to distally, first as a tingling sensation that
rapidly progresses to an extreme burning, throb-
bing pain.8–10  Warmth cannot be tolerated and sol-
diers become more comfortable with cooling of the
extremity.9  Hypesthesia replaces anesthesia except
for the most distal areas, which may remain anes-
thetic for weeks or months.  The feet rapidly swell
and become warm, dry, and erythematous, with
bounding pulses.9,10
In milder cases, this stage peaks at 24 hours.  Severe
cases, however, may progress for 48 to 96 hours and
produce areas of blistering and circulatory compromise
that are more likely to become gangrenous.  Hemor-
rhage and ecchymosis may be present.8,11
Milder cases of trench foot subside slowly over 1
to 4 weeks and are frequently accompanied by a
variably scarring exfoliation6,9 of the affected areas.
More severe cases progress to the posthyperemic
stage.  Although trench foot patients are susceptible
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Fig. 4-1. Mild edema and a mottled appearance of the
plantar aspect of the feet are characteristic of the early
hyperemic stage of trench foot. Prolonged exposure to
cold, damp conditions leads to prolonged incapacity.
Photograph: Courtesy of David Corbett, CDR, Dermatol-
ogy Branch, National Naval Medical Center, Bethesda, Md.
to sepsis, the uncomplicated course of this injury
has no systemic manifestations.
The posthyperemic or postinflammatory stage is
prolonged.  The previously hot, dry foot becomes
cool, moist, mottled or entirely cyanotic, with pulses
difficult to find.  The extreme pain of the hyperemic
stage subsides to a deep ache, noted especially
distally and often associated with the smaller
joints.8,9  Hyperesthesia and paresthesia disappear
rapidly, whereas anesthesia tends to remain for
months or years.6,9  Late changes in more severely
affected soldiers may include atrophy of the skin,6
osteoporosis,9 and muscular atrophy and deformity
(especially of the clawfoot type).9,11
Histologically, trench foot is a manifestation of
injury to the microvasculature.8,10  Peterson and
Hugar12 state that prolonged exposure to cold causes
increased blood viscosity and sludging of red cells
within the vessels.  Combined with sympathetic
vasoconstriction and loss of serum proteins through
damaged endothelium, the result is thrombosis,

Immersion Foot Syndromes
63
ischemia, and cell injury.
Thrombosed vessels of the dermis and subcuta-
neous tissue, reflex vascular dilation, capillary rup-
ture, and increased vascular permeability all con-
tribute to the edema, vesiculation, and ecchymoses
of the hyperemic stage.8–10  The work of Smith et al,8
in which trench foot was duplicated in rabbits, also
showed fibrin deposition in vascular walls and
muscle bundles, edema and neutrophilic infiltra-
tion of dermal collagen and muscles, edema of nerve
axons, and vacuolization of muscular fibers of vas-
cular endothelium.  Smith and coworkers observed
variable damage to lymphatic tissue.
Biopsies of tissue in the posthyperemic stage
have demonstrated atrophy and thinning of the
dermis, fibrosis and collagen deposition around
nerve endings and blood vessels, and replacement
of muscle bundles and fibrils by scar tissue.6
Immersion Foot
Immersion foot can be considered the sailor’s
counterpart of the soldier’s trench foot.  The term
“immersion foot” was first used during World War
II to describe a syndrome of clinical conditions
occurring in extremities exposed to prolonged, con-
tinued immersion in water of temperature ranging
from above freezing to 15°C.  Seen most dramati-
cally during World War II, immersion foot typically
develops in shipwrecked persons who are adrift
either in water or in lifeboats partially filled with
water.6,7,9,10  It also was reported in Vietnam, the
result of prolonged immersion in rice paddies.11
Clinically, soldiers with immersion foot show
the same prehyperemic, hyperemic, and post-
hyperemic stages as do those affected with classic
trench foot.6,9–11  In immersion foot, however, the
injury may extend more proximally to include the
knees, thighs, and buttocks, depending on the depth
of immersion.6  Also, because of the continuous
exposure, immersion foot may begin the first day,
whereas trench foot usually begins after several
days of lesser and, perhaps, intermittent exposure.
The histopathological findings seen in immersion
foot are similar to those of trench foot.
Management
Treatment of nonfreezing injuries such as trench
foot and immersion foot is based on reversing the
ischemia while not aggravating the edema, red cell
extravasation, or inflammation of the hyperemic
stage.  With rewarming, damaged tissue cells have
a greatly increased need for effective blood flow to
remove products of necrosis.  As this reflex vasodi-
lation occurs, previous thrombosis and direct in-
jury to endothelial cells by cold and anoxia cause a
massive transudation of plasma and red blood cells,
which leads to variable degrees of edema, vesicula-
tion, and hemorrhage.6
To reduce metabolic demand and reflex vasodi-
lation, the healthcare provider must raise the core
temperature of the body while keeping the affected
extremities cool.6,9,10  Elevating the patient’s uncov-
ered feet in a stream of cool air from a fan while
keeping the remainder of the body warm and well
nourished usually achieves this goal.  Patients no-
tice a decrease in pain, and edema, hyperemia, and
vesiculation subside.6  Cooling of the extremities
continues until the hyperemic stage has subsided
and circulation is reestablished.  The practice of
rubbing the affected extremity with snow or ice
further injures already compromised tissue and has
no place in modern therapy.6,8–10
Other general measures include avoidance of
weight bearing and direct trauma, aseptic precau-
tions, prophylactic antibiotics, avoidance of smok-
ing, tetanus prophylaxis, analgesics, a nutritious
high-protein diet, and possible plasma transfusion
as indicated.  Surgical treatment should be delayed
as long as possible to allow natural demarcation of
tissue loss, and amputation should be correspond-
ingly conservative.6,9,10
Other forms of therapy suggested for frostbite
have not been specifically investigated for
nonfreezing injuries and are not recommended.
These treatments include rapid rewarming, low
molecular weight dextran, sympathetic blockade,
ultrasound, continuous epidural anesthesia,
anticoagulation, and regional sympathectomy.12–15
Treatment of the posthyperemic stage is mostly
symptomatic, utilizing physiotherapy, exercise, and
surgical correction of deformity.9  Early sym-
pathectomy in more severe cases may prevent late
sequelae such as fibrosis, contractures, and scar-
ring,6 but such intervention awaits further study.
Prevention of trench foot and immersion injury
is difficult, especially in wartime circumstances.  Of
primary importance is the proper choice, use, and
care of protective footgear.  Individual education in
first aid and recognition of impending injury, atten-
tion to personal hygiene, frequent rotation out of
wet and cold areas, maintenance of nutritional sta-
tus and morale, and informed command personnel
are all necessary to prevent trench foot.  Immersion
foot may be prevented by the use of enclosed sur-
vival craft and by the availability of cold water
protective suits for individuals on ships at sea.

Military Dermatology
64
INJURIES IN WARMER CLIMATES
OK to put on the Web
OK to put on the Web
considerably warmer environment in troops fight-
ing in the Philippines during World War II.9  A
similar hot, wet environment experienced by ground
forces in Vietnam was recognized as the cause of
many foot casualties.  Such casualties frequently
resulted in greater loss of combat unit strength than
did all other medical causes combined and often
were instrumental in limiting the duration of field
operations.16
Tropical immersion foot, commonly known as
“paddy foot,” occurs after continuous or near-con-
tinuous immersion of the foot in water or mud of
temperatures above 22°C for periods ranging from
2 to 10 days.9,16–18  The first symptoms include burn-
ing16 and itching18 sensations on the dorsum of the
foot.  With continued exposure, walking becomes
progressively more difficult. 9,18
When footgear is removed, the foot is edematous
(Figures 4-2 and 4-3).  Usually, the shoes cannot be
replaced.9,16  The feet may initially appear pale,9 but
they rapidly become intensely erythematous in a
distribution sharply demarcated at shoe- or boot-
top level (Figures 4-4 and 4-5).  This erythema
affects the dorsum of the foot but not the plantar
surfaces—an important differentiating point from
warm water immersion foot.9,16–19  Papules, vesicles,
or both may appear, sometimes with a hemorrhagic
component.18–20
As with trench foot and immersion foot, pain and
disability characterize the following two prevent-
able warm water syndromes.  While the healing
time is shorter for the warm water syndromes—
several days to 2 weeks as compared with several
weeks to months in cooler climates—the impact on
fighting strength is obviously dramatic.  Prevention
by responsible policies and adherence to them by
the commander are of paramount importance to the
accomplishment of the unit’s mission.
Tropical Immersion Foot
Investigators first referred to what they felt was
a variant of classic immersion foot occurring in a
Fig. 4-2. Physical examination of this soldier whose feet
had been continuously immersed in the warm water of a
rice paddy for several days reveals tropical immersion
foot with striking edema. Photograph: Courtesy of David
Taplin, PhD, Dermatology Department, University of
Miami School of Medicine, Miami, Fla.
Fig. 4-3. The erythema of tropical immersion foot (shown
here in an early stage) affects the dorsal surface of the
foot. Warm water immersion foot, which results from
intermittent rather than continuous exposure to warm,
wet conditions, affects only the soles. Photograph: Cour-
tesy of David Taplin, PhD, Dermatology Department,
University of Miami School of Medicine, Miami, Fla.

Immersion Foot Syndromes
65
OK to put on the Web
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Fig. 4-4. On close examination of a patient with early
tropical immersion foot, erythema, peeling, and fissures
are present. Skin changes such as these are often accom-
panied by adenopathy and fever. Photograph: Courtesy
of David Taplin, PhD, Dermatology Department, Uni-
versity of Miami School of Medicine, Miami, Fla.
Fig. 4-5. In tropical immersion foot, the erythema extends
up the leg to a point of sharp demarcation at boot-top
level. Photograph: Courtesy of David Taplin, PhD, Der-
matology Department, University of Miami School of
Medicine, Miami, Fla.
Although tenderness and pain (especially on
weight bearing) are often prominent in tropical
immersion foot, hyperesthesia, paresthesia, and
anesthesia are more common.  Most notable are the
systemic reactions.  Severely affected soldiers have
tender unilateral or bilateral femoral adenopathy
and a fever of 38°C to 39°C.9,16–18
No definite predisposing factors are known, but
physicians and commanders estimate that severe
tropical immersion foot develops within 4 days in
3% to 5% of exposed individuals.  These individuals
seem predisposed to repeat injury.16  In about 80%
of those exposed, some degree of the disorder de-
velops after 10 to 12 days.18
Histologically, tropical immersion foot shows
epidermal parakeratosis and acanthosis,20 dermal
edema and telangiectasia, and a lymphocytic
perivascular infiltrate with associated extravasation
of red blood cells.16,18–20 Willis,21 in an experiment
exposing the backs and arms of volunteers to con-
trolled continuous water contact, achieved similar
histological changes.  He postulated that such
changes are caused by loss of barrier function of the
swollen stratum corneum, with secondary irrita-
tion or damage to the underlying tissues.
Management of tropical immersion foot consists
of bed rest, elevating and drying the feet, analgesics
if necessary, and antibiotics if indicated.  Usually,
fever and adenopathy resolve within 72 hours, and
the erythema and edema subside in 5 to 7 days,
followed by a fine branny desquamation resulting
in normal-appearing feet.16,18  Even the most severe
cases usually resolve within 2 weeks without
sequelae such as gangrene, persistent sensory
changes, or orthopedic disability.
Prevention is easily accomplished if a 24-hour

Military Dermatology
66
drying-out period is alternated with each 48 hours
of water exposure.16,18  In a military setting, the
commander’s attention to this matter is critical.  Al-
though rapid-drying boots and socks may delay the
onset of tropical immersion foot,16 silicone greases
used as a barrier ointment have not proved effective.20
Since persons affected with the disorder seem pre-
disposed to reinjury,16,19 special attention to preven-
tive measures is indicated for these individuals.
Warm Water Immersion Foot
Although warm water immersion foot may seem
the most innocuous of the immersion foot syn-
dromes, it can incapacitate an individual for 3 to 14
days.  This condition occurred in many service
members in Vietnam when they were subjected to
variable periods of intermittent exposure to wet,
warm conditions.  More recently, warm water im-
mersion foot has been noted in persons wearing
insulated boots, without water exposure, presum-
ably from the buildup of perspiration—the so-called
“moon-boot syndrome.”22,23
After 1 to 3 days of exposure, affected individu-
als begin to note pain on weight bearing, tingling,
and a sensation described as “walking on rope.”16
When footwear is removed, the soles of the feet are
thickened, severely wrinkled, and macerated (Fig-
ure 4-6).16,17,24,25  Although these changes may extend
to the sides of the foot, they do not affect the dor-
sum.
Warm water immersion foot appears to develop
faster at higher water temperatures.13  Persons with
thicker, callused soles tend to experience more se-
vere (although not earlier) symptoms.16,17,24,26  Mi-
croscopically, hyperhydration of the stratum
corneum is the only finding.27
Treatment consists of bed rest and drying the
feet.16–18  The wrinkles and maceration resolve within
24 hours, but tenderness may last 2 to 3 days.  The
patient is asymptomatic by the third day.  Shortly
thereafter, however, thick portions of the sole begin
to fissure and peel, shedding completely within 1 to
2 weeks.  During this peeling, the stratum corneum
may be more susceptible to infection via the fis-
sures,17 and patients experience tenderness on walk-
ing as new calluses develop.18
Prophylaxis consists of drying the feet for 6 to 8
hours (overnight) of every 24 hours.16,17,28  Silicone
grease applied to the entire foot24,25,28 or to the soles
alone15 retards the development of warm water
immersion foot.  Footgear with adequate drainage
and composed of rapidly drying materials may also
slow the development of this condition.
Fig. 4-6. (a) Warm water immersion foot is the mildest of the
immersion foot syndromes; however, it can incapacitate
soldiers for 3 to 14 days. The clinical appearance results
from hyperhydration of the stratum corneum. (b) Closer
view of characteristic thickened, wrinkled skin. Photo-
graphs: Courtesy of David Taplin, PhD, Dermatology De-
partment, University of Miami School of Medicine, Miami, Fla.
OK to put on the Web
OK to put on the Web
b
a

Immersion Foot Syndromes
67
SUMMARY
As is the case for most cutaneous diseases seen in
soldiers, the counterpart of immersion foot exists in
the civilian community.  Immersion foot problems
in homeless individuals have recently been reported
following continuous exposure to a damp environ-
ment over a period of days to weeks.29  Ski instruc-
tors have also been reported to develop this syn-
drome.11
Military medical history continues to teach re-
curring critical lessons; the kinds and amounts of
skin disease occurring in soldiers can be predicted
on the basis of knowledge of such factors as climate,
terrain, and environmental conditions.  In order to
significantly decrease the impact of skin disease on
combat effectiveness, military dermatologists
should be integrated at the division level, so that
command policies and tactical considerations can
incorporate these medical matters and ensure logis-
tical support for the successful outcome of military
operations.
In wartime, a soldier who becomes a “foot casu-
alty” is as useless to his commander as one who
sustains a bullet wound.  It is up to the soldier-
physician to advise commanders appropriately on
the prevention of these environmental injuries.  A
familiarity with the clinical and pathophysiological
aspects of immersion foot syndromes also enables the
physician to render appropriate care, which in turn
may prevent or ameliorate long-term disability.
(The sections “Injuries in Cool or Cold Climates” and “Inju-
ries in Warmer Climates” and Table 4-1 are reprinted from:
Adnot J, Lewis CW. Immersion Foot Syndromes. J Assoc Mil
Derm. 1985;11(1):87–92.)
REFERENCES
1.
Gillett MC. The Army Medical Department, 1775–1818. Washington, DC: Medical Department, US Army, Office of
The Surgeon General, and Center of Military History; 1981: 192.
2.
Brown HE. The Department of the United States Army from 1775 to 1873. Washington, DC: The Surgeon General’s
Office. 1873: 104.
3.
Risch E. The Quartermaster Corps: Organization, Supply, and Services. Vol 1. Washington, DC: Office of the Chief of
Military History, Department of the Army; 1953: 102–103, 108, 110.
4.
Allen AM. Skin Diseases in Vietnam, 1965–72. In: Ognibene AJ, ed. Internal Medicine in Vietnam. Vol 1. Washing-
ton, DC: Medical Department, US Army, Office of The Surgeon General, and Center of Military History;
1977: 7, 81.
5.
Pillsbury DM, Livingood CS. Dermatology. In: Infectious Diseases and General Medicine. Vol 3. In: Havens WP,
Anderson RS, eds. Internal Medicine in World War II. Washington, DC: Medical Department, US Army, Office of
The Surgeon General; 1968.
6.
White JC, Scoville WB. Trench foot and immersion foot. N Engl J Med. 1945;232:415–422.
7.
Green, R. Frostbite and kindred ills. Lancet. 1941;2:689–693.
8.
Smith JL, Ritchie J, Dawson J. On the pathology of trench frostbite. Lancet. 1915;2:595–598.
9.
Whayne TF, DeBakey ME. Cold Injury, Ground Type, in World War II. Washington, DC: Office of The Surgeon
General, Department of the Army, 1958.
10.
Webster DR, Woolhouse FM, Johnston JL. Immersion foot. J Bone Joint Surg Br. 1943;24:785–794.
11.
Gold RH. A review of immersion foot. J Am Podiatry Assoc. 1966;56:414–415.
12.
Peterson G, Hugar DW. Frostbite: Its diagnosis and treatment. J Foot Surg. 1979;18:32–35.

Military Dermatology
68
13.
Bouwman DL, Morrison S, Lucas CE, et al. Early sympathetic blockade for frostbite—Is it of value? J Trauma.
1980;20:744–749.
14.
Weatherly-White RCA, Sjostrom B, Paton BC. Experimental studies in cold injury. Part 2: The pathogenesis of
frostbite. J Surg Res. 1964;4:17–22.
15.
Weatherly-White RCA, Paton BC, Sjostrom B. Experimental studies in cold injury. Part 3: Observation on the
treatment of frostbite. Plast Reconstr Surg. 1965;36:10–18.
16.
Allen AM, Taplin D. Tropical immersion foot. Lancet. 1973;2:1185–1189.
17.
Samitz, M.H. Immersion injuries. In: Cutaneous Disorders of the Lower Extremities. 2nd ed. Philadelphia: JB
Lippincott; 1981: 179–183.
18.
Akers WA. Paddy foot: A warm water immersion foot syndrome variant. Milit Med. 1974;139:605–618.
19.
Allen AM. Taplin D, Lowy JA, et al. Skin infections in Vietnam. Milit Med. 1972;137:295–301.
20.
Douglas JS, Eby CS. Silicone for immersion foot prophylaxis: Where and how much to use. Milit Med. 1973;137:386–
387.
21.
Willis I. The effects of prolonged water exposure on human skin. J Invest Dermatol. 1973;60:166–171.
22.
Blogg H. Moon-boot foot syndrome. Br Med J. 1982;285:1774–1775.
23.
Philipp R. Moon-boot foot syndrome. Br Med J. 1983;286:562.
24.
Taplin D, Zaias N. Tropical immersion foot syndrome. Milit Med. 1966;131:814–818.
25.
Rietschel RL, Allen AM. Immersion foot: A method for studying the effects of protracted water exposure on
human skin. Milit Med. 1976;141:778–780.
26.
Taplin D, Zaias N, Blank H. The role of temperature in tropical immersion foot syndrome. JAMA. 1967;202:546–
549.
27.
Gill KA. Naval Medical Field Research Laboratory Report: Field study on silicone ointments MDX-4-4056 and MDX-4-
4078. Camp Lejeune, NC: Department of the Navy; 1967: 1–7.
28.
Buckles LJ, Gill KA, Gustave TA. Prophylaxis of warm-water immersion foot. JAMA. 1967;200:681–683.
29.
Wrenn K. Immersion foot: A problem of the homeless in the 1990s. Arch Intern Med. 1991;151:785–788.

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
69
CUTANEOUS REACTIONS TO NUCLEAR,
BIOLOGICAL, AND CHEMICAL WARFARE
Chapter 5
SCOTT D. BENNION, M.D.* AND KATHY DAVID-BAJAR, M.D.†
INTRODUCTION
HISTORY
Nuclear Warfare
Biological Warfare
Chemical Warfare
NUCLEAR WARFARE
Thermal and Radiation Effects
Therapy of Cutaneous Radiation Injury
Late Sequelae of Radiation Exposure
BIOLOGICAL WARFARE
Anthrax
Tularemia
Plague
Hemorrhagic Fevers
Botulism
Mycotoxins
CHEMICAL WARFARE
Chemical Warfare Doctrine and Weaponry
Sulfur Mustard and Nitrogen Mustard
Arsenical Vesicants
Management of Vesicant Injury
Halogenated Oximes
Nerve Agents and Cyanides
SUMMARY
*Colonel, Medical Corps, U.S. Army; Dermatology Service, Fitzsimons Army Medical Center, Aurora, Colorado 80045
†Major, Medical Corps, U.S. Army; Dermatology Service, Fitzsimons Army Medical Center, Aurora, Colorado 80045

Military Dermatology
70
INTRODUCTION
Throughout the history of warfare, adversaries
have continually utilized new technology in an
attempt to gain the advantage.  In recent history, a
great deal of effort has been centered on the devel-
opment of nuclear, biological, and chemical weap-
ons by many countries in pursuit of this goal.  Al-
though in the United States the military has been
aware of the situation, the military medical commu-
nity has been slow to react to these threats.  Conse-
quently, research and development of new and more
effective drugs, therapeutic approaches, and pro-
phylaxis for nuclear, biological, and chemical (NBC)
casualties have not received adequate attention.
This problem persists in the field of dermatol-
ogy.  Although basic research has suggested many
potential therapies for the treatment of NBC casual-
ties, the application of these findings in the devel-
opment and fielding of treatments for NBC casual-
ties on the battlefield has been slow in developing.
It is incumbent on all military physicians, including
dermatologists, to become aware of the NBC threat,
to know how NBC weapons induce pathology, and
to utilize current and potential therapies to treat
NBC casualties.
Clearly, many new developments in medicine
can be applied to improve the standard NBC treat-
ment regimens now in place; but to reach this objec-
tive, physicians must have a clear understanding of
the effects of NBC weapons at the clinical and physi-
ological levels and how these weapons may by used
in future wars.
To this end, a brief discussion of the tactics of
NBC warfare is presented, the clinical data com-
piled over the last 80 years on the effects of NBC
weapons are summarized, and the most recent cases
of mustard gas use from the Iran-Iraq War are
discussed.  Standard NBC therapies that have been
developed during the two world wars are recounted
and new therapeutic regimens based on more re-
cent research are detailed.
HISTORY
Some weapons not only inflict casualties but
manage to strike considerable fear in the enemy.  It
is this unique blend of real and perceived danger
that makes nuclear, biological, and chemical weap-
ons so appealing for nations and groups to acquire.
Nuclear Warfare
The history of nuclear warfare encompasses a
fairly short time, dating back to the bombing
of Nagasaki and Hiroshima in 1945.  Despite the
brevity of the nuclear era, it has been an extraordi-
nary time when the way nations have had to deal
with each other both politically and militarily has
changed dramatically.  This situation is due to
the magnitude of destructive power that nuclear
weapons possess.  The threat of the destruction of
global civilization has given the leaders of the
nuclear nations pause when contemplating future
conflicts.
The destructive physical power of the atomic
bomb in the form of thermal and blast energy was
acutely apparent after the atom bombs were
dropped on Japan, but the lingering effects of radia-
tion were not fully realized until weeks and months
after the bombing.
That radiation could cause tissue damage has
been known since Roentgen discovered X rays in
1896.  Shortly after the discovery, Thomas Edison
noted that his assistant, Clarence Dally, who had
been working with X rays, developed an acute in-
flammation of his hands followed by scaling, blis-
tering, ulceration, and eventual malignancy.  This
type of effect became apparent in the aftermath of
the bombing of Hiroshima.  Dr. Michihiko Achiya
published her diary elucidating those times.1  Some
of the excerpts from her diary clearly describe the
evolution of radiation symptoms and the constella-
tion of signs associated with radiation poisoning.
The following excerpt describes the thermal effects
of a nuclear explosion as related by Dr. Tabuchi:
“It was a horrible sight,” said Dr. Tabuchi.  “Hun-
dreds of injured people who were trying to escape
to the hills passed our house.  The sight of them was
almost unbearable.  Their faces and hands were
burnt and swollen; and great sheets of skin had
peeled away from their tissues to hang down like
rags on a scarecrow.  They moved like a line of ants.
All through the night, they went past our house,
but this morning they had stopped.  I found them
lying on both sides of the road so thick that it was
impossible to pass without stepping on them.

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
71
“The sight of the soldiers, though, was more dread-
ful than the dead people floating down the
river...they had no faces!  Their eyes, nose and
mouths had been burned away, and it looked like
their ears had melted off.  It was hard to tell front
from back.  One soldier, whose features had been
destroyed and was left with his white teeth sticking
out, asked me for some water, but I didn’t have any.
I clasped my hands and prayed for him.  He didn’t
say anything more.  His plea for water must have
been his last words.  The way they were burned, I
wonder if they didn’t have their coats off when the
bomb exploded.”1(p15)
Dr. Achiya noted the following long-term effects of
radiation poisoning in her notes:
Another observation was that the severity of gas-
trointestinal symptoms appeared to bear no rela-
tion to the extent of burns and other injuries.  Many
patients with severe wounds recovered rapidly
whereas there were patients with the symptoms
described who did not appear to be injured at all
but who, nevertheless, died.  Among those who
died, many had a bloody diarrhea similar to that
seen in dysentery, and others had bloody urine or
sputum.  Severe uterine hemorrhage, which at first
we mistook for derangements of menstruation, was
common among the women.  Some, who lingered
as long as a week, died with stomatitis or gangre-
nous tonsillitis.  Now, with the death curve rising
again, stomatitis appeared and with it petechiae.
The occurrence of petechiae followed the same
pattern we had observed in patients with gas-
trointestinal symptoms.  They bore no relationship
to the type or severity of injury, and those who
appeared to be uninjured and had even felt well
enough to help in the care of other patients were
beginning to show these blood spots beneath the
skin.  We had several instances of presumably
healthy people who developed petechiae and died
before persons who were obviously critically ill.
You can understand what an ominous portent the
development of petechiae had for us.1(pp97–98)
The events of the nuclear holocaust in Japan have
led the leaders of the nations with nuclear capabil-
ity to avoid the use of nuclear weapons.  However,
as more nations develop the technological capabil-
ity to construct nuclear devices, the threat of a
repeat of the devastation of Hiroshima becomes
more likely.  Therefore, medical officers must be
prepared to treat the casualties of nuclear warfare.
Biological Warfare
The use of biological weapons in warfare is not a
recent development.  In the 14th century, at the
siege of the fortress of Kaffa by the Tartars, corpses
infected with plague were catapulted into the fort to
infect its occupants.2 There are several reports of
American Indians receiving articles contaminated
with smallpox given to them in an attempt to infect
the Indians with smallpox.  The British troops un-
der the orders of Amherst supplied the Amerindians
with smallpox-infested blankets.3  During World
War I, it is believed that attempts were made to
produce an epidemic of plague in the city of
Petrograd.  Also, anthrax and glanders are believed
to have been used in World War I, primarily di-
rected at infecting horses.  These latter efforts in-
volved the use of scientific discoveries (ie, the dis-
covery of pure cultures and infection chains) and
the application of these recent scientific discoveries
for warfare.  During World War II, the Japanese are
believed to have organized industrial production of
disease pathogens and carriers.  Our own involve-
ment in the research and development of biological
weapons began in 1941.4
In April 1979, Sverdlovsk, a small village in the
Soviet Union, was decimated by an anthrax epi-
demic in which many of the people of the town died
of a pneumonic form of anthrax.5,6  Although the
Soviet government vehemently denied the charge
that this tragedy was caused by a biological war-
fare–agent accident, it is unlikely that an epidemic
of pneumonic anthrax could have been caused by
any other circumstance.
Historical accounts also exist concerning the pa-
thology caused by the by-products of microbes.
The effects of fungal toxins have been known for
centuries even though the cause was not.  The ear-
liest mention is on an Assyrian tablet dated from
600 BC, which refers to a noxious pustule in the ear
of grains.  The tablet probably refers to the infection
of rye grains by the fungus Claviceps purpurea (Fig-
ure 5-1), which produces ergot alkaloids, the caus-
ative agents in ergotism.7,8  During the Middle Ages,
large epidemics of hallucinations, delirium, con-
vulsions, and severe limb ischemia leading to dry
gangrene and autoamputation were attributed to
the ingestion of rye contaminated with ergot fun-
gus (Claviceps purpurea).8  One of the most vivid
presentations of this malady is by Hieronymos Bosch
in his painting The Last Judgment.  In Figure 5-
2, a detailed area of the painting, the signs and
symptoms associated with ergot poisoning are
shown.
During the latter part of World War II, the Soviets
experienced an outbreak of human alimentary
aleukia that caused numerous fatalities.9  The out-
break was attributed to a fungal contamination of

Military Dermatology
72
OK to put on the Web
Fig. 5-2. (below) Detail of Hieronymus Bosch’s The Last
Judgment depicting the signs and symptoms of ergot
poisoning. The painful paresthesias are represented by
the “frying” extremities in the pan, the man roasting on
the spit, and the webbed feet of the figure in the lower left
corner. The cutaneous manifestations of blackened
ischemic extremities and ascites are depicted in the fig-
ure in the upper right. Photograph: Courtesy of Akademie
der bildenden Kunste, Vienna, Austria.
Fig. 5-1. (left) Rye grain infected with Claviceps purpurea,
a fungus that produces ergot alkaloids. The darkening of
the grains is characteristic of the infection. Photograph:
Courtesy of Dr. Werner Schreiber, Nuremberg, Germany.
OK to put on the Web

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
73
grains (corn, barley) by fungi that produce
trichothecene mycotoxins.  The lethality of these
fungal toxins apparently impressed the Soviets be-
cause they incorporated trichothecenes into weap-
ons.  The subsequent use of trichothecene by the
Russians in Afghanistan and Southeast Asia was
supported by several reports that there have been
chemical attacks on individuals in those areas, with
resultant symptoms suggestive of trichothecene
poisoning.10,11  Although the validity of the findings
has been questioned, the discovery of Soviet gas
masks in Afghanistan, contaminated with fungal
toxins, is strong supportive evidence that these
agents have been used by the Soviets.12
Chemical Warfare
Since the first employment of mustard and chlo-
rine gases in World War I, the use of chemical
weapons has been sporadic.  This restraint has been
based in part on a fear engendered in world leaders
by the effectiveness with which chemical weapons
were used in that war.  Due to the infrequency of
chemical warfare in the last 75 years, the belief
prevails that chemical weapons are a recent inven-
tion; however, the use of chemical weapons to gain
advantage in war dates back to the Peloponnesian
War in 428 BC.  In this incident, which was the first
recorded use of chemical weapons, the Spartans
started a fire with sulfur-saturated wood under the
walls of a city defended by the Athenians.  Chronicles
of ancient history also record that the Greeks used
pots filled with a mixture of sulfur, pitch, tow, and
resins; the pots were ignited and hurled into towns,
producing suffocating smoke and fire.13
Despite protests by the clergy and others, the
production of more effective weapons based on the
technology of the day continued.  An example of
this was the crossbow.  In 1139, Pope Innocent III
and the Ecumenical Council to the Lateran expressed
horror at its lethality in battle and banned its use
(except against non-Christians) under penalty of
excommunication.13  Although the Pope had far-
reaching influence at that time, the use of the cross-
bow in war became standard and widespread.  Its
use ebbed only when the more effective bow and
arrow was demonstrated to possess a more rapid
rate of fire in battle.
Attempts to introduce new and more effective
weapons to gain advantage in battle continued into
the 19th century.  For example, the use of chlorine
gas in warfare was not a German invention but one
of an American named John W. Doughty.  And
chlorine might have been used in the U.S. Civil War
if the War Department of 1862 had followed up on
a suggestion of Doughty’s that was contained in a
letter with an illustration (Figure 5-3).  This docu-
ment is now kept in the Old Records division of
the Adjutant General’s Office in the Archives Build-
ing, Washington, D.C.  The letter clearly predic-
ted the details of the use of chlorine gas by the
Germans in World War I.14  The War Department
concluded that there was no merit in Mr. Doughty’s
invention.
Efforts to prevent the use of certain weapons
continued in the 19th century when the Hague
Conference of 1899 was convened.  At that time, a
resolution was being contemplated (later rejected)
that would ban the use of poisonous gases in war.
The United States’ representative, Admiral Mahan,
was opposed to such a ban and stated:
The reproach of cruelty and perfidy, addressed
against those supposed (gas) shells, was equally
uttered formerly against firearms and torpedoes,
both of which are now employed without scruple
…It was illogical, and not demonstrably humane,
to be tender about asphyxiating men with gas when
all were prepared to admit that it was allowable to
blow the bottom out of an ironclad at midnight,
throwing four or five hundred men into the sea, to
be choked by water with scarcely the remotest
chance to escape.15(p686)
Since then, the United States has continued to
have an ambiguous position on the use of chemical
warfare.  This position was demonstrated by the
United States’ refusal to ratify the Geneva Gas Pro-
tocol in 1926.16  In 1972, the Biological and Toxin
Weapons Convention was written to supplement
the Geneva Protocol, and it was signed by 103
nations including the United States.10  However,
this treaty does not limit research in the defense of
biological warfare.
During World War I, a stalemate existed on
Germany’s Western Front between the allied forces
of Britain and France, and the Germans.  To break
this stalemate, the Germans actively searched for a
new weapon that could enhance their ability to
wage effective maneuvers on the battlefield and
break through the entrenched allied positions.
Alerted to the possibilities of gas warfare by their
scientists, they enlisted the help of two eminent
German chemists, Professor Walther Nernst14 and
L. F. Haber.  With their guidance, the Germans
delivered the first gas attack of modern times near
a small village in Belgium called Ypres.  On April
22, 1915, late in the afternoon, they released large
amounts of chlorine gas, the same chemical as that

Military Dermatology
74
Hon. Edwin M. Stanton
Secretary of War
Sir
The above is a representation of a projectile which I have devised to be used as a means for routing an entrenched enemy.
Believing it to be new and valuable, I send the War Department a brief description:  Chlorine is a gas so irritating in its effects
upon the respiratory organs, that a small quantity diffused in the atmosphere, produces incessant & uncontrollably violent
coughing.  It is 2 1⁄2 times heavier than the atmosphere, and when subjected to a pressure of 60 pounds to the inch, it is
condensed into a liquid, its volume being reduced many hundred times.  A shell holding two or three quarts, would therefore
contain many cubic feet of the gas.
If the shell should explode over the heads of the enemy, the gas would, by its great specific gravity, rapidly fall to the
ground: the men could not dodge it, and their first intimation of its presence would be by its inhalation, which would most
effectually disqualify every man for service that was within the circle of its influence; rendering the disarming and capturing
of them as certain as though both their legs were broken.
To silence an enemy’s guns or drive him from his entrenchments, it would be only necessary to explode the shells over
his head or on his windward side.  If exploded in rapid succession over or within a fort, evacuation or surrender could not
be delayed beyond fifteen minutes.  Casemates and bomb-proofs would not protect the men.
This kind of shell would, I think, in the present advanced state of military engineering, be a very efficient means for
warding off the attacks of iron-clad vessels and steam rams; for, as to the steam ram, a ten inch gun that would carry a shell
containing a gallon or two of the liquid, would with ordinary accuracy, be able at the distance of 3⁄4 of a mile, to envelop him
in an atmosphere that would cause his inmates to be more anxious about their own safety than about the destruction of their enemy.
It may be asked if the gas which drove the enemy from his guns, would not prevent the attacking party who used the gas
from taking possession of the abandoned position.  I answer it would not: for, this shell does not, like the Chinese stink-pots,
deposit a material emitting a deleterious gas lighter than the atmosphere, but suddenly projects into the air a free gas much
heavier than the atmosphere, which does its work as it descends to the earth, where it is soon absorbed.
Experiment alone can determine whether this shell has any practical merit.  Possibly, I overrate its value; but it must not
be forgotten, that while it does the work of an ordinary shell, it also carries with it a force against whose effect the most skillful
military engineering can not possibly make any adequate provision.
As to the moral question involved in its introduction, I have, after watching the progress of events during the last eight
months with reference to it, arrived at the somewhat paradoxical conclusion, that its introduction would very much lessen
the sanguinary character of the battlefield, and at the same time render conflicts more decisive in their results.
If I have erred, I have, at least meant well.
Yours,
Respectfully,
John W. Doughty
April 5th, 1862, 419 Eighth Avenue, New York
Fig. 5-3. Reproduction of original drawing by John W. Doughty, showing the chlorine gas weapon he proposed in 1862.
Redrawn by Karen Wyatt, Medical Illustrator, Fitzsimons Army Medical Center, Aurora, Colorado.  Letter reprinted
from the Old Records division of the Adjutant General’s Office in the Archives Building, Washington, D.C.

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
75
mentioned in John Doughty’s letter almost half a
century before.  The yellow-green gas drifted to-
ward the entrenched British soldiers and, being
heavier than air, filled all the low-lying areas in-
cluding the trenches where the British soldiers had
taken refuge against a preceding bombardment.
The cloud engulfed the 15,000 soldiers.  After 15
minutes the attack was over; it had caused total chaos
and perhaps 5,000 deaths (the exact number remains
controversial).17  The desired effect occurred and the
British line was broken; however, the Germans did
not take advantage of the situation and eventually
were pushed back.  The birth of modern chemical
warfare had occurred and the use of the weapon that
could “shoot around corners” had begun.
Although the German potential for waging chemi-
cal warfare was known to the U.S. forces in Europe,
the full impact of these new weapons was not real-
ized until Ypres.  This battle, with its resultant
casualties, arrested the American Expeditionary
Forces’ attention and forced the U.S. Army quickly
to develop a chemical capability of its own.  An
excerpt from a 1918 army technical report titled
History of the First Gas Regiment18 is indicative of the
prevailing doctrine of that era:
It is impossible to conclude otherwise than that gas
warfare is an extremely effective agent...However
[as] much [as] the elimination of gas in the future as
an agent in warfare might be desired, to make its
elimination a certainty is impossible, for it is rea-
sonable to suppose that a nation that would violate
its treaties would not be scrupulous about the use
of weapons to obtain its ends.
Had Germany waited until she had sufficient chlo-
rine and was ready to gas the whole British and
French Armies upon every suitable front, she could
have won the war in one gas attack.  She erred
vitally in trying gas on a small scale.18(p57)
After World War I, concerns persisted about the
use of chemicals in future wars and, although no
chemical warfare occurred in World War II, the
history of that era is replete with isolated anecdotes
in which one country used chemical weapons against
another.  Italy utilized a mustard agent against
Ethiopia in 1935.16  In 1941, the Japanese employed
mustard gas against the Chinese at Ichang.  A little-
known incident in the northern Italian port city of
Bari resulted in the only gas casualties in the Euro-
pean theater during World War II.  The USS John
Harvey, a supply ship carrying mustard gas muni-
tions anchored in the harbor, was attacked by the
Germans and destroyed.  The contamination of the
waters and surrounding area resulted in over 600
casualties.19  Although many feared the use of chemi-
cals in World War II and Germany had the ability to
deploy both blistering and nerve agents, they were
not used.  This outcome may have been due to a
combination of factors including the fact that the
Allied Forces had the capability to retaliate in kind.
Hitler’s reluctance to use chemicals may have also
been due to his own personal aversion to chemical
weapons based on his experience of being gassed in
World War I.  In Mein Kampf, he relates his experi-
ence from 1918:
...the English gas attack on the southern front be-
fore Ypres burst loose; they used yellow-cross gas
(mustard gas), whose effects were still unknown to
us as far as personal experience was concerned.  In
this same night I myself was to become acquainted
with it.  On a hill south of Wervick, we came on the
evening of October 13 into several hours of drumfire
with gas shells which continued all night more or less
violently.  As early as midnight a number of us passed
out, a few of our comrades forever.  Toward morning
I, too, was seized with pain which grew worse with
every quarter hour, and at seven in the morning I
stumbled and tottered back with burning eyes.  A
few hours later my eyes had turned into glowing
coals; it had grown dark around me.20(pp201–202)
In 1967, reports surfaced that Egypt had used a
form of mustard gas against Yemen.16  During the
1980s, reports from Vietnam and Afghanistan have
pointed toward the use of chemical weapons in
conflicts in those areas.  Most recently, the use of
vesicants (blistering agents, eg, mustard gas) and
nerve gas by Iraq against its own Kurdish popula-
tion and against the Iranians in the Iran-Iraq War
has focused our attention on the likelihood that U.S.
forces will face adversaries who are able and will-
ing to use chemical weapons on the battlefield.
In 1987, the Vesicant Workshop was held at The
Johns Hopkins University Applied Physics Labora-
tory under the sponsorship of the U.S. Army Medi-
cal Research and Development Command.  In his
keynote address, General Richard T. Travis noted
that the workshop was being held
because of the use of sulfur mustard by Iraq in the
Gulf War and the subsequent recognition of the
availability and effectiveness of vesicant agents on
the battlefield....Mustard’s threat is critical, partly
because it incapacitates so many more combatants
than it kills and partly because it is so easily pre-
pared from commercially available chemicals.  Re-
cently, a Belgian company was alleged to have
exported 500 tons of thiodiglycol to Iraq in 1983.
This chemical, when combined with hydrochloric
acid, produces mustard in excellent yield.  Clearly,

Military Dermatology
76
the synthesis of sulfur mustard is within the capa-
bility of any third world country.10(p645)
Despite the naysayers who deny the possibility
of chemical warfare in future wars, an increasing
body of evidence, especially that gleaned from the
Iran-Iraq War, cannot be ignored and strongly sug-
gests that chemicals will be used.
In his book titled The Reformation of War, General
J. F. C. Fuller describes the ideal weapon:
1.
Its production should not detrimentally affect
prosperity.
2.
It should be simple to manufacture in peace or
war.
3.
Its nature should be unknown to the enemy.
4.
It should be capable of incapacitating without
killing, and the incapacity should not be per-
manent.
5.
It should permit of a defense against it being
well-known in advance and prepared for by
the side using it.
6.
It should inflict no permanent damage upon
property.14(p10)
These characteristics fit chemical agents pre-
cisely, and mustard in particular.  In today’s world,
one could conclude that the ideal weapon, espe-
cially for countries without a nuclear capability, is
a chemical agent.
The types of casualties produced by a nuclear
explosion depend on where the explosion occurs
but are always due to one of three effects: blast
injuries (direct and indirect), thermal burns, and
radiation injuries.  Thermal and blast energy ac-
count for 80% of the energy released by an atomic
bomb (Figure 5-4).  A discussion of blast injuries is
beyond the scope of this chapter; therefore, we will
limit the review to the dermatologic aspects of ther-
mal burns and radiation injuries.
Thermal and Radiation Effects
Thermal burns can be caused directly by the
initial flash of the thermonuclear explosion or by
fires that are secondary to the explosion.  The flash
NUCLEAR WARFARE
burns, which are caused by radiant or infrared
energy from the initial fireball, occur on unpro-
tected skin or skin under a light garment.  Figures 5-
5 and 5-6 illustrate the effect of garment protection
from the thermal effects of the initial blast.
The treatment of thermal burns and blast injuries
is greatly complicated by the effects of ionizing
radiation.  This radiation occurs in the form of
neutrons, X rays, beta particles (electrons), and
gamma radiation produced within the first minutes
of the nuclear fireball, and alpha, beta, and gamma
radiation from the residual fallout.  The charged
alpha and beta particles can only penetrate the skin
layers, causing an initial erythema that can progress
to superficial and deep ulcers (Figure 5-7).  Such an
occurrence took place in 1946 during the Bikini
BRAVO shot, in which many Marshall Islanders
were exposed to fallout from the large amount of
coral picked up in the blast.  The fallout in the form
of lime “snowflakes” fell on 239 islanders, causing
an initial burning and itching during the first 2
days, followed by epilation and a “wet” superficial
ulceration that occurred 2 to 3 weeks after the expo-
sure.21  Conversely, gamma rays, X rays, and neu-
trons, all of which have no charge, penetrate deeply
into the body and can cause severe damage to vital
tissues, especially those such as the hematopoietic
tissue with a high rate of cell division.  The loss of
significant numbers of bone marrow cells can lead
to an immunosuppressed state in which the casu-
alty is highly susceptible to bacterial infections.  In
addition, the epidermal healing process can be de-
layed by the same mechanism, leading to a pro-
tracted recovery period.
The effects of radiation on the human body fall
into several different categories dependent on ra-
Fig. 5-4. Partition of energy of a nuclear air blast. Note that
the majority of energy from a nuclear device is blast and
thermal energy, the same energy released from a conven-
tional bomb. Fallout and nuclear energy account for only 20%.
Blast (50%)
Thermal (30%)
Fallout (15%)
Nuclear
Radiation (5%)

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
77
Fig. 5-5. A Japanese nuclear casualty with thermal burns caused by the initial fireball. Note the lack of burns on the
upper scalp and forehead (a) secondary to the protective effect of the cap (b). Photograph: Courtesy of the Defense
Nuclear Agency, Washington, D.C.
essentially unaffected.  At doses of 100 to 200 rads,
a transitory erythema can occur within minutes and
last 2 to 3 days.23  This erythema is thought to be
caused by vascular dilation secondary to the release
of histamine and other vasoactive peptides.  Then a
deeper erythema develops around day 7 and lasts
through day 14.  The subsequent scaling, suggestive
of a sunburn and hyperpigmentation, appears 14 to
21 days after radiation exposure in many cases.
Doses of 200 to 1,000 rads typically produce epilation
at approximately 1 to 3 weeks that at the lower
doses (100–300 rads) is transient, and at doses greater
than 700 rads is permanent.24  The onset of epilation
can be an indicator of radiation dose because higher
doses induce earlier epilation.25  In the 700-rad
range, the number of casualties will be significant.
In case reports in which patients received high
doses of radiation (4,000–8,000 rads), patients de-
scribe an acute burning sensation of their skin.  In
addition, if the patients survive over several days,
diation dose (Figure 5-8).22  At doses greater than
100 to 150 rads, patients typically develop the radia-
tion hematopoietic syndrome, which, after a latent
period of 2 to 3 weeks, is manifested by bone mar-
row suppression, cutaneous and internal hemor-
rhage, and immunosuppression.  Between 400 and
1,000 rads, the gastrointestinal syndrome occurs.
This syndrome consists of edema, pseudomembrane
formation in the gastrointestinal tract, and submu-
cosal hemorrhage in the bowel and is accompanied
by prolonged nausea, vomiting, watery diarrhea,
shock, and death.  Above 1,000 to 2,000 rads, casu-
alties are likely to develop the cardiovascular/cen-
tral nervous system (CNS) syndrome, which is in-
variably fatal.  In this syndrome, CNS symptoms
can occur within minutes, culminating in confu-
sion, prostration, seizures, and coma.  Patients with
this syndrome typically die in shock or secondary to
CNS complications.
With doses of less than 100 rads, the skin is
b
a

Military Dermatology
78
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Delayed effects
Performance decrement (2,000 rads)
Neurovascular (1,000 rads)
Gastrointestinal (400 rads)
Hematological/Immunological
(100 rads)
500
2000
1750
1500
1250
1000
750
250
0
0
2
4
6
8
10
14
12
16
18
20
22
Days
Years
Radiation Dose (rads)
Fig. 5-8. (below) The effects of acute radiation exposure.
Adapted from Walker RI, Cerveny TJ, Young RW. Acute
radiation syndrome in humans. In: Walker RI, Cerveny
TJ, eds. Medical Consequences of Nuclear Warfare. Part I,
Vol2. In: Textbook of Military Medicine. Washington, DC:
Office of The Surgeon General, US Department of the
Army; 1989: 21.
Fig. 5-6. ( left) A pattern burn in a Japanese nuclear
casualty caused by headgear protection at the time of the
atomic bomb fireball. Photograph: Courtesy of the De-
fense Nuclear Agency, Washington, D.C.
Fig. 5-7. (above) Superficial radiation burns caused by
beta radiation from nuclear fallout. Photograph: Cour-
tesy of the Defense Nuclear Agency, Washington, D.C.

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
79
vascular damage in the cutaneous tissues can result
in diffuse bullae formation over the exposed skin
surfaces (Figures 5-9 and 5-10).26  The histological
picture of skin exposed to high doses of radiation
consists of keratinocyte damage with pyknotic nu-
clei, severe dermal edema, and subepidermal vesicle
formation.23  With higher doses, endothelial cell
swelling, intravascular thrombi, and fibrosis can be
seen.23
Skin manifestations that occur over weeks to
months, in addition to those noted above, include25
• late erythema that occurs after 6 to 8 months
and is associated with vasculitis, edema, and
pain;
• moist desquamation that is usually manifest
at the 3-week period with doses of 1,200 to
2,000 rads; and
• necrosis with onset at a few weeks to months,
accompanied by fibrosis, atrophy, and vas-
cular proliferation (Figures 5-11 and 5-12);
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Fig. 5-10. Bullae on the hands of an individual involved
in a nuclear incident in which he received a 1,000-rad
dose. The patient developed a cardiovascular/central
nervous system radiation syndrome secondary to the
exposure, and he subsequently died. Photograph: Cour-
tesy of the Defense Nuclear Agency, Washington, D.C.
necrosis occurs at doses of greater than 2,500
rads.
The systemic effects of ionizing radiation can
also manifest cutaneously.  At doses of greater than
100 rads, depletion of the platelets and their precur-
sors can cause cutaneous petechiae and hemor-
rhage.  Bone marrow damage can also cause immu-
nosuppression, which could lead to increased skin
infections.
The patient who survives the acute phase of
radiation exposure is at increased risk for chronic
radiation dermatitis and cutaneous neoplasms (de-
layed effects).
Therapy of Cutaneous Radiation Injury
Participation of dermatologists in the treatment
of thermal injuries after a strategic nuclear encoun-
ter will be, of necessity, significant.  Overwhelming
numbers of casualties will quickly saturate the ca-
pabilities of surgical personnel, leaving others to
care for the burn victims who do not need intensive
surgical or burn care.  Dermatologists, with their
broad experience in and knowledge of skin patho-
physiology, will be uniquely qualified to care for
this type of casualty.
Treatment for the cutaneous effects of ionizing
radiation remains largely symptomatic.  The initial
step in caring for these patients is decontamination.
Fallout particles can cause superficial burns to the
Fig. 5-9. Bullae on the hands of a Los Alamos nuclear
accident victim 24 days after exposure. Photograph: Cour-
tesy of the Defense Nuclear Agency, Washington, D.C.

Military Dermatology
80
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Fig. 5-11. Two cases of chronic radiation necrosis, ulceration, and scarring secondary to radiation therapy for breast cancer.
skin but pose a relatively minimal risk for systemic
problems.  Of importance to medical personnel is
the fact that patient contamination poses little risk
to them and should not hinder appropriate lifesav-
ing measures in an emergent situation.27
After decontamination, care of acute radiation
injuries should consist of gentle cleansing and wash-
ing of denuded blisters and superficial and deep
ulcerations.  As with burns, frequent changes of
sterile dressings and silver sulfadiazine and
mafenide antibiotic creams are useful in the inhibi-
tion of local bacterial infections.  Careful monitor-
ing for signs of local and systemic infections is
paramount because these patients are often immu-
nosuppressed and are at increased risk for the de-
velopment of infection.
Because of the damage to the mucosal barrier of
the gastrointestinal tract secondary to the radia-
tion, these patients are particularly susceptible to
enteric pathogens.  For this reason, it has been
recommended that nonabsorbable antibiotics be
given to decrease the intestinal flora.24  In addition,
fevers of unknown origin should be treated imme-
diately with broad-spectrum antibiotics that cover
Entero- bacteriaceae and Bacteroides fragilis.  In ra-
diation patients who exhibit an increased potential
for Gram-negative organisms as well as avascular
ulcerations, ciprofloxacin offers coverage for cuta-
neous infections with many Gram-negative
organisms including Enterobacter and Pseudo-
monas species, and moderate coverage for Staphylo-
coccus species, especially those that are methicillin
resistant.28
Hydrogel and hydrocolloid gel dressings such as
Vigilon (manufactured by C.R. Bard, Inc., Murray
Hill, N.J.) and DuoDERM (manufactured by
ConvaTec, Princeton, N.J.) may decrease wound
Fig. 5-12. Chronic telangiectasia, scarring, and pigmen-
tary changes of the skin following radiation therapy.
b
a

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
81
discomfort and wound healing time in radiation
ulcers and should be considered, if available.29
Surgical treatment of chronic, painful nonhealing
ulcers is often necessary in patients exposed to
radiation doses greater than 1,000 rads.  Surgical
debridement of necrotic tissue, early treatment of
cutaneous infections, and grafting are essential to
ensure optimal healing.30  Because the ulcer base
often has a compromised blood supply secondary
to vascular damage, the use of pedicled flaps that
have an intrinsic blood supply may offer an im-
proved recovery (lower graft-failure rate).31
Over the past decade, there has been increased
study of drugs with an apparent systemic radio-
protective effect.  Animal studies of sulfhydryl drugs
such as cysteamine (MEA) have demonstrated that
both systemic and topically applied sulfhydryl drugs
exert a significant radioprotective effect (taken ei-
ther prophylactically or shortly after exposure) for
acute and late sequelae of radiation exposure.32
Histological examination of the animals receiving
MEA at the time of irradiation demonstrated that
fewer vascular abnormalities existed than in
nonprotected animals.  This finding suggests that
both acute and late skin changes may be, in part,
due to vascular damage.  A study of radiation
therapy patients who received the hemorrheologic
drug pentoxifylline demonstrated significantly
shortened healing time of skin ulcerations and du-
ration of pain.33  This study also suggests that drugs
that act to maintain blood flow to irradiated skin
help the healing process.
Another drug found to exert a protective effect
on animal tissue is cuprozinc-superoxide dismutase
(CSD).34  Treatment with CSD reduces the bone
marrow cell toxicity from irradiation in mice by a
factor of two.  The exact mechanism by which CSD
protects the cell is unclear, but studies have demon-
strated that it inhibits the action of poly(ADP [ad-
enosine diphosphate]-ribose) synthetase, which is
activated by DNA strand breaks.35,36  Poly(ADP-
ribose) synthetase, when upregulated by breaks in
the DNA, depletes the cellular NAD (nicotinamide
adenine dinucleotide) and thereby deprives the cell
of substrates to produce ATP (adenosine triphos-
phate), which is necessary for cell function.36  Fur-
ther studies of CSD will be needed to determine its
efficacy in humans.  Other researchers have used
cytokines to stimulate bone marrow precursors in
radiation syndrome patients.  Interleukin- (IL) 1,
alone and in combination with tumor necrosis fac-
tor, IL-6, and colony stimulating factors, has pro-
moted recovery in irradiated mice.37  In eight pa-
tients with bone marrow failure due to cesium 137
exposure, the use of granulocyte-macrophage stimu-
lating factor resulted in a prompt increase in bone
marrow granulocytes.38  Other drugs that are avail-
able and may have some beneficial effect on the
course of radiation-induced skin injuries include
the antioxidants such as ascorbic acid, α-tocopherol,
and butylated hydroxyanisole (BHA).39
Late Sequelae of Radiation Exposure
Radiodermatitis and an increased propensity for
cutaneous neoplasms are the late sequelae of radia-
tion exposure.  The onset of radiodermatitis is de-
pendent on several variables including type of ra-
diation, total dose, duration of dose, and density of
radiation.  Most of the clinical experience with the
cutaneous effects of radiation has been with pa-
tients who have received radiation therapy.  Pa-
tients who have received fractionated radiation
therapy in the 4,000 to 6,000 rad range experience an
acute erythema, blistering, necrosis, and sloughing
of tissue, leaving an ulcer that heals slowly or is
nonhealing (see Figure 5-11).23  Fractionization of
the radiation dose allows for high doses of radiation
to be given with minimal skin damage; therefore,
one high-dose exposure can cause significantly more
skin damage than a higher dose that is fractionated.
Case studies of radiation accident victims, which
report that blistering and ulcer formation can occur
with as little as 1,000 rads, support this contention.24
The ulcerations heal with mottled hyper- and
hypopigmentation, atrophic scarring, dermal fibro-
sis, and telangiectasia (see Figure 5-12).23  Histologi-
cally, chronic radiation damage resembles severely
actinically damaged skin, with epidermal hyper-
keratosis, keratinocyte atypia, and elastotic changes
in the dermis.  In addition, there are dermal vessel
changes with thickened walls and thromboses.  The
appendages, especially sebaceous glands and hair
follicles, which are fairly sensitive to ionizing radia-
tion, are often absent.40  Skin cancers arising in
radiation dermatitis include both squamous cell
and basal cell carcinomas.  These tumors tend to be
more aggressive than tumors arising from skin not
affected by ionizing radiation.40
The therapy of chronic radiation sequelae of the
skin is largely palliative.  The treatment of chronic
ulcerations due to ionizing radiation is excision and
graft placement.30  The vascular changes of vessel wall
thickening and thrombosis secondary to ionizing ra-
diation exposure often lead to ischemia, poor healing,
and increased chance of infection.  Cell culture stud-
ies of fibroblasts exposed to ionizing radiation have
demonstrated that irradiated fibroblasts have a

Military Dermatology
82
significantly prolonged generation time when com-
pared to normal fibroblasts.41  Therefore, it is impor-
tant to remove all ischemic, necrotic, and infected
tissue, including the ulcer bed and the surrounding
affected epidermis, to obtain viable margins in which
to place a graft.30  The best graft is that of a pedicled
flap from a site distant from the affected area to
ensure viability of tissue, or musculocutaneous or
muscle flaps with their own blood supply to in-
crease vascularity in the damaged area.31
Other problems attendant with skin radiation
injuries, especially those with large areas of cutane-
ous involvement, are severe pain, hepatorenal fail-
ure, and encephalopathic coma.  These problems
were especially prevalent during the Chernobyl
nuclear reactor disaster in 1986.42  Therapy for
these patients consists of plasmapheresis for the
hepatorenal failure and analgesics includ-
ing antiinflammatory drugs and narcotics for the
pain.
BIOLOGICAL WARFARE
Biological weapons, perhaps the most feared tools
of war, are potentially much more destructive than
any other nonnuclear munitions.43  In a U.S. Army
manual prepared for Operation Desert Shield, bio-
logical warfare was defined as “the use of microor-
ganisms or toxins derived from living organisms to
produce death or disease in humans, animals, or
plants.”44(p74)  Some authorities have broadened the
concept of biological warfare to include herbicides,
defoliants, and other biologically active substances.
Others define biological warfare more narrowly
and exclude toxins because they are active outside
their organism of origin.  Two international agree-
ments relate to the use of biological weapons in war:
one that prohibits first use of chemical and bacterio-
logical weapons in war (1925 Geneva Protocol) and
another that prohibits the development, produc-
tion, and stockpiling of biological and toxin weap-
ons (Biological and Toxin Weapons Convention of
1972).45  Despite these international agreements and
widespread moral disapproval of the use of biologi-
cal weapons, they have existed for many years, and
there is continued evidence of development and
production of biological weapons by the former
Soviet Union and other countries.
A number of features make biological weapons
attractive.
• Compared to other types of munitions, pro-
duction costs are low.
• International monitoring of production is
difficult.
• They are well suited for secret warfare op-
erations.
• They are selective in their effects on the
enemy: while biological weapons preserve
industrial complexes, supply routes, and
other military facilities, enemy personnel
are either incapacitated or killed.
• Specific agents can be selected to achieve a
high fatality rate, or to cause a high morbid-
ity rate with a relatively low fatality rate,
depending on the military objectives.
• Biological weapons may be used for both
strategic and tactical objectives.
A number of criteria are used to select specific
agents for use in biological warfare.  One character-
istic that makes an agent particularly attractive as a
biological weapon is its ability to be aerosolized,
especially if a particle size of 1.0 to 5.0 µm can be
achieved.  At this size, the agent generally is invis-
ible and can also reach the lower parts of the respi-
ratory tract (small bronchi, bronchioli, and alveoli).
Resistance to environmental conditions, such as
sun, heat, or cold, as well as to usual disinfectant
agents, is also a desired characteristic.  Preferred
agents are highly virulent and able to produce se-
vere illness, and are resistant to the usual chemo-
therapeutic agents.  For production purposes, the
ability to propagate the agent easily and to preserve
it, particularly by lyophilization, is desired.  Lastly,
agents that produce atypical biological actions, par-
ticularly in the form in which they are delivered
militarily (eg, anthrax by aerosolization) lead to
difficulty in differential diagnosis and thus are also
desirable.  Agents currently believed to be fully
developed as biological weapons that produce some
dermatologic signs or symptoms include anthrax,
tularemia, plague, hemorrhagic fevers, botulism,
and mycotoxins.
Anthrax
Anthrax is caused by Bacillus anthracis, a large
Gram-positive rod, either aerobic or anaerobic, that
is nonhemolytic, encapsulated, and capable of form-
ing spores.  The toxin produced by B anthracis is

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
83
complex and includes three separate soluble pro-
teins called protective antigen, edema factor, and
lethal factor.  All three have been purified, charac-
terized, and their structural genes cloned and se-
quenced.  A fragment of protective antigen binds to
the membrane of target cells and serves as a specific
receptor for edema factor or lethal factor, allowing
entry of either factor by receptor-mediated endocy-
tosis.  Edema factor is a calmodulin-dependent ade-
nylate cyclase, expressed only in target cells that
provide the required calmodulin activator and ATP
substrate, which is converted to cyclic AMP (ad-
enosine monophosphate).  The biological effects of
edema factor, edema and inhibition of phagocytosis
by polymorphonuclear leukocytes, are believed to
be due to the actions of cyclic AMP in the intoxi-
cated cells.  The mechanism of action of lethal factor
is unknown.46  The usual source of human disease
from B anthracis is contact with infected animals or
contaminated animal products, usually manifested
initially by cutaneous lesions.  When used as a
biological warfare weapon, the method of delivery
would most likely be via aerosol, producing inhala-
tion anthrax, a rare form of the naturally occurring
disease, with a mortality rate approaching 100%.
The skin and the gastrointestinal tract are other
possible portals of entry when B anthracis is used as
a biological weapon.
Cutaneous Findings
When the skin is the portal of entry, the charac-
teristic finding in anthrax is a macule that progresses
Fig. 5-14. Cutaneous anthrax. Photograph: Courtesy of
Armed Forces Institute of Pathology, Washington, D.C.
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through papular, vesicular, or pustular stages lead-
ing to an ulcer with a blackened, necrotic eschar and
surrounding, nonpitting, gelatinous, and painless
edema (Figures 5-13 and 5-14).  The lesion usually
occurs on an exposed surface.  Satellite vesicles may
surround the lesion.  Painful regional lymphadenitis
is common.  Pruritus may be an early symptom;
however, advanced lesions are often asymptomatic.
Other Clinical Findings
The majority of patients with cutaneous anthrax
do not have systemic symptoms; however, severe
edema and septic shock may occur.  Anthrax men-
ingitis occurs rarely.  If it is acquired via the gas-
trointestinal tract, symptoms include abdominal
pain, enteritis, ascites, bloody diarrhea, fever, and
nausea and vomiting.  Usually, mesenteric adenitis
is present.  Oropharyngeal anthrax is associated
with fever, sore throat, dysphagia, and, occasion-
ally, respiratory distress.  The most severe form of
anthrax is acquired via inhalation, with fulminant
pneumonitis and hemorrhagic mediastinitis the
characteristic features.
Diagnosis
Gram’s stains or cultures from cutaneous an-
thrax lesions usually yield B anthracis.  Blood, pleu-
ral fluid, and cerebrospinal fluid may also be posi-
tive using routine culture techniques.  Impression
smears of mediastinal lymph nodes and spleen as
well as smears from pleural and cerebrospinal fluid
should be positive by Gram’s or Giemsa stains.
Direct fluorescent antibody staining of tissues is
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Fig. 5-13. Large necrotic lesion of cutaneous anthrax.
Photograph: Courtesy of Armed Forces Institute of Path-
ology, Washington, D.C.

Military Dermatology
84
available.  Lastly, anthrax toxin may be detected in
the blood by immunoassays.
Treatment
Penicillin G, 2 million units every 6 hours until
edema subsides, followed by a 7- to 10-day course
of oral penicillin is the recommended therapy for
cutaneous anthrax, with erythromycin, tetracycline,
or even chloramphenicol used in adults unable to
take penicillin.  For gastrointestinal or inhalation
anthrax, high-dose penicillin G, 2 million units ev-
ery 2 hours, is recommended.  Specific therapy
recommended in a primer developed for medical
personnel involved in Operation Desert Shield in-
cludes ciprofloxacin 1,000 mg initially, followed by
750 mg by mouth twice daily, or intravenous
doxycycline, 200 mg initially, followed by 100 mg
every 12 hours.  The duration of these regimens
should be dictated by symptoms.  Supportive
therapy for shock and respiratory compromise may
also be needed.
Prophylaxis
A vaccine consisting of purified protective anti-
gen has been developed, with limited data from
human studies suggesting that protection against
both cutaneous and inhalation anthrax occurs with
doses given at 0, 2, and 4 weeks, and then at 6, 12,
and 18 months.  Animal studies suggest that good
protection lasting 2 years may be afforded after just
two doses, 10 to 16 days apart.44  Live, attenuated
spore vaccines are used for both animals and hu-
mans in the former Soviet Union.
Prophylaxis with antibiotics, specifically
ciprofloxacin (500 mg by mouth twice daily) or
doxycycline (100 mg by mouth twice daily), has
been suggested if information is received that a
biological weapon attack is imminent.44
Military Significance
Anthrax has many characteristics that make it a
good choice as a biological weapon.  It can be
produced very quickly in almost unlimited quanti-
ties, and it produces a spore form that is highly
resistant to heat, disinfectants, sunlight, and other
environmental factors.  It can be delivered in wet or
dry form and produces an aerosol of optimum size.
Although high numbers of spores are required to
kill 50% of exposed individuals (the LD50 [median
lethal dose] is between 8,000 and 10,000), such
doses would not be difficult to deliver using cur-
rently available techniques.45  An outbreak of an-
thrax in the Soviet Union city of Sverdlovsk in April
1979 is regarded by the United States as an acciden-
tal release of dry anthrax spores, presumably from
an explosion within the Microbiology and Virology
Institute, a military facility.  Although the official
Soviet explanation for this incident was that an-
thrax-contaminated meat was the cause of the out-
break, an analysis by the United States suggests this
incident was the result of an accident within a
biological warfare facility.45
Tularemia
Tularemia is caused by Franciscella tularensis, a
small, Gram-negative, pleomorphic, bipolar rod.
Under ordinary conditions, the disease is acquired
by contact with infected animals or via an insect
vector.  Delivery by aerosol would be the likely
method for tularemia used as a biological weapon,
causing typhoidal tularemia.  For a further discus-
sion of tularemia, see Chapter 13, Bacterial Skin
Diseases.
Plague
Plague is caused by Yersinia pestis, a Gram-nega-
tive bacillus with pleomorphic or coccoid variants.
The disease is usually acquired by skin inoculation
via a flea bite or through direct animal contact.
When used as a weapon of biological warfare, an
aerosol would most likely be the method used.  For
a detailed discussion of plague, see Chapter 13,
Bacterial Skin Diseases.
Hemorrhagic Fevers
Hemorrhagic fevers include a number of viral
infections, such as the Marburg virus and Lassa
and Ebola fevers.  All the viruses in this group are
highly infectious.  The clinical picture is similar for
many of these diseases.  A more complete discus-
sion can be found in Chapter 10, Viral Hemorrhagic
Fevers.
Cutaneous and Other Clinical Findings
The cutaneous eruptions seen with the hemor-
rhagic fevers have been described as maculopap-
ular in nature, becoming petechial with time.  A
generalized erythema may be present (Figure 5-15).
Extensive purpura may develop (Figure 5-16).

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
85
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Fig. 5-15. (a) The scarlatiniform eruption and (b) the characteristic blanching that occur in the scarlatiniform type of
dengue fever. Photograph: Courtesy of U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Md.
b
a
Mucous membranes may be involved, with blisters
leading to ulcerations as well as petechiae and
hemorrhages (Figures 5-17 and 5-18).  Conjunctivitis
may also be seen.
Hemorrhagic fevers usually begin with a flulike
syndrome following a 3- to 10-day incubation pe-
riod.  Deterioration often occurs about the third day
after symptoms begin, with high fever, weakness,
nausea, vomiting, diarrhea, headache, chest pain,
joint pains, and an eruption.  Bleeding may be a
significant problem, and death secondary to shock
may occur in as many as 50% of patients.47
Diagnosis
Definitive diagnosis of hemorrhagic fevers may
be difficult; however, the virus may be identified
using electron microscopy or fluorescent micros-
copy on peripheral blood or cell cultures.  Serologic
tests by enzyme-linked immunosorbent assay
(ELISA) or hemagglutination are available in some
cases.  Clinical criteria for dengue hemorrhagic
fever have been established by the World Health
Organization.
Treatment
Currently, treatment of hemorrhagic fevers con-
sists of symptomatic support.  Control of hemor-
rhagic diathesis and fluid and electrolyte manage-
ment are particularly important.  Use of convalescent
serum has been helpful in isolated cases but would
not be practical for mass casualties.  Ribavirin might
be useful in the treatment of viral hemorrhagic
fevers, including Crimean-Congo hemorrhagic fe-
ver.  The dose of ribavirin recommended is 400 mg
by mouth every 4 hours for 24 hours, then 400 mg by
mouth every 8 hours for 7 to 10 days or, if given
intravenously, a 2-g loading dose, then 1 g every 8
hours for 4 days, then 500 mg every 8 hours for 6

Military Dermatology
86
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Fig. 5-16. Large purpuric lesion in a hemorrhagic fever
patient. Photograph: Courtesy of U.S. Army Medical
Research Institute of Infectious Diseases, Frederick, Md.
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Fig. 5-17. Gingival petechiae characteristically seen in
cases of Argentine and Bolivian hemorrhagic fever. Pho-
tograph: Courtesy of U.S. Army Medical Research Insti-
tute of Infectious Diseases, Frederick, Md.
OK to put on the Web
Fig. 5-18. The characteristic petechial lesions of the soft
palate, which are seen in several hemorrhagic fevers.
Photograph: Courtesy of U.S. Army Medical Research
Institute of Infectious Diseases, Frederick, Md.
days.  When given intravenously, ribavirin should
be diluted in saline or 5% dextrose in water and
should be administered over 15 to 20 minutes.  Strict
isolation of affected individuals is mandatory and
should include contact, body fluids, blood, and
respiratory isolation.44
Prophylaxis
A number of vaccines for the hemorrhagic fevers
have been studied, with none currently licensed for
use in humans.
Military Significance
The hemorrhagic fevers fulfill many of the crite-
ria for effective biological agents including stability

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
87
in aerosol form, high virulence and the ability to
produce severe illness, and the absence of specific
prophylactic measures or specific treatments for
the disease produced.
Botulism
Botulism refers to the disease produced by the
potent neurotoxins of the organism Clostridium botu-
linum.  C botulinum is a Gram-positive, incompletely
aerobic, spore-forming bacillus.  Its neurotoxins are
large proteins of molecular weight approximately
150,000 daltons, and are identified by their anti-
genic specificities as types A, B, C, D, E, F, and G.
Their toxic effects are due to inhibition of acetylcho-
line release from cholinergic terminals at the motor
end plate.48  Human disease occurs after ingestion
of preformed toxin (food poisoning), by enteric
production and subsequent absorption of toxin (in-
fant botulism, shaky foal disease, adult sudden
death), or via absorption from infected wounds.  It
is speculated that the most likely method of deliver-
ing botulism via weapons would be by aerosolization
of alpha toxin, a highly toxic phospholipase C.
Cutaneous and Other Clinical Findings
Dry mucous membranes, with extreme dryness
of the mouth, perhaps with crusting, are the only
mucocutaneous findings in clostridial food poison-
ing; dilated pupils and a clear sensorium are seen;
gastrointestinal symptoms are variable.  Sensory
functions are intact, but cranial nerve weakness
and descending peripheral motor weakness pro-
gressing to paralysis occurs, which may result in
respiratory failure.  In infant botulism, feeding prob-
lems from cranial nerve weakness, altered cry, hy-
potonia, poor head control, and constipation are
seen.  Wound botulism results in disease similar to
that seen in clostridial food poisoning.  No informa-
tion is available on the precise toxic effects of
inhalation botulism; however, it is presumed to
result in a serious pulmonary insult, with associ-
ated vascular leak, hemolysis, thrombocytopenia,
and liver damage.44
Diagnosis
The clostridial enterotoxin can be detected in
fecal samples, vomitus, or gastric fluid from indi-
viduals with clostridial food poisoning.  An animal
bioassay is available for detection of toxin in serum
but may be falsely negative.
Treatment
In addition to supportive care for cranial nerve
paralysis, respiratory failure, and autonomic dys-
function, an equine antitoxin is available, and a
human pentavalent antitoxin is being tested in the
treatment of botulism.44  Attempts to remove re-
maining toxin from the gastrointestinal tract may
be helpful, as well as antibiotics.
Prophylaxis
A pentavalent toxoid of C botulinum types A, B,
C, D, and E is currently being tested.  This toxoid is
not yet available for general prophylactic use.44
Military Significance
Botulinum toxins are dangerous as biological
warfare agents because they produce illness with a
high mortality rate.  The toxins are readily available
and are relatively stable, resisting degradation by
acid and proteolytic enzymes, and requiring heat-
ing to 100°C for 10 minutes for inactivation.  They
can be delivered in aerosol form.  In addition to
being highly lethal, those individuals who survive
botulism intoxication often require several weeks
of convalescence; thus, effects on troop strength are
potentially very serious.
Mycotoxins
Mycotoxins are toxins produced by many strains
of fungi that grow on food products and produce
toxic effects in animals and people exposed to them.
Mass outbreaks of disease in animals caused by
moldy foods have been documented in animals and
humans.  The only human outbreak with extensive
documentation occurred in the USSR during the
later years of World War II, producing a syndrome
termed alimentary toxic aleukia, a panleukopenia.49
Interest in mycotoxins has increased in recent years
due to reports of their use as biological warfare
agents in various regions of the world, including
Southeast Asia and Afghanistan.50–54  Trichothecene
mycotoxins are a family of sesquiterpenes, all de-
rived from a trichothecene ring system (Figure 5-19).
They are insoluble in water, but can be solubilized
in lipids, propylene glycol, and dimethyl sulfoxide
(DMSO).  They are produced by many species of
molds in the genera Fusarium, Myrothecium,
Trichothecium, Trichoderma, and Cephalosporium.
They produce a wide range of toxic effects in ani-

Military Dermatology
88
H3C
R4
R3
R1
R2
CH2
O
O
H
OH
CH2
O
OH
O
R4
R3
R2
CH2
CH3
R1
H3C
H
Fig. 5-19. Diagram of the basic trichothecene ring.
in death, have been reported from presumed
trichothecene toxin exposure.  Extensive bleeding,
acute leukopenia, septicemia, and bone marrow
function failure may all be seen.  Based on evalua-
tion and questioning of presumed victims of
trichothecene toxin exposures in Cambodia, Laos,
and Afghanistan, the clinical signs and symptoms
of trichothecene toxicosis are believed to occur in
four stages56,57:
1.
The initial findings consist of a burning
sensation of the skin and mucous mem-
branes, headache, dizziness, weakness, ab-
dominal pain, vomiting and diarrhea, fe-
ver, sweating, tachycardia, and cyanosis.
This stage may last up to 9 days.
2.
Next, from 2 to 4 weeks following exposure,
anemia, leukopenia, granulocytopenia,
thrombocytopenia, and lymphocytosis are
seen, along with symptoms of headache,
fatigue, vertigo, and the clinical finding of
petechiae.
3.
The third stage is not well characterized as
to duration and may result in death.
Petechiae, focal necrotic lesions, ulcerative
pharyngitis, gastrointestinal and mucosal
hemorrhage, lymphadenopathy, and pro-
gression of hematological abnormalities
occur.
4.
Lastly, resolution of hemorrhage and ne-
crotic lesions may occur, with slow improve-
ment of hematological abnormalities, and a
prolonged risk of infectious complications.
Diagnosis
The diagnosis of mycotoxin-related disease will
be a challenge for medical personnel.  The specific
signs and symptoms that result from exposure de-
pend on a large number of variables including the
specific mycotoxin or mycotoxins involved, the
method of delivery, the dose received, the specific
vehicle used, the portal of entry into the body,
climatic conditions, the use of protective gear, and
the nutritional status and general health of the
casualty.  Because of the large number of variables
determining the clinical presentation, the spectrum
of disease resulting from exposure to mycotoxins
will likely be very broad.  Differential diagnosis
should include exposure to other toxins, such as the
vomiting agents (adamsite, diphenylchloroarsine),
mustards, Lewisite, phosgene oxime, and nerve
agents.57  The vomiting agents have a shorter dura-
tion of action, about 30 minutes, compared to 1 to 2
mals, depending on dose, specific metabolites
present, and even the particular combinations of
toxins present.55  The biochemical changes leading
to cell death induced by the toxins are not com-
pletely known; however, it has been shown that
protein synthesis is impaired at the initiation, elon-
gation, and termination phases, and marked
polysomal disaggregation is evident.49,56  It is be-
lieved that trichothecene mycotoxins are very po-
tent inhibitors of protein synthesis in eukaryotic
cells.56  The most toxic trichothecene toxin identi-
fied is called T-2 toxin.  Others include deoxy-
nivalenol (DON, also called vomitoxin), diacetoxy-
scirpenol (DAS), and zearalenone.  Most of the
information that follows is derived from the study
of the T-2 toxin.
Cutaneous Findings
Exposure to trichothecene toxins often causes
prominent cutaneous findings.  Erythema, which
may be generalized, occurs within minutes to hours
of exposure.  It may be accompanied by itching,
burning, tingling, or even painful sensations.  Eva-
nescent “scattered red spots” have also been re-
ported.  Blisters, which may be large, and red pap-
ules have also been described.  A Red Cross physician
described erythematous 5- to 10-mm papules with
fine vesicles that developed 6 to 24 hours after
exposure as characteristic lesions.  The lesions later
become black and crusted.  When blisters erode or
form ulcers, prolonged healing, up to several
months, may be noted.  In severe cases, large sheets
of skin were shed.  Alopecia has also been reported,
along with necrotic oral ulcers.57
Other Clinical Findings
Severe systemic symptoms, sometimes resulting

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
89
days for mycotoxins, and also generally cause less
severe vomiting.  Mustard agents produce symp-
toms that are not quite as delayed as with mycotox-
ins, and less often cause burning, dysesthesias, gen-
eralized erythema, or hemorrhagic lesions.  Healing
following mustard exposure is delayed even longer
than that seen after mycotoxin injury.  Lastly,
mustard generally does not cause hemoptysis,
hematemesis, or toxic pulmonary edema.  Lewisite
may cause many signs and symptoms similar to
mycotoxins; however, they occur much sooner, usu-
ally within a few minutes of exposure.  In addition,
hematemesis and other hemorrhagic signs and
symptoms are more often seen with mycotoxin ex-
posure than with Lewisite.  Phosgene oxime causes
immediate effects on the skin and eye, and also
causes less hemorrhage than the mycotoxins.  With
nerve agents, miosis, severe bronchoconstriction,
wheezing, hypersecretion, and polyuria are promi-
nent, and skin changes are not seen.  Pulmonary
edema, massive hemoptysis, and hematemesis are
not sequelae of nerve agents.
Although optimal field detection of mycotoxins
is not yet available, a number of detection methods
have been developed or are under study including
radioimmunoassay in biological fluids, gas chro-
matograph mass spectrometry, polarography, thin-
layer chromatography, gas–liquid chromatography,
high-performance liquid chromatography, infrared
spectroscopy, and nuclear magnetic resonance spec-
troscopy.  The most promising area of development
of detection methods is in the use of immune-based
systems such as monoclonal antibodies.57
Treatment
Immediate treatment of mycotoxin exposure
should include lavage of eyes and skin with any
nontoxic liquid.  Absorption from the skin is slow;
therefore, thorough cleansing with soap and water
is very important in limiting the amount of systemic
toxin exposure.  Wounds should be irrigated with
saline or other solutions, blotted with sterile dress-
ings, then managed like other wounds.  The U.S.
Army’s M258 kit, which is used in mustard decon-
tamination, has been found to be unsatisfactory for
decontaminating mycotoxins from the skin.  Per-
sonnel performing the decontamination should wear
eye and skin protection.  Contaminated water should
be considered toxic.  Instruments that become con-
taminated must be handled carefully, because even
autoclaving may not eliminate the mycotoxins.  If
heavy exposure is suspected, stripping of the stra-
tum corneum from the hands and face with tape
may remove a reservoir of mycotoxin, as significant
binding to the stratum corneum may occur.
In addition to skin, the bowel may serve as a
reservoir for mycotoxins.  Toxin is excreted in the
bile and subsequently reabsorbed.  Emesis is often
associated with mycotoxin exposure and probably
eliminates some toxin.  Activated charcoal, bento-
nite powder, and cholestyramine given orally may
be used to bind the toxin and remove it from the
gastrointestinal tract.  Once in the circulation, my-
cotoxins are excreted primarily in urine, so one
might consider dialysis or hemoperfusion; how-
ever, such treatments have not been adequately
studied and may even be contraindicated if
coagulopathy or hypotension is present.
Systemic steroids and vitamins A, C, and E are
mycotoxin treatments supported by animal studies.
If significant skin exposure has occurred, consider-
ation of therapy with microsomal enzyme inducers
such as phenobarbital may be reasonable, as this
treatment may speed clearance of toxin that is being
slowly absorbed.57
Prophylaxis
Standard protective clothing and chemical war-
fare masks are believed to provide some protection
from mycotoxins.57  In addition, a variety of drugs
have been proposed as possible pretreatments for
mycotoxin exposure.  A number of compounds
have been studied in animal models; however, no
single pretreatment is known to prevent disease
from mycotoxins without causing side effects.  Drugs
that are proposed as possibly useful include mi-
crosomal enzyme-inducing compounds such as
phenobarbital; free-radical protectants or antioxi-
dants such as vitamins A, C, and E; membrane-
stabilizing drugs such as the systemic steroids;
detoxifying compounds such as the thiazolidines;
and antimuscarinic drugs such as atropine.  In addi-
tion, maintaining normal stores of intracellular
glutathione may be an important protective mea-
sure and could be accomplished by adequate nutri-
tion, avoidance of alcohol, tobacco, and drugs, and
possibly by dietary supplementation with D-L
methionine.57  The decision to pretreat troops, and
the specific agents employed, will need to be care-
fully considered in view of the possible adverse
effects caused by pretreatment.
Military Significance
Characteristics of trichothecenes that make them
good candidates for biological warfare agents

Military Dermatology
90
include their irritating and damaging effects on
many organs vital to effective combat, such as
the eyes, skin, upper and lower respiratory tracts,
mouth, throat, and entire gastrointestinal tract.
Effects are also seen in the peripheral and central
nervous systems; skeletal and cardiac muscles;
and the hematopoietic, clotting, and immune sys-
tems.  In large doses, death may occur within min-
utes to hours, whereas smaller doses cause delayed
death or incapacitation that may last for days to
weeks.  As adjuncts to more toxic agents, mycotox-
ins may irritate the skin enough to prevent wearing
of protective gear.57  Production of mycotoxins is
relatively simple, and reports of mycotoxins found
in high concentrations, along with man-made mate-
rials such as DMSO, suggest that the incorporation
of trichothecenes into weapons has already been
successful.  It is believed that delivery can be
accomplished by aircraft via spraying, dusting,
rockets, or dropped exploding containers, as well as
artillery and mortar rounds.57  Trichothecenes
are moderately potent, with nanogram levels caus-
ing skin erythema.  Field detection is not yet
reliable.  In addition, mycotoxins are persistent,
difficult to decontaminate, and have no specific
treatment or prophylaxis.  Thus, their potential use
as biological weapons must be considered a serious
threat.
CHEMICAL WARFARE
The technology for the development of chemical
agents is readily available and the manufacture of
these agents is relatively simple.  Compounding the
problem is the willingness of some countries with
the technology to manufacture tactical weapons to
supply other countries with the arms that are ca-
pable of delivering chemical weapons.  Reports
suggesting that Iraq has produced thousands of
tons of sarin, tabun, and mustard gas demonstrate
how real the problem has become.58  Therefore, the
likelihood is quite high that one will encounter the
use of chemical weapons in future conflicts.
Chemical Warfare Doctrine and Weaponry
To understand the potential for chemical casual-
ties in modern warfare, one needs to understand
why chemicals might be used on the battlefield.
Many think that the main purpose for using chemi-
cal warfare would be to inflict fatalities; however,
close scrutiny of the chemical tactics and doctrine of
the former Soviet Union suggests otherwise.  Their
goal in the use of chemical weapons was to degrade
the enemy’s combat effectiveness.  This feat was
accomplished through inflicting nonlethal casual-
ties, denying key terrain, and necessitating the wear-
ing of chemical protective clothing.  To accomplish
these goals, massive amounts of chemical agents
have to be delivered, and it appears that the Soviets
acquired both the necessary quantities of agent and
the means with which to deliver it.
It is estimated that at one time Soviet chemical
munitions consisted of 350,000 tons of various agents
that composed up to 20% of the artillery munitions
stockpile and 30% of the FROG and Scud rocket
warheads.59  Although this stockpile is now being
rapidly destroyed, substantial amounts will remain,
and the possibility that these weapons could fall
into the hands of third-world nations or terrorists is
strong.  Additional means of chemical delivery in-
clude the multiple rocket launcher, mortars, aerial
sprays, and bombs.  In combination, these weapons
would be used to degrade our ability to wage war.
Figure 5-20 shows the various areas of the battle-
field that would be subject to attack.  Areas likely to
receive persistent chemical agents would include
key terrain, necessitating that those positions would
either have to be evacuated or the troops in those
areas would have to don chemical protective gear
and lose a significant portion of their combat effec-
tiveness.  The former Soviet doctrine also required
the chemical attack of rear areas in which command
centers, hospitals, and logistical supply areas are
located.  This strategy would be well within the
capabilities of Soviet-made weapons including the
artillery (20-km range), FROG missiles (60-km range,
300-kg payload), the Scud missiles (280-km range,
1,000-kg payload),15,16 and the FROGGER aircraft.
Nearer the forward edge of the battle area, smaller
weapons such as mortars could be used.  In addi-
tion, the multiple rocket launchers of the Soviet
Army have been noted for their capacity to deliver
large quantities of chemical agents over a company-
sized defensive area (Figure 5-21).59,60  Intelligence
estimates suggest that the main chemical threats
developed by the former Soviet Union include mus-
tard gas, cyanide gas, and various nerve agents.
Sulfur Mustard and Nitrogen Mustard
The mustard used in World War I, called sulfur
mustard (H), Yperite, or LOST, has a chemical struc-

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
91
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Fig. 5-20. A depiction of a chemical warfare attack based on Soviet tactics. Note the use of persistent agents such as
mustard in rear areas where hospitals may be located. Reprinted from US Department of the Army. Desert Storm.
Washington, DC: DA; 1992. DA PAM S-8.

Military Dermatology
92
similar properties that make them useful as chemi-
cal weapons:
• Mustard is highly toxic in low concentra-
tions to all organ systems.
• An initial period of latency is exhibited in
mustard casualties, which can last from hours
to days dependent on the dose of mustard
received.
• Mustard has an ability to adhere to fomites
such as clothing, weapons, and other per-
sonal articles, which can injure individuals
such as medical personnel who come in con-
tact with mustard casualties.
• Mustard is highly stable in storage and per-
sistent on the battlefield.
• The density of mustard in vapor form is
higher than that of air and therefore mustard
will remain stationary and sink into trenches
and other protective structures in the deliv-
ery area.
• Mustard can be delivered effectively with a
variety of weapons.
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Fig. 5-21. Two Russian-made multiple rocket launchers that were captured from the Iraqi Army during Operation
Desert Storm. On the left is the BM-21 122-mm multiple rocket launcher.
ture that contains two reactive chloroethyl bonds,
which are reactive with a variety of organic com-
pounds including DNA molecules.61
N
CH2CH2C1
CH2CH2C1
CH2CH2Cl
S
CH2CH2Cl
R - N
CH2CH2C1
CH2CH2C1
Mechlorethamine, mustargen, or nitrogen mustard
(NH) is the alkylating agent used currently as a
chemotherapeutic agent.  It is a congener of Yperite
with a nitrogen substituted for sulfur.
Although nitrogen mustard is considered more toxic
and less persistent than sulfur mustard, they have
R-N
CH2CH2Cl
CH2CH2Cl

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
93
• Production is simple and relatively inexpen-
sive.
• Mustard casualties typically have a low mor-
tality and a long recuperation, which can
overwhelm the capacity of the medical treat-
ment facilities all along the echelons of care.
The mustards are colorless to light yellow vis-
cous liquids that, in high concentrations, smell like
garlic or fish.  Hydrolysis of mustard, which ren-
ders it relatively nontoxic, occurs in water, albeit
slowly over hours.  The process of hydrolysis can
be greatly accelerated by the addition of a strong
base or acid; however, the reaction between mus-
tard and concentrated acids can produce high
amounts of heat and possibly fire.  Therefore, dilute
acid solutions should be used in mustard decon-
tamination.  Decontamination agents include so-
dium thiosulfate, chloramine, potassium perman-
ganate, sodium bicarbonate, hypochlorite, hydrogen
peroxide, sodium chlorate, super tropical bleach,
sodium hydroxide, soap and water, and ammonia
solutions.  Absorbants that bind mustards include
fuller’s earth, activated charcoal, and other avail-
able absorbent powders including earth and flour.
Mustards are soluble in organic solvents such as
petroleum distillates and alcohols, and these agents
may be used to assist in removal of mustards; how-
ever, care must be used to avoid increased skin
absorption of mustards with these solvents.
Pathophysiology of Mustard Poisoning
Mustard is a local and pulmonary irritant and
vesicant, and a systemic poison.  Whether in gas or
liquid form, mustard binds to tissue and reacts
irreversibly within minutes or is taken into the
circulation.62  The action of mustard involves the
release of alkylating chemical linkages that inter-
fere with DNA synthesis by binding to the nucle-
otides within the DNA strands; this is the radiomi-
metic effect of mustard (ie, it mimics the effect of
radiation in producing DNA molecule breaks).61
This characteristic appears to result in the death of
the cell.  The exact mechanism is not understood but
may involve the upregulation of cellular DNA re-
pair enzymes, which decrease the intracellular stores
of NAD that are normally used to produce ATP, the
energy storage molecule of the cell.63  The loss of
ATP in the epidermal cells of the skin may also
induce a hypoxemia-like state, which may result in
oxygen radical formation and subsequent cell-struc-
ture damage from reaction with the free radicals.64
Another mechanism of cell death has been postu-
lated that involves the effect of mustard on the Ca2+
adenosinetriphosphatase (ATPase) in the cell mem-
brane.  The alkylation of the sulfhydryl groups in
this enzyme leads to an increase in cytosolic cal-
cium and cell death.65  Direct DNA damage, inacti-
vation of cellular enzymes such as pyruvate oxi-
dase, increased cell-membrane permeability, and
the resultant loss of the cell’s ability to maintain the
integrity of the cell membrane may all contribute to
cell death.  Despite the fact that the action of mus-
tard at the molecular level is not completely under-
stood, the knowledge already gained over the past
2 decades has led to new insights into potential
therapeutic modalities for mustard casualties, which
will be discussed later in this chapter.
At a cellular level, skin damage is related to the
amount of exposure to mustard, either as a gas or a
liquid.  Although the fixation of mustard to the
tissue occurs within several minutes, histological
changes within the epidermis are not evident until
30 to 60 minutes after exposure and do not become
fully manifest until 2 to 3 days after exposure.  The
earliest changes are in individual keratinocytes,
which become pyknotic and dyskeratotic (Figure
5-22).  In 24 hours, inspection reveals more
keratinocytes that are dyskeratotic and swollen,
invasion of inflammatory cells into the epidermis,
and intra- and subepidermal vesicle formation as a
result of widespread cellular edema and death.
This process often occurs over 2 to 10 days and is
slowly progressive.  In the affected areas, at the
height of the reaction, dermal vessels are contracted
and necrotic.  This feature probably contributes
to the dermal edema and epidermal necrosis seen
histologically during this period.66,67  Typically,
an absence of thrombi in vessels and a mild,
mixed, perivascular infiltrate are found.  Histologi-
cal specimens taken from Iranian mustard casual-
ties revealed that blister formation was intra-epi-
dermal, with the periodic acid-Schiff– (PAS) positive
basement membrane located on the floor of the
vesicle (Figure 5-23).68  A sparse, inflammatory in-
filtrate in the blister and upper dermis are present.
The picture of a necrotic epidermis with minimal
inflammation mimicked the histology of toxic
epidermal necrolysis.  When these blisters healed,
the histological picture of the areas of dark pigmen-
tation included increased amounts of melanin
throughout the epidermis (especially along the
basal layer) and in dermal macrophages and was
consistent with postinflammatory hyperpigmentation
(Figure 5 -24).68

Military Dermatology
94
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Fig. 5-22. Micrograph of a human skin
graft on a nude mouse 24 hours after
mustard exposure. Note the epidermal
cell necrosis, infiltration of inflamma-
tory cells, and incipient blister forma-
tion along the dermal– epidermal junc-
tion. Photograph: Courtesy of Dr. Bruno
Papirmeister, Science Applications In-
ternational Corporation, Joppa, Md.
Fig. 5-23. Histological picture of a newly
formed blister in an Iranian casualty
exposed to mustard gas. The stain is
periodic acid-Schiff (PAS); note that the
PAS-positive basement membrane is at
the floor of the blister. Photograph:
Courtesy of Dr. Luis Requena, Univer-
sidad Autónoma de Madrid, Madrid,
Spain.
Fig. 5-24. Biopsy of an area of residual
hyperpigmentation in a mustard casu-
alty reveals increased melanin deposi-
tion along the basal cell layer of the
epidermis (Fontana-Masson’s stain).
Photograph: Courtesy of Dr. Luis
Requena, Universidad Autónoma de
Madrid, Madrid, Spain.

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
95
Clinically, mustard blisters result in superficial
ulcerations not unlike those that develop in chemi-
cal or thermal burns.  Although the ulcers look like
burns, reepithelialization and the propensity to in-
fection are altered due to the radiomimetic effects of
mustard.  These effects include prolonged healing
due to the suppression of cell division and systemic
immunosuppression via immune cell damage and
death.
Clinical Signs and Symptoms of Mustard Exposure
The experience with mustard poisoning in World
War I until recently has been the chief source of
information on the effects of mustard on human
subjects.  A classic description of the effects of
mustard on an unprotected individual was pro-
vided in 1925:
On exposure to the vapor or to a finely atomized
spray of mustard, nothing is noticed at first except
the faint though characteristic smell.  After the
lapse of several hours, usually four to six, the first
symptoms appear.  The systemic symptoms are
intellectual dullness or stupidity, headache, op-
pression in the region of the stomach, nausea or
vomiting, malaise and great languor and exhaus-
tion.  In many cases these symptoms may not be
noticed, and the local symptoms first attract atten-
tion.  The eyes begin to smart and water.  There is
a feeling of pressure or often of a foreign body, and
photophobia, and when examined the conjunctiva
is found to be reddened.  The nose also runs with
thin mucus as from a severe cold in the head, and
sneezing is frequent.  The throat feels dry and
burning, the voice becomes hoarse, and a dry harsh
cough develops.  Inflammation of the skin now
shows itself as a dusky red erythema of the face and
neck which look as though they had been sun-
burned, but are almost painless.  The inner surfaces
of the thighs, the genitals, the buttocks, the arm-
pits, and other covered portions of the body are
similarly affected.  Mustard affects more severely
those parts of the body where the skin is tender and
well supplied with sweat glands.  Itching and burn-
ing of the skin may be spontaneous, or first noticed
as the result of washing.  Even these mild symp-
toms may be sufficiently irritating to cause sleep-
lessness.  At the end of twenty-four hours a typical
appearance is presented.  The conjunctivitis has
steadily increased in intensity, the vessels are deeply
injected, and one of the main items of distress is
caused by the pain in the eyes which may be very
intense.  The patient lies virtually blinded, with
tears oozing from between bulging edematous eye-
lids, over his reddened and slightly blistered face,
while there is a constant nasal discharge, and con-
tinuous harsh, hoarse coughing.  Frontal headache
is often associated with pain in the eyes and
photophobia and blepharospasm is always marked.
During the second day the burned areas of the skin
generally develop into vesicles, and the scrotum
and penis and other badly burned areas become
swollen, edematous and painful to the touch.  Bron-
chitis now sets in with abundant expectoration of
mucus, in which there may later be found large
actual sloughs from the inflamed tracheal lining.
The temperature, pulse rate and respiration rate
are all increased.
These symptoms now increase in intensity for sev-
eral days if the case has been severely burned.  On
the other hand, cases that have been only slightly
poisoned may never proceed to the blister
stage.69(p327)
Recent United Nations observers sent to Iran to
evaluate chemical casualties have given descrip-
tions of sulfur mustard victims that essentially mir-
ror this description.68  In the aftermath of a chemical
attack on the Iranian towns of Oshnaviyeh and
Abadan, the victims were described with initial
symptoms of severe coughing, discharge from the
nose and eyes, conjunctivitis (Figure 5-25), and skin
irritation, all of which occurred from 20 minutes to
several hours after the chemical exposure.  The first
skin symptom was often itching, and with heavy
gas exposure was accompanied by nausea and
vomiting.  The skin then developed an erythema not
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Fig. 5-25. Conjunctivitis in an Iranian soldier exposed to
mustard. Although the skin is minimally affected, eye
involvement is relatively severe. As demonstrated in this
patient, the eyes are significantly more sensitive to the
effects of mustard than the skin. Photograph: Courtesy of
Dr. Luis Requena, Universidad Autónoma de Madrid,
Madrid, Spain.

Military Dermatology
96
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Fig. 5-26. Mild erythema with some mucosal involve-
ment in an Iranian mustard casualty. Note the yellow
crusting below the mouth, which is suggestive of a sec-
ondary bacterial infection. Photograph: Courtesy of Dr.
Luis Requena, Universidad Autónoma de Madrid,
Madrid, Spain.
Fig. 5-28. Diffuse superficial ulcerations secondary to the
rupture of bullae in an Iranian casualty of a mustard
attack. Note the involvement of the inguinal area. Al-
though this area was probably protected with at least two
layers of clothing, the increased moisture in the area
resulted in significant blistering. The characteristic hy-
perpigmentation seen in mustard casualties is apparent
around this individual’s waist and neck areas. Photo-
graph: Courtesy of Dr. Luis Requena, Universidad
Autónoma de Madrid, Madrid, Spain.
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Fig. 5-27. Diffuse bullae in an Iranian mustard casualty.
This type of blistering usually occurred in relatively
heavy mustard exposures. The intensity of the blistering
was usually greater in the intertriginous areas, where
there was increased moisture. Photograph: Courtesy of
Dr. Luis Requena, Universidad Autónoma de Madrid,
Madrid, Spain.

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
97
unlike that seen with a moderate sunburn (Figure 5-
26).  After 1 to 4 days, blisters appeared on exposed
areas of the extremities (Figure 5-27).  In some pa-
tients, the blisters coalesced to form large bullae that
broke, leaving large superficial ulcers that covered in
excess of 85% of the surface area (Figure 5-28).70,71  In
patients in the Abadan attack, intertriginous areas
such as the axillae and inguinal areas became in-
tensely involved (Figures 5-29 and 5-30).  The af-
fected skin developed black and blue discoloration
and became infected in many areas.70  Other signs
and symptoms included hemoptysis, bronchitis,
pulmonary edema, severe leukopenia, thrombo-
cytopenia, and pancytopenia.  Death was usually a
result of respiratory compromise, infection, fluid
imbalance, or any combination.
The course of the signs and symptoms of mus-
tard exposure depends on dose, type of exposure
(liquid versus vapor), individual susceptibility, and
other variables such as protective equipment worn
and decontamination measures.  Therefore, symp-
toms ranging from mild, transient, respiratory symp-
toms to severe, widespread, systemic involvement
can be seen in the casualties from a single gas attack.
The clinical course of skin signs and symptoms of
mustard poisoning can be divided into five phases:
the latent phase, erythema phase, blistering phase,
necrosis phase, and healing phase.  In cases of mild
exposure to vaporized mustard (concentrations
around 1 µL/L), often the course consists only of the
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Fig. 5-29. Intertriginous (axillary) accentuation of blister-
ing in an Iraqi mustard casualty. Photograph: Courtesy
of Dr. Luis Requena, Universidad Autónoma de Madrid,
Madrid, Spain.
Fig. 5-30. Axillary accentuation of skin blistering and
erosion in an Iraqi vesicant casualty. Photograph: Cour-
tesy of Dr. U. Imobersteg, United Nations Observation
Team, Gunten, Switzerland.
latent and erythema phases without the blistering
and necrosis phases.  In moderate-to-severe expo-
sures to high concentrations of gas or to liquid
mustard (concentrations above 10 µL/L), all phases
occur and often at an accelerated pace.  In mild
exposures, the latent skin phase, in which no symp-
toms occur, may last up to 24 to 48 hours; but in
heavy exposures, skin symptoms such as itching,
burning, and erythema have been noted in as short
a time as 5 minutes.  Although there can be variabil-
ity in the clinical course, Table 5-1 summarizes the
chronology of the different phases of the acute signs
and symptoms of mustard poisoning utilizing clini-
cal data from several sources, including case histo-
ries of some Iranian mustard casualties reported by
the World Health Organization.70–73  Skin lesions

Military Dermatology
98
TABLE 5-1
SKIN MANIFESTATIONS OF MUSTARD TOXICITY
Time of Onset
Phase
(range)
Skin Signs and Symptoms
Associated Systemic Symptoms
Latent
0–6 h (0–24 h)
Itching; exposed area
Nausea and vomiting (early
can be dry and pale
onset: 19–20 min)
Erythema
6–48 h (1 h–5 d)
Itching, burning, edema, cyanosis (no
Nausea and vomiting
progression to blisters in mild cases)
Blistering
6–48 h
Increased itching, pain; blisters
(usually occurs only
usually at periphery of erythema;
with relatively high
maximal expression at day 3–4:
doses of mustard)
ulceration with trauma, infection
development in area
Necrosis
1–2 d
Upper dermis with necrosis of  vessels;
Increased incidence of infection;
severe pain associated
leukopenia at day 7–10
Healing
2–8 wk
Superficial blisters with ulceration will
heal in 2 wk without scarring; deep
ulcers heal with scarring in 4–8 wk
or remain as indolent ulcers. Post-
inflammatory hyperpigmentation
common in both
Data source: US Department of the Army. Treatment of Chemical Agent Casualties and Conventional Military Chemical Injuries.
Washington, DC: DA; 1974. Army TM 8-285: 2–7.
Fig. 5-31. Minimal residual hypopigmentation in an area
exposed to a small amount of distilled mustard.
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Fig. 5-32. Iranian mustard fatality. Note the large area of
involvement with the characteristic blistering and skin
darkening. Photograph: Courtesy of Dr. Peter Dunn,
Materials Research Laboratory, Victoria, Australia.
may vary in the severity of tissue damage and
course of healing according to the amount of mus-
tard absorbed at the site.  A mild exposure to sulfur
mustard at a testing facility resulted in a superficial
blister that healed with mild hypopigmentation
within 2 weeks (Figure 5-31).  At the opposite end of
the spectrum are the mustard casualties who re-
ceived a heavy mustard exposure and percutane-
ous absorption, which led to necrosis of the epider-
mis and dermis over large areas (Figure 5-32).  The

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
99
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Fig. 5-33. A localized mustard lesion. In this lesion, a
gradation of skin damage is apparent in a targetlike
pattern. In the central area, blistering and superficial
ulceration occurred. Surrounding the area of most in-
tense exposure is an area of intact necrotic skin and
peripherally, an area of skin darkening. Photograph:
Courtesy of Dr. Peter Dunn, Materials Research Labora-
tory, Victoria, Australia.
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Fig. 5-34. Residual hyperpigmentation in the healing
phase of a mustard lesion. Typically, the hyperpigmenta-
tion would be greatest in the areas of highest mustard
exposure. Photograph: Courtesy of Dr. U. Imobersteg,
United Nations Observation Team, Gunten, Switzerland.
TABLE 5-2
HEALING TIME OF MUSTARD BURNS
OF THE SKIN
Type of Burn
Days
Weeks
Erythema
3–7
—
Facial blisters
5–8
—
Pinpoint blisters
—
1–2
Large nonfacial blisters
—
2–4
Feet and genital blisters
—
4–6
Mustard burns with coagulation
necrosis
—
6–8
Adapted from McNamara BP. Medical Aspects of Chemical War-
fare. Alexandria, Va: Defense Technical Information Center;
1960. Report AD 240713: 18.
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Fig. 5-35. Another example of hyperpigmentation in a
mustard lesion. The mechanism of the hyperpigmenta-
tion as shown here is probable postinflammatory deposi-
tion of melanin in the dermis and is directly related to the
severity of the primary lesion. Photograph: Courtesy of
Dr. Peter Dunn, Materials Research Laboratory, Victoria,
Australia.
dose–response relationship of skin damage and
mustard dose is clearly demonstrated in Figure 5-33.
In this mustard patient, an isolated exposure to
mustard produced a graded response, from severe
necrosis of the skin in the central area of greatest
mustard concentration to a mild erythema in the
areas of lesser mustard concentration at the periph-
ery of the lesion.  The dose of mustard also has a
significant effect on the healing time (Table 5-2).74
As the blistered areas heal, characteristically a dark

Military Dermatology
100
red-brown hyperpigmentation occurs at the per-
iphery of the lesion (Figures 5-34 and 5-35).
Many organ systems are affected by mustard
poisoning.  Because the mucosal surfaces are ex-
posed in the cornea and the lining of the upper
airways, the eyes and respiratory tract are the most
frequently involved organ systems.  Eye injuries
range from conjunctivitis in mild exposures to cor-
neal damage, scarring, and iritis in severe expo-
sures (Figure 5-36).  Respiratory compromise oc-
curs in vapor exposures.  Mustard gas in concen-
trations less than that which can be detected by
smell can cause significant upper airway signs and
symptoms if inhaled over a several-day period.
Respiratory injuries range from mild inflammation
of the upper airway to bronchopneumonia, pulmo-
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Fig. 5-36. Residual corneal opacity secondary to mustard
exposure. Photograph: Courtesy of Dr. Luis Requena,
Universidad Autónoma de Madrid, Madrid, Spain.
nary edema, and, in severe exposures, adult respi-
ratory distress syndrome.  The onset of mustard
poisoning symptoms in the skin, respiratory sys-
tem, and eye often occur concurrently, beginning
within the first several hours after exposure and
peaking within the first 72 hours.  As with skin
symptoms, an early onset of eye and pulmonary
symptoms suggests a worse prognosis.  Table 5-3
shows the relative frequency of the various signs
and symptoms of Iranian mustard casualties.
Absorption of mustard through epithelial sur-
faces or ingestion of mustard via contaminated food
or water can lead to hematopoietic, neurological,
and gastrointestinal involvement.  When ingested,
mustard can cause acute nausea and vomiting.  Later
symptoms include oral and esophageal pain and
desquamation, abdominal pain, hemorrhage, diar-
rhea, and prolonged anorexia.  These symptoms can
interfere with the maintenance of adequate hydra-
tion and electrolyte balance in patients who may
already have difficulties secondary to compromise
of the skin barrier.
Neurological involvement can produce nystag-
mus, decreased motor activity, disturbed conscious-
ness, anxiety, hearing loss, motor paralysis, and
coma.61,66  Case reports of acute and delayed (3 mo
after mustard administration) neurotoxicity from
nitrogen mustard (mechlorethamine) describe
mental confusion, ataxia, amnesia, headache,
hyperreflexia, and localizing CNS signs as
additional symptoms occurring after mustard
therapy.75,76  In both cases, an increased ventricular
pressure was noted, and measures taken to de-
crease the intraventricular pressure resulted in
clinical resolution of the symptoms.  These symp-
toms may be misdiagnosed as nerve agent poison-
ing if the physician is unaware of the CNS effects of
mustard poisoning.
Mustard toxicity to the hematopoietic system can
result in myelosuppression within 7 to 15 days after
exposure.61  The resultant drop in leukocyte and
platelet counts can lead to increased susceptibility
to infection and bleeding during this period.  The
implications for therapy during bone marrow sup-
pression are significant.  An immunocompromised
patient with large areas of denuded epidermis is at
great risk for sepsis and must be followed closely
and treated when evidence of infection is discovered.
The synergistic effect of combined injuries in a
casualty must also be considered when triaging and
treating a patient.  These patients typically have
injuries secondary to conventional weapons such as
shrapnel wounds in combination with an NBC in-
jury such as mustard poisoning.  Past experience

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
101
TABLE 5-3
FREQUENCY OF SIGNS AND SYMPTOMS IN
94 MUSTARD CASUALTIES DURING THE
IRAN-IRAQ WAR
Signs and Symptoms by Organ System
Frequency (%)
Ophthalmic
Conjunctivitis
94
Blurred Vision
80
Photophobia
72
Temporary blindness
4
Skin
Erythema
86
Pigmentation
82
Blistering
69
Severe burning
12
Skin (scrotal)
Erythema
25
Edema
21
Pain
18
Ulceration
10
Respiratory
Coughing
86
Dyspnea
45
Wheezing
40
Rales
22
Adapted with permission from Balali M. Clinical and laboratory
findings in Iranian fighters with chemical gas poisoning. Arch
Belg. 1984(suppl):256.
with these casualties has revealed that the lethality
and morbidity of the combination of injuries is
higher than that expected from the added effects of
either injury alone.
Arsenical Vesicants
Chlorovinyldichloroarsine, or Lewisite (L), is an
arsenical vesicant.  It is a colorless to brown liquid
with a fruity to geranium-like odor, is more volatile
than mustard, and is soluble in organic solvents.
Lewisite is considered to be a lesser threat than
mustard and will be described briefly.
Lewisite’s mode of action in many ways appears
to mimic that of mustard.  It appears to bind to thiol
(sulfhydryl) groups on enzymes, which results in
decreased cell metabolism and death.  Clinically,
Lewisite skin injuries are similar to those caused by
mustard gas (Exhibit 5-1).  The main differences
include an earlier onset of pain (occurring within
minutes of exposure), a decreased incidence of skin
infection, and a shortened healing time (2–3 wk).
Like mustard compounds, Lewisite has an effect on
multiple systems including the eye, respiratory tract,
gastrointestinal tract, musculoskeletal system, ner-
vous system, and the hematopoietic system, among
others.  Since Lewisite is an arsenical compound
and some of its toxicity involves the arsenical group,
Lewisite therapy includes the use of the chelator
British anti-Lewisite (BAL).  Topical application of
BAL ointment within 5 minutes after exposure and
intramuscular injection of a 10% solution at a dose
of 0.025 mL/kg every 4 hours for a total of 4 to 6
injections may decrease some of the epidermal and
systemic toxicity of Lewisite.
Management of Vesicant Injury
Management of blister agent casualties can be
divided into several chronological phases: prophy-
laxis, decontamination, and treatment of lesions.
Prophylaxis consists of the use of protective cloth-
ing, avoidance of contaminated areas, and destruc-
tion of the enemy’s chemical capability.  Because
these prophylactic measures can, at best, only
minimize chemical casualties in a war rather than
eliminate them, we must be prepared to decontami-
nate and treat vesicant injuries with all effective
means at our disposal.
Decontamination
Protection for the medical personnel who are
caring for blister agent casualties is perhaps the
single most important aspect in mustard casualty
treatment.  Mustards are notorious for their persis-
tence and ability to adhere to fomites.  In 1956,
an incident of mustard poisoning occurred in
North Africa that illustrates the potential for symp-
tomatic vesicant exposure of individuals including
medical personnel, who are not exposed to the
actual chemical attack but come in contact with
contaminated casualties, their clothing, and other
fomites.  This incident involved three children who
were playing with a mustard gas shell that ex-
ploded.  During their transport to the hospital and
the initial period of care, nine contacts including a
physician, a nurse, and several medical assistants,
experienced symptoms of mustard gas poisoning
ranging from conjunctivitis to severe blistering,
nausea, and vomiting.77
Once medical providers become blister agent
casualties, they are unable to provide further care,
producing a significant degradation of the medical

Military Dermatology
102
EXHIBIT 5-1
DIFFERENTIAL CHARACTERISTICS OF LEWISITE AND MUSTARD TOXICITY
1.
Liquid Lewisite is absorbed into the skin more rapidly.
2.
Erythema appears more rapidly with Lewisite and is intense red instead of pink.
3.
The area between normal surrounding skin and affected skin is less well defined in Lewisite lesions.
The demarcation becomes clear after 2 to 3 days.  The areas of injured skin of mustard lesions are well
defined from the beginning.
4.
Edema is much more pronounced with Lewisite.
5.
Instead of the single, large blister produced by Lewisite, mustards create tiny blisters at the periphery
of the injury (“pearl necklace”) that later join to form large blisters.
6.
Maximum development of inflammatory reaction occurs earlier with Lewisite than with mustards.
7.
A Lewisite ulcer is bright red with a multitude of hemorrhages at the base.  The base of a mustard ulcer
is gray and has a single hemorrhage that is usually superficial.
8.
Secondary infections are rare with Lewisite and frequent with mustard.
9.
Pigmentation is less frequent with Lewisite-induced lesions than with mustard-induced lesions.
10.
Wounds contaminated with Lewisite change color sharply and more rapidly than those contaminated
with mustards; the tissues may show gray-black spots with a silver sheen that later turn red-brown.
Wounds contaminated with Lewisite will give off the characteristic odor of geranium for 8 hours or
longer.
11.
Wounds contaminated with Lewisite present additional problems and increased risk of systemic
effects.  The casualty notices sharp pain in the wound out of proportion to the trauma.
12.
Coagulation is poor and bleeding can become life-threatening with Lewisite injuries.  The edges of the
wound may turn pale yellow and, after a period of erythema (18–24 h), inflammatory blisters develop
in the adjacent skin.
Adapted from Augerson WS, Sivak A, Marley WS. Chemical casualty treatment protocol development—treatment
approaches. In: Lewisite. Vol 3. Air Force Chemical Defense Report. AD-B112 916, September 1986: 1–55.
unit’s ability to sustain its mission.  Therefore, it is
necessary to ensure that affected soldiers are decon-
taminated before medical treatment.  In emergent
cases, soldiers may be treated before decontamina-
tion by personnel wearing appropriate protective
gear.  However, chemical protective gear worn by
the patient or the physician poses a significant ob-
stacle in the evaluation and treatment of the patient.78
Decontamination of mustard casualties and
fomites exposed to mustard can be accomplished by
absorption and deactivation of the chemicals.  The
U.S. Army’s M13 decontamination kit contains
dusting pads of fuller’s earth, which absorbs
liquid mustard, and chloramide powder, which in-
activates mustard.  The army’s newer M258 skin
decontaminating kit contains solutions of chlora-
mide and a mixture of ethanol, phenol, and sodium
hydroxide to inactivate mustard compounds.  In the
absence of standard decontaminating kits, other
decontaminants can be used.  For example, washing
repeatedly with soap and warm water can inacti-
vate large quantities of mustard on the skin.  If
water is not available, mechanical scraping and
application of absorbents such as activated char-
coal or grain flours can be used to decontaminate
the skin.  Strong basic solutions such as ammonia
and lye, or chlorinated acids such as sodium hy-
pochlorite (household bleach), may be used to de-
contaminate fomites.
Conventional Therapy
Conventional therapy for mustard wounds con-
sists of symptomatic care (burn care) of the lesions

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
103
and their attendant symptoms.  Patients with areas
of involvement less than 20% of the total body
surface are unlikely to develop significant compli-
cations secondary to fluid and electrolyte imbal-
ances79 and can be treated in a nonacute care setting.
Dermatologists are uniquely qualified to care for
this group of patients.
After thoroughly decontaminating and cleans-
ing the involved areas, topical care is initiated.
Application of anti-infectious creams such as
Sulfamylon (mafenide acetate, manufactured by
Sanofi Winthrop, New York, N.Y.) or Silvadene
(silver sulfadiazine, manufactured by Marion
Merrell Dow, Kansas City, Mo.) inhibits bacterial
colonization and infection of the denuded skin and
should be routinely used in mustard casualties with
blisters and superficial ulcers.  Use of antibacterial
ointments and creams such as Neosporin (poly-
myxin B sulfate, bacitracin zinc, and neomycin,
manufactured by Burroughs Wellcome, Research
Triangle Park, N.C.) and bacitracin also are useful
in protecting blister wounds and promoting
reepithelialization.80  The new biosynthetic dress-
ings such as hydrogel and hydrocolloid gel acceler-
ate reepithelialization, induce faster healing, re-
duce wound contamination, and decrease pain.81
They also absorb fluid (sera) from the occluded area
into their biosynthetic matrix, and this action may
allow binding and inactivation of any free mustard
compounds from the wound.  Constant vigilance of
the denuded areas to monitor for early signs of
bacterial infection is of paramount importance.
Daily debridement and cleansing of the wounds is
necessary to avoid undue risk of developing infection.
Symptoms related to skin injury by sulfur mus-
tard include pain and itching.  Symptomatic therapy
for the itching includes potent antihistamines such
as Atarax (hydroxyzine hydrochloride, manufac-
tured by Roerig, New York, N.Y.) and Sinequan
(doxepin hydrochloride, manufactured by Roerig,
New York, N.Y.).  Topical steroids may help in areas
of severe itching resistant to antihistamines, but
caution should be used since steroids may slow
healing.  In addition to standard analgesics such as
codeine, nonsteroidal antiinflammatory drugs
(NSAIDs) such as Clinoral (sulindec, manufactured
by Merck and Co., West Point, Pa.) and Naprosyn
(naproxen, manufactured by Syntex, Humacao, P.R.)
help relieve pain and may reduce inflammation.
Because NSAIDs can adversely affect renal func-
tion, careful consideration should be given before
utilizing them in blister patients, who are suscep-
tible to fluid and electrolyte imbalances.
Potential New Therapies
Research into new treatments for mustard gas
injury has focused on two areas: deactivating the
compounds before they can cause significant dam-
age and reducing the mustard’s deleterious effects.
Both approaches require rapid application for best
results.
Inactivation of Mustard Compounds.  Because
mustard reacts with tissue within minutes of expo-
sure, specific therapy designed to inactivate the
chemical or to slow its rate of absorption must be
initiated within minutes to be maximally effective.
Most casualties, however, appear to continue to
absorb free, nonfixed mustard compounds from
their skin surface or from mustard-contaminated
fomites, so therapy specifically used to inactivate
mustard externally or internally may be useful long
after the initial mustard exposure.
Studies have shown that thiols or compounds
containing sulfhydryl groups decrease the toxic
effects of mustard.82,83  Their action, in part, appears
to be mediated through the direct inactivation of
mustard compounds.  The list of the thiols that have
been used is long but only a few thiol compounds
are readily available currently.  A thiol compound
that has been used orally in the past to treat
acetominophen toxicity is Mucomyst (acetyl-
cysteine, manufactured by Apothecon, Princeton,
N.J.).  That regimen includes an oral loading dose of
140 mg/kg followed by doses of 40 mg/kg every 4
hours for a total of 17 doses.  The drug is relatively
innocuous, with side effects including nausea, vom-
iting, and, rarely, urticaria.  Another thiol that is
available for parenteral use is sodium thiosulfate.
Currently, it is used to treat cyanide poisoning.
Dosage is 50 mL of a 25% solution (12.5 g) given
intravenously over 10 minutes.  At this dose, the only
significant side effect is that of hypovolemia sec-
ondary to an osmotic diuresis caused by the drug.
Theoretically, thiols could also be used topically
in wounds and areas where routine decontamina-
tion may be contraindicated.  The only drawback to
these drugs is that they do not react with mustard
already bound to tissue; therefore, their ideal use
would be as a pretreatment.  Studies have shown
that thiols have a systemic protective effect even
when given up to 15 minutes after exposure.83  Re-
search in Germany in 1950 utilized iontophoresis of
a cysteine hydrochloride solution on human sub-
jects exposed to varying amounts of sulfur mus-
tard.84  The results demonstrated that the therapy,
which was begun after erythema developed, re-

Military Dermatology
104
sulted in significant amelioration in the clinical
course of blister formation and healing.
Other substances that could inactivate mustard
compounds when applied topically include albu-
min, collagen, powdered milk, gel or collagen dress-
ings, and activated charcoal slurry, all of which
have an affinity for mustard agents and will bind
and inactivate them.66
Reduction of Untoward Reactions to Mustard.
Two therapies greatly reduce the effects of mustard
compounds on the skin62: cooling the skin and using
trichloroacetic acid crystals to prevent desiccation.
Cooling the skin with ice bags appears to inhibit
vesication of mustard-exposed skin.  The physiol-
ogy of the inhibition of mustard toxicity with cool-
ing is unknown but may be related to decreased
transport through the skin and into the bloodstream,
or a decrease in the rate of mustard reaction with
substrates within the tissue at lower temperatures.
The application of trichloroacetic acid crystals after
the erythema of mustard exposure develops pre-
vents vesication.  Dermatologists routinely use 20%
to 50% solutions for cosmetic peels without compli-
cation; however, trichloroacetic acid at 50% con-
centrations and above can cause significant dermal
scarring85 and the medical officer should use great
caution in considering this therapy in a soldier who
already has significant compromise to the integrity
of the epidermis.
Other readily available drugs that have been
reported to ameliorate the toxic effects of mustards
on the skin by interfering with primary mustard
reactions at the molecular level include vitamin E
(antioxidants), Mandelamine (methenamine
mandelate, manufactured by Parke-Davis, Morris
Plains, N.J.), and niacin.66
Treatment of Complications
Complications from exposure to mustard com-
pounds arise from (a) systemic toxicity of the ab-
sorbed mustard and (b) direct insult to the epider-
mal barrier.  Damage to the epidermal barrier results
in increased fluid loss from the body and electrolyte
imbalance.  With areas of involvement greater than
20%, the casualty must be evacuated to a hospital
capable of treating burn patients, if possible.  If the
area of epidermal barrier loss is less than 20%, the
patient can be managed in a nonacute care setting.79
However, the patient must be carefully monitored
to avoid the complications of hypovolemia and
electrolyte imbalance.  Another complication asso-
ciated with epidermal barrier loss in mustard casu-
alties is the increased incidence of cutaneous and
systemic infection.  Therefore, mustard casualties
must be monitored closely for signs and symptoms
of infection.  If an infection is suspected, blood and
the appropriate tissue cultures must be obtained
and the patient placed on antibiotics.  Typically,
two of the most common pathogens in burn patients
are Staphylococcus aureus and Pseudomonas aeruginosa;
therefore, broad-spectrum antibiotics should be
used.  The patients should not be placed on prophy-
lactic systemic antibiotics because this only results
in the colonization of the wounds with drug-resis-
tant organisms.
The suppressive effect of mustard on the im-
mune system can increase the likelihood of cutane-
ous and systemic sepsis.  Leukopenia secondary to
mustard exposure typically is the greatest approxi-
mately 7 to 10 days after mustard exposure.  At this
time, the patients are most likely to become septic,
and close monitoring during this period is
paramount.
As noted earlier, mustard patients usually de-
velop symptoms concurrently in several organ sys-
tems after exposure.  When the skin is involved in
mustard toxicity, the eyes, respiratory system, gas-
trointestinal system, hematopoietic system, heart,
and central nervous system can also be affected.
Although treatment of the effects of mustard on
these systems is beyond the scope of this chapter,
the same basic principles of skin therapy can be
applied to the treatment of mustard toxicity in these
systems.  A good review of the treatment of mustard
casualties is available elsewhere.66
When triaging and treating chemical casualties,
the synergistic effect on the morbidity and mortal-
ity of casualties with injuries that involve a combi-
nation of conventional and NBC injuries must be
kept in mind.
Halogenated Oximes
Phosgene oxime (CX) is a colorless liquid or solid
(melting point 40°C) that has an intense, disagree-
able odor.  It belongs to a class of chemical agents
called urticants or nettle gases.  It should not be
confused with phosgene (CG), which is primarily a
choking agent and exerts its effects mainly in the
upper airways and lung.  Phosgene oxime’s pri-
mary sites of action are the skin, eyes, and upper
respiratory system.  In these areas, it is extremely
irritating to the epidermal and mucosal tissues.86  Its
mechanism of action is not completely understood,
but studies suggest that it is an alkylating agent and

Cutaneous Reactions to Nuclear, Biological, and Chemical Warfare
105
its toxicity is mediated via binding to sulfhydryl
and NH2
 groups.  The action on the skin, like
Lewisite, is immediate, with development of irrita-
tion and burning suggestive of the reaction to sting-
ing nettle.  With the characteristic pain that is felt
almost immediately with exposure, a white area
surrounded by erythema develops.  An urticaria-
like edema ensues within the first hour, followed by
blistering after 24 hours.  The skin can become
necrotic, and healing may take up to 3 months.86,87
Specific treatment consists of immediate decon-
tamination with copious amounts of water and any
mild base (buffer) such as sodium bicarbonate solu-
tion.  After initial therapy, symptomatic burn
therapy is indicated.
Nerve Agents and Cyanides
Although nerve agents (tabun [GA], sarin [GB],
soman [GD], and VX) and the cyanides (hydrogen
cyanide [AC] and cyanogen chloride [CK]) are consid-
ered threat agents by the allied forces, their cutaneous
effects are minimal and will be described briefly.
The cutaneous effects of nerve agents are mostly
limited to the areas of exposure.  In these areas,
nerve agent casualties may develop increased sweat-
ing secondary to the muscarinic-like effect of the
agents on eccrine sweat gland innervation.86  The
muscarinic effects of nerve agents on the erector pili
muscles may cause contraction and the develop-
ment of “goose-bumps” on exposed areas.  Fascicu-
lations of the striated muscle underlying the ex-
posed area can occur as a result of the nicotinic-like
effects of the absorbed nerve agents.  Tabun and
sarin have caused a cyanotic redness and edema of
the skin, respectively.66
Treatment of nerve agents consists of the admin-
istration of atropine to inhibit the muscarinic effects
of the agent, and pralidoxime chloride (2-PAM) to
reactivate acetylcholinesterase.
The cyanides (blood agents) act by inactivating
cytochrome oxidase, which prevents the cells from
utilizing oxygen.  They are acutely lethal, causing
apnea, convulsions, and death within minutes.
Because the cells cannot utilize oxygen, the blood
remains oxygenated and the mucosal membranes
and skin of a blood agent casualty appear dark red.
Although this sign is nonspecific, it is very sugges-
tive of cyanide poisoning in the context of convul-
sions and acute loss of consciousness.  Acutely, the
only effective therapy is amyl nitrite inhalation,
which generates methemoglobin, which, in turn,
binds cyanide.  After an intravenous line is estab-
lished, sodium thiosulfate can be given.  Sodium
thiosulfate reacts with cyanide to form thiocyanate,
which can be excreted by the kidneys.
The threat of chemical warfare today is real and
medical officers must be prepared to treat chemical
casualties if the need arises.  In the past, this area
has been neglected; however, the possibility that
U.S. military forces could sustain a substantial num-
ber of nuclear, biological, and chemical (NBC) casu-
alties in future conflicts is very high.  Therefore, it is
incumbent on us, as physicians, to ensure that we
are capable of rendering the best care possible.
In preparation for cutaneous lesions found in
NBC casualties, medical personnel should under-
stand some fundamental principles that have been
noted in this chapter:
• Basic supportive measures for NBC casual-
ties are based on the same medical prin-
ciples, such as wound and burn care, that are
already contained in the present literature
and known to most physicians.
• There is an overriding need to protect medi-
cal personnel in an NBC environment to
SUMMARY
ensure they do not become casualties and
thus severely hinder the medical team’s ca-
pabilities.
• Although supportive care of NBC casualties
requires no NBC training, specific therapy
with NBC antidotes and decontamination of
patients requires specialized knowledge
gained only through extensive review of
medical literature or through attendance of
military medical NBC courses.  Therefore,
military physicians should actively prepare
for the possibility that they may treat NBC
casualties by reading the NBC literature and
attending NBC training courses.
• If placed in a situation with an NBC threat
such as that of the Persian Gulf War, the
medical officer should immediately evalu-
ate the preparedness of his medical unit to
treat casualties.  This evaluation should in-
clude the availability of specific NBC anti-
dotes such as sodium thiosulfate for cyanide

Military Dermatology
106
poisoning, NBC protective gear for the medi-
cal personnel, and decontamination supplies
and equipment for area and patient decon-
tamination.
• Triage procedures will be complicated by
NBC casualties.  Medical officers should be
capable of triage and treatment of combined
injuries, in which patients have conventional
wounds such as blast injury in addition to
exposure to chemical or biological agents.
Often these patients would be treatable if
they had only one type of injury but would
be expectant (ie, seriously injured or with
poor chance of survival) with the combina-
tion of injuries.
• NBC doctrine often targets rear areas, where
hospitals and other medical facilities are lo-
cated.  Therefore, medical officers should be
aware of the enemy’s NBC doctrine and
should be prepared for movement and de-
contamination of medical facilities if the
threat is high.
Future wars involving NBC undoubtedly will be
very different from those since World War I.
However, if physicians, nurses, and other medical
personnel are prepared and cognizant of the threat,
the impact of an enemy NBC offensive on
the combat effectiveness of U.S. forces will be
minimized.
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Allergic and Irritant Contact Dermatitis
111
Chapter 6
ALLERGIC AND IRRITANT CONTACT
DERMATITIS
MARK A. CROWE, M.D.* AND WILLIAM D. JAMES, M.D.†
INTRODUCTION
ALLERGIC CONTACT DERMATITIS
Allergic Contact Dermatitis due to Plants: Offending Agents
Allergic Contact Dermatitis due to Plants: Geographical Distribution
Other Allergic Contact Dermatitides
IRRITANT CONTACT DERMATITIS
Alkalis and Acids
Hydrocarbons
Diethyltoluamide Dermatitis
Chloracne
Irritant Contact Dermatitis due to Plants
OTHER CONTACT DERMATITIDES
Mechanical Injury
Pharmacological Reactions
Contact Urticaria
CONTACT DERMATITIS BY ANATOMICAL SITE
Eyelids
Face
Neck
Trunk
Abdomen
Groin
Hands and Feet
PATCH AND USE TESTING
TREATMENT
Removal of the Irritant
Nonsteroidal Therapy
Steroids
SUMMARY
*Lieutenant Colonel, Medical Corps, U.S. Army; Dermatology Service, Madigan Army Medical Center, Tacoma, Washington  98431-5000;
formerly, Walter Reed Army Medical Center, Washington, D.C.  20307-5001
†Colonel, Medical Corps, U.S. Army; Chief, Dermatology Service, Walter Reed Army Medical Center, Washington, D.C.  20307-5001

Military Dermatology
112
INTRODUCTION
One of the most frequent dermatologic disorders
requiring both outpatient and inpatient therapy
that arises during military conflicts is dermatitis
caused by contact with exogenous materials.  In
some regions of the world, contact dermatitis pro-
duces a significant proportion of those battlefield
casualties that are dermatologic in nature.1  During
World War II, the Office of The Surgeon General
reported 75,371 hospital admissions for treatment
of contact dermatitis, with over 99% of those sol-
diers being returned to duty.1  Under wartime con-
ditions, inadequate facilities may limit proper per-
sonal hygiene, and the exposure to common chemical
irritants and allergens can be prolonged.
During World War II, toxicodendrons (poison
ivy and related plants) were the most frequent cause
of plant dermatitis,2 and reactions to topical thera-
pies were also exceedingly common.3–5  In 1944,
Woolhandler6 reported that over 10% of his military
dermatologic practice was related to contact der-
matitis, with fungus infections being the only der-
matologic disorder that was more frequent.  After
the war, a report7 of cutaneous diseases in U.S.
Army Air Force personnel revealed that contact
dermatitis to greases, solvents, and zinc chromate
was the most common skin disease encountered.
In this population, contact dermatitis was more
frequent than pyodermas, fungus infections, or
verrucae.
More recently, Allen reported that contact der-
matitis was infrequent among troops in Vietnam
but at times was an important source of discomfort
and disability.8  Although contact dermatitis re-
sulted in only a small percentage of the total num-
ber of clinic visits to the 95th Evacuation Hospital in
Da Nang, Vietnam, it was listed as one of the top ten
dermatologic conditions treated.8  Contact dermati-
tis also caused many minor casualties who were
treated at battalion aid stations and returned to
duty.  Much of the decrease (from World War II
rates) in the rate of contact dermatitis casualties
referred to the evacuation hospital in Vietnam was
believed to be related to the development of antibi-
otics, steroid preparations, and nonsensitizing
creams after World War II.  Thus, there is extensive
information suggesting that contact dermatitis re-
sults in a constant drain on troop strength and
readiness.8  In addition, a delay in diagnosis may
result in the prolonged loss of a soldier to a disorder
that can be treated easily and effectively.
With the exception of phytodermatitis (plant-
related dermatitis), contact dermatitis related to
individual contactants rarely causes a significant
impact on troop strength.  The most likely situation
in which contact dermatitis might produce signifi-
cant numbers of casualties is if large numbers of
soldiers were exposed to the same chemical agents
(eg, mass exposure of soldiers in Vietnam to insect
repellents and defoliants).  Additional casualties
can be avoided if the causative agent is identified
and further exposure prevented.
In general, because dermatologic diagnoses tend
to rely heavily on visual clues, the clinical history is
less important to dermatologists than it is to most
subspecialists.  However, in the field of contact
dermatitis, a detailed history is extremely impor-
tant.  When contact dermatitis is suspected and the
contactant is not obvious, the medical officer must
specifically query the soldier regarding environ-
mental exposures.  An occupational exposure his-
tory should include a detailed description of daily
activities with emphasis on exposures to materials
such as paints, dyes, cleaning solutions, soaps, and
other materials used in the work environment.  Often
a site visit is productive.  The soldier should be
asked whether symptoms improve or worsen over
weekends or vacations.  It is important to inquire
into exposures in the home and during recreational
activities, exposures related to hobbies, and expo-
sures from the use of any topical or oral therapy.
This chapter will emphasize potential sources of
contact-related dermatitis in a battlefield environ-
ment.  The modern U.S. Army includes support
personnel who perform essentially every occupa-
tion encountered in the civilian sector, from combat
laundry to the maintenance of sophisticated hard-
ware.  Materials other than plants that have re-
sulted in contact dermatitis will be discussed if they
have particular significance or are unusual and
enlightening causes of contact dermatitis.  Several
excellent texts cover the topic of contact dermatitis
in great detail.9–11

Allergic and Irritant Contact Dermatitis
113
ALLERGIC CONTACT DERMATITIS
Contact dermatitis is generally subdivided into
allergic contact dermatitis (ACD) and irritant con-
tact dermatitis.  ACD is an acquired, type IV hyper-
sensitivity response generated after exposure to an
allergen.  Not everyone will react to the allergen,
and the allergic response does not occur during the
primary exposure unless the soldier has been ex-
posed to a closely related compound in the past.
Type IV hypersensitivity reactions consist of two
distinct phases: the induction phase and the elicita-
tion phase.  During the induction phase, an aller-
gen, or hapten, penetrates the epidermis where it is
picked up and processed by an antigen presenting
cell.  Antigen presenting cells include Langerhans
cells, dermal dendrocytes, and macrophages.  The
processed antigen is then presented to T lymphocytes,
which undergo blastogenesis in the regional lymph
nodes.  One subset of these T cells differentiates into
memory cells, while others become effector T lym-
phocytes that are released into the bloodstream.
The elicitation phase occurs when the sensitized
individual is reexposed to the antigen.  The antigen
penetrates the epidermis and is again picked up and
processed by an antigen presenting cell.  The pro-
cessed antigen is then presented to the circulating
effector T lymphocytes, which, in turn, produce
lymphokines.  These lymphokines mediate the pro-
duction of the inflammatory response that is char-
acteristic of an ACD.
As a type IV hypersensitivity reaction, ACD has
symptoms that usually develop hours to days after
exposure.  The dermatitis associated with allergic
reactions is frequently very pruritic and may ex-
tend beyond the borders of the region exposed to
the allergen.  ACD is generally much more edema-
tous and vesiculation is much more common than
that seen in an irritant contact dermatitis.  Relative
to irritant contactants, very small quantities of
allergens are required to stimulate allergic derm-
atitis.  The most common causes of ACD are
toxicodendrons (poison ivy, oak, or sumac), p-
phenylenediamine, nickel, rubber compounds,
ethylenediamine, potassium dichromate, and
thimerosal.9
Patch testing can often confirm the etiology of an
ACD.  By placing standard concentrations of com-
mon allergens or specific ingredients in an impli-
cated product on the skin and leaving them covered
for 2 days, one can identify the cause of the derma-
titis.  If the soldier has been previously sensitized to
one of the agents under occlusion, the reexposure
will produce the elicitation phase of a type IV hy-
persensitivity reaction resulting in pruritus,
erythema, and vesiculation.
Irritant dermatitis, which is also called primary
irritant dermatitis, is due to a nonallergic reaction
resulting from exposure of the skin to an irritating
substance and is much more common than ACD.
Examples of irritant contact dermatitis include the
reactions that result from contact with acids; alka-
lis; and metal salts such as cyanides of calcium,
copper, mercury, nickel, silver, and zinc.  Contact
with the halogens and many hydrocarbons also
produces irritant dermatitides.  With a high-enough
concentration, an irritant will cause dermatitis in
any individual and the reaction may follow the first
exposure.  Significantly higher concentrations are
required to induce irritant contact dermatitis than
are required to stimulate an allergic reaction.
Soldiers with an irritant contact dermatitis may
develop symptoms within minutes of the exposure.
The dermatitis is often localized to the site of expo-
sure and a burning sensation is more common than
the intense pruritus often associated with ACD.
The severity of the dermatitis depends on the con-
centration and dwell time of the irritant as well as
the site and condition of the skin.  Areas of the body
with thick, dry skin are the most resistant to the
effects of irritants.
Allergic Contact Dermatitis due to Plants:
Offending Agents
The family Anacardiaceae probably accounts for
more cases of ACD than all other plant families
combined.  It is composed of about 70 genera and
600 species of trees, shrubs, and vines that are found
mostly in the tropics but with some species in tem-
perate regions.  Genera of the family Anacardiaceae
include Anacardium, Gluta, Mangifera, Semecarpus,
and Toxicodendron.  Poison ivy, poison oak, and
poison sumac were classified in the genus Rhus
until recently, when they were reclassified to the
genus Toxicodendron.  For example, poison ivy is

Military Dermatology
114
now termed Toxicodendron radicans rather than Rhus
radicans.  True members of the genus Rhus rarely
cause contact dermatitis.  The term rhus dermatitis
is still commonly encountered and refers generi-
cally to ACD produced by exposure to poison ivy,
poison oak, or poison sumac.
The antigen in these plants is an oleoresin known
as urushiol, from the Japanese word kiurushi, mean-
ing sap.12  In poison ivy and poison oak, the active
agent in urushiol is pentadecylcatechol.  Slight
molecular variations in catechols may result in large
variations in the degree of antigenicity.  Poison ivy
and poison oak sap contain a near maximal percent-
age of these allergenic catechols.13
Prevention of ACD begins by educating the sol-
dier in the recognition of common plants that may
produce eruptions.  The soldier should keep ex-
posed skin to a minimum when in areas of high risk
for exposure to toxicodendrons.  If exposure to
contactants is suspected, the exposed skin should
be washed thoroughly with soap and water as soon
as feasible.  Soldiers returning from an area en-
demic for toxicodendrons should shower with soap
to remove residual allergens.  Soldiers should also
be aware that plant resins on clothing, field jackets,
and equipment can produce ACD many months
after it was deposited.
Poison Ivy and Poison Oak
Plants in the genus Toxicodendron produce a large
percentage of the cases of phytodermatitis.  The
genus Toxicodendron includes two species of poison
ivy, Toxicodendron rydbergii, a nonclimbing shrub,
and T radicans, which can be either a shrub or a
climbing vine.  In addition, there are many subspe-
cies of T radicans (Figures 6-1 and 6-2).  The genus
Toxicodendron also includes western poison oak (T
diversilobum—Figure 6-3), eastern poison oak (T
toxicarium—Figure 6-4), and poison sumac (T vernix).
These plants do not contain resin canals and conse-
quently uninjured plants do not induce a dermati-
tis: the plant must be injured or bruised before
oleoresin containing the urushiol can contact the
skin.  Smoke from burning plants can cause a severe
dermatitis.  All parts of the plant are antigenic and,
under controlled conditions, over 70% of the popu-
lation in the United States will react to the urushiol
in poison ivy and oak.14  Vernacular names for poi-
son ivy include (English) climbing or three-leaved
ivy, climath, trailing or climbing sumac, mercury,
black mercury vine, markry, mark-weed, picry;
(French) sumac radicant, lierre toxique; and (German)
Kletter-Gift Sumach, Rankender Sumach, and Gift Efeu.
Vernacular names for poison oak include (English)
western or Pacific poison oak, eastern poison oak;
(French) sumac irrégulièrement lobé; and (German)
Verschiedenlappiger Sumach.10
Oleoresin adheres to skin, clothes, equipment,
and pets.  Contaminated clothes can cause the erup-
tion to recur even after prolonged storage.  Oleo-
resin on the hands can be unintentionally spread to
the face and genitals resulting in very severe erup-
tions (Figures 6-5 and 6-6).  Blister fluid, on the
other hand, does not contain urushiol and will not
result in further contamination of the affected sol-
dier or care providers.
The oleoresin that exudes from damaged areas of
poison ivy, poison oak, and poison sumac will fre-
quently form into a black deposit on the leaves,
stems, or trunk.  The patient seen in Figure 6-7
developed a characteristic dermatitis after expo-
sure to oleoresin from poison ivy.  In addition, the
oleoresin on the skin darkened into a black,
enamellike deposit.  This characteristic of the oleo-
resin to darken on exposure to the air is found in
many other members of the Anacardiaceae family.
Beaman15 reported sleeping on a foundation of poles
in an area of rocky terrain in Malaysia.  The next
morning he discovered the poles, which were most
likely from a species of Gluta that had been cut by
his guide, had developed obvious black deposits.
Dermatitis developed within 15 to 20 hours.  It is
this same attribute of the oleoresin that makes it
useful as a marking agent when obtained from
Semecarpus anacardium (the India marking nut tree)
and that produces the color associated with the
lacquer of the Japanese lacquer tree (T verniciflua).
Leaves from plants suspected of being related to
poison ivy can be crushed between sheets of white
paper.  The leaves are discarded and the oleoresin
on the paper allowed to dry for a few minutes.
Oleoresin from Toxicodendron should darken mark-
edly.16  Although no one characteristic is reliable for
identifying Toxicodendron, the finding of dark black
deposits on damaged plants and trees should alert
the physician to the distinct possibility that the sap
or resin can produce ACD.
Signs and Symptoms.  Clinically, the typical
urushiol eruption is manifested by erythema, edema,
papules, vesicles, and bullae (Figure 6-8).  Linear
streaks are characteristic, but not always noted.
Daily contact with the plant may result in an erup-
tion 9 to 14 days after initial contact even in some-
one not previously sensitized.14  In previously sen-
sitized individuals the eruption can occur within
hours to several days of exposure.  Different parts of
the body are more sensitive to urushiol or may be

Allergic and Irritant Contact Dermatitis
115
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Fig. 6-1. Toxicodendron radicans subsp radicans. Poison ivy
species found commonly in the eastern United States.
The mature plant has leaflets that are usually unlobed
and ovate (widest below the center). It climbs by aerial
rootlets. Reprinted courtesy of J. D. Guin, Department of
Dermatology, University of Arkansas, Fayetteville, Ark.
Fig. 6-2. Toxicodendron radicans subsp radicans. Poison ivy
species found commonly in the eastern United States.
Reprinted courtesy of J. D. Guin, Department of Derma-
tology, University of Arkansas, Fayetteville, Ark.
Fig. 6-4. Eastern poison oak (Toxicodendron toxicarium).
Much smaller than western poison oak, this plant is
found primarily in the southeastern United States. It is a
small subshrub that does not climb, does not have aerial
rootlets, and is found in sandy soil with poor mineral
content. Leaflet morphology is extremely variable and
may closely resemble white oak leaves. Reprinted cour-
tesy of J. D. Guin, Department of Dermatology, University
of Arkansas, Fayetteville, Ark.
Fig. 6-3. Western poison oak (Toxicodendron diversilobum).
This plant grows in a variety of soil types in California,
Oregon, and Washington. It may develop aerial roots and
climb, although it is often seen as a shrub. The fruit is the
largest of any of the toxicodendrons and often dangles
like ripe cherries. The leaflets have rounded lobes resem-
bling the leaves of a live oak. Reprinted courtesy of J. D.
Guin, Department of Dermatology, University of Arkansas,
Fayetteville, Ark.

Military Dermatology
116
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Fig. 6-5. Rhus dermatitis. Oleoresin may be easily spread
from the hands to other sites of the body, as in this
patient. Severe facial dermatitis may also result when
sensitized soldiers are exposed to smoke from burning
toxicodendrons.
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Fig. 6-6. Rhus dermatitis involving the genital region.
Oleoresins on the hands may be spread to this area of thin
skin during the process of voiding, with unfortunate
results. Severe perianal dermatitis may result when leaves
are used to wipe the area following defecation. Reprinted
courtesy of L. Lieblich, Department of Dermatology, State
University of New York Downstate.
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Fig. 6-8. Typical rhus dermatitis with linear vesicles,
erythema, edematous papules, and bullae. The allergen
that produces this dermatitis is an oleoresin, urushiol.
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Fig. 6-7. Rhus dermatitis. The black deposit is residual
oleoresin that has turned black on exposure to the air.
Many members of the family Anacardiaceae possess this
characteristic. Damaged trees and shrubs may develop
black deposits as oleoresin oxidizes on exposure to the air.

Allergic and Irritant Contact Dermatitis
117
exposed at different times, resulting in the false
impression that the eruption is spreading or is in-
fectious.  On rare occasions Toxicodendron exposure
can result in urticaria or an erythema multiforme
pattern.14
Field Identification.  Several features of poison
ivy, oak, and sumac may be useful in field identifi-
cation.  All species of poison ivy and oak have three
leaflets per leaf (see Figures 6-1 through 6-4).  Poi-
son sumac contains 7 to 13 leaflets per leaf.  The leaf
stalk (petiole) has a groove where it attaches to the
branch.  Blooms and fruits arise in the angle be-
tween the leaf and the branch.  Toxicodendrons
change color earlier than most other plants.  Old
flower and fruit stalks often persist through the win-
ter and the following growing season.  Young leaves
are frequently reddish in color and the mature fruit of
toxicodendrons is tan or cream colored.13
The plant family Anacardiaceae has many other
species that contain urushiol and also cross-react
with poison ivy.  The following plants are discussed
because they represent a common source of sensiti-
zation in certain regions of the world or are of
historical interest.
Poison Sumac
Poison sumac (T vernix, T pinnatum, Rhus venerata)
is a shrub or small tree usually only 2 to 3 m tall but
occasionally as tall as 7 m.  Compound leaves are up
to 40 cm in length with 7 to 13 oval leaflets.  Poison
sumac is highly antigenic, resulting in severe con-
tact dermatitis in sensitized soldiers.  It is a native
plant of eastern North America, growing in swampy
areas.  A related species, T succedanea, known as the
wax tree, is native to Japan and China.  T succedanea
is used as a source of lacquer in Indochina and as a
source of wax in Japan.  Vernacular names include
(English) poison sumac, poison dogwood, swamp
sumac, poison elder; (French) sumac vernig, bois
chandler; and (German) Giftsumach.10,13,14
India Marking Nut Tree: “Dhobie Mark” Dermatitis
During World War II in the China-Burma-India
theater of operations, service personnel developed
an epidemic of patchy dermatitis caused by expo-
sure to the India marking nut tree.  The dermatitis
consisted of circumscribed patches of intense
pruritus, vesiculation, oozing, and, sometimes, a
more chronic eczematoid reaction.17
In India and Malaysia, the black sap of the
Semecarpus anacardium (also called the Ral or Bella
gutti [bhilawa]) tree is used as marking ink, hence
its common name, marking nut tree.  A pin is used
to pierce the hard capsule of the nut and enough
brown or black fluid is obtained to place a relatively
permanent identifying mark on garments.  Further
investigation at the time revealed that this tree is a
member of the Anacardiaceae family and is related
to poison ivy.  Shortly after their arrival, service
personnel began having their clothes laundered by
native washermen (dhobies).  The service person-
nel developed patches of dermatitis at the site of the
laundry (dhobie) mark.17
Fifteen to twenty percent of personnel whose
clothes were laundered by dhobies developed
dhobie mark dermatitis.17  Most soldiers who react
to poison ivy will develop an allergic dermatitis to
the nut of the marking nut tree and to other plants
and trees in this family.  Before World War II, this
condition had been known as dhobie itch or
washerman’s itch and was believed to result from a
tropical dermatophytosis.  In India and other coun-
tries, the terms dhobie itch and tinea cruris are
sometimes used interchangeably.17  However, it
was never proved that cutaneous fungal infections
resulted from having clothes washed by dhobies.
Dhobie itch or dhobie mark dermatitis is a true ACD
resulting from contact with a marking fluid that
contains allergens very similar to those seen in
poison ivy.17
The marking nut tree is a moderate-sized decidu-
ous tree with large alternate, leathery oblong leaves
measuring 20 to 60 cm long and 10 to 25 cm across.
Flowers are small and greenish white, on stout,
branching panicles about the same length as the
leaves.  The fruit is a 2.5-cm-long, smooth, black nut
(Figure 6-9).  The tree is native to India.  Two related
species (S forstenii and S heterrophylla) located in
Java and Sumatra are also potent sensitizers.  About
60 related species are distributed from India to
Ceylon, Burma, Thailand, Indochina, Taiwan, Aus-
tralia, Micronesia, the Solomon Islands, New
Caledonia, and Fiji.  Contact dermatitis can result
from contact with the stem, small branches, leaves,
or juice of the nut.  Vernacular names include (En-
glish) marking nut tree, bhilawa tree; (French)
anacarde d’orient; and (German) Tintenbaum.1,10,17,18
Japanese Lacquer Tree
The Japanese lacquer tree (T verniciflua) is 15 to
20 m tall with 25- to 50-cm-long leaves composed of
7 to 13 oblong or oval leaflets (Figure 6-10).  The
tree is native to Japan and central and western

Military Dermatology
118
China.  Its sap is used as lacquer in varnishes for
floors and for lacquering boxes, tea pots, and furni-
ture.  “Lacquer dermatitis” affects areas of the body
that come in contact with a lacquered surface.  After
World War II, American soldiers who were sensi-
tive to poison ivy developed dermatitis after han-
dling Japanese rifles that had been lacquered, and
12 American officers developed dermatitis on their
arms from leaning on a recently varnished bar in
Japan.19  There are occasional reports of dermatitis
to lacquered furniture even hundreds of years after
application.  Vernacular names include (English)
Japanese lacquer tree, varnish tree; (French) sumac a
laque, vernis urai; (German) Lacksumach; (Japanese)
urushi; and (Chinese) qi su.10,20,21
Mango
The mango (Mangifera indica) is a large tropical
tree growing to heights of 15 to 18 m.  The mango
has wide, spreading branches, and produces a deli-
cious greenish, yellowish, or reddish ovoid fruit
measuring 10 to 20 cm in length (Figure 6-11).  Some
35 species exist and are widely distributed natu-
rally and through cultivation in Southeast Asia,
India, Malaysia, and Burma.  It is also extensively
cultivated in tropical regions of southern Florida,
Hawaii, and California, as well as Central and South
America.  Contact dermatitis develops most com-
monly in the perioral region (Figure 6-12) and on
the hands and results from exposure to the peel,
not the juice.  The mango is eaten raw or made into
jams, jellies, pickles, mango powder, and chutney.
Timber is used for the production of furniture
and boats, and for planking and plywood.  The
timber is known in some areas as asam.  Vernacular
names include (English) mango tree; (French)
manguier; (German) Mangobaum; and many varia-
tions of mango such as mangii, mangga, manga,
maga, and mangka.10,11
Cashew
The cashew (Anacardium occidentale) is a small (4–
6 m) tree with a thick, crooked trunk that is native to
Central America and northern South America and
is cultivated throughout the tropical regions of the
world and India.  It is primarily cultivated for its
nut, oil, and gum.  Its timber, known as acajou, is
used in house and boat building in South America.
The wood produces a yellow gum that can blister
the skin.  Cashew sap blackens on exposure to the
air and can produce contact dermatitis.
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Fig. 6-9. The nut of the marking nut tree or bhilawa of
India (Semecarpus anacardium). Resins were removed by
piercing the nut with a needle. As with other members of
the family Anacardiaceae, the fluid turns black after
exposure to the air. The black resin was used by
washermen to mark clothing. This resulted in contact
dermatitis at the site of the laundry mark. Reprinted
courtesy of J. D. Guin, Department of Dermatology, Uni-
versity of Arkansas, Fayetteville, Ark.
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Fig. 6-10. Japanese lacquer tree (Toxicodendron verniciflua).
The tree grows up to 20 m in height and is native to Japan
and central and western China. Leaves are odd-pinnate.
Reprinted courtesy of J. D. Guin, Department of Derma-
tology, University of Arkansas, Fayetteville, Ark.

Allergic and Irritant Contact Dermatitis
119
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Fig. 6-11. Mango tree (Mangifera indica). Mango trees are
widely distributed naturally and through cultivation.
They grow to 18 m in height. Reprinted courtesy of J. D.
Guin, Department of Dermatology, University of Arkan-
sas, Fayetteville, Ark.
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Fig. 6-12. Allergic contact dermatitis after consumption
of a mango fruit. Dermatitis results from exposure to
the peel, not the juice. Reprinted courtesy of R. Horn,
Ithaca, N.Y.
Apples from the cashew may be red or yellow,
and the cashew nut dangles from the apex.  The
cashew “apple” is not a fruit, but the thickened stem
at the base of the cashew nut.  The cashew nut is
innocuous unless contaminated with the shell oil;
smoke from fires used to roast the freshly fallen
nuts may be irritating to the skin and mucous mem-
branes.  The gum is used as a varnish to protect
books and woodcarvings.  Dermatitis may result
from contact with all parts of the cashew tree except
the roasted nut.  Vernacular names include (En-
glish) cashew nut tree; (French) anacardier (noix et
pomme d’acajou); and (German) Kaschu, Acajuba,
Acajoubaum, and Westindischer Nierenbaum.10,22
Ginkgo
The ginkgo (Ginkgo biloba) is now mostly grown
as an ornamental tree in yards or along roadways in
temperate regions.  It is widely cultivated in Japan
and is grown in Asia around Buddhist temples.  The
tree is sparsely branched and may grow to 40 m in
height.  Usually only the male plant is used in
plantings because the female of the species pro-
duces yellowish fruits with a foul-smelling pulp
and acidic outer coat (Figures 6-13 and 6-14).  Epi-
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Fig. 6-13. Ginkgo (Ginkgo biloba). The ginkgo is an orna-
mental tree which may grow to 40 m. This a male ginkgo.
The female is seldom planted as an ornamental tree
because the fruits are foul smelling and can produce
allergic contact dermatitis. Reprinted courtesy of J. D.
Guin, Department of Dermatology, University of Arkan-
sas, Fayetteville, Ark.
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Fig. 6-14. Ginkgo (Ginkgo biloba). Typical fan-shaped
leaves and fallen fruit. Allergic contact dermatitis results
from exposure to the fruit.

Military Dermatology
120
demic contact dermatitis may be produced in groups
exposed to the fallen fruits.23  The kernel of the fruit
is sweet and edible.  Ginkgolic acid is thought to be
the possible allergen.  Vernacular names include
(English) maiden hair tree, gingko tree; (French)
arbre aux quarante écus, abricotier d’argent; and (Ger-
man) Ginkyobaum.10,23,24
Gluta
The genus Gluta of the family Anacardiaceae
includes approximately 30 species of trees and large
shrubs that are distributed throughout most of
Southeast Asia.  In this region Gluta is a major cause
of dermatitis.  The timber of many species
has blood-red heartwood and like many of the
Anacardiaceae, the sap turns black on exposure to air.
Furniture made from wood of a Gluta species can
produce dermatitis in sensitized individuals years
after being harvested.15  Even sitting under these
trees may produce a dermatitis due to resins being
washed down from the leaves in raindrops.
Some species grow in peat swamps and along
rivers, where they may be the dominant vegetation.
Individual trees are also widely scattered in low-
land forest regions of Borneo.  Vernacular names
include rengas or renghas (Malaya) and jitong.15  Other
names include hangus (Penang), rangus (Sankar),
ruengas (Sudan), ingas (Indonesia), and angus and
ligas (Philippines).  These names are also used for
many trees in the genus Melanorrhoea, which is now
combined with Gluta.20
Allergic Contact Dermatitis due to Plants:
Geographical Distribution
The standard approach for discussing plants that
produce contact dermatitis is to identify a few im-
portant species, as was done in the preceding text.
However, the military physician has a practical
need to know which plants are common sensitizers
in different climates and different continents.  This
regional report is not meant to serve local practi-
tioners, who are usually well aware of the native
plant offenders, but to help recently assigned medi-
cal officers, who are frequently unfamiliar with
local flora.  With the transplantation of exotic spe-
cies to gardens in the United States, such a report
also may benefit physicians in the United States.
However, many factors make this approach diffi-
cult.  Plant species can have a variety of common
names and may vary markedly in appearance when
grown in different climates within the same coun-
try.  Limited botanical information is available from
some areas or this information may be buried in
encyclopedic floral reviews.  An excellent attempt
at this type of review can be found in Clinics of
Dermatology, April–June 1986.11  It is beyond the
scope of this chapter to provide more than a short
review of the worldwide significance and distribu-
tion of certain allergenic plants.
Hawaii
Although poison ivy, T radicans, is not found in
Hawaii, related plants in the family (Anacardiaceae)
are the most common cause of ACD.  The mango (M
indica) and the India marking nut tree (S anacardium)
are in this family and are found in Hawaii.  The
flower of the kahili tree (Grevillea banksii) is a sig-
nificant cause of ACD in Hawaii, but contact with
other parts of the plant does not result in dermati-
tis.25  The kahili is a small tree originally from Aus-
tralia that produces cylindrical spikes of red or
white flowers.
A photosensitive contact dermatitis may result
from exposure to furocoumarin- (psoralen-) con-
taining members of the Rutaceae family.  The peel of
limes (Citrus aurantifolia) and black seeds and leaves
of the mokihana tree (Pelea anisata) contain psoralens.
The black mokihana seeds are strung into leis.26
Seaweed dermatitis results in intense itching and
burning and affected over 100 people after swim-
ming in the ocean on the windward shore of Oahu
in 1958.27  The areas of the body that were affected
were always areas that had been covered by bathing
suits.  Symptoms developed a few minutes to sev-
eral hours after exposure.  The affected areas often
resembled an acute burn.  The etiology has been
proven to be a blue-green algae, Microcoleus
lyngbyaceus.  This algae has a pantropic distribu-
tion, and episodic cases have been reported else-
where in the Pacific and in Florida.27
Nettle dermatitis may occur from exposure to the
native nettle, Hesperocnide sandwicensis, or to the
stinging nettle, Urtica ureus, which was accidentally
introduced from the continental United States.
The Americas and the Caribbean
In North, Central, and South America and the
Caribbean Islands, each region contains its own
subspecies of Anacardiaceae with little or no cross-
over into neighboring areas.  For example,
• the subspecies of poison ivy found com-
monly in the United States extend no farther
south than Florida, the northern Bahamas,

Allergic and Irritant Contact Dermatitis
121
and northern Baja California;
• the three subspecies of poison ivy in Mexico
are found no farther north than the southern
borders of Texas and Arizona;
• with few exceptions, dermatitis-producing
Anacardiaceae of the genera Metopium,
Comcladia, and Pseudosmodingium are re-
stricted to Central America; and
• only two species from the genera of South
American dermatitis-producing Anacard-
iaceae are indigenous to southern Central
America.
Botanical information on Central America and
the Caribbean is incomplete.  Some flora studies11
are being revised and few medical reports of plant
dermatitis exist.  Information is known about the
introduced species such as the cashew, A occidentale,
and the mango, M indica.11,22  In addition, the Brazil-
ian pepper tree, Schinus terebinthifolius (Figure 6-
15), was introduced into these regions as an orna-
mental plant from South America.  The cashew is
found in much of the Caribbean and Central
America.  In these regions, the mango is the most
popular fruit tree, having been introduced from
tropical Asia.  It is cultivated in areas of southern
Florida, Texas, and California, and now grows
throughout Central America and the Caribbean.
Laportea aestuans, a stinging nettle with particularly
persistent symptoms lasting a week or longer, has
been accidentally introduced to southern Florida.28
Plants in the genus Comocladia are confined es-
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Fig. 6-16. Poisonwood (Metopium toxiferum). This tree is
found in the Florida Keys, the West Indies, and Central
America. The leaves are pinnately compound, usually
with five but sometimes three or seven leaflets. Allergic
contact dermatitis results from exposure to all exterior
parts of the tree. The bare wood and pollen are toxin free.
Reprinted courtesy of J. D. Guin, Department of Derma-
tology, University of Arkansas, Fayetteville, Ark.
sentially to the Caribbean islands.  Comocladia glabra
is a small tree and like many plants that cause ACD,
when damaged a whitish latex is produced that
turns black on exposure to air.
Metopium consists of three species and is found in
southern Florida, the West Indies, and Central
America (southern Mexico, Belize, and Guatemala).
Contact dermatitis can result from contact with all
exterior parts of the tree except the pollen and wood
(Figure 6-16).  A large outbreak of dermatitis due to
Metopium occurred among British Royal Air Force
personnel clearing underbrush in the Bahamas.29
Four subspecies of T radicans, poison ivy, extend
into southern Florida and Central America.  T
striatum is primarily a South American species, but
it is very common in regions of Guatemala and
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Fig. 6-15. Brazilian pepper tree (Schinus terebinthifolius).
This tree is also known as Florida holly. Latex from the bark
and crushed berries have been implicated as the most
common cause of allergic contact dermatitis in south Florida.
Reprinted courtesy of J. D. Guin, Department of Dermatol-
ogy, University of Arkansas, Fayetteville, Ark.

Military Dermatology
122
Costa Rica.  Newly formed leaves are bright red,
pinnate, and have 11 to 15 leaflets.
The Brazilian pepper tree, Schinus terebinthifolius
(see Figure 6-15), is found in Florida, the Bahamas,
Cuba, Puerto Rico, and Mexico.  In Florida, where it
is known as Florida holly, it has been implicated as
the most common cause of ACD.28
The manchineel tree, Hippomane mancinella, or
beach apple, grows in southern Florida, the West
Indies, and Central America.  Because of its reputa-
tion for producing dermatitis,11,28 it has been eradi-
cated from the inhabited parts of Florida and per-
sists only in remote areas of the Everglades.
Appearing in protected areas away from the sea-
shore, the beach apple is a compact, densely leaved
tree about 10 m tall.  The deciduous leaves are
elliptical and glossy.  It produces large numbers of
small, pleasant-smelling, crabapplelike fruits (Fig-
ure 6-17).  The manchineel exudes a creamy white
latex that produces an irritant dermatitis.  Biting
into the fruit produces severe oral pain, profuse
salivation, and occasional dysphagia.  Kerato-
conjunctivitis and possibly an ACD may also be
produced.  Rain or dew falling off the leaves
has been reported to produce conjunctivitis and
dermatitis.28
Few Anacardiaceae have been described in South
America, with the majority coming from the genera
Toxicodendron, Lithraea, Maurin, Tapirira, and
Loxopterigium.  The cashew, mango, and Brazilian
pepper tree are widespread and abundant in much
of South America and are all well-known sources
of contact dermatitis.
T succedanea, also known as charao or the
Indochina lacquer tree, was introduced into Brazil
from Indochina for the production of lacquer.  T
verniciflua and T radicans have also been cultivated
in Brazil.  T diversilobum has been cultivated in
Argentina as an ornamental.
Lithraea caustica, or litre, is a large tree that grows
abundantly in Chile and that to Chileans is synony-
mous with the family Anacardiaceae.  Despite its
high potential for causing contact dermatitis, it is
burned as a source of heat and its hard wood is used
in the construction of homes and boats.  Several
species of Lithraea cause contact dermatitis and all
are generally restricted to southern South America.30
Asia
As elsewhere, in Asia members of the family
Anacardiaceae probably cause more dermatitis than
all other families combined.  Asia may well have the
greatest number of dermatitis-producing species of
any continent, with some 250 native species.  The
largest concentration of Anacardiaceae is in South-
east Asia.  Five genera are well known as docu-
mented causes of ACD: Anacardium, Gluta, Mangifera,
Semecarpus, and Toxicodendron.  Another group
of genera probably contain plants of similar aller-
genic potency, but are much less well studied:
Campnosperma, Drimycarpus, Holigarna, Melanochyla,
Nothopegia, Pentaspadon, and Swintonia.  The genera
Buchanania, Lannea, Parishia, and Spondias include
plants that may cause contact dermatitis, but spe-
cific documentation is lacking.31
Most of the allergenic Anacardiaceae of tropical
Asia are trees in primary forests.  The genus
Anacardium is represented by A occidentale (cashew),
which is widely planted in the Asian tropics.  The
genus Gluta includes about 30 species of trees and
large shrubs and is a major cause of plant dermatitis
in Southeast Asia.31  M indica, mango, is only one of
the 35 or so species of Mangifera distributed through-
out Southeast Asia.31  Although a perioral dermati-
tis following ingestion of mangos is the most com-
mon occurrence (see Figure 6-12), dermatitis has
also resulted from the sap, bark, smoke from bon-
fires, and raindrops that have dripped off the leaves
of the more toxic species of Mangifera.  Members of
the genus Semecarpus include 60 species distributed
from India through Southeast Asia to Fiji.31  S
anacardium, the India marking nut tree discussed
previously, is only one example.  Many species of
Toxicodendron are found in China, Japan, and South-
east Asia.  Several of these are used commercially as
a source of lacquer.  T verniciflua is generally known
Fig. 6-17. Manchineel or beach apple (Hippomane man-cinella).
The tree is compact and densely leaved, and grows to 10 m
in height. Dermatitis can result from exposure to latex from
the trunk, from the fruits, or from rain dripping from the
leaves. Reprinted courtesy of J. D. Guin, Department of
Dermatology, University of Arkansas, Fayetteville, Ark.
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Allergic and Irritant Contact Dermatitis
123
in English as the Chinese lacquer tree, in Japanese
as krushi, and in Chinese as qi su.31
Australia
The flower of the kahili tree (Grevillea banksii, also
found in Hawaii) can produce an ACD.  An Austra-
lian stinging nettle, Dendrocnide moroides, produces
piloerection, local vasodilation, sweating, and se-
vere pain.  Superficial lymphatics and proximal
lymph nodes become tender.28
Other Allergic Contact Dermatitides
Although less likely than toxicodendrons to pro-
duce numerous battlefield casualties, many prod-
ucts in the soldier’s environment may produce acute,
chronic, or recurrent dermatitis resulting in incon-
venience to the soldier or temporary loss of his or
her services from the unit: p-phenylenediamine,
nickel, rubber, ethylenediamine, potassium chro-
mate, and many other chemicals are major sources
of ACD.  Often the pattern of dermatitis in these
cases is not instantly recognizable as ACD, and,
unless the correct diagnosis is considered, the sol-
dier may suffer recurrent, preventable episodes of
dermatitis requiring further evaluation and lost
time from the unit.  Reactions to each individual
item may be relatively uncommon, but ACD after
exposure to these agents as a group is very com-
mon.
Topical Drugs
Overtreatment with irritating and sensitizing
drugs during World War II frequently caused more
disability than the diseases that were being treated.3,5
Tincture of iodine, Frazier’s solution, topical peni-
cillin, sulfonamide ointments, strong salicylic acid
preparations, and Whitfield’s ointment were fre-
quently misused, resulting in increased casualties.3,5
Ointments, pastes, and occlusives should be used
with extreme care, particularly in warm tropical
climates, because they may produce significant
maceration.  Frazier’s solution, an antifungal agent
supplied in jungle kits during World War II, was
responsible for much overtreatment because of self-
medication by soldiers.3
During World War II, topical use of penicillin
resulted in frequent reports of allergic dermatitis.
Since the banning of topical penicillin, neomycin
has become the most sensitizing topical antibacte-
rial preparation used.9  Neomycin is particularly
likely to result in sensitization when applied on
stasis ulcers, in chronic otitis externa, and on chronic
eczematous dermatitis.  Intermittent use of the drug
on minor cuts and wounds probably is not associ-
ated with an increased risk of sensitization.  Neo-
mycin has been included as a topical antibiotic in
many ointments, creams, and lotions (Figure 6-18).
It cross-reacts with gentamicin, kanamycin,
spectinomycin, streptomycin, and tobramycin.
Neomycin-sensitive patients who are given these
antibiotics intravenously may develop a severe sys-
temic eczematous contact-type dermatitis.  The sol-
dier shown in Figure 6-19 developed itching and
redness on the lower leg near the edge of the boot
but was negative on patch testing to samples from
the boots.  The eruption proved to be an allergic
reaction to neomycin that the soldier had used as
self-medication for a local irritation.  Patch testing
for neomycin was strongly positive.
Skin eruptions resulting from topical antibiotics
are not limited to neomycin.  Topical bacitracin,
polymyxin, gentamicin, clindamycin, erythromy-
cin, chloramphenicol, tetracycline, and nystatin are
all causes of allergic dermatitis, though somewhat
rare.
Whitfield’s ointment contains 6% salicylic acid
and 12% benzoic acid in petrolatum.  It is a rare
sensitizer, but the benzoic acid may produce a
nonallergic contact urticaria, particularly when used
in an intertriginous area.  Antifungal agents such as
tolnaftate, haloprogin, clotrimazole, miconazole,
and econazole are very rare sensitizers but may
cause an irritant dermatitis when used in intertrigi-
nous areas.
Benzocaine is a common and potent sensitizer
found in hundreds of topical medications including
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Fig. 6-18. Allergic contact dermatitis to neomycin.
Neomycin is included in numerous topical antibiotic
creams and is a common sensitizer.

Military Dermatology
124
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Fig. 6-19. Allergic contact dermatitis to neomycin. The
soldier was initially felt to have an allergic reaction to
material in his boots. That the soldier had been using an
antibiotic cream containing neomycin was only discov-
ered after negative testing of the boot material. Patch
testing to neomycin was strongly positive.
burn remedies, athlete’s foot therapies, topical an-
algesics, sore throat lozenges, astringents, wart rem-
edies, and various antibacterial compounds (Figure
6-20).  Eczematous, ulcerated, or burned skin is
particularly likely to become sensitized to
benzocaine.  Because benzocaine cross-reacts with
procaine, tetracaine, and cocaine, these should be
avoided when treating the benzocaine-sensitive
soldier.  In addition, because benzocaine is a deriva-
tive of p-aminobenzoic acid (PABA), benzocaine-
sensitive soldiers should avoid using sunscreens
that contain PABA or glyceryl PABA (Figure 6-21).
Benzocaine-sensitive soldiers can be safely treated
with lidocaine, mepivacaine, prilocaine, pramoxine,
and nupercaine.  Amide anesthetics such as lidocaine,
dibucaine and mepivacaine are very rare sensitizers.
Methylparaben, a preservative found in some anes-
thetic solutions, is also a sensitizer.9
A variety of ingredients are added to topical
agents including preservatives, stabilizers, antioxi-
dants, and emulsifying agents.  Ethylenediamine is
a stabilizer in medicated creams.  Mycolog cream
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Fig. 6-20. Allergic contact dermatitis to Lanacane
(benzocaine). Benzocaine is an anesthetic in numerous
topical preparations used to treat burns, bug bites, and
abrasions.
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Fig. 6-21. Allergic contact dermatitis to PABA. p-Ami-
nobenzoic acid (PABA) is an active ingredient in sun-
screens and can produce allergic contact dermatitis  in
sensitized patients.

Allergic and Irritant Contact Dermatitis
125
contained ethylenediamine and was a very com-
mon cause of sensitization until its replacement
with Mycolog-II (nystatin and triamcinolone
acetonide, manufactured by Westwood-Squibb,
Buffalo, N.Y.), which lacks ethylenediamine,
neomycin, or gramicidin (Figure 6-22).  Ethyl-
enediamine-sensitive soldiers should avoid
aminophylline (which contains theophylline and
ethylenediamine), hydroxyzine (Vistaril [manufac-
tured by Pfizer, New York, N.Y.] or Atarax [manu-
factured by Roerig, New York, N.Y.]), and Vasocon-
A eye drops (naphazoline hydrochloride and
antazoline phosphate, manufactured by Cooper-
Vision, Rochester, N.Y.).
Sunscreens
PABA, PABA esters, cinnamates, and benzophe-
nones are used in sunscreens to block primarily
ultraviolet B (UV-B) radiation.  UV-B is that part of
the sun’s radiation that is most responsible for pro-
ducing sunburns.  The longer wavelength light,
ultraviolet A (UV-A), can potentiate the effects of
UV-B.  The UV-A–blocking ingredient, dibenzoyl-
methane, is used in Photoplex (avobenzone and
padimate O, manufactured by Allergan Herbert,
Irvine, Calif.).  Opaque sunscreens such as zinc
oxide, titanium dioxide, kaolin, talc, and iron oxide
reflect and scatter UV radiation.  The opaque sun-
screens and dibenzoylmethanes rarely produce ACD.32
PABA and its esters can produce an ACD, and
PABA-sensitive soldiers may develop cross-reac-
tions on exposure to p-phenylenediamine, procaine,
sulfonamides, and azo dyes.33  The patient shown in
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Fig. 6-22. Allergic contact dermatitis to Mycolog.
Ethylenediamine is a very common sensitizer that was in
Mycolog cream. It has been removed from Mycolog-II.
Figure 6-21 developed a severe perioral contact
dermatitis from the PABA in RVPaba Lip Stick.
Benzocaine is a PABA derivative and benzocaine-
sensitive soldiers should be cautioned to avoid
PABA or glyceryl sunscreens.  PABA esters, digalloyl
trioleate, or cinnamates also may produce an aller-
gic photosensitization reaction.
Benzophenones used in sunscreens can produce
ACD, immediate urticarial reactions, and photo-
allergic reactions.34  Benzophenones are also widely
used in textiles and plastics to provide colorfastness
and protection from UV radiation.9
Metals
Metal dermatitis most frequently results after
exposure to nickel, chromates, and mercury, but
can also follow exposure to arsenic, gold, platinum,
and other metallic compounds.  With the exception
of nickel, most pure metals do not cause ACD and
must be in the form of a metallic salt in order to
produce hypersensitivity.  Positive patch test re-
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Fig. 6-23. Allergic contact dermatitis to nickel. Nickel in
chains that are used to hold identification tags and jew-
elry can produce dermatitis in sensitized soldiers.

Military Dermatology
126
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Fig. 6-25. Nickel dermatitis from a watch band and ring.
Gold- or silver-plated jewelry may produce dermatitis
when the plate is worn away, exposing underlying nickel.
Fig. 6-24. (a) Nickel dermatitis from metal buttons in cloth-
ing. Allergic contact dermatitis from nickel may result from
exposure to metal buttons, zippers, snaps, coins, etc. (b)
Closer view of nickel dermatitis from metal buttons in
clothing. Reprinted courtesy of D. Cuozzo, Dermatology
Service, Walter Reed Army Medical Center, Washington, D.C.
a
b
sults to a metallic salt do not usually indicate sensi-
tivity to the pure metal.  Allergic sensitivity to
metals is usually highly specific, and cross-sensitiv-
ity with other metals is exceptional.
Nickel.  Nickel-containing products are extremely
common and cause more cases of ACD than all other
metals combined.  Nickel dermatitis has resulted
from contact with hair pins, earrings, spectacle
frames, metal identification tags35 (Figure 6-23), chains,
metal buttons in clothing (Figure 6-24), zippers, metal
coins carried in pockets, watch bands, bracelets,
metal arch supports, and nickel in bullets and shrap-
nel.  The patient shown in Figure 6-25 developed
nickel dermatitis under both his watch and ring.
Women are more commonly allergic to nickel
than men.  The most common cause of nickel der-
matitis in women is contact with jewelry that con-
tains nickel.  Women who have their ears pierced
with nickel-plated instruments very frequently be-
come sensitized.  Earlobe dermatitis is almost
pathognomonic for nickel dermatitis (Figure 6-

Allergic and Irritant Contact Dermatitis
127
Fig. 6-26. Nickel dermatitis of the earlobe. Earlobe der-
matitis such as this is almost pathognomic for nickel
sensitivity.
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26).36,37  Men tend to become sensitized to nickel
more commonly through industrial exposures.
Perspiration containing sodium chloride can com-
bine with nickel to form nickel chloride, resulting in
a more severe dermatitis.  Even extremely small
quantities of the metal will produce dermatitis.
Widespread nickel dermatitis may result when
nickel contaminates perspiring fingers.  Sweat, fric-
tion, and pressure will all increase the frequency of
contamination and severity of the eruption.  Pre-
vention of sweating can decrease or prevent nickel
dermatitis.
Patch testing for nickel is done with 5% nickel
sulfate solution.  The U.S. Indian head nickel can
also be used in patch testing.  Trace amounts of
soluble nickel can be detected in suspected metal
objects using the dimethylglyoxime (DMG) spot
test.  Two or three drops of 1% DMG and 10%
ammonium hydroxide solution are placed on a white
cotton-tipped applicator.  This applicator tip is then
rubbed against any objects that are suspected of
containing soluble nickel.  Appearance of a pink
color on the applicator tip is a positive result (Fig-
ure 6-27).  This technique can be used to test jewelry,
buttons, keys, scissors, door knobs, or other metal-
lic objects.  A positive test is proof of the presence of
nickel.  Although this test is sensitive, a negative
test result does not absolutely eliminate the possi-
bility that nickel is present.38–40
Chromates.  Chrome salts are used in the pro-
cessing of leather goods and may cause an allergic
dermatitis.  Chromates are corrosive and irritating
as well as sensitizing.  In addition to leather goods,
exposure to chrome salts can occur during contact
with matches, paints, cement, diesel engines, and
photographic processing solutions.  Chromium
metal and stainless steel (which contains chromium)
do not cause allergic dermatitis.  Apparent contact
dermatitis related to these metals may be due to
associated nickel.  Patch testing for chrome is per-
formed with 0.5% potassium dichromate.
Mercury.  Mercury salts can cause irritant or
allergic dermatitis.  Phenylmercuric salts are used
Fig. 6-27. Dimethylglyoxime (DMG) spot test showing a
positive (pink) reaction for nickel. The test is performed
by adding a few drops of each test solution to a cotton
swab and rubbing the metallic object.

Military Dermatology
128
as weed killers, fungicides, and insecticides and
may cause an allergic dermatitis on exposed skin.
Mercuric compounds may also be found in cosmetic
creams, suppositories, dental amalgams, and sol-
der used in dry batteries.  Merthiolate is an organic
mercurial compound that can result in sensitiza-
tion.  Patch testing is done with 0.05% mercuric
bichloride.
Arsenic.  Arsenic is a sensitizer in dyes used in
wallpaper, chalk, artificial flowers, and fabrics, and
in some disinfectants and weed killers.  Arsenic is
also used in embalming, animal skin preservation
(tanning), printing, farming, and gardening.
Gold.  Gold dermatitis is uncommon, but may
occur as a result of exposure to gold salts in jewelry.
In cases where gold dermatitis is suspected, the
article of jewelry should be tested with dimethyl-
glyoxime to assure that nickel is not present.  Patch
testing for gold salt allergy is done with 1% gold
chloride solution.
Many cases of gold dermatitis were reported in
association with gold rings manufactured using
gold contaminated with radon.  The source of the
contamination was apparently gold from reclaimed,
decayed radon-gold seeds.  The contaminated gold
rings may produce radiation dermatitis and squa-
mous cell carcinoma of the finger.41
Other Metal Dermatitides.  Platinum dermatitis
may occur after exposure to platinum salts.  Plati-
num in jewelry causes a dermatitis similar to that
caused by nickel.  Patch testing can be performed
with 1% platinum chloride solution.  Zinc, alumi-
num, copper, and antimony are rare sensitizers, but
are frequent irritants.
Shoes
Despite the warm, humid environment inside
shoes, shoe dermatitis is relatively uncommon.  To
identify the likely allergens involved in shoe der-
matitis, the healthcare provider must ascertain how
the shoe is manufactured and what products and
chemicals are used.  Unfortunately, this task is
frequently extremely difficult.  Most shoes sold in
the United States are now manufactured in part or
wholly outside the United States.  The combina-
tions of glues, resins, fabric, rubber, dyes, metals,
finishes, and leathers that may be combined in a
modern shoe or boot make it impossible to identify
every potential allergen.  However, several specific
agents are routinely used in patch testing when
shoe dermatitis is suspected.  These agents include
antimildew agents (creosol, phenylmercuric nitrate,
phenylphenol); nickel; dyes (aminoazobenzene,
lanolin, p-phenylenediamine); leather tanning
agents (formaldehyde, glutaraldehyde, potassium
dichromate); neoprene and neoprene cements; poly-
urethanes and polyurethane cements; and rubber
and rubber cements (carba mix, thiuram mix,
colophony, mercapto mix, mercaptobenzothiazole,
and isopropyl-p-phenylenediamine [IPPD]).42,43
ACD caused by leather is usually related to tan-
ning agents and dyes.  Most cases are associated
with chrome used in the tanning process.44,45  ACD
rarely results from formaldehyde and glutaralde-
hyde used as leather tanning agents or by leather
dyes.  Scutt46 reported an epidemic of 86 cases of
leather shoe dermatitis in sailors of the British Royal
Navy assigned to the Far East.  The dermatitis was
caused by chromates in leather sandals that were
worn in direct contact with the skin.  A severe,
debilitating dermatitis resulted.  Contact dermatitis
to trivalent chrome salts used in tanning is detected
by patch testing with 0.5% potassium dichromate.
Although synthetic materials are replacing rub-
ber in many shoes, rubber allergy is still the most
common cause of shoe contact dermatitis in the
United States.  The rubber accelerators mercapto-
benzothiazole and tetramethylthiuram disulfide are
the most common allergens found in rubber shoe
dermatitis.  IPPD is a rubber antioxidant and is a
less common cause of contact dermatitis, but it has
been shown to produce a purpuric shoe dermatitis.
Patch testing can be done using pieces of the shoe
soaked in water and applied under occlusion to the
medial forearm or back for 48 hours.  Depending on
the location of the allergen in the shoe, dermatitis
can involve the dorsal or plantar surface (Figure 6-28).
The instep, toe webs, and flexural crease areas of the
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Fig. 6-28. Allergic contact dermatitis to shoes. Allergic
shoe dermatitis may result from exposure to glues, res-
ins, fabric, rubber, dyes, metals, finishes, or leather.

Allergic and Irritant Contact Dermatitis
129
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Fig. 6-29. Allergic contact dermatitis from the black rub-
ber liner of a standard issue military gas mask. An M4D
silicon gas mask should be obtained for soldiers with a
documented allergic reaction to the standard issue gas
mask.
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Fig. 6-30. Allergic contact dermatitis from a rubber chemi-
cal protective glove. Symptoms of allergic contact der-
matitis developed a few hours after exposure. Reprinted
courtesy of C. Samlaska, Dermatology Service, Tripler
Army Medical Center, Honolulu, Hawaii
toes are usually spared.  Involvement of these areas
should suggest the possibility of a secondary bacte-
rial infection or tinea pedis.  The differential diag-
nosis also should include a mechanical irritant der-
matitis, dyshidrosis, pustular psoriasis, lichen
planus, and epidermolysis bullosa simplex.
Rubber Compounds
One potentially very significant allergen in the
military is the rubber liner in the standard-issue gas
mask.  The soldier whose arm is shown in Figure 6-
29 gave a history of burning, pruritus, and erythema
shortly after putting on her gas mask.  A small
sample of the black rubber liner was taped to her
forearm.  Within 2 hours she noted significant
pruritus and within 24 hours she developed the
erythema and vesiculation characteristic of ACD.  The
patient in Figure 6-30 developed a similar response
from exposure to rubber chemical-protective gloves.
Soldiers may show either an acute contact
urticaria or a delayed-type hypersensitivity reac-
tion in response to rubber.  Most reactions to rubber
represent a delayed hypersensitivity reaction.  With
only rare exceptions, reactions to rubber are due not
to the rubber itself, but to the chemicals added in the
manufacturing process.  Antioxidants and accelera-
tors used in the manufacturing process cause most
of the ACD associated with processed rubber.  An-
tioxidants are added to help preserve the rubber;
p-phenylenediamine is a common antioxidant and
sensitizer.  Vulcanization or curing of raw rubber
results in cross-linking of polymer chains and is the
process that gives rubber its elasticity.  This process
is hastened with accelerators such as disulfiram,
thiuram, mercaptobenzothiazole, and diphenyl-
guanidine.  ACD may result from exposure to rub-
ber in gloves, gas masks, condoms, tires, heavy-
duty rubber goods, boats, and undergarments.
Patch testing is usually done using rubber chemi-
cal “mixes” rather than single ingredients.  For
soldiers with a proven allergic reaction to the rub-
ber in gas masks, M4D silicon masks may be ob-
tained from the U.S. Army Medical Research Insti-
tute for Chemical Defense (ICD), Aberdeen Proving
Grounds, Aberdeen, Maryland  21010-5425.
Clothing
Natural and synthetic fabrics used in the manu-
facture of clothing seldom result in dermatitis.  When
dermatitis does result, it is usually in response to
products added to the fabric, with the most com-
mon culprits being dyes, rubber compounds,

Military Dermatology
130
chromates, nickel, glues, permanent-press finishes
(formaldehyde resins), or sizing.
Dermatitis from additives to the fabric of pants
most commonly results in an eruption on the inner
and anterior thighs or popliteal fossa.  An eruption
in the axillary folds and antecubital fossa can be
caused by shirts or dresses.  A local eruption may
occur on the midabdomen from exposure to nickel
in belt buckles.
Allergic dermatitis to natural wool is uncom-
mon; however, irritant dermatitis, especially in a-
topic soldiers, commonly occurs at body sites where
the wool is in contact with the skin.  Woolen khaki
shirts worn by soldiers in World War II were
noted to cause an occasional purpuric eruption that
probably resulted from exposure to lubricating oils
used in the manufacture of the fabric.47  Chrome
also causes an allergic dermatitis when used in
the dying process of green woolen military
textiles.48  Dermatitis caused by untreated man-
made fibers such as nylon, dacron, orlon, and rayon
is rare.
Pure spandex fibers are used as a rubber substi-
tute in many undergarments because spandex is
lighter in color and weight.  It is an excellent substi-
tute for soldiers who are allergic to rubber.  The
antioxidants and accelerators that cause most of the
dermatitis from rubber are not used in the manufac-
ture of spandex.
Many textile additives such as softeners, water
repellents, biocides, antistatic agents, lubricants,
moth proofers, and antislip finishes are not sensitiz-
ers.  However, formaldehyde and formaldehyde
resins used to make permanent-press finishes may
cause allergic contact reactions.  Dermatitis as a
result of residual detergents after washing of clothes
is uncommon49 but can be related to perfumes in the
detergents.  Textile dyes may cause an ACD.  Forty
percent of textile dyes are azo dyes.  Azo dyes are
among the most common causes of textile dye der-
matitis and may cross-react with p-phenyl-
aminediamine.  Regardless, ACD resulting from
exposure to dyes is rare.49
Skin eruptions may also result from occlusive,
tightly fitting garments.  Pressure urticaria, acneform
eruptions, and exacerbation of preexisting eczema-
tous skin conditions may result from clothing that
fits too snugly.  Patch testing for clothing dermatitis
can be performed using a 1-in. square of fabric
soaked in water for 10 minutes and applied under a
closed patch on an uninvolved medial forearm or
the back for 3 days.
Blousing garter dermatitis is a syndrome of hy-
perpigmentation of the ankles and feet below the
level of application of elastic garters used to keep
fatigues neatly in place.  Chronic pressure of this
kind may result in mild edema and a subsequent
form of stasis dermatitis with the associated depo-
sition of melanin and hemosiderin.  This condition
is not a contact dermatitis.
Preservatives
Quaternium-15 is a common preservative in cos-
metics and creams and is a common cause of aller-
gic dermatitis (Figure 6-31).  Imidazolidinyl urea is
a very common preservative used in cosmetics but
is a less common sensitizer.  Bronopol is another
sensitizer but is a less commonly used preservative.
Formaldehyde is a preservative used in shampoos,
cosmetics, and many paper products.  It is a signifi-
cant sensitizer.  Although sensitization after use of
a formaldehyde-containing shampoo is uncommon,
sensitized soldiers may develop an eruption after
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Fig. 6-31. Allergic contact dermatitis from quaternium-
15 in a moisturizing cream. Quaternium-15 is a common
preservative in cosmetics and creams. Severe edema and
pruritus developed a few hours after a single exposure.

Allergic and Irritant Contact Dermatitis
131
contact with newspaper, magazines, books, paper
towels, tissues, or photographic paper.50
Paraben esters (methyl, ethyl, propyl, and bretyl
p-hydroxybenzoates) are used in combinations as
preservatives in some cosmetics, foods, drugs, and
suppositories.  Paraben sensitization is evaluated
using a 12% paraben mix in petrolatum.
Fragrances
Fragrances, or perfumes, are the leading cause of
ACD due to cosmetics (Figure 6-32).51  Besides being
found in cosmetics, they are used in detergents,
toothpastes, sanitary pads, fabric softeners, and
many other products.  In addition to allergic reac-
tions, fragrances may produce photodermatitis
(sun-related), contact urticaria, primary irritation,
or depigmentation.  Some of the more common
offenders are cinnamic alcohol and aldehyde,
hydroxycitronella, eugenol, and isoeugenol.  Other
fragrances that can cause dermatitis include corian-
der, geraniol, heliotropine, hydroxycitronella, jas-
mine, linalool, lavender, lemon, lemon grass, neroli,
origanum, oil of cloves, peppermint, spearmint,
and wintergreen.
Other Sensitizers
p-Phenylenediamine is a common sensitizer
used in hair dyes, photographic processing, and
rubber vulcanization.  p-Chloro-m-xylenol is a chlo-
rinated phenol antiseptic sensitizer used in
Absorbine Jr. (wormwood, thymol, and chlor-
oxylenol, manufactured by W.F. Young, Spring-
field, Mass.), Desitin powder (talc, manufactured
by Leeming/Pacquin, New York, N.Y.), and
Unguentine spray (benzocaine, manufactured by
Mentholatum Co., Buffalo, N.J.).  Propylene glycol
is widely used as a vehicle for cosmetics, emollient
lotions, and topical medications.  It is also used in
brake fluids, automotive antifreeze, lubricants for
food machinery; in additives for food colors; and in
antiperspirants.  Propylene glycol is both an irritant
and a sensitizer.
Lanolin (wool fat, wool wax, wool alcohol) and
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Fig. 6-32. Perfume dermatitis. Fragrances, or perfumes,
are the leading cause of allergic contact dermatitis due to
cosmetics and may be ingredients in many other products.
related compounds are found in many topical medi-
cations.  Lanolin is a common sensitizer found in
creams, hair products, lipsticks, moisturizers, oint-
ments, soaps, furniture polishes, leather, shoe pol-
ishes, fur, and textile finishes.  Lanolin is a signifi-
cant cause of allergic dermatitis when it contacts
eczematous skin.  The risk of sensitization when
contact is with normal skin is much lower.
Balsam of Peru is used widely in topical thera-
pies.  It has mild antibacterial activity and is used in
toothpastes, sore throat lozenges, and dental ce-
ments.  It may also be found in sunscreens, cosmet-
ics, perfumes, and a variety of suppositories.  Cross-
reactions can occur with benzoin, rosin, benzyl
alcohol, cinnamic acid, orange peels, clove, benzyl
benzoate, and wood tars.  Balsam of Peru is a well-
documented sensitizer and also produces a
nonallergic contact urticaria.9
Rosin (colophony) is a natural resin used widely
in topical medications, adhesives, cements, and
cleaners.  It is used on violin bows and in rosin bags
for baseball players.  Rosin is a sensitizer, and
sensitized soldiers may cross-react with Balsam of
Peru.  Thiuram is a common sensitizer in rubber
products but may also be found in adhesives, fungi-
cides, disinfectants, paints, pesticides, soaps, repel-
lents, and putty.
Many substances produce a nonallergic inflam-
matory reaction of the skin.  Any soldier exposed to
sufficiently high concentrations of the substance
will develop dermatitis.  No prior exposure is re-
quired, and the effect is evident within minutes or a
few hours.  Variations in severity of the reaction to
these irritants—from soldier to soldier or from time
to time in the same soldier—are due to the condition
of the skin and the duration of exposure to a given
concentration of irritant.  Excessive humidity, heat,
IRRITANT CONTACT DERMATITIS

Military Dermatology
132
cold, pressure, or friction may adversely affect the
epidermal barrier, making the skin more vulner-
able to the irritant effects of a substance.  Cold
weather and low humidity may produce chapping,
excessive dryness, and pruritic skin and predispose
to irritant dermatitis.  High temperatures and hu-
midity in the summer predispose to maceration and
increased frequency of irritant dermatitis.  Thick
skin of the palms and soles is more resistant to
irritants than thin skin.  Repeated exposure of the
skin to some mild irritants may, in time, produce a
“hardening” effect, which makes the skin more
resistant to an irritant.
Alkalis and Acids
Alkalis are composed primarily of sodium hy-
droxide, potassium hydroxide, ammonium hydrox-
ide, and calcium hydroxide compounds; they pen-
etrate deeply and destroy the skin because they
dissolve keratin.  These agents are frequently asso-
ciated with hand eczemas after exposure to soaps;
detergents; bleaches; ammonia preparations; lye;
and drain pipe, toilet bowl, and oven cleaners.  Ex-
posure to concentrated alkalis may be buffered by
rinsing the site with a weak acid solution such as
vinegar, lemon juice, or 0.5% hydrochloric acid.
Exposure to acids (eg, hydrochloric, nitric, sulfu-
ric, and hydrofluoric) causes an irritant burn.  Hy-
drochloric acid produces more superficial damage
than the others and more frequently results in blis-
ter formation.  Nitric acid, which is used in the
production of some explosives, causes deep burns
while turning the skin yellow.  Sulfuric acid is used
extensively in industry and results in a brownish
charring of the skin, which ulcerates and heals
slowly.  Hydrofluoric acid is a very potent inor-
ganic acid that will dissolve glass, but may be slow
to cause dermatitis.  If left in contact with the skin,
progression from erythema to vesiculation, ulcer-
ation, and finally necrosis occurs.
Acid burns should be treated by rinsing with
copious amounts of water.  Alkalization of the site
can be done with sodium bicarbonate, calcium hy-
droxide (lime water), or soap solutions.
Hydrocarbons
Hydrocarbons in crude petroleum and lubricat-
ing and cutting oils may cause an irritant dermati-
tis.  Chronic exposure can also result in pruritus,
folliculitis, calcifications, or acneform eruptions.
Exposure to creosote, asphalt, and other tar prod-
ucts may result in melanoderma.  Creosote is a
contact irritant, sensitizer, and photosensitizer.
Diethyltoluamide Dermatitis
Insect repellents containing diethyltoluamide
(DEET) were first extensively used in a military
conflict during the Vietnam conflict.  Although it
was not suspected of being capable of causing sig-
nificant skin reactions, during the Vietnam conflict
DEET was discovered to result in a bullous eruption
in some personnel.  Although this chemical was a
relatively uncommon cause of significant dermati-
tis, it did result in pain, disability, and permanent
scarring in some individuals.8,52,53
DEET eruptions were characterized by a distinc-
tive clinical course and by their restriction to the
antecubital fossae.  The eruption was first noted by
soldiers on morning awakening.  A red, tender area in
one or both antecubital fossae was noted.  This area
would evolve over 24 hours into blisters on a tender
base.  Lamberg and Mulrennan53 showed in 1969
that about half the people tested will develop a
reaction to DEET when it is applied to the antecubital
fossa, but none of the 62 patients tested reacted to
DEET applied to the upper inner arm.  Besides
proving that the eruption was an irritant reaction,
not an allergic one, Lamberg and Mulrennan pointed
out that when DEET is used in the antecubital fos-
sae, a large percentage of the populace will be at risk
for this eruption.  Besides being capable of produc-
ing an irritant dermatitis, DEET produces contact
urticaria in some individuals.52
Chloracne
Chloracne was first described by Herxheimer in
1899 as a form of acne that is distinct from all other
forms of acne, such as acne vulgaris and acne
rosacea.54  Chloracne may result from exposure to a
variety of aromatic chlorinated hydrocarbons.
During the Vietnam conflict, Agent Orange was
by far the most commonly used defoliant.  The
herbicide is composed primarily of a mixture of
2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4-
dichlorophenoxyacetic acid (2,4-D).  These two prod-
ucts are potentially toxic, but a contaminant, 2,3,7,8-
tetrachlorodibenzo-p-dioxin (TCDD), poses more
significant health concerns.  In addition to the many
other health concerns associated with it, TCDD is a
known chloracne-producing agent.
The distribution of lesions in soldiers with
chloracne is of particular diagnostic importance.

Allergic and Irritant Contact Dermatitis
133
The most frequently involved areas are on the
face, below and lateral to the eyes, and behind the
ears.  These areas may be the only sites involved,
and chloracne in these areas may persist for years
after lesions in other parts of the body have re-
solved.  The scrotum is also a particularly sensitive
area.  If the exposure is sufficient, lesions also may
appear on the penis, shoulders, chest, back, and
eventually, the buttocks and abdomen.  The nose is
uniformly spared and the distal extremities are
seldom involved.
The primary lesion of chloracne is the comedo.
With mild exposure, small numbers of comedones
on the face may be all that is noted.  With more
severe exposure, soldiers also develop pale yellow
cysts 1 to 10 mm in diameter that are mingled with
the comedones.  Soldiers may develop large inflam-
matory cysts and cold abscesses with very severe
exposures, but even these cysts tend to be much less
inflammatory than those seen in cystic acne.
The clinical course of chloracne varies depend-
ing on the method of exposure, chemical involved,
and dose.  Simple comedones usually do not de-
velop until 2 to 4 weeks after exposure.  After
exposure ceases, most persons will clear all lesions
within 4 to 6 months.  However, some patients have
shown chloracne lesions for 15 to 30 years after the
last known exposure.54
Chloracne may be relatively unresponsive to
therapy.  Topical 0.05% Retin-A (tretinoin, manu-
factured by Ortho Pharmaceutical Corp., Raritan,
N.J.) may be effective with comedonal lesions, and
oral retinoids may be tried in more severe cases.54
Irritant Contact Dermatitis due to Plants
Numerous common plants and even edible fruits
can cause an irritant contact dermatitis.  The derma-
titis frequently occurs only after exposure to a par-
ticular part of the plant, and the degree of toxicity
may vary with the season, type of exposure, stage of
maturity of the plant, locality, and anatomical fac-
tors such as thickness of the stratum corneum.
The majority of cases of irritant contact dermati-
tis can be traced to only a few plant families.  The
largest is the spurge family (Euphorbiaceae).
Spurges such as the poinsettia (Euphoria pulcherrima),
crown-of-thorns (E splendens), candelabra cactus (E
lactea), and pencil tree (E tirucalli) contain a highly
irritating, white, milky sap that may cause erythema,
desquamation, and bulla formation.  The active
agent in the sap is known as euphorbin.14  Another
family of irritant plants, Brassicaceae, includes the
mustard seed plant and butter cups.  Calcium ox-
alate, another irritant, is found in a number of
plants including Dieffenbachia, daffodils, hyacinths,
and pineapples.
Many of these plants produce dermatitis only
after chronic exposure and symptoms frequently
consist only of erythema, burning, or pruritus.  On
rare occasions severe bullous eruptions occur, or oral
exposure may result in oral or esophageal lesions.
OTHER CONTACT DERMATITIDES
Certain skin disorders are not typically classified
as either ACD or irritant contact dermatitis.  These
dermatitides include mechanical injury, pharmaco-
logical reactions, and contact urticaria.
Mechanical Injury
Aside from the obvious risks of a combat envi-
ronment, the soldier may be exposed to a variety of
natural agents that can result in direct trauma to the
skin.  Traumatic injury from plants is a frequent
cause of dermatitis, but seldom requires the care of
a medical officer.  Secondary bacterial and fungal
infections around implanted thorns, needles, splin-
ters or spines are not uncommon, even though these
injuries are frequently sterile.  Sporothrix schenckii (a
dimorphic, imperfect fungus) infection should be
considered following wounds produced by roses,
trees, grasses, and sphagnum moss (Figure 6-33).55
Cactus needles that remain imbedded in the skin
may produce aseptic foreign-body granulomas.
Coral cuts produced by the exoskeleton of the cor-
als, order Milleporina, have a largely undeserved
reputation for producing inflammatory lesions that
heal slowly.  This reputation is probably related
chiefly to the injuries’ location—most frequently on
the feet—and the occasional implantation of small
coral fragments.  In general, coral cuts should be
treated with vigorous cleansing as soon after the
injury as is feasible.
Pharmacological Reactions
On contact with the skin, some plants cause der-
matitis through the release of pharmacologically
active agents.  Essentially all persons will develop a

Military Dermatology
134
laxis.  Nonimmunological contact urticaria is the
most common and is caused by agents that directly
stimulate the release of vasoactive substances from
mast cells.
Agents that produce allergic contact urticaria
include silk, wool, rubber, animal hair, dander,
saliva, serum, seminal fluid, cockroaches, moths,
insect stings, milk, eggs, fish, meat, fruits, potatoes,
phenylmercuric propionate (as an antibacterial
agent in the laundry), beer, penicillin, neomycin,
nickel, formaldehyde, and rubber.
Contact urticaria from rubber occurs almost ex-
clusively from the use of rubber gloves.  Dentists,
surgeons, operating room nurses, and numerous
other healthcare providers may demonstrate a con-
tact urticaria reaction to rubber gloves.  The sensiti-
zation rate may be up to 10% in highly exposed
personnel.56
Allergies to latex pose a risk to both the healthcare
provider and his or her patients.  Severe anaphylac-
tic reactions have occurred in patients exposed to
latex during surgery, obstetrical deliveries, and
barium enemas.  It is therefore recommended that
before performing these procedures the history in-
clude questions regarding signs and symptoms of
latex allergy.  This point is of particular importance
when the patient is a healthcare provider.  Most of
the patients who have developed intraoperative
reactions to latex have been healthcare providers.56
Many items in the operating room may be the source
of latex.  Sensitive individuals may react to latex in
gloves, endotracheal tubes, syringes, intravenous
tubing and bags, multidose vials, and enema and
catheter tubing.
Agents that produce a nonimmunological con-
tact urticaria include jellyfish, the Portuguese man-
of-war, Balsam of Peru, caterpillar hair, moths, in-
sect stings, benzoic acid, nettles (plants), dimethyl
sulfoxide, cobalt chloride, trafuril, sorbic acid, and
cinnamic acid.
Skin testing for contact urticaria is performed as
an open patch test, and the suspected agent
should initially be applied to previously uninvolved
skin.  If no reaction occurs, the agent can be placed
on previously affected skin.  If there is still no
reaction, the agent may then be gently rubbed
into a superficial scratch.  Immediate contact
urticarial reactions should be read at 20 minutes
after application.  Because anaphylaxis may result
from such testing in highly allergic individuals,
epinephrine and resuscitation equipment should
always be available.
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Fig. 6-33. Sporothrix schenckii infection. Infection can
follow wounds produced by roses, trees, grasses, and
sphagnum moss.
reaction to significant exposure.  Most of these
reactions are produced by plants in the family
Urticuceae.  Stinging nettles (Urtica ureus), common
in dry, disturbed soil or woodland margins, are
characterized by sawtoothed, heart-shaped leaves
and are densely covered with coarse, stinging hairs.
The hairs consist of a tiny capillary tube that breaks
off at a predetermined line on contact with the skin.
Pressure on a small bladderlike base injects fluid
containing histamine, acetylcholine, and serotonin.
The result is a typical triple response (erythema,
flare, and wheal) with pruritus noted in seconds
and lasting a few hours.  Most stings are benign and
require little or no therapy.14
Contact Urticaria
Contact urticaria may be defined as a wheal-and-
flare reaction that occurs after topical exposure to
an agent.  It may be immunological, nonimmuno-
logical, or of unknown mechanism.  The immuno-
logical type may be severe, with associated anaphy-

Allergic and Irritant Contact Dermatitis
135
CONTACT DERMATITIS BY ANATOMICAL SITE
Many areas of the body are particularly sensitive
to contact allergens, and some areas are affected
most commonly by a few specific allergens.  From a
practical standpoint, it is important to be aware of
these associations.  Some material from earlier in
the chapter is repeated here in order to assist the
medical officer in rapid diagnosis and treatment.
Eyelids
The eyelid is one of the most sensitive and fre-
quently affected parts of the body (Figure 6-34).
Any allergen that contacts the face, scalp, or hands
may be inadvertently transferred to the lids, result-
ing in an eczematous dermatitis even when the
primary sites remain clinically uninvolved.  Eyelid
dermatitis occurs most commonly from products
applied to other parts of the body and then acciden-
tally transferred to the lids.  Frequently only one
eyelid is involved.  Severe edema of the eyelids is
frequently associated with exposure to T rydbergii
and T radicans (poison ivy).  Preservatives in oph-
thalmic medications and contact lens solutions can
produce eyelid dermatitis and conjunctivitis.
The most common preservatives implicated include
benzalkonium chloride, thimerosal, chlorobutanol,
chlorhexidine, and phenylmercuric nitrate and
acetate.  Cosmetics such as mascara and eye
shadow, lemon and orange peels, and exposure to
phosphorous sesquisulfide in “strike anywhere”
matches can cause eyelid dermatitis.57  Airborne
contactants such as insecticides and volatile occu-
pational chemicals can also produce a dermatitis of
the lids.
Face
Contact dermatitis involving the face may result
from direct contact or from inadvertent transfer of
an allergen.  In addition, sun- and plant-related
dermatitis are often most severe on the face.  Facial
dermatitis due to rubber compounds may be of
particular importance to military personnel.  A se-
vere eruption may occur after exposure to rubber
used in gas masks (see Figure 6-29).  Although the
scalp is resistant to contact dermatitis, the fore-
head, ears, and posterior neck may become inflamed
after contact with hair dye, hair spray, shampoo,
and permanent-wave solutions.  Dermatitis of the
forehead may result from contact with leather or
rubber compounds in hat bands or protective hel-
mets.  The forehead may also be affected after
exposure to pomade hair straighteners.  Pomade
acne occurs primarily in black males and consists
of closely packed, multiple, closed comedones
along the hairline and temples (Figure 6-35).
Perioral dermatitis may result from reactions to
toothpaste or chewing gum.  Earlobe dermatitis
most commonly results from nickel found in ear-
rings (see Figure 6-26).  Severe contact dermatitis of
the face may result after exposure to smoke from
burning toxicodendrons (poison ivy).  Other causes
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Web
Fig. 6-34. Allergic eyelid dermatitis. Eyelids are frequently
sites of contact dermatitis. Allergens may be inadvert-
ently transferred to the lids from the face, scalp, or hands.
Fig. 6-35. Pomade acne. Pomade hair straighteners can
produce an acneform eruption along the hairline and
temples.

Military Dermatology
136
airborne allergens, perfume, and aftershave
lotion (see Figure 6-32).
Trunk
The trunk is infrequently afflicted with contact
dermatitis.  Metal identification tags and related
covering materials may result in a dermatitis of the
central chest.  Dye or finish in clothing may occa-
sionally result in a dermatitis of the chest or axilla.
Dermatitis of the axillary vault is seen in reactions
to deodorants (Figure 6-36).  Elastic materials or
metal wires and snaps found in brassieres may
result in a contact dermatitis.  Other sensitizers can
include topical medications or sunscreens.
Abdomen
Dermatitis of the belt line may result from elastic
material in undergarments.  The central abdomen
may develop a dermatitis under nickel-containing
zippers, buttons, snaps, and belt buckles (see
Figure 6-24).
Groin
The penis or scrotum may become inadvertently
exposed to poison ivy oleoresins on the hands,
resulting in severe contact dermatitis (see Figure 6-6).
The patient in Figure 6-37 developed a severe con-
tact dermatitis after using spray deodorant in his
genital area.  Penile dermatitis may also result from
condoms.  The allergen in these cases is usually a
rubber antioxidant or accelerator.
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Fig. 6-37. Contact dermatitis from using spray deodor-
ant. Dermatitis of the scrotum or groin area can result
from inadvertent transfer or inappropriate application of
irritants or allergens.
Fig. 6-38. Allergic contact dermatitis from hand cream.
Hand dermatitis can result from exposure to foods,
toxicodendrons, oils, solvents, metals, topical medica-
tions, rubber gloves, soaps, or detergents.
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Fig. 6-36. Contact dermatitis produced by deodorant.
Irritant reactions to aluminum salts can occur. Allergic
reactions are most frequently due to fragrances.
of facial dermatitis include cosmetics, sunscreens,
acne medications, aftershave lotion, and moisturiz-
ing creams.
Neck
Nickel found in metal identification tags and
chains and in necklaces may result in an underlying
erythematous and eczematous eruption of the neck
(see Figure 6-23).  The dermatitis may occur just
under the clasp of a necklace or just under
the identification tag.  An eruption in this area
might also result from contact with rubber used
to insulate or quiet the identification tag and
chain.  Dermatitis of the neck may result from

Allergic and Irritant Contact Dermatitis
137
Hands and Feet
Contact dermatitis of the feet most commonly re-
sults from leather, rubber, or adhesive materials used
in shoes and boots (see Figure 6-28).  Hand dermatitis
may result from exposure to foods, toxicodendrons,
oils, solvents, metals, topical medications, rubber
gloves, soaps, or detergents (Figure 6-38).
Although an extensive discussion of patch test-
ing is beyond the scope of this text, Table 6-1 shows
a list of agents frequently used in the process.  Phy-
sicians experienced in performing patch tests fre-
quently maintain their own stock of additional
agents that can be used in patch testing.  In addition,
small samples of each of the ingredients in a product
may be obtained from the manufacturer.  Only stan-
dardized concentrations of each allergen should be
applied.  In no case should undiluted, nonstandard-
ized mixes of chemicals be applied under occlusion.
PATCH AND USE TESTING
TABLE 6-1
STANDARD PATCH-TEST SCREENING TRAY
Allergen
Common Sources of Exposure
Balsam of Peru 25%
Cosmetics, perfumes
Benzocaine 5%
Topical anesthetics, medications
Black rubber mix 0.6%
Rubber products
p-Tert-butylphenol formaldehyde resin 1%
Adhesives, rubber products
Carba mix 3%
Rubber cements and sealants
Cinnamic aldehyde 1%
Fragrance, flavorings
Colophony (rosin) 20%
Adhesives, cements, cleaners, topical medications
Epoxy resin 1%
Glue, pastes
Ethylenediamine dihydrochloride 1%
Mycolog, aminophylline, hydroxyzine, eye drops
Formaldehyde 1%
Glues, paper, clothing, cosmetics, leather
Imidazolidinyl urea 2%
Preservative in creams and cosmetics
Lanolin (wool) alcohol 30%
Cosmetics, medicated creams, leather, polishes, fur
Mercapto mix 1%
Shoes, rubber products
Mercaptobenzothiazole 1%
Rubber products
Neomycin sulfate 20%
Topical medications
Nickel sulfate 2.5%
Jewelry, metal fasteners, ID tags/chains, tools
p-Phenylenediamine 1%
Hair dyes, inks, rubber products
Potassium dichromate 0.25%
Cement, leather, green woolen military textiles
Quaternium-15, 2%
Cosmetics
Thimerosal 0.1%
Eye, ear, and nose preparations
Thiuram mix 1%
Rubber products
Data source: Fisher AF. Contact Dermatitis. Philadelphia, Pa: Lea & Febiger; 1986: 21–28.
Patch testing of solid objects may be performed
by trimming off a small (0.5–1.0 cm2) sample and
applying it to the skin, or if small enough, the object
in question may be taped to the skin.  Small pieces
of shoes or clothing can be moistened and applied
under occlusive hypoallergenic tape.  Suspect agents
are usually left against the skin for 48 hours.  The
agent is removed and the site is examined; the exam
is repeated 48 hours later.  A significant allergen
will produce pruritus, erythema, edema, and even
vesiculation at the site.

Military Dermatology
138
Use testing may be performed with nonirritating
creams, ointments, oils, and sprays that are be-
lieved to contain possible allergens by applying
the material to the inner surface of the distal upper
arm three times a day for 1 week.  If no reaction
occurs, the test is considered negative, but false-
negative results are not uncommon with this form
of testing.
TREATMENT
reduce serous drainage from the site.  Clean water,
isotonic saline, and Burow’s solution can all be used
with good success.  Topical calamine lotion usually
is of limited benefit.
Affected sites should be cleared of adherent crusts
and a thin coat of antibacterial ointment should be
applied.  Most episodes of contact dermatitis will
not require antibiotic therapy, if they are treated
promptly and adequate wound care can be pro-
vided.  But oral antibiotics may be of benefit if a
significant degree of purulent material or crust is
present.  Adequate coverage for staphylococci and
streptococci can usually be achieved with a 5- to 10-
day course of oral therapy with dicloxacillin,
erythromycin, or Keflex (cephalexin, manufactured
by Dista, Indianapolis, Ind.) at 250 mg four times
a day.
Severe pruritus may respond to antihistamines
such as Atarax (hydroxyzine, manufactured by
Roerig, New York, N.Y.), 25 to 50 mg nightly, or
chlorpheniramine, 4 to 8 mg nightly.
Steroids
Potent topical steroids such as Temovate
(clobetasol propionate, manufactured by Glaxo,
Research Triangle Park, North Carolina) or
Diprolene (betamethasone dipropionate, manufac-
tured by Schering, Kenilworth, N.J.) applied twice
daily for 1 to 2 weeks are effective in the therapy of
small areas of moderate-to-severe ACD.  However,
the mainstay of therapy for the soldier with an acute
episode of extensive ACD, or severe contact derma-
titis involving the face and intertriginous areas, is
systemic steroids.  Without therapy, and barring
secondary infection or reexposure, an episode of
Toxicodendron dermatitis can be expected to persist
up to 3 or 4 weeks.  Early, adequate use of prednisone
or intramuscular Kenalog (tri-amcinolone acetonide,
manufactured by Westwood-Squibb, Buffalo, N.Y.)
can significantly shorten this course, allowing the
soldier to return to duty.  Prednisone should be
started at 40 to 80 mg (1.0–1.2 mg/kg) per day as a
single oral dose and tapered over approximately 3
weeks.  Soldiers who stop prednisone therapy pre-
maturely will frequently experience a relapse that
As with most medical conditions, making the
correct diagnosis is crucial to providing appropri-
ate therapy.  The diagnosis of poison ivy dermatitis
may be obvious in the soldier who presents with a
linear bullous dermatitis on exposed skin.  How-
ever, contact dermatitis may be neglected for sev-
eral days, and a secondary infection may cloud the
clinical picture.  The medical officer must be alert to
this possibility and attempt to come to the correct
diagnosis with a thorough history and insightful
physical examination.  Once the correct diagnosis
has been established, many affected soldiers’ con-
ditions will improve with adequate hygiene and
avoidance of the primary contactant.  Depending
on the degree and duration of involvement, and the
presence or absence of secondary infection, each of
the following therapies may be considered.
Removal of the Irritant
In cases of acute irritant dermatitis from strong
irritating chemicals, the first goal must be to remove
the irritant from the skin to prevent further damage.
Oral and topical steroid therapy do not benefit
the soldier who has a nonallergic, irritant contact
dermatitis.
Acid burns from such agents as hydrochloric,
nitric, and sulfuric acids should be treated immedi-
ately with copious amounts of water and alkalization
with sodium bicarbonate or soap solutions.  Alkalis
such as soaps, detergents, bleaches, ammonia prepa-
rations, lye, and drain pipe, toilet bowl, and oven
cleaners all can cause significant irritant contact
dermatitis.  Alkalis may cause deep tissue destruc-
tion because they dissolve keratin.  Strong alkaline
solutions may be neutralized by rinsing the skin
with a weak acid solution such as vinegar, lemon
juice, or 0.5% hydrochloric acid.  The site should
also be rinsed with large quantities of water.
Nonsteroidal Therapy
Many cases of localized, mild contact dermatitis
will respond well to cool compresses and adequate
wound care.  Cool, wet soaks applied for 5 to 10
minutes followed by air drying may significantly

Allergic and Irritant Contact Dermatitis
139
may result in additional days lost from service.  The
duration of prednisone therapy should be long
enough that the soldier will complete therapy 2 to 3
weeks after the initial onset of symptoms.  Alterna-
tively, a single dose of 4 mg of Celestone (beta-
methasone sodium phosphate, manufactured by
Schering, Kenilworth, N.J.) may be mixed with 40 to
60 mg of triamcinolone (Kenalog) for use as intra-
muscular therapy, providing fairly rapid onset of
action and prolonged action over 2 to 4 weeks.
Celestone expedites recovery and Kenalog provides
the duration required to maintain clearance of symp-
toms.  If used alone, the Celestone dose may be
increased to 12 mg but must usually be repeated in
5 to 7 days.  Intramuscular therapy is efficacious
and ensures compliance.
SUMMARY
Contact dermatitis may result from either an
immunological or nonimmunological reaction of
the skin after exposure to various agents.  A com-
mon form of immunological reaction or ACD is
produced when sensitized individuals are exposed
to urushiol, the antigen in Toxicodendron species
(eg, poison ivy, poison oak, and poison sumac).  The
concentration of the contactant required to produce
dermatitis is very low, and not everyone who is
exposed to the antigen will develop dermatitis.  In
contrast, irritant contact dermatitis is a nonimmuno-
logical process and will develop in all soldiers who
are exposed to a sufficiently high concentration of
the irritating substance.
Soldiers may also develop dermatitis after expo-
sure to plants for reasons other than contact with
allergens or irritants.  Mechanical injury from plants
may result in infection from bacteria and fungi or
foreign body reactions to residual material such as
cactus needles or coral fragments.  Dermatitis may
result from pharmacologically active agents such as
histamine, acetylcholine, and serotonin found in
stinging nettles.  Contact urticaria can be produced
by a variety of substances and may be immunologi-
cal, nonimmunological, or of unknown mechanism.
Contact urticaria can be severe, with associated
anaphylaxis.
Contact dermatitis is a very common disorder,
and a high index of suspicion should be maintained
in the evaluation of all cases of eczematous derma-
titis.  Contact dermatitis should be considered in
cases of recurrent dermatitis or when dermatitis
fails to respond to appropriate therapy.  It should be
considered in the evaluation of dermatitis that dem-
onstrates patterns such as symmetry and linearity,
or location at common sites of exposure to allergens
such as the earlobes or belt buckle area.  The evalu-
ation of such dermatitis begins with a detailed his-
tory of exposure to plants, creams, lotions, solvents,
and topical medications.  The diagnosis may be
strongly suspected based on thepatient’s history
and may be confirmed in many cases with use
testing or patch testing.
Effective therapy for contact dermatitis exists,
and soldiers should report for medical intervention
as soon as dermatitis develops.  Early diagnosis and
therapy may significantly shorten the course of the
dermatitis, allowing the soldier to return to full
duty with minimal delay.
The battlefield is a harsh environment for the
skin, with many potential allergens and irritants.
Some of these may be indigenous to the local area,
while others may be imported with the troops.  If
the healthcare provider is alert to the clinical ap-
pearance of contact dermatitis, makes the proper
diagnosis promptly, and institutes appropriate
therapy, significant morbidity can be avoided and
troop strength and readiness will be enhanced.
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Livingood CS, Rogers AM, Fitz-Hugh T. Dhobie mark dermatitis. JAMA. 1943;123: 23–26.
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Goldsmith NR. Dermatitis from Semecarpus anacardium (bhilawanol of the marking nut). JAMA. 1943;123:277–
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Coomber RB. Dermatitis from contact with varnish of Japanese rifles. Arch Dermatol. 1947;55:110–111.
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Mitchell JC, Rook A. Botanical Dermatology: Plants and Plant Products Injurious to the Skin. Vancouver, Canada:
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Little C. Dermatitis produced by Japanese lacquer. Br Med J. 1924;1:1112–1113.
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Becker LE, Shipworth GB. Ginkgo tree dermatitis, stomatitis, and proctitis. JAMA 1975;231:1162–1163.
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Thompson G, Maibach HI, Epstein J. Allergic contact dermatitis from sunscreen preparations complicating
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37.
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Fisher AA. Nickel dermatitis. Dermatology. Dec 1981:19.
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Epstein E. Shoe contact dermatitis. JAMA. 1969;209:1487–1492.
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Lynde CW, Warshawski L, Mitchell JC. Patch test results with a shoewear screening tray in 119 patients, 1977–
80. Contact Derm. 1982;8:423–425.
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Mali JWH, Malten K, Van Neer, FCJ. Allergy to chromium. Arch Dermatol. 1966;93:41–44.
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Farkas J. Chronic shoe dermatitis from chromium tanned leather. Contact Derm. 1982;8:140.
46.
Scutt RWB. Chrome sensitivity associated with tropical footwear in the Royal Navy. Br J Dermatol. 1966;78:337–
339.
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Davies JH, Barker AN. Textile dermatitis. Br J Dermatol Syphil. 1944;56: 33–37.
48.
Fregert S, Gruvberger B, Göransson K, Normark S. Allergic contact dermatitis from chromate in military textiles.
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49.
Hatch K, Maibach HI. Textile dermatitis. J Am Acad Dermatol. 1985;12: 1079–1092.
50.
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Tindall JP. Chloracne and chloracnegens. J Am Acad Dermatol. 1985;13:539–560.
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Cutaneous Trauma and Its Treatment
143
CUTANEOUS TRAUMA AND ITS
TREATMENT
Chapter 7
MICHAEL MULVANEY, M.D.* AND ALLAN HARRINGTON, M.D.†
INTRODUCTION
FRICTION BLISTERS
Pathogenesis
Risk Factors
Prevention and Treatment
CUTANEOUS TRAUMA
Anatomy
Evaluation and First Aid
Microbiology
SURGICAL INTERVENTION
Anesthesia
Surgical Technique
Wound Healing
Wound Dressings
Complications
SUMMARY
*2 Corporate Plaza, Albany, New York  12203; formerly, Major, Medical Corps, U.S. Army, Dermatology Service, Walter Reed Army Medical
Center, Washington, D.C.  20307-5001
†Major, Medical Corps, U.S. Army; Dermatology Service, Walter Reed Army Medical Center, Washington, D.C.  20307-5001

Military Dermatology
144
INTRODUCTION
The skin presents itself on the front lines of de-
fense against the outside world, affected by the
harsh effects of the environment: high and low
humidity and temperature, solar radiation, wind,
dirt, arthropods, and infectious agents.  The soldier’s
skin may also be assaulted by nuclear, biological,
and chemical agents.  Finally, skin on the feet is
frequently subjected to frictional forces, which
causes blisters.  Dermatologists have had a tradi-
tional role in caring for skin disease resulting from
many of these insults.
With the advent of dermatologic surgery, knowl-
edge and experience in caring for wounded skin has
been established.  Present requirements for derma-
tology residency mandate knowledge of principles
and practical competence in basic skin surgery,
including excisional surgery with simple and lay-
ered closures.  Knowledge of principles is also man-
datory for scar revision, skin grafts, and local cuta-
neous flaps.  It is a natural extension of this exper-
tise for the dermatologist to be involved in caring
for traumatic injury to the skin.  Most of the derma-
tologists deployed during Operations Desert Shield
and Desert Storm were in general medical officer
positions.  Those stationed at battalion aid stations
were likely to receive and treat soldiers with trau-
matic skin injuries.
Treatment of cutaneous traumatic injuries draws
on knowledge that is well established in dermato-
logic surgery: anatomy, anesthesia, microbiology,
wound healing, surgical technique, dressings, and
scar revisions.  An approach based on this knowl-
edge will be presented in this chapter.  In addition,
because of the prevalence of friction blisters in the
military, a comprehensive review of this area will
be presented.
FRICTION BLISTERS
Even experienced and well-conditioned soldiers
can have a blister rate approaching 50% as a result
of a long march.4
Friction blisters of the feet may be a short-lived
medical problem, but for soldiers they are not a
trivial condition.  The treatment of these blisters
accounts for a significant loss of time for the medi-
cal staff and the troops.  The morbidity associated
with friction blisters sometimes extends beyond the
pain and discomfort of the lesion.  One study
reported that 84% of the cellulitis treated in a
navy recruit population was caused by friction blis-
ters, with an average loss of 8 days per case.5  Of
note, cellulitis composed over 17% of all recruit
admissions.
Pathogenesis
To better understand the pathogenesis of friction
blisters, it is first necessary to review briefly the
superficial anatomy of the skin.  The most superfi-
cial layer of the skin is the epidermis, consisting of
several layers of cells, with the stratum corneum its
outermost layer.  The next layers are the stratum
granulosum, followed by the stratum malpighian,
and finally the stratum basale.  The stratum basale
is the deepest layer of the epidermis and is located
adjacent to the dermis.
Friction blisters are believed to be confined to
humans, occurring with such frequency that they
are considered one of the most common reactions to
trauma.1  Friction blisters are especially important
in the military, where they can jeopardize mission
performance by decreasing a soldier’s work toler-
ance and increasing manpower loss.  Friction blis-
ters are also of significance in athletics, especially
distance running, where they adversely affect per-
formance.  Finally, this type of blister can provide
an important diagnostic clue to a group of inherited
diseases called epidermolysis bullosa.  This
genodermatosis has as a hallmark blisters that are
easily induced by friction.
Despite the prevalence of friction blisters, there
has been a paucity of scientific study in this area.
This deficiency stands in marked contrast to the
well-researched classic bullous dermatoses (eg,
pemphigoid, pemphigus, and dermatitis herpeti-
formis).  The military has been an important con-
tributor to the present fund of knowledge on fric-
tion blisters.
In the military, friction blisters have long been
recognized as a significant medical problem.2  The
high incidence of friction blisters at military train-
ing centers is especially well documented.  It has
been estimated that 20% or more of soldiers sustain
friction blisters during the early weeks of training.3

Cutaneous Trauma and Its Treatment
145
The histology of a friction blister has a character-
istic pattern.  One observes necrosis of keratinocytes
in the stratum malpighian, which leads to separa-
tion of the epidermis.  The cleavage plane always
shows the roof of the blisters to consist of stratum
corneum, stratum granulosum, and some cellular
debris.  The epidermis below the cleft does not show
any significant cellular damage.6
A blister is not the only possible endpoint when
friction is encountered.  If the friction is applied in
small amounts over a longer time (weeks to months),
then the result is epidermal hypertrophy (thicken-
ing of the skin).2  One example of this endpoint is a
callus, which is known to protect against the devel-
opment of friction blisters.  If a significant friction
force is applied acutely to areas of the body where
the epidermis is not thick, then an abrasion results.1
As a result, friction blisters typically form on the
palms and soles, which have a very thick epidermis.
The most important forces in the formation of a
friction blister are the dynamic shear forces.  These
are believed to be composed of interrelated forces
consisting of vertical forces, fore and aft shear,
lateral shear, and torque.7–9  The complexity of the
physics of shear force, along with the variability of
gait and bone structure of the foot, make it impos-
sible to quantify a specific force required to produce
a blister.
Separation of the epidermis is determined not
only by the net shear force transferred to the skin
surface but also by the frictional characteristics of
the skin–environment interface.2  Knowledge of
factors that can influence this frictional force is
important in helping to understand and prevent the
formation of friction blisters.  The surface condi-
tions of the skin influence the development of fric-
tion blisters by altering the coefficient of friction
between the skin and the boot.  Keeping the foot dry
has been shown to reduce the formation of friction
blisters by lowering the coefficient of friction.10  Wet
skin also lowers the coefficient of friction, decreas-
ing the risk for friction blisters.  Moderately moist
skin, however, will tend to cause more blisters be-
cause the coefficient of friction is increased.10–12
Risk Factors
In addition to moderately moist skin, several
other risk factors are known to influence friction
blister formation.  Improperly fitting or poorly de-
signed shoes have long been recognized as a con-
tributing factor.  Several studies of basic training
soldiers have shown that the majority of blister
problems appear in the first 2 to 3 weeks.13,14  A
recent study done with Reserve Officer Training
Corps (ROTC) cadets in initial officer basic train-
ing revealed less blister formation in officers who
frequently ran long distances.15  This same study
showed no advantage to wearing broken-in boots
on road marches.
Additional risk factors were identified when
studying ROTC cadets at summer camp.15  Females
had a relative risk 1.6-fold greater than that of
males.  Cadets with a history of blisters in the 2
years before camp had an increased risk of blister
formation.  Cadets who reported wearing their boots
less than 20 hours per week during the 2 weeks
immediately before camp had an elevated risk of
friction blister formation.  One of the conclusions
drawn from this study was that prevention of blis-
ters primarily through conditioning the foot with a
skin-thickening response was one of the most im-
portant steps that could be made in preventing
friction blisters.
Another very important risk factor for friction
blister formation is socks and their fiber composi-
tion.16  Poorly fitting or worn-out socks have been
identified as an important agent in the formation of
friction blisters.  Of even more significance is
the information obtained after studying long-dis-
tance running.  The results showed that an acrylic
fiber sock was associated with fewer and smaller
blisters when compared directly with cotton fiber
socks.  The Thor-lo brand of sock (manufactured by
Thorneburg Hosiery Co., Inc., Statesville,
N.C.) appears to have been associated with fewer
blisters for army-tested soldiers when compared
against the standard issued sock: acrylic wicks
away moisture from the foot.17  Socks made of
natural fibers like cotton and wool absorb moisture,
resulting in a harder, bulkier sock that promotes
larger and more frequent blisters.  It is important to
note that the Thor-lo sock contains higher-density
padding where frictional forces are greatest and
snug-fitting, low-density padding in the arch area,
to allow for better conformity.  This differential in
sock thickness may also be important in reduced
blister formation.  All acrylic socks do not possess
this type of construction.
Prevention and Treatment
Prevention of friction blister formation is the
most important front-line approach in dealing with
this common problem.1  Preventive measures
should begin with preenlistment evaluation for
congenital or acquired anomalies of the feet and
skin as well as assuring adequate fit of shoes.  Foot-

Military Dermatology
146
care lectures to recruits and recruit commanders’
stressing prevention and early recognition of blis-
ters are also important strategies.
Prevention of friction blisters can be divided into
two categories: toughening the skin and reducing
shear force.  Currently, no adequate commercially
available topical products exist to harden the skin
surface.  The use of tincture of benzoin has been
reported anecdotally but the inconvenience and
the high incidence of contact dermatitis makes
this impractical.3  The development of epidermal
hypertrophy through conditioning the skin
results in a decreased susceptibility to friction blis-
ters.15  This approach is very effective when it can be
implemented.
Shear force has been decreased with several mo-
dalities.  Insoles and teflon sprays successfully re-
duce the shearing effect, but their limited availabil-
ity and considerable expense make these items
impractical for large-scale military use.3  A study of
U.S. Marine Corps recruits showed that the use of
an antiperspirant foot powder resulted in fewer
friction blisters.18  This outcome was seen because a
dryer foot has a decreased coefficient of friction.
Similar results were revealed in a study of U.S.
Army soldiers that showed a reduction in friction
blisters with the use of antiperspirant solutions.19
However, the frequent finding of irritant dermatitis
(38%) made this therapeutic option impractical.
The most exciting recent advances in the preven-
tion of friction blisters have involved sock studies,
as noted above.  Acrylic socks with different pad-
ding densities have been shown to decrease the
number and size of friction blisters in marathon
runners and soldiers.16,17
The most common approach to the treatment of
friction blisters involves first draining the blister
with a sterile needle.  A doughnut shape of mole-
skin is then cut to surround the blister, and a cap of
moleskin is placed over the blister.  Other aspects of
treatment include daily cleaning, preferably with
hydrogen peroxide, followed by the application of
an antibacterial ointment.  Surveillance for the de-
velopment of lymphangitis or cellulitis is impor-
tant.  Finally, if the epidermal roof has been com-
pletely lost, then another membrane covering is
needed to provide optimal conditions for wound
healing.  Some of the newer synthetic hydrocolloid
dressings (eg, DuoDERM, manufactured by
ConvaTec, Princeton, N.J.) or hydrogel dressings
(eg, Vigilon, manufactured by C.R. Bard, Inc.,
Murray Hill, N.J.) are effective options.
The facial nerve exits the stylohyoid foramen at the
base of the skull, entering the parotid gland near the
angle of the jaw, where it separates into five
branches.  These branches fan out across the face,
ranging from the temple and forehead down to the
neck and mandible.  The facial nerve supplies motor
nerves for the muscles of facial expression.  Injury
to these branches will give a noticeable deficit to
facial movement.20
The temporal branch of the facial nerve is the
branch most superficially located and easily injured.
The nerve exits the parotid gland and traverses the
zygomatic arch and temporal region, terminating in
the occipitofrontal muscle at the forehead.  The
nerve is located in the superficial temporalis fascia,
which is covered by a thin subcutaneous tissue
layer and overlying skin.  This thin protective layer
is easily breached by a laceration.  Once the nerve
has entered the occipitofrontal muscle fascia, it ar-
borizes sufficiently to maintain function in the event
of a localized injury to the forehead.
The zygomatic and buccal branches of the facial
nerve supply motor nerves to the lower eyelid, nose,
and lip elevators.  These nerves exit the parotid
Cutaneous trauma treated by a dermatologist is
restricted to superficial soft-tissue injuries.  Ana-
tomically, all of these lesions have in common dis-
ruption of at least the epidermis.  The dermis, sub-
cutaneous fat, and superficial fascia can also be
injured.  Common examples of cutaneous trauma
include lacerations, burns, blisters, and traumatic
tattoos from blast injuries.
Anatomy
Evaluating a wound for the extent of cutaneous
damage and planning for repair rely heavily on a
thorough knowledge of the injured area’s anatomy.
The initial evaluation should consider the possibil-
ity of underlying bone or visceral injury.  In wounds
confined to the skin and subcutaneous tissue, cer-
tain areas of the body contain extremely important
nerves, arteries, muscles, and other specialized
structures.  These danger areas will be discussed in
detail in this section.  Discussion of the orbit, al-
though vital, is beyond the scope of this chapter.
The face contains an abundance of superficially
located structures that may be damaged by trauma.
CUTANEOUS TRAUMA

Cutaneous Trauma and Its Treatment
147
fascia under a fairly thick cheek fat pad and emerge
at the undersurface of the facial muscles they inner-
vate.  Injury of the lateral (proximal) third of their
route would involve the parotid gland.  This would
cause extensive loss of function from these branches
and possibly others.  Injury along the middle third
would require a deep penetration into the cheek fat
pad.  This injury would also threaten Stenson’s duct,
which traverses the parotid gland inferior to the zy-
goma before entering the mouth at the buccal mucosa.
Localized injury of the distal third of these branches
may not yield significant loss of muscle function
due to the extensive branching of these nerves.
The marginal mandibular nerve exits the parotid
gland and usually runs behind the ramus of the
mandible.  In some cases, however, it may be lateral
and inferior to the ramus, exposing it to injury.  The
branch then runs protected by the medial surface of
the mandible.  It reaches the body of the mandible
and, along with the facial artery, travels medially
and superiorly toward the lateral commissure of
the mouth.  The nerve arborizes and innervates the
muscles around the mouth, especially the orbicu-
laris oris and the downward depressors of the lips.
The probable points of injury are the ramus and
the body of the mandible.  Injury of the body of
the mandible could be accompanied by profuse
hemorrhage if the facial artery were severed.  The
cervical branch of the facial nerve innervates the
platysma and has little clinical significance.20
The sensory innervation of the face is supplied by
the trigeminal nerves.  The nerves exit foramina
of the skull in distinct locations.  The ophthalmic
branch (V1) gives rise to the supraorbital and
supratrochlear nerves, which provide sensory (af-
ferent) function to the forehead and anterior scalp.
The infraorbital nerve of the maxillary branch
(V2) surfaces at the infraorbital foramen 1 cm below
the infraorbital ridge in the midpupillary line.  The
nerve spreads out to innervate the lateral nose,
upper lip, medial cheek, and lower eyelid.  The
mental nerve arises from the mandibular branch
(V3), passing through the mental foramen of the
mandible approximately 1 cm above the jaw line in
the same midpupillary line that aligns the supraor-
bital and infraorbital nerves.
The arterial supply of the face is provided mostly
by the facial artery, a branch of the external carotid
artery.  The artery emerges from under the man-
dible and travels in a superior and medial direction
along the lateral aspect of the mouth.  The inferior
and superior labial arteries branch medially to sup-
ply the lips.  These arteries are on the posterior
labial surfaces between the submucosa and the
orbicularis oris, and they can produce significant
hemorrhage.  They may bleed from both sides of a
laceration.  The angular artery continues after the
labial arteries branch off the facial artery.  It lies
along the side of the nose in the nasofacial sulcus
and passes into the medial canthal region, where it
anastomoses with the dorsal nasal artery.  This
latter artery is a branch of the internal carotid ar-
tery, which exits the side of the nasal bone in the
medial canthal region.20
The auriculotemporal artery, also a branch of
the external carotid artery, progresses in the
preauricular fold, branching into the superficial
temporal artery.  Other arteries travel along with
the previously named sensory nerves.  The scalp is
a rich anastomotic plexus of arteries and veins.
In general, any artery that is transected can be
ligated without concern for ischemia of the supplied
skin, provided the other anastomotic connections are
intact.  If a strip of skin is partially avulsed, then the
blood supply may be significantly compromised.
The neck contains several vital structures that, if
damaged, are beyond the expertise of the dermato-
logic surgeon.  The trachea, thyroid gland, carotid
arteries, and jugular vein are located in the anterior
neck.  Injury to these structures is life threatening.
The lateral and posterior neck are relatively free
from subcutaneous vital structures.  The architec-
ture is defined by large muscles located deep to the
skin and subcutaneous tissue.  The only important
nerve to be aware of in this region is the spinal
accessory nerve, located posterior to the upper one
third of the sternocleidomastoid muscle.  This nerve
travels posterocaudally into the trapezius muscle.
It is located on the fascia overlying the scalenus
muscle.  Injury to this nerve would lead to a deficit
in abducting the arm laterally and fixing the scapula.
Injuries to the skin and subcutaneous tissues of
the trunk that do not penetrate into pleura, perito-
neum, or muscle do not approach any significant
arteries or nerves; therefore, potential damage is
limited.  Injury to the extremities must be carefully
evaluated, especially in areas of the forearm, hand,
and foot.  Many arteries, nerves, tendons, and joint
spaces are close to the skin surface and are easily
injured.  Surgeons with special competence, such as
orthopedic surgeons, plastic surgeons, or podia-
trists, would be logical choices for definitive care of
these injuries.  Detailed description of this anatomy
is beyond the scope of this chapter.
The arms and thighs consist of large areas of skin
covering muscle tissue.  Except near the elbow and
knee, most important structures are well protected
by these muscles.

Military Dermatology
148
The genitalia have tremendous psychological
importance in addition to their structural impor-
tance.  Injury to the urethra or other deeper struc-
tures of the penis or scrotum would best be handled
by a urologist or plastic surgeon.  Superficial
wounds, however, may be treated like those in any
other area.
Evaluation and First Aid
In emergent care, basic initial evaluation takes
little time but may be lifesaving.  Airway patency,
breathing, and adequate circulatory system func-
tion should be evaluated first.  Skin and soft-tissue
injury care must be delayed until circulatory vol-
ume is adequate and internal injuries have been
ruled out.  With any significant facial trauma, cervi-
cal fracture should be suspected, even in the ab-
sence of symptoms.21  Bleeding should be controlled
by pressure until the patient is proved to be free of
serious underlying injury.  Casualties should be
appropriately stabilized and triaged if further care
is needed.
The types of wounds that a dermatologist would
be most helpful with include abrasions, lacerations
of the skin, and traumatic tattoos.  Evaluation of
these wounds requires a historical account of the
injury.  The nature of the wound, the amount of
contamination that has entered the skin, the amount
of delay in reaching care, and first aid rendered
since the injury are ascertained.  The medical status of
the casualty including medications, significant medi-
cal problems such as diabetes or bleeding disorders,
and tetanus immunization status are determined.
Examination of the wound proceeds with con-
cern for loss of function, depth of injury, and cos-
metic impact.  Functional considerations include
damage to major sensory or motor nerves, arterial
supply, and muscle and tendon damage.  These
injuries would best be managed by a specialist with
experience with such injuries.  Similarly, injuries
deeper than the skin and subcutaneous tissue are
beyond the dermatologist’s expertise.  Highly spe-
cialized areas such as eyelids, hands, and genitalia
would also be referred if the injury is extensive.21
Neurological testing of the surrounding skin may
be hampered by the pain of the injury, but it needs
to be thoroughly performed and documented be-
fore the area is anesthetized for debridement and
closure.  Knowledge of neuroanatomy is required
to predict what motor nerves may be in the injured
area.  In an emergency, testing with standard
pinpricks should be adequate for determining sen-
sory nerve function.  Frequently, small cutaneous
nerves will be transected by the injury.  This finding
should be documented before beginning any repair
of the skin, and the patient should be reassured that
sensory function usually returns.  Regional loss of
sensory function would mandate further evalua-
tion by an experienced specialist in this form of
injury.  Nerve repair could then be done immedi-
ately, or in 10 to 12 days.  Nerve grafts may also be
indicated.
After the neurological exam is complete, the
wound should be cleaned and debrided to evaluate
the wound further.  Local anesthesia, regional anes-
thesia, or both make the process comfortable and
efficient.  Anesthesia will be described later.
Irrigation with saline will remove blood and clots;
dirt and other foreign-body material; and gross
bacterial contamination.  Antibacterial agents with
detergents may also be used: Betadine (povidone-
iodine, manufactured by Purdue Frederick,
Norwalk, Conn.), Hibiclens (chlorhexidine glucon-
ate, manufactured by Stuart, Wilmington, Del.), or
pHisoHex (hexachlorophene, manufactured by
Sanofi Winthrop, New York, N.Y.).  To prevent
further contamination of the wound, surgical asep-
tic technique should be employed, including sterile
drapes, gloves, instruments, and bowls for solu-
tions.  Battlefield wounds should be assumed to be
contaminated from injury and reasonable means
should be undertaken to prevent further contami-
nation, thereby reducing the chance of wound in-
fection.  In the military environment, several ech-
elons of care may be used to treat an individual
patient.  Each manipulation of the wound will bring
another chance for bacterial contamination.  There-
fore, all reasonable efforts should be made to re-
duce such contamination.22
With all the clots and foreign bodies removed,
careful inspection with good lighting should reveal
the extent of the injury.  If bleeding is present, then
control by means of electrocoagulation (biterminal)
or electrodesiccation (monoterminal) should be ef-
fective.23  Bleeding from larger skin arteries may
need to be controlled by ligation.  The artery is first
clamped with a hemostat at its bleeding point, then
a loop of absorbable suture is placed around the
vessel and tied firmly.  The hemostat is slowly
released to check for the adequacy of the ligature.
For major arteries, nonabsorbable suture is recom-
mended.  Hemostasis should be careful and com-
plete.  Bleeding after surgery may lead to hematoma
formation.  The surgeon should be aware that the
addition of epinephrine to the anesthetic solution

Cutaneous Trauma and Its Treatment
149
may temporarily constrict vessels, which may then
bleed several hours later.
Many arteries travel near nerve bundles.  Over-
zealous electrosurgery or sloppy ligation may cause
permanent damage to nearby nerves.  All hemostasis
should be meticulous and complete, especially in
wounds that are to be closed by suture.
Microbiology
It is reasonable to assume that all wounds are
contaminated with bacteria and particulate matter.
With aggressive wound irrigation and debridement,
most of the foreign material is removed.  The use of
antibiotics to prevent clinically apparent infections
may be helpful in some instances.21
From the history and examination of the wound,
the approximate type and quantity of contamina-
tion can be determined.  The length of time from
injury to care will have a large impact on the wound.
Many combat-related injuries will be delayed in
receiving initial care.  The healthcare delivery system
in the field involves echelons of service.  This contrib-
utes to multiple delays in transportation and evalua-
tion.  Most non–life-threatening soft-tissue injuries
will be triaged less urgently than more serious
wounds.  The health of the individual also must be
taken into account.  Exhausted, poorly nourished
soldiers who have had prolonged exposure to cold
or heat may have less resistance to infection.
Bacteria that commonly have been found to cause
wound infections in wartime are staphylococci (S
aureus and S epidermidis), streptococci (hemolytic,
nonhemolytic, and enterococci), coliforms (enteric
Gram-negative rods), Pseudomonas aeruginosa, Pro-
teus species, Hemophilus influenza, Clostridium
species(C tetanus and C perfringens), and Bacillus
subtilus.  The type of organism encountered will
vary with the type of contamination, climate, and
the location of the wound.24
Animal bites may be contaminated with Pas-
teurella multocida.25  Human bites contain a mixed
flora of streptococci (group A, non–group A),
Bacteroides species, diphtheroids, Hemophilus influ-
enza, and enterococci.  Soil-contaminated wounds
may have multiple organisms present including
clostridia, Bacillus species, and various Gram-nega-
tive rods.  Sandy soil is less contaminated with
bacteria than nonsandy soil.26
Traumatic wounds should be treated with pro-
phylactic antibiotics to prevent postoperative infec-
tions.  The antibiotic is best given shortly before or
within 2 hours after the procedure.  However, this
protocol is not possible with most traumatic wounds,
which are usually hours or days old and heavily
contaminated.  The contaminating bacteria have
had an opportunity to colonize or infect the wound
before any prophylactic antibiotic could be utilized.
Antibiotics in these cases would be used to prevent
overt infection and sepsis.  The potential causes of
the infection must be adequately covered.  The use
of antibiotics should not replace the use of proper
wound-management techniques including wound
toilet, debridement, and careful surgical technique.
In general, penicillin, erythromycin, and cephalospor-
ins are useful against most of the common infecting
organisms.27  The exudate from overtly infected,
draining wounds should be cultured and Gram-
stained before antibiotic coverage is instituted.
Contaminated wounds that are left open are much
less likely to become infected than those closed
primarily.  The wound may be closed 4 days or more
after the initial evaluation with less risk of infection
and sepsis, provided wound infection is not present
at the time of delayed closure.  If the wound exudate
contains less than 106 organisms per milliliter, then
clinical infection is unlikely.  Experiments have
been performed demonstrating that an inoculum of
greater than 106 S aureus bacteria was necessary to
produce pus, but lower numbers of bacteria pro-
duce redness and swelling.28  Surgeons have com-
mented29 that what is surprising is not that wound
infection occurs, but that it does not occur more
frequently.
SURGICAL INTERVENTION
The goals of surgical intervention on a traumatic
wound are restoring function and achieving a cos-
metically appealing result.  Prevention of further
morbidity due to the surgery is paramount and
implicit.  Through careful planning and meticulous
techniques, all these objectives may be met.
Much of the planning should be preceded by
evaluation of the type of wound, extent of injuries,
and anatomical considerations.  The first question
for the dermatologist should be whether the man-
agement of the wound exceeds his or her ability; if
so, appropriate consultation or referral should be
made.  If the dermatologist feels competent, then
the planning begins.

Military Dermatology
150
Anesthesia
Any soft-tissue wound that is to be properly
cleaned, debrided, and repaired must be anesthe-
tized.  For the wounds that a dermatologist would
treat, local anesthesia, occasionally augmented
with intravenous sedation, is all that should be
needed.  As was mentioned previously, a thorough
neurological exam must precede the instillation of
any anesthetic.
Because of the efficacy, safety, short duration of
onset, and familiarity by dermatologists, lidocaine
(1% or 2%) is the most anesthetic agent.  Others have
properties such as longer action (ie, bupivacaine),
which may be desired.  Etidocaine combines shorter
duration of onset with longer duration of anesthesia.30
The addition of epinephrine (1:100,000–1:200,000)
will control bleeding and increase the duration of
anesthesia when combined with a local regional
anesthetic.  Caution must be used in areas where
tenuous blood supply exists.  Danger areas include
acral skin, digital arteries, partially avulsed skin
flaps, lower legs, and feet.  Patients at high risk
include those with significant vascular compromise
due to diabetes, atherosclerosis, or other causes.  If
the patient is taking medications known to interact
with epinephrine such as monoamine oxidase
(MAO) inhibitors, propranolol, or tricyclic antide-
pressants, significant blood pressure elevation may
result.29
The technique for anesthetizing the skin would
be similar to that for elective soft-tissue surgery.
The major difference is the pain the patient has
prior to starting.  Anxiety may also be much greater
because of the circumstances of the injury and the
pain present.  Vocal anesthesia (ie, coaching)
will make a tremendous impact on the success of
the anesthetic experience.  Reassurance, explana-
tions, and compassion will relieve the anxiety and
make the anesthetic administration easier for the
patient and the physician.  A recently described
technique will significantly decrease the stinging
effect of local anesthesia.  The addition of sodium
bicarbonate (1 mEq/mL) to the anesthetic solution
will adjust the pH closer to the physiological
range.  This adjustment is accomplished by adding
1 mL of sodium bicarbonate solution for every 10
mL of anesthetic solution to be made.  The solution
should be used within 1 week of mixing to ensure
effectiveness.31
Inserting a small-gauge needle (nos. 27–30) per-
pendicularly through the skin into the subcutane-
ous tissue will cause only slight discomfort.  Slow
instillation of anesthetic agent will decrease the
pain of injection.  The needle is then advanced in the
subcutaneous plane to minimize the number of
needle sticks.  Reinsertion of the needle should be
through previously anesthetized areas.  Rushing
will greatly increase the pain for the patient.
A variety of strategies can be used for anesthetiz-
ing a skin wound.  Wounds may be quite large, and
regional nerve blocks can decrease both the amount
of anesthetics used and the discomfort of large
amounts of local infiltration.  Knowledge of the
sensory innervation of the skin will allow planning
of appropriate blocks.  When performing a regional
block, the objective is to bathe around rather than to
inject directly into the nerve bundles.  This tech-
nique will lessen the pain of injection and prevent
possible nerve damage.
Important regional facial sensory nerve blocks
include supraorbital, supratrochlear, infraorbital,
and mental.  Digital blocks of the fingers are also
useful.  Unless one has experience with regional
anesthesia of the extremities, these should not be
attempted.
If individual nerves are not suitable for regional
block, then a field block can be utilized.  Also, by
injecting initially into the proximal path of the nerve
supply and then advancing distally, the physician
can lessen the pain of anesthesia.  Local infiltration
of the wound should be performed last because
injection of tender tissue is more painful than injec-
tion of normal tissue.
Once the area is anesthetized, cleaning, debride-
ment, and wound repair can proceed.  Instillation of
a long-acting anesthetic such as bupivacaine may
give postoperative pain relief for several hours.
Surgical Technique
The decision to close the wound or to allow
second-intention healing with possible delayed clo-
sure or grafting depends on several factors, including
• the length of time from injury to repair,
• the amount of contamination in the wound,
• the amount of devitalized or damaged tis-
sue, and
• the location of the wound.
Although immediate closure offers quicker and
easier repair of the defect, it greatly increases the
risk of infection.  Bacteria proliferate rapidly in the
necrotic debris and clots of an open wound.  Foreign
bodies offer safe haven for these bacteria.  The
longer the time between injury and repair, the higher
the bacterial counts.  Wounds over 6 hours old

Cutaneous Trauma and Its Treatment
151
should be considered for second-intention healing
or delayed repairs.
Contamination is inevitable in traumatic wounds.
Relatively clean lacerations caused by glass or clean
sharp objects may be cleaned of most foreign bodies
and repaired.  Grossly contaminated wounds, or
those contacted by feces or saliva, should remain
open.  Devitalized tissue and necrotic skin are much
more likely to harbor bacteria and, unless thor-
oughly excised, will lead to infection.  Finally, the
location of the wound or, more importantly, the
adequacy of the blood supply also is considered in
planning the closure.  Wounds of the lower extrem-
ity are much more likely to be infected.  These
wounds are at high risk of infection if closed.  How-
ever, due to the high volume of blood flow and
generous collateral blood supply, facial and scalp
lacerations are more resistant to infection and
should be closed immediately.
The necrotic tissue and foreign body must be
removed.  Copious irrigation and direct scrubbing
are very useful in preparing the wound.  Irrigation
should be carried out with a high-pressure system
consisting of a 20- to 50-mL syringe with an 18- to
21-gauge needle.  This will remove dirt and bacteria
but will not embed these materials more deeply in
the wound.  Direct scrubbing with a sponge will
remove gross material but probably does not re-
duce infection.
Clearly devitalized tissue should be excised care-
fully.  Any recalcitrant foreign body should be
removed also.  The surface shape of the wound
should be contoured to a smooth, symmetrical con-
figuration.  The sides of the wound should be at a
90° angle to the surface of the skin to prevent inver-
sion of the scar.  Reshaping should be tempered
with the resultant defect’s ability to close without
undue tension or distortion at adjacent free edges
such as eyelids, lips, or nostril rims.  It may be more
prudent to keep the wound small and irregular,
with plans for later reconstruction, than to make a
neat, but time-consuming, closure that may be both
difficult to close and at greater risk for infection.
Skin grafts, flaps, or reexcision with possible z-
plasty, w-plasty, or v to y repairs may be done after
healing is completed, under more controlled and
less contaminated conditions.
Surgical debridement should remove all attached
necrotic debris, devitalized tissue, and irregular
jagged wound edges.  On noncritical areas such as
the trunk and extremities, the debridement can
involve an excision around all wounded tissue.
When vital structures such as nerves, muscles, and
specialized structures of the face are close to the
wound, then conservative debridement is recom-
mended.  When tissue vitality is uncertain, a delay
of several days will allow a demarcation to develop,
thus guiding further debridement.
If the wound is to be closed primarily after
debridement, one should evaluate the direction and
shape of the wound.  Traumatic wounds often do
not conform to the relaxed skin tension lines (RSTLs).
Shifting the direction of closure may require a z-
plasty to put the tension of closure perpendicular to
these RSTLs.  This additional surgery may be best
delayed until after healing of the first repair.  Scar
revision under more controlled conditions will de-
crease the risk of infection.
The choice of suture materials should minimize
the risk of both infection and wound dehiscence.
Subcuticular sutures such as vicryl, dexon, or
polydioxone (PDS) should be reserved for rela-
tively clean wounds and those under moderate
tension.  High-tension closures, hematoma, and
gross contamination are risk factors for infection
that will be compounded by the foreign body of
absorbable suture.  Attention should be given to the
tension of the sutures.  Careful approximation must
be observed, and strangulation must be avoided.
Low-tension wounds may be closed with a
monofilament nonabsorbable suture such as prolene
or nylon.  Adhesive strips are also useful in super-
ficial or low-tension wounds; they may be used
without anesthesia, and negate surface removal.
They also have a low incidence of wound infection
compared with percutaneous sutures.32  As with all
surgical techniques, gentle handling of the tissue is
mandatory.  Gentle traction with skin hooks or
delicate pressure from forceps with teeth will pre-
vent further crushing of the tissue.  Hemostasis
should be complete, especially if immediate closure
is anticipated.  For small blood vessels, light electric
desiccation or electrofulguration will produce less
depth of necrosis than electrocoagulation.  If larger
vessels are encountered, then electrocoagulation or
suture ligation should be considered.
If the wound closure is delayed, then a dressing
is applied.  (Opinions may differ as to whether to
change the dressing daily or to leave it in place for
several days.)  After 4 to 7 days the wound will have
gone through the inflammatory stage of wound
healing and will be entering into the granulation
tissue stage.  This highly vascular state is resistant
to infection.  At this time, the wound can be closed
or a flap or skin graft can be placed.  Some wound
construction may be started at this time, and more
complicated or involved closure may be attempted.
Healing may be completed by second intention.

Military Dermatology
152
Wound Healing
The process of healing in the skin and subcutane-
ous tissue depends on the depth and nature of the
injury.  Superficial abrasions need only to restore
the epidermis.  Full-thickness skin lacerations, with-
out loss of tissue, can be reapproximated easily and
healed in a short period of time.  Full-thickness
defects of skin and subcutaneous tissue with sig-
nificant tissue loss, which preclude primary clo-
sure, require a lengthy and involved process of
wound repair.  The defect must restore a volume of
tissue before the epidermis can regrow or be grafted
over the wound.
Despite these clinical differences in wound heal-
ing, many similarities are found in the biochemical
and physiological stages.  Several models for wound
healing exist, most with three or four stages.  Al-
though these stages overlap in time and interact
with the other stages, they are distinct enough in
function to be separated.  The classification in this
chapter will include inflammation, granulation,
fibroplasia and wound contraction, epidermization,
and maturation.33
Inflammation
Inflammation initiates all the subsequent steps of
wound healing.  It primes the wound for the construc-
tion phases of granulation, fibroplasia, and epiderm-
ization.  Many authorities break this stage into early
and late phases.  The early inflammatory phase begins
immediately with platelet aggregation and the re-
lease of vasoactive substances.  Vasoconstriction of
severed vessels aids in hemostasis, and vasodila-
tion of local intact vessels allow for the influx of
plasma proteins and neutrophils into the wound.33
The plasma proteins involved in the formation of
fibrin help to stabilize the clot and also elaborate
vasoactive and other biologically active substances.
The platelets and fibrin pathway generate a multi-
tude of products including prostaglandins,
leukotrienes, growth factors, and kinins.  Comple-
ment activation occurs, generating products in-
cluding C3a and C5a.  One of the first cellular
responses to all of these substances is the influx
of neutrophils, whose purpose is to destroy and
phagocytize bacteria and foreign-body debris.
The late inflammatory stage is characterized by
the arrival of the monocyte.  This critical cell arrives
at the wound at about the third day and is converted
to a tissue macrophage.  Because it can survive low
oxygen tension and pH, it is able to survive in the
wound and effectively clean up what the neutro-
phils have not been able to finish.  Besides being a
highly effective scavenger, the macrophage is also a
manager of early fibroblast function and prolifera-
tion.  Lymphocytes are also present at this time and,
although not essential, have a control function in
wound healing.33
Granulation
The second stage of wound healing, granulation,
is the beginning of reconstruction of the skin.  Granu-
lation tissue is composed of a rich plexus of new
capillaries within a loose stroma of glycosaminogly-
cans, fibrin, fibronectin, and immature collagen.
During the inflammatory phase, the fibrin clot forms
a scaffolding matrix, which is then coated with
fibronectin derived from serum and fibroblast
sources.  Activated fibroblasts and endothelial cell
buds migrate over this fibronectin coating, which
acts as a glue to the underlying fibrin.  As the
fibroblasts migrate into the fibrin matrix, they syn-
thesize more fibronectin, glycosaminoglycans, and
new collagen.  Gradually, the fibrin is lysed and
collagen replaces it.  Endothelial cells and new
capillaries also invade this matrix, driven by low
oxygen and high lactate concentrations.  Complete
granulation tissue replacement of a deep wound
may take several weeks.33
Fibroplasia and Wound Contraction
In the third stage of wound healing, the fibro-
blast undergoes a morphologic change in order to
migrate into the wound.  The appearance of con-
tractile proteins in the cytoplasm provides a mecha-
nism for motility.  Because these cells greatly re-
semble muscle cells, they are called myofibroblasts.
Within 7 days, these myofibroblasts have pene-
trated the matrix enough to begin exerting their
contractile force on the surrounding wound edges.
This force increases as more cells participate, and
clinically measurable contraction takes place.  This
phase lasts for several weeks, even after epiderm-
ization has occurred.  The clinical effect is helpful in
large wounds to decrease the size of the scar and to
shorten healing time.  Contracted scars can cause
serious morbidity in function and appearance if
they are located near joints or on the face near
eyelids, lips, or other movable structures.33
Epidermization
Epidermization begins within a few days in su-
perficial wounds where the appendages are intact.

Cutaneous Trauma and Its Treatment
153
Hair follicles, sweat glands, and the surrounding
wound edges all contribute to the advancing front
of keratinocytes.  In full-thickness wounds, this
front must wait until granulation tissue has filled
the defect, and the keratinocytes come only from
the edge of the wounds.29
Maturation
Maturation is the final stage of wound healing.  It
begins when all the other stages end and is variable
in time, depending on the wound.  The noticeable
features are the loss of redness and induration from
the wound.  The scar becomes softer and white or
skin-colored.  Histologically, the fibroplasia and
hypervascularity of the wound disappear, to be
replaced by a hypocellular and hypovascular scar.
The collagen produced early in wound healing is
more soluble with less cross-linkage.  With matura-
tion, collagen bundles are thicker and less soluble
with more cross-linking.33
Two clinically different types of wound healing
exist: primary intention and second intention.  An
example of primary intention healing would be a
simple laceration that is reapproximated by suture.
The granulation and contraction stages are mini-
mal, and epidermization is complete within a few
days.  Second intention healing involves a full-
thickness loss of skin volume.  The stages of wound
healing as described previously must all occur.34
Wound Dressings
The care of a wound in a military field setting will
differ from care in a medical center.  Resources such
as time, personnel, and materials may be limited.
The surgeon must pick from the available dressing
materials, with the best choice based on the criteria
discussed below.
Tremendous advances in the understanding of
wound healing and technology have radically
changed the approach to wound dressings.  Whereas
wounds were previously covered with dry gauze or
left uncovered, it is now standard to use moist,
semiocclusive dressings of ever-increasing sophis-
tication.35  Growth factors, bioactive dressings, and
even cultured epidermal coverings are now being
used in major medical centers to facilitate wound
healing.34,36  An effective dressing for wound heal-
ing should
• absorb drainage,
• prevent contamination,
• provide pressure to control bleeding,
• immobilize or splint the wound,
• prevent desiccation of tissue,
• be easy to change with minimal discomfort,
and
• cushion the wound from further trauma.
In addition, the dressing should be readily avail-
able at reasonable cost.
No dressing is perfect for every wound.  Grossly
contaminated or actively draining wounds require
that their dressings be changed more often and
have greater absorption.  Later, when the wound
may be cleaner and have less drainage, a less-ab-
sorptive dressing needing less-frequent changes
may be used.
Complications
The most common and devastating problem of
traumatic wounds is infection.  As previously men-
tioned, many factors contribute to wound infection.
These wounds are at risk for much greater problems
such as sepsis, gas gangrene, and necrotizing
fasciitis.  Early recognition and treatment of these
serious conditions is vitally important.  With these
more involved situations, consultation with a gen-
eral surgeon will be required.
Prolonged bleeding and hematomas are also prob-
able complications of traumatic wounds.  Inad-
equate hemostasis at the time of surgery and de-
layed bleeding are the likely causes.  Congenital or
acquired coagulopathies would be unusual but
should be considered in patients with persistent
bleeding.  Disseminated intravascular coagulation
may be accompanied by sepsis in the wounded
patient.  The presence of excess blood in the wound,
coupled with the pressure effects on tissue from a
hematoma, will increase the likelihood of infection.
Early hematomas should be drained and the of-
fending vessels controlled.  If a hematoma has been
present for several days, drainage will be difficult
until the clot liquefies.  Drainage with a large bore
needle may be attempted when the clot feels more
fluid.  Many hematomas will resolve spontane-
ously.24
Necrosis of skin is caused by inadequate blood
flow to tissue.  Contributing causes include exces-
sive tension, hematoma, infection, crush injuries,
desiccation, or severe disruption of the arterial sup-
ply of the skin.
Wound dehiscence may result from infection,
hematoma, or excessive tension on the wound edges.
It causes delayed healing and an unattractive spread
scar.24

Military Dermatology
154
Traumatic scars frequently will benefit from some
form of reconstructive procedure, which tradition-
ally falls in the realm of the plastic and reconstructive
surgeon.  Experienced dermatologic surgeons may be
able to accomplish many of these procedures.
Many dermatologists now perform dermabrasion
for the improvement of surgical or acne scarring.
An irregular scar surface may be planed smooth by
a brief, simple procedure that utilizes local anesthe-
sia.  Dermabrasion may be performed for blast
tattoo (ie, an accidental depositing of pigmented
particles within the dermis, often as the result of an
explosion) to remove the pigment.  A field-expedi-
ent method employs a stiff toothbrush rather than a
diamond fraise.  Because proper dermabrasion
equipment does not exist in the field, this method
allows prompt treatment of the tattoo before the
pigment has been trapped by macrophages.37,38
Hypertrophic scars or keloids may develop on
the trunk, extremities, or occasionally on the face.  A
nonsurgical scar improvement may be obtained by
intralesional steroid injection.  A concentration of
2.5 to 40 mg/mL of triamcinolone acetonide may be
injected at 3- to 6-week intervals, depending on the
size, location, and aggressiveness of the excess scar
tissue.
Finally, many scars improve with time.  In young
individuals, the scar line will be red for several
months to a year.  Many thick scars will soften, and
contracted scars will relax.  Before attempting a
significant surgical revision, the treatment of time
should be allowed.
SUMMARY
The skin is vulnerable to injury due to environ-
mental hazards in the battlefield environment.  Ex-
tremes of weather, ultraviolet radiation, arthropod
bites, chemical agents, frictional forces and lacera-
tions from missile injury or accidents all may alter
the natural barrier we depend upon to protect us
from life-threatening insults.  Dermatologists pos-
sess the clinical fund of knowledge and soft-tissue
surgical skills to make them critical participants in
the care of traumatic injuries to the skin.
Friction blisters have long been recognized as a
significant medical problem in the military.  The
morbidity associated with friction blisters some-
times extends beyond the pain and discomfort of
the lesion: secondary bacterial infection is common
and often extends time lost per case to as long as a
week.  The most important forces in the formation
of a friction blister are dynamic shear forces.  Mod-
erately moist skin, improperly fitting or poorly de-
signed shoes, poorly fitting or worn-out socks, and
wearing boots less than 20 hours per week during
the 2 weeks immediately before training are all
recognized risk factors for friction blisters.  Preven-
tion of friction blister formation is the most impor-
tant front-line approach in dealing with this com-
mon problem and involves techniques designed to
toughen the skin and reduce shear force.  The devel-
opment of epidermal hypertrophy through condi-
tioning the skin, the use of an antiperspirant foot
powder, and the use of acrylic socks are all impor-
tant preventive strategies.
Cutaneous trauma treated by a dermatologist is
restricted to superficial soft-tissue injuries.  In emer-
gent care, basic initial evaluation takes little time
but may be lifesaving.  Airway patency, breathing,
and adequate circulatory system function should
be evaluated first.  Skin and soft-tissue injury care
must be delayed until circulatory volume is ad-
equate and internal injuries have been ruled out.
The types of wounds that a dermatologist is helpful
with include abrasions, lacerations of the skin, and
traumatic tattoos.  Battlefield wounds should be
assumed to be contaminated from injury.  Aggres-
sive wound irrigation and debridement, and treat-
ment with prophylactic antibiotics to prevent post-
operative infections, are crucial for traumatic
wounds.  In general, penicillin, erythromycin, and
cephalosporins are useful against most of the com-
mon infecting organisms.
The goals of surgical intervention on a traumatic
wound are restoring function and achieving a cos-
metically appealing result.  Local anesthesia, cleans-
ing, debriding, repair, and dressing of such injuries
to the skin are all aspects of wound care for which
dermatologists are well trained.  They should be
incorporated into the surgical care team as needed
in the particular medical care setting to which they
are assigned.

Cutaneous Trauma and Its Treatment
155
REFERENCES
1.
Sulzberger MB, Cortese TA, Fishman L, et al. Studies on blisters produced by friction. Part 1: Results of linear
rubbing and twisting techniques. J Invest Dermatol. 1966;47:456–465.
2.
Akers WA, Sulzberger MB. The friction blister. Milit Med. 1977;16:369–372.
3.
Jagoda A, Madden H, Hinson C. A friction blister prevention study in a population of marines. Milit Med.
1981;146:42–45.
4.
Coopers DS. Research into foot lesions among Canadian Field Forces. CDA 2. Directorate of Clothing, General
Engineering and Maintenance, Ottawa, Canada. Prepared for the 13th Commonwealth Defense Conference on
Operational Clothing and Combat Equipment. Malaysia, 1981.
5.
Hoeffler DF. Friction blisters and cellulitis in a navy recruit population. Milit Med. 1975;140:332–337.
6.
Lever WF, Schaumburg-Lever G. Histopathology of the Skin. Philadelphia, Pa: JB Lippincott Co; 1990: 142.
7.
Spence WR, Shields MN. Prevention of blisters, callosities and ulcers by absorption of shearing forces. J Am
Podiatry Assoc. 1968;58:428–435.
8.
Naylor PF. The skin surface and friction. Br J Dermatol. 1955;67:230.
9.
Root ML, Orien WP, Weed JH. Normal and Abnormal Function of the Foot. Los Angeles, Calif: Clinical Biomechan-
ics Corporation; 1977.
10.
Naylor P. The measurement of epidermal strength. Trans St John Hosp Dermatol Soc. 1952;31:29.
11.
Naylor PE. Experimental friction blisters. Br J Dermatol. 1955;67:327–342.
12.
Whitfield A. On development of callosities, corns and warts. Br J Dermatol. 1932;44:580.
13.
Ressman RJ. Epidemiology of friction blisters. J Assn Mil Derm. 1972;2:13–17.
14.
Marks JG, Miller WW, Garcia RL. March cellulitis. Milit Med. May 1978:314.
15.
Patterson HS, Woolley TW, Lednar WM. Foot blister risk factors in an ROTC summer camp population. Milit
Med. 1994;159:130–135.
16.
Herring KM, Richie DH. Friction blisters and sock fiber composition: A double-blind study. J Am Podiatr Med
Assoc. 1990;80:63–71.
17.
Greene CA. Operational forces interface group soldier enhancement program. Final report on the phase 1
evaluation of the improved sock systems. Natick, Mass: US Army National Research Center. 9 March 1993.
18.
Hamlet M. Analysis of USMC boot sock and foot powder evaluation. Washington, DC: Marine Corps Research,
Development and Acquisition Command. December 1990.
19.
Darringrand A, Reynolds K, Jackson R, et al. Efficacy of antiperspirants on feet. Milit Med. 1992;157:256.
20.
Salasche SJ, Bernstein G, Senkarik M. Surgical Anatomy of the Head and Neck. Norwalk, Conn: Appleton & Lange;
1988: 100–139.

Military Dermatology
156
21.
Schwartz GR, Cayten CG, Mangelsen MA, et al. Principles and Practice of Emergency Medicine. 3rd ed. Philadel-
phia, Pa: Lea & Febiger; 1992: 879–1141.
22.
Bellamy RF, Zajtchuk R. The management of ballistic wounds of soft tissue. In: Bellamy RF, Zajtchuk R, eds.
Conventional Warfare: Ballistic, Blast, and Burn Injuries. Part 1, Vol 5. In: Textbook of Military Medicine. Washington,
DC: US Department of the Army, Office of The Surgeon General, and Center of Excellence in Military Medical
Research and Education; 1991: Chap 5.
23.
Boughton RS, Spencer SK. Electrosurgical fundamentals. J Am Acad Dermatol. 1987;16:862–867.
24.
Salasche SJ. Acute surgical complication: Cause, prevention, and treatment. J Am Acad Dermatol. 1986;15:1163–
1185.
25.
Weber DJ, Wolfson JS, Swartz MN, et al. Pasteurella multocida infection: Report of 34 cases and review of
literature. Medicine. 1984;63:133–154.
26.
Noble WC. Microbiology of Human Skin. 2nd ed. London, England: Lloyd-Luke; 1981: 117.
27.
Feingold DS, Wagner RF. Antibacterial therapy. J Amer Acad Dermatol. 1986;14:535–548.
28.
Elek SD. Experimental staphylococcal infections in the skin of man. Ann NY Acad Sci. 1956;65:85.
29.
Bennett RG. Fundamentals of Cutaneous Surgery. St. Louis: CV Mosby Company; 1988: 56, 144, 219.
30.
Winton GB. Anesthesia for dermatologic surgery. J Dermatol Surg Oncol. 1988;14:41.
31.
Tromouitch TA, Stegman SJ, Glogau RG, et al. How to make lidocaine injection painless. The Schoch Letter.
38:16,1988.
32.
Bennett RG. Selection of wound closure materials. J Amer Acad of Dermatol. 1988;18:619–637.
33.
Clark RF. Cutaneous wound repair: Molecular and cellular controls. Progress in Derm. 1988;22:1–12.
34.
Carver N, Leighim IM. Keratinocyte grafts and skin equivalents. Int J Dermatol. 1991;30:540–551.
35.
Nemeth AJ, Eaglestein WH, Taylor JR, et al. Faster healing and less pain in skin biopsy sites treated with an
occlusive dressing. Arch Dermatol. 1991;127:1679–1683.
36.
Brown GL, Curtsinger L, Jurkiewicz MJ, et al. Stimulation of healing of chronic wounds by epidermal growth
factor. Plast Reconstr Surg. 1991;88:189–196.
37.
James WD, Guiry CC. Treatment of wounds received during live fire exercises. J Assoc Milit Dermatol.
1984;10:632–634.
38.
Notaro WA. Dermabrasion of the management of traumatic tattoos. J Dermatol Surg Oncol. 1983;9:916–919.

Arthropod and Other Animal Bites
157
Chapter 8
ARTHROPOD AND OTHER
ANIMAL BITES
MARK W. COBB, M.D.*
INTRODUCTION
ARTHROPOD BITES: GENERAL CONSIDERATIONS
CENTIPEDES AND MILLIPEDES
INSECTS
Caterpillars and Moths
True Bugs
Lice
Mosquitoes and Flies
Beetles
Stinging Insects
Fleas
ARACHNIDS
Ticks
Scabietic Mites
Nonscabietic Mites
Scorpions
Spiders
REPTILES
Snakes
Gila Monsters
CATS AND DOGS
SUMMARY
*Commander, Medical Corps, U.S. Navy; Dermatology Branch, National Naval Medical Center, Bethesda, Maryland 20814

Military Dermatology
158
INTRODUCTION
The phylum Arthropoda contains more species
than all other phyla combined, comprising literally
billions of organisms.  Only a small percentage of
this myriad of creatures attack humans with any
frequency.  The consequences of these attacks, how-
ever, can be more than trivial, especially in the
military setting.  Cutaneous wounds inflicted by
arthropods, although often insignificant in size,
frequently become secondarily infected in the com-
bat environment.  In some cases, severe systemic
reactions including anaphylaxis may result from the
bite or sting.  An additional concern, the role of
arthropods as vectors of human disease, is discussed
in Chapter 9, Arthropod Infestations and Vectors of
Disease, and Chapter 11, Rickettsial Diseases.
Four classes of arthropods are of dermatologic
interest and are covered in this chapter: Chilopoda,
including centipedes; Diplopoda, including milli-
pedes; Insecta, including caterpillars, moths, bed-
bugs, lice, flies, mosquitoes, beetles, bees, wasps,
hornets, fire ants, and fleas; and Arachnida, includ-
ing ticks, mites, scorpions, and spiders.  Bites in-
flicted by reptiles, specifically snakes and lizards,
and by mammals such as cats and dogs are also
discussed.
Documents from three of the major military con-
flicts of this century (World War I, World War II,
and Vietnam) underscore the significant role played
by arthropods in wartime illness.1–3  Among troops
in France during the later stages of World War I, one
army reported that 90% of all sickness was due to
scabies, infections of the skin, and fevers of un-
known origin.  Because most cases of skin infection
were associated with scabies, pediculosis, or both,
these two infestations accounted for much of the
illness of that army.  Records from Number 25
General Hospital in Hardelot, France, a central hos-
pital established for the care of skin diseases, showed
that scabies was responsible for 65% of all forms of
pyoderma.  In the forward areas during times of
active combat, infestation with Pediculus humanus
var corporis (body louse) was of greater significance
than scabies.  One British division evacuated 11.5%
of its troops to field hospitals for treatment of para-
sitic disease (primarily pediculosis) during the year
1918.  The intimate contact of individuals, their
clothing, and equipment, as well as the lack of clean
clothing and bed linen during combat situations,
promotes the spread of pediculosis and scabies.  Of
the two, the body louse is more easily transferred
from one individual to another and survives much
more readily off humans.
During World War II, the majority of U.S. sol-
diers with dermatologic complaints were treated at
company or camp dispensaries by medical officers
with little or no training in dermatology.2  This
situation resulted in the overtreatment of minor
dermatologic diseases including scabies and insect
bites, frequently resulting in major disabilities.  In
1945, a number of stateside hospitals organized to
care for troops returning from overseas experienced
a marked increase in the incidence of scabies, re-
flecting the frequency of the infestation in Europe.
The dermatology clinic at Camp Lee, Virginia, had
more cases of scabies in 1945 than any other skin
disease (9.3% of cases).2 In the European theater,
scabies likewise accounted for a disproportionately
large percentage of hospital admissions.
During the winter of 1942 to 1943 at the 21st
Evacuation Hospital, 10% of all medical admis
sions were for dermatologic disease and, of these,
30% were scabies.2  Among six hospitals in the
Mediterranean theater surveyed in 1943,
parasitic infestation accounted for 4% to 18.5% of
the admissions to dermatologic services.2  Once
again, soldiers often presented with pyoderma
 such as furunculosis, cellulitis, and impetigo due
to underlying parasitic infestation, so the actual
percentages were much higher.  Once the field
medical officers were instructed on the diagnosis
and treatmentof scabies (benzyl benzoate and
sulfur ointment were used), disability from the
complications of scabietic infestation sharply
decreased and hospitalization for this condition
became uncommon.  Pediculosis, unlike the case
in World War I, was seen infrequently in World
War II.1
During the 8-year span of significant U.S. mili-
tary involvement in Vietnam (1965–1972), dermato-
logic disease accounted for 7.4% of all medical hos-
pital admissions.3  The annual incidence of
hospitalization for skin disease was 3- to 5-fold
higher than that seen among the active-duty army
population in the continental United States over
those 8 years.  Pyoderma accounted for approxi-
mately one third of the cases.  Interestingly, scabies
and pediculosis were not reported as significant
dermatologic diagnoses during the Vietnam con-
flict, and insect bites represented only about 1% of
skin disease seen.  One arthropod reaction reported,

Arthropod and Other Animal Bites
159
however, was blister beetle dermatitis, a blistering
eruption resulting from contact with cantharidin, a
cutaneous irritant contained in certain beetles.  Men
lying on the ground were most susceptible, and the
resultant denuded skin was vulnerable to second-
ary bacterial infection.1–3
ARTHROPOD BITES: GENERAL CONSIDERATIONS
The clinical reaction to an assault on human skin
by an arthropod is influenced by a variety of fac-
tors.4  The injury itself can be due to any combina-
tion of mechanical trauma, secondary infection, sen-
sitization phenomena, and toxic effects.  The nature
of the host also plays a crucial role in the expression
of clinical disease.  Children tend to react more
severely to toxins and superficial irritants and more
frequently suffer secondary infection.  They are
more likely to handle and play with arthropods and
pets harboring arthropods, and will present with
bites on the hands and forearms more commonly
than adults.  The elderly may react more severely to
toxic venoms but are less likely to develop hyper-
sensitivity reactions to bites.
The human skin contains substances that both
attract and repel insects.  It has been demonstrated4
that the attractants are found in sweat, while the repel-
lents are concentrated in the epidermal lipids.  The
individual’s immune status is critical in determining
the reaction to an arthropod assault.  This observation
is perhaps most graphically illustrated in the condi-
tion known as Norwegian scabies.  These patients are
debilitated, immunosuppressed, or both, and when
infested with Sarcoptes scabiei, develop extensive
crusted, hyperkeratotic lesions that teem with mites.
In 1946, Mellanby described five stages of immu-
nity to arthropod bites in the normal host5:
• First, in a person with no prior exposure to a
particular arthropod, no reaction takes place.
• With repeated bites, a sensitivity develops
that manifests as a delayed reaction begin-
ning about 24 hours after the bite and sub-
siding in about a week.
• Weeks, months, or even years later, the bites
may be followed by an immediate wheal
reaction that clears in a few hours and is
succeeded by a delayed papule.
• With further exposure, only the immediate
wheal develops after the bite.
• Finally, a stage is reached where once again
no reaction develops to the bite.
Antigens found in arthropod saliva are responsible
for most of these immediate and delayed hypersen-
sitivity reactions.
Toxic venoms found in salivary and sting secre-
tions provide an important mechanism for cutane-
ous (and systemic) injury to arthropod bites.  These
venoms contain a variety of biologically active com-
pounds including proteases, hyaluronidase, phos-
pholipase A, kinins, histamine, 5-hydroxytrypt-
amine, acetylcholine, adrenaline-like substances,
neurotoxins, and hemolytic toxins.  From this list,
one can see that the result of envenomation can
range from cutaneous inflammation, pain, and ne-
crosis to severe and potentially life-threatening sys-
temic reactions.  Some arthropods secrete irritants
onto the surface of the skin from body parts unre-
lated to feeding.  Examples are the vesicants se-
creted by blister beetles and the urticants found on
the hairs of some caterpillars.
The act of biting varies among different
arthropods and may produce different clinical re-
sponses.  Mosquitoes, with their fine proboscises,
can penetrate capillaries with minimal damage,
while tsetse flies cause significant laceration and
bleeding.  The mouthparts of ticks tend to break off
within the skin and may cause a dense granu-
lomatous or lymphoid dermal reaction that can be
quite persistent.
Finally, environmental factors influence the na-
ture of reactions to arthropod bites.  The amount of
clothing obviously determines the extent of exposed
skin susceptible to bites.  Some arthropods such as
midges, black flies, and mosquitoes limit their at-
tacks to exposed skin; fleas prefer covered areas.
Body lice live in clothing and, therefore, their bites
are found on covered skin as well.  Pets and live-
stock can be a source of parasites, so grooming and
disinfestation become important measures.  Over-
crowded living conditions, poor sanitation, and
inadequate garbage disposal all facilitate the breed-
ing of potentially harmful arthropods.  Spiders and
scorpions live in wood and litter piles as well as
outhouses.  Dark crevices in homes may also pro-
vide a breeding ground.  In the construction of
temporary military housing, infestation can be
greatly reduced by such simple measures as pro-
viding mesh netting for doors and windows; elevat-
ing the floor from the ground; and separating live-
stock, wood piles, and latrine and garbage sites
from living quarters.

Military Dermatology
160
CENTIPEDES AND MILLIPEDES
American centipedes have a slender, segmented
body that ranges in color from yellow to green to
brown or black, and may vary in length from 1 to 30
cm (Figure 8-1).6  While the Scutigera species found
in the eastern United States does not sting humans,
the Scolopendra species of the western United States
and Hawaii can inflict a painful sting.7  Centipedes
are nocturnal carnivores and prefer a dark, moist
environment like that found under rocks and logs.
Envenomation occurs by means of two hollow fangs,
each connected to a venom gland.  The immediate
reaction consists of local burning pain and a pair of
hemorrhagic puncta surrounded by erythema and
edema at the sting site.  Occasionally, local necrosis,
regional lymphangitis and lymphadenopathy, anxi-
ety, irregular peripheral pulses, headache, and diz-
ziness may develop.  Therapy for a centipede sting
should include cleansing the wound, injecting a
local anesthetic into the wound, tetanus prophy-
laxis, and administering systemic antihistamines.
Millipedes are multisegmented, with a hard, of-
ten brightly colored exoskeleton.  Some tropical
species may reach 30 cm in length.  They are noctur-
nal vegetarians and, like centipedes, prefer dark,
moist environments.  When disturbed, millipedes
will coil into a tight spiral and can then secrete a
toxic liquid from repugnatorial glands located on
the sides of each segment.  This liquid causes an
immediate burning sensation when it contacts hu-
man skin.  The skin then becomes yellow-brown,
and in 24 hours develops intense erythema and
often vesiculation.  Erosions may develop but usu-
ally heal without scar formation unless secondarily
infected.  Dyspigmentation, however, is a common
OK to put on the Web
Fig. 8-1. The centipede has a multisegmented body, with
a pair of legs on each segment. Its color ranges
from yellow to green or brown to black. It may grow to
30 cm in length. Photograph: Courtesy of Entomology
Department, Walter Reed Army Institute of Research,
Washington, D.C.
sequelae in dark-skinned patients.  If the toxic liq-
uid should come in contact with an eye, the result is
instantaneous and severe pain lasting 2 to 3 days.  A
chemical conjunctivitis ensues and corneal ulcer-
ation may develop.  Skin contact with the toxin
should be treated immediately with copious lavage
of the area.  Alcohol is a good solvent for the con-
taminating liquid, but water may be used.  Manage-
ment of the blisters and erosions with a topical
antibiotic is similar to that of a superficial second-
degree burn.  Topical corticosteroids may be helpful.
The class Insecta comprises arthropods whose
adult forms have three pairs of legs.  Injury to
humans can be inflicted by bites, stings, and contact
with noxious hairs, venom, or excretions.
Caterpillars and Moths
Among the order of insects known as Lepidoptera,
comprising butterflies and moths, contact with the
poison hairs or spines of the larval form (caterpil-
lars) or the poison hairs of the adult (moths) causes
cutaneous disease.8,9  In the United States, the ven-
omous caterpillars (Figure 8-2) most frequently en-
INSECTS
countered are the brown-tail moth caterpillar, puss
caterpillar, saddleback caterpillar, crinkled flannel
moth caterpillar, slug caterpillar, and flannel moth
caterpillar.  They are present most often in the
autumn and are usually found in trees.  Their poi-
son hairs may come in contact with the skin and
mucous membranes directly by handling the cater-
pillars; however, the contact is usually indirect,
involving hairs falling from trees, free wind-borne
hairs, or objects that have been contaminated by
hairs.  Cocoons and egg cases can also contain the
hairs.  Venomous moths causing dermatitis in the
United States include the brown-tail, gypsy, puss,

Arthropod and Other Animal Bites
161
OK to put on the Web
Fig. 8-2. Caterpillars, the larval form of moths and butter-
flies, may have venomous spines and hairs as shown
here.  Photograph: Courtesy of Entomology Department,
Walter Reed Army Institute of Research, Washington, D.C.
io, and tussock moths.  In Latin America, a genus of
moth known as Hylesia is a frequent cause of moth
dermatitis (Figures 8-3 and 8-4).  Epidemics have
resulted from the dust produced by massive num-
bers of this particular moth.
The cutaneous reaction to contact with poison
moth hairs can range from an immediate pruritic or
burning sensation to a delayed painful eruption
developing 2 to 12 hours later and persisting for up
to 2 weeks.  The skin lesions are most commonly
found on exposed areas of the upper extremities
and neck, less frequently on the face, and consist of
erythematous wheals, papules, vesicles, or pus-
Fig. 8-3. This moth belongs to the genus Hylesia, a com-
mon cause of moth dermatitis in Latin America. Photo-
graph: Courtesy of Entomology Department, Walter Reed
Army Institute of Research, Washington, D.C.
OK to put on the Web
OK to put on the Web
tules.  Conjunctivitis can result from contact with
the eye.  Contaminated clothing may cause wide-
spread lesions associated with systemic symptoms
including rhinitis, nausea, vomiting, and low-grade
fever.  The puss caterpillar can cause a painful
hemorrhagic lesion with marked edema and re-
gional lymphangitis and lymphadenopathy.  In rare
instances, hypotensive shock can develop.
Immediate treatment for contact with poison
moth hair consists of stripping the skin with adhe-
sive tape to remove the poison hairs.  Cool com-
presses and oral antihistamines can be tried, and
systemic corticosteroids may be useful in more se-
rious cases.  Oral analgesics are at times required
for the pain.
True Bugs
The order Hemiptera contains the true bugs, two
of which commonly bite humans: the bedbug and
the kissing bug.  The bedbug, Cimex lectularius, is a
worldwide parasite that feeds nocturnally on hu-
man blood.10  It is a flat, oval, reddish brown insect
that varies in length from 3 to 6 mm (Figure 8-5).  A
pair of mandibular stylets are used to pierce the
skin, and a salivary anticoagulant is injected into
the wound prior to the blood meal.  The bedbug
lives within crevices found in walls, floors, and
furniture and can be detected by a characteristic
pungent odor.  The adult can survive more than a
year without feeding and travels well in baggage.
The initial bite is painless and the first manifesta-
tion may be the discovery of blood-stained bed
Fig. 8-4. An example of the dermatitis produced by con-
tact with the hair of the Hylesia moth. Photograph: Cour-
tesy of Entomology Department, Walter Reed Army
Institute of Research, Washington, D.C.

Military Dermatology
162
OK to put on the Web
Fig. 8-5. The bedbug, Cimex lectularius, is reddish brown
and ranges in length from 3 to 6 mm. Photograph: Cour-
tesy of Entomology Department, Walter Reed Army In-
stitute of Research, Washington, D.C.
agent of Chagas’ disease (discussed in Chapter 12,
Tropical Parasitic Infections).  Treatment of the bite
includes topical corticosteroids, systemic antihista-
mines, and antibiotics if secondarily infected.
Lice
Three varieties of lice, Pediculus humanus var
capitis (head louse), Pediculus humanus var corporis
(body louse), and Pthirus pubis (pubic or crab louse),
are obligate parasites of humans.4  After attaching
to human skin, they feed on blood that they suck.7
These flattened, wingless insects have a tough in-
tegument that varies in color from gray to black.
The body and head lice vary in length from 2.4 to 3.6
mm (Figures 8-7 and 8-8), while the shorter and
wider pubic louse is about 2 mm long (Figure 8-9).
The pubic louse is also distinguished by prominent
claws on its second and third pair of legs.12  Lice will
die of starvation if kept off the body for more than
10 days.  They are also killed by washing in water at
53.5°C for 5 minutes.  The life span of a louse is
about 30 to 45 days.
Head Lice
Head lice primarily infest children, although
adults certainly may be affected.  Women are more
commonly infested than men.  The distribution of
the disease is worldwide and tends to be much more
clothes and linen.  Salivary antigens can elicit a
hypersensitivity reaction producing urticarial pap-
ules with central hemorrhagic puncta.  Lesions may
be bullous and can become secondarily infected.
Systemic hypersensitivity reactions including gen-
eralized urticaria, asthma, arthralgia, and even ana-
phylaxis have been reported.  Of particular concern
have been laboratory studies10 showing that trans-
mission of hepatitis B, Rickettsia, and Leishmania by
these bugs is possible.  Treatment of the bites in-
cludes topical antipruritic lotions, topical corticos-
teroids, systemic antihistamines, and antibiotic cov-
erage if secondarily infected.  Insecticides such as
pyrethrins or malathion should be used to treat
bedbugs’ dwellings.
Kissing bugs comprise 14 genera of the Redu-
viidae insect family, several species of which are
found in the western and southeastern United
States.11  These bugs are 1.5 to 2.5 cm long and
brownish black with red or yellow stripes on the
abdomen (Figure 8-6).  They are nocturnal preda-
tors, falling on their prey from trees or the ceiling
and feeding on exposed skin.  In humans, the bite is
often on the face, hence the name “kissing bug.”
The bites are usually painless and appear as grouped
papules with hemorrhagic puncta or vesiculobullous
lesions.  A localized or generalized urticarial reac-
tion may occur, probably secondary to salivary
antigens.  A variety of systemic effects including
laryngeal edema, bronchospasm, angioedema,
hypotension, syncope, generalized pruritus, vomit-
ing, uterine bleeding, headache, and abdominal
cramps have been reported.11  In Latin America, this
bug is a vector of Trypanosoma cruzi, the etiologic
OK to put on the Web
Fig. 8-6. Pictured here are various stages in the develop-
ment of the kissing bug. The adult grows to 1.5 to 2.5 cm
in length and is brownish black with red or yellow stripes
in the abdomen. Photograph: Courtesy of Entomology
Department, Walter Reed Army Institute of Research,
Washington, D.C.

Arthropod and Other Animal Bites
163
OK to put on the Web
OK to put on the Web
Fig. 8-7. The body louse is a wingless, gray to black insect
whose length ranges from 2.4 to 3.6 mm. Photograph:
Courtesy of Entomology Department, Walter Reed Army
Institute of Research, Washington, D.C.
Fig. 8-9. The pubic louse is shorter (about 2 mm long) and
wider than body or head lice.  It has prominent claws on
the second and third pairs of legs to grasp hair. Photo-
graph: Courtesy of Entomology Department, Walter Reed
Army Institute of Research, Washington, D.C.
OK to put on the Web
Fig. 8-8. The head louse is similar in size and shape to the
body louse. Its clawlike legs allow it to grasp the hair of
its host. Photograph: Courtesy of Entomology
Department, Walter Reed Army Institute of Research,
Washington, D.C.
OK to put on the Web
Fig. 8-10. The oval eggs (nits) of a head louse are ce-
mented onto hair shafts and move distally with hair
growth. Photograph: Courtesy of Entomology
Department, Walter Reed Army Institute of Research,
Washington, D.C.
prevalent in crowded urban centers.  Once on the
scalp, the female louse will lay her eggs (nits) at the
base of the hair.  The nits are cemented to the side of
the hair shaft and move distally with hair growth
(Figure 8-10).  Often these nits are the only clinical
evidence of infestation, as the lice are difficult to
find.  The nits are usually found in the warm areas
of the scalp such as behind the ears and on the
posterior neck.  Patients generally note an itching or
pricking sensation and the hair may appear luster-
less and dry.  The scalp can become secondarily
infected from scratching, presenting as an impetigo
or folliculitis.  Adequate treatment requires that
both the adult lice and the nits be killed.  Because

Military Dermatology
164
the nits hatch in 7 days, two treatments a week apart
are recommended to ensure complete eradication
of the lice.  Although lindane (gamma benzene
hexachloride, or Kwell [manufactured by Reed &
Carnrick, Jersey City, N.J.]) shampoo or lotion is
most frequently used, a recent study found
malathion lotion to be significantly more effective
in killing both adult lice and nits.13  Natural pyre-
thrin products (A-200 [manufactured by SmithKline
Beecham, Pittsburgh, Pa.], RID [manufactured by
Pfizer, Parsippany, N.J.]), and synthetic permethrin
(Nix, manufactured by Burroughs Wellcome, Re-
search Triangle Park, N.C.) are also effective.  The
nits are best removed with a comb after soaking the
hair in a vinegar solution.  Family members and
other personal contacts should also be treated.
Body Lice
Unlike head lice, body lice live and lay eggs in the
seams of clothing and contact human skin only to
feed.  They generally infest individuals with
poor hygiene, producing what has been named
vagabond’s disease.  This louse can be a vector for
epidemic typhus, louse-borne relapsing fever, and
trench fever.  Patients present with pyoderma in-
volving areas covered by clothing, most notably the
trunk, axillae, and groin.  Erythematous macules,
papules, and wheals, as well as excoriations may
also be seen.  The most significant symptom is
severe pruritus.  In endemic cases, pediculocides
are unnecessary and adequate treatment consists of
a hot shower and clean clothes.  A hot wash will kill
the organisms on infested clothing.  Antibiotics are
necessary if secondary infection is present.  For
epidemics of body lice, as may be seen in wartime
situations, heavy infestation requires the use of
insecticides such as dichlorodiphenyltrichloro-
ethane (DDT) powder, lindane 1% powder, or
malathion 1% powder.  Resistant organisms have
emerged from all of these regimens, however.
Pubic Lice
Pubic lice limit their infestation to areas where
the hair is short and are found primarily in the
pubic hair.  They may, however, spread to body
hair, axillary hair, beard hair, eyebrows, eyelashes,
and occipital scalp hair.  Pediculosis pubis is spread
most commonly by sexual contact and should
prompt a search for other sexually transmitted dis-
eases.  Patients can remain asymptomatic for up to
a month before pruritus develops.  Nits, similar to
those in pediculosis capitis, are seen.  The lice are
found wrapped around a single hair in the case of
larvae; adults grasp two adjacent hairs.  Blue macules
(maculae ceruleae) are often seen on the surround-
ing skin and are believed to be produced by louse
saliva acting on blood products.  Pubic lice should
be treated with lotions or shampoos containing 1%
lindane, 0.3% pyrethrins, or 5% permethrin.  These
drugs should be applied topically, left on for 10
minutes, then reapplied once 7 to 10 days later.
Infestation of the eyelashes has been treated in the
past with physostigmine ointment or yellow oint-
ment of mercury; however, plain petrolatum, ap-
plied two to five times daily for several days, ap-
pears to work as well and is much safer.  Clothing
should be washed in hot water.
Mosquitoes and Flies
Mosquitoes and flies are two-winged, biting in-
sects belonging to the order Diptera.7  They all
require a blood meal at some time in their develop-
ment.  To acquire this meal, they often attack human
skin, causing a bite reaction.14  These bites can
manifest as immediate urticarial papules, delayed
erythematous papules, or both, depending on the
host’s state of immunity, as discussed previously.
Fly larvae (maggots) may also invade tissue, pro-
ducing a condition known as myiasis.  If the eggs
are deposited on an open wound, the larvae cause
wound myiasis; eggs deposited beneath the skin via
a puncture cause furuncular myiasis.
OK to put on the Web
Fig. 8-11. Mosquitoes are characterized by their delicate
wings, long, thin legs, and long feeding proboscises. The
Anopheles mosquito is shown here. Photograph: Courtesy
of Entomology Department, Walter Reed Army Institute
of Research, Washington, D.C.

Arthropod and Other Animal Bites
165
TABLE 8-1
MOSQUITOES AND FLIES AS VECTORS OF INFECTIOUS DISEASE
Adapted with permission from Alexander JO. Arthropods and Human Skin. Berlin, Germany: Springer-Verlag; 1984: 117.
Mosquitoes
Mosquitoes, belonging to the family Culicidae,
are delicate winged insects with long proboscises
and long, thin legs (Figure 8-11).  They require
water to mature through the larval and pupal stages,
explaining the presence of mosquitoes near stand-
ing water.  A number of factors attract mosquitoes
to humans including moisture, warmth, carbon di-
oxide, estrogens, and L-lysine in sweat.15  Mosqui-
toes can be the vector for filariasis, yellow fever,
dengue fever, and malaria, among other diseases
(Table 8-1).  Cutaneous reactions to mosquito bites
include urticarial wheals, delayed papules, bullous
lesions, hemorrhagic necrotic lesions, excoriations,
eczematous patches, and granulomatous nodules.16
Mosquito bites can be treated with topical cortico-
steroid creams, antipruritic lotions, and/or a dilute
solution of meat tenderizer (containing the enzyme
papain, which provides rapid relief of pruritus).
Bites can be prevented by repellents that contain
diethyltoluamide (DEET, marketed as Off!,
Sportsmate II cream, or Cutter Laboratories’ Insect
Repellent) or ethyl hexanediol (6-12 Plus).  Interest-
ingly, Avon’s Skin-So-Soft moisturizer acts as an
excellent repellent.  Protective clothing and mos-
quito netting are both effective for the outdoor
setting.
Flies and Maggots
A variety of flies commonly bite humans, includ-
ing sandflies (Phlebotomus and Lutzomyia species),
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Fig. 8-12. The sandfly is a vector of leishmaniasis and
bartonellosis. Photograph: Courtesy of Entomology De-
partment, Walter Reed Army Institute of Research,
Washington, D.C.
black or buffalo flies (Simulium species), Cera-
topogonidae (biting midges), members of the fam-
ily Tabanidae (which includes the deerfly and horse-
fly), and tsetse flies (Figure 8-12).  The common
housefly does not bite, but rather feeds on the sur-
face of the skin (Figure 8-13).  A number of infec-
tious diseases can be transmitted by biting flies (see
Table 8-1).  The cutaneous reaction to these bites,
like those of mosquitoes, may be immediate, de-
layed, or both.  Relief is provided by antipruritic
lotions and topical corticosteroids.  Repellents ap-
plied topically or impregnated in clothing can pre-
Table 8-1 is not shown because the copyright permission granted to the Borden Institute, TMM, does not
allow the Borden Institute to grant permission to other users and/or does not include usage in electronic
media. The current user must apply to the publisher named in the figure legend  for permission to use
this illustration in any type of publication media.

Military Dermatology
166
OK to put on the Web
Fig. 8-13. The housefly feeds on the surface of the skin
rather than biting. Photograph: Courtesy of Entomology
Department, Walter Reed Army Institute of Research,
Washington, D.C.
vent fly bites.  DEET, ethyl hexanediol, chlorodiethyl
benzamide, and Avon’s Skin-So-Soft are all good
topical repellents.  An effective combination repel-
lent is topical DEET and permethrin-impregnated
clothing.
Myiasis, or infestation with fly maggots, has an
almost worldwide prevalence, although it is more
common in the tropics.  The disorder is caused by
many different species of fly and affects any
exposed surface.  Cerebral, facial, nasal, aural,
oral, ophthalmological, urethral, rectal, and vagi-
nal disease have all been reported.14  In North
America, wound myiasis is probably the most
common form.  Flies first lay their eggs on the
injured surface where the soft larvae or maggots
hatch.  Some species ingest only necrotic material;
others may attack adjacent normal tissue.  A
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Fig. 8-14. The human botfly is the most common cause of
furuncular myiasis in Latin America. Photograph: Cour-
tesy of Entomology Department, Walter Reed Army In-
stitute of Research, Washington, D.C.
OK to put on the Web
Fig. 8-15. The larval form of the botfly burrows into the
skin and subcutaneous tissue, producing a furuncular
lesion (ruler in cm). Photograph: Courtesy of Entomol-
ogy Department, Walter Reed Army Institute of Research,
Washington, D.C.
variety called screwworms can burrow deeply
into living tissue, causing extensive damage.  In
 the past, larvae of the black blowfly were commer-
cially available for wound debridement.  Wound
myiasis is treated by extraction of the maggots after
prior application of 10% chloroform in vegetable
 oil or ether to the wound.  For deep or extensive
infestation, repeated chloroform irrigation may be
required.4
Furuncular myiasis is produced when (a) adult
flies puncture the skin to lay their eggs, (b) flies lay
their eggs on the skin surface and hatched larvae
burrow into the skin and subcutaneous tissue, or (c)
fly eggs, which have been attached to the body of
a mosquito, tick, or stable fly, are deposited
on human skin and enter via the bite wound of
these vectors.  The human botfly, Dermatobia hominis,
is the most common cause of furuncular myiasis
in Central and South America (Figures 8-14 and
8-15).  Infants and young children are the most
frequently affected, although patients of all ages
are seen.17
Clinically, a raised, erythematous papule devel-
ops at the site of the bite, most frequently on the
distal extremity or scalp.  Over the next 3 weeks it
gradually enlarges to become an indurated nodule
with a central punctum, which is the breathing tube
for the larva (Figure 8-16).  Serum and pus may be
discharged from this highly pruritic and intermit-
tently painful lesion.  Regional lymphadenopathy,
as well as a papulovesicular hypersensitivity erup-
tion on the surrounding skin and hands, may be
seen.  In about 7 weeks, the larva will mature and
emerge from the nodule, although patients usually
seek treatment much earlier because of pain (Figure
8-17).  Effective therapy requires surgical incision

Arthropod and Other Animal Bites
167
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Fig. 8-16. The furuncular lesion of myiasis is an indu-
rated nodule with a central punctum, which serves as the
breathing tube for the larva. Photograph: Courtesy of
Entomology Department, Walter Reed Army Institute of
Research, Washington, D.C.
of the nodule and extraction of the larva, after
anesthetizing the lesion and larva with lidocaine
or chloroform.  Natives in endemic areas cover the
lesions with a thick layer of pork fat, occluding
the breathing tube.  Within 24 hours, the larva
migrates out and can easily be removed.
Beetles
Blister beetles cause cutaneous injury when a
potent vesicating agent, cantharidin, is released
from their bodies and contacts human skin.  When
handled, these insects excrete the vesicant in
hemolymph from their knee joints, prothorax, and
genitalia.4  Lytta vesicatoria, also known as “Spanish
fly,” is the source of cantharidin, which is used
medicinally for the treatment of warts.  Two spe-
cies, Epicauta vittata and E pennsylvanica, are found
in the southern and southwestern United States.18
They can be up to 1 in. long and are found in alfalfa
fields, along fence rails, and in flower beds.  Several
minutes after contact with the vesicant, the patient
experiences a tingling or burning.  Blisters develop
within a day, then dry up and desquamate in about
a week (Figure 8-18).  Extensive contact with
cantharidin can cause toxic symptoms including
stomatitis, salivation, hematemesis, abdominal pain,
diarrhea, and dysuria.  The affected skin should be
washed immediately with alcohol, acetone, ether,
or soap to dissolve or dilute the cantharidin.  The
blisters are treated with wet compresses and topical
corticosteroids.
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Fig. 8-18. Resolving lesions induced by the blister beetle
desquamate in about 1 week. Photograph: Courtesy of
Entomology Department, Walter Reed Army Institute of
Research, Washington, D.C.
OK to put on the Web
Fig. 8-17. A larva is shown emerging from a furuncular
lesion. Patients are often unable to wait for this to occur
because of the pain of the lesion. Photograph: Courtesy of
Entomology Department, Walter Reed Army Institute of
Research, Washington, D.C.

Military Dermatology
168
Stinging Insects
Insects of the order Hymenoptera, including bees,
wasps, hornets, and fire ants, are known for pro-
ducing a painful sting that may, rarely, result
in anaphylaxis and death.19  The venoms of these
insects have not been completely characterized,
but contain biogenic amines (histamine, nor-
epinephrine, dopamine, serotonin, and acetylcho-
line), enzymes (phospholipase A and B, hyalu-
ronidase, esterases, and phosphatases), and other
peptides (kinins and mast cell degranulation
peptide).20
The reactions produced by Hymenoptera stings
are classified as (a) local, (b) systemic toxic, (c)
systemic allergic, and (d) other (Table 8-2).  The com-
mon local reaction is erythema, edema, and pain at the
site of the sting, resolving in several hours.  The
swelling can occasionally extend to involve a large
area (eg, an entire limb) and last for several days.
Wells’ syndrome, consisting of erythematous,
edematous plaques composed histologically of eosi-
nophilic granulomatous dermatitis, may be related
to stings.4,21  Systemic toxic reactions are produced
by the pharmacological action of a large dose of
venom from multiple stings.  Constitutional symp-
toms such as nausea, malaise, fever, and even ana-
phylactoid reactions may result.  Systemic allergic
reactions are produced when specific immunoglo-
bulin (Ig) E antibodies fixed to the surface of baso-
phils and mast cells bind to antigens in the venom,
causing degranulation and the release of vasoactive
OK to put on the Web
Fig. 8-19. Honeybees are found around flowering plants
and are unique among stinging insects, having a barbed
stinger that causes it and venom sac to be left on the
victim. The bee is eviscerated and dies after stinging.
Photograph: Courtesy of Entomology Department, Walter
Reed Army Institute of Research, Washington, D.C.
substances.  Symptoms range from urticaria and
angioedema, which may be associated with nausea,
vomiting, dizziness, and wheezing, to a fully devel-
oped anaphylactic reaction including hypotension,
laryngeal edema, and bronchospasm.  Every year,
insect allergy accounts for approximately 40 fatali-
ties in the United States.21  Severe allergic reactions
are more common in men, especially when stung on
the head and neck.  Finally, there have been case
reports21 in which serum sickness, acute glomerulo-
nephritis, and Guillain-Barré syndrome have been
associated with Hymenoptera stings.
Bees, Wasps, and Hornets
The Apoidea family includes honeybees and
bumblebees (Figure 8-19).  Honeybees feed on flow-
ering plants and can be encountered in the wild,
such as on clover, or in commercial hives.  They are
unique among the stinging insects in that their
stinger contains a barb, causing it to be left on the
victim along with the venom sac.  This act eviscer-
ates and kills the bee and also allows the sting to be
identified as that of a honeybee, for the venom sac
is visible.  In 1957, swarms of African bees escaped
from a laboratory in Brazil, where they were being
used in cross-breeding experiments attempting to
improve honey production.  These African or “killer”
bees are known for their aggressive stinging behav-
ior in defense of their colonies.  Their steady march
northward through Central America and Mexico
has been well documented in the press.
TABLE 8-2
REACTIONS TO HYMENOPTERA STINGS
Type of Reaction
Effects
Local
Immediate erythema and edema,
extensive swelling (may include
entire extremity), eosinophilic
cellulitis (Wells’ syndrome)
Systemic toxic
Nausea and vomiting, malaise,
fever, anaphylactoid reaction
Systemic allergic
Urticaria or angioedema, or both;
nausea, vomiting, dizziness, and
wheezing; anaphylaxis
(hypotension, laryngeal edema,
and bronchospasm)
Other
Serum sickness, acute renal
failure, possible Guillain-Barré
syndrome

Arthropod and Other Animal Bites
169
Wasps, yellow jackets, and hornets are members
of the Vespidae family.  Paper wasps build hives
under the eaves of buildings; yellow jackets are
ground-nesting, and hornets reside in shrubs and
trees.  These insects are often found around trash
containers or discarded food.  They may sting mul-
tiple times, although usually only when provoked.
After a honeybee sting, care must be taken in
removing the stinger and attached venom sac, for
pressure will release more venom.  Lateral scraping
with a knife blade is recommended.  The local
reactions produced by Hymenoptera stings can be
treated with ice packs, elevation, topical corticos-
teroids, systemic antihistamines, and, if necessary,
analgesics.  Application of a dilute solution of meat
tenderizer will provide rapid pain relief.  Systemic
corticosteroids are helpful in the more extensive
local reactions.  Anaphylaxis is a medical emer-
gency requiring airway protection and the mainte-
nance of systemic blood pressure with parenteral
epinephrine, intravenous fluids, and, in some cases,
vasopressor agents.  Individuals who have experi-
enced an anaphylactic reaction should carry a bee-
sting kit, such as Ana-Kit or Epi-Pen, which in-
cludes epinephrine and antihistamines.  Medic-
Alert jewelry should also be worn.  Individuals
with Hymenoptera allergy, documented by history
and skin testing, are candidates for hyposensitiza-
tion therapy.  This treatment involves venom im-
munotherapy, which generally provides partial
protection.  Outdoor dining and the wearing of
brightly colored clothing should be avoided by
these individuals.
Fire Ants
Fire ants, included in the Formicidae family, are
unique among the Hymenoptera in several ways.
Their venom is composed primarily of nonimmuno-
genic, low-molecular-weight alkaloids with only a
small percentage of the immunogenic proteins found
in the venom of bees, wasps, and hornets.  They
sting by first biting the victim with their powerful
set of pincer jaws, then swiveling about their at-
tached head and stinging in a circular pattern.  Fire
ants may be red or black and live in ground colonies
in the southeastern United States.  They are aggres-
sive and tend to attack in swarms, with up to 5,000
bites in a single attack being reported.22  These
painful stings are very distinctive clinically: two
central hemorrhagic puncta are surrounded by a
ring of erythematous papules that first become
vesicles, then sterile pustules.  Associated seizures
and mononeuropathy have been reported.7  Ana-
phylaxis may occur, but is less likely than with
other Hymenoptera.  Local therapy, including meat
tenderizer,22 is generally ineffective for these pain-
ful stings, and a specific antivenin is not available.
Fleas
Fleas are wingless insects that, in pursuit of their
blood meals, can infest most warm-blooded ani-
mals.7  Humans may be bitten by the human flea
(Pulex irritans) as well as by the cat, dog, rat, squir-
rel, mouse, chicken, and sand fleas.  Among the
various species are found the vectors for bubonic
plague, endemic typhus, tularemia, and intestinal
tapeworm.4  Their distribution is cosmopolitan, fa-
voring overcrowded environments.  Although wing-
less, fleas are equipped with powerful legs that
allow them to jump from host to host (Figure 8-20).
Their bites are probably the most common skin
lesions inflicted by arthropods (Figure 8-21).
Fleas often bite at the ankle, wrist, or waistline,
where they encounter the edge of clothing.  The
bites are frequently grouped in twos and threes
with a somewhat irregular distribution.  The indi-
vidual lesions are papules, vesicles, or bullae, often
with a central hemorrhagic punctum and an
erythematous halo.  Due to their pruritic nature,
they commonly become excoriated and secondarily
impetigenized.  Chronic reinfestation in a hyper-
sensitive host can produce a variety of hivelike and
OK to put on the Web
Fig. 8-20. Fleas are wingless insects with powerful legs
allowing them to jump from host to host. Photograph:
Courtesy of Entomology Department, Walter Reed Army
Institute of Research, Washington, D.C.

Military Dermatology
170
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Fig. 8-21. Flea bites are often encountered in areas at the
edge of clothing, such as the ankle, wrist, and waistline.
The lesions usually have a hemorrhagic central punctum
and erythematous halo. Photograph: Courtesy of Ento-
mology Department, Walter Reed Army Institute of
Research, Washington, D.C.
neous lesions.  Antibiotics may be required for
treatment of secondary infection.  Topical repel-
lents effective for fleas include DEET and pyre-
thrins, and clothes impregnated with benzyl ben-
zoate.  Household pets should be treated with a
pesticide such as pyrethrin powder.  Carpets, floors,
furniture, and draperies need to be treated with a
pesticide as well.  Pyrethrins, malathion, and car-
baryl are all effective and should be used monthly
for two or three applications.
The sand flea (Tunga penetrans) produces a unique
clinical lesion in humans.  It is found in Central and
South America, equatorial Africa, and the southern
United States.  The gravid female burrows into the
skin and enlarges to the size of a pea.  If allowed to
remain in the skin, she extrudes her eggs through a
surface opening after 1 to 2 weeks, then dies.  The site
of invasion is usually the feet, particularly around the
toes, but can also be the thighs, perineum, and genita-
lia.  The cutaneous lesion is a 1- to 2-cm, firm, tender
nodule with a black spot in the center.  Secondary
infection and regional adenopathy may occur.  Treat-
ment of sand flea infestation (tungiasis) consists of
excision or curettage of the flea, tetanus prophylaxis,
and, if infection is present, antibiotic coverage.
persistent papules known as papular urticaria.
Antipruritic lotions and topical corticosteroid
creams will provide symptomatic relief for the cuta-
ARACHNIDS
The class Arachnida is composed of arthropods
whose adult forms have four pairs of legs.  They
may cause human injury by biting, burrowing in
and feeding on skin, stinging, and delivering toxic
venom.
Ticks
There are two families of ticks: the hard ticks
(Ixodidae), with a hard chitinous dorsal shield,
and the soft ticks (Argasidae), which lack this dor-
sal shield (Figures 8-22 and 8-23).  Hard ticks can
endure cold, humid weather, while soft ticks
prefer drier environments.23  Both types are fre-
quently found in shrubby or wooded areas.  Ticks
are natural parasites of many different animals
including mammals, birds, reptiles, and amphib-
ians.  Varieties from both tick families will occasion-
ally attack humans.  Once attached to human
skin, they can remain feeding for several days until
becoming so engorged with blood that they drop
off.  Although the cutaneous reaction from a
tick bite may be quite symptomatic, ticks are most
notorious as vectors for numerous infectious dis-
OK to put on the Web
Fig. 8-22. A soft tick (Dermacentor sp). Photograph: Cour-
tesy of Entomology Department, Walter Reed Army In-
stitute of Research, Washington, D.C.
eases (Exhibit 8-1).  The six-legged larvae, the eight-
legged nymphs, and adult ticks can all transmit
disease.

Arthropod and Other Animal Bites
171
OK to put on the Web
Fig. 8-23. Two hard ticks (Ixodes scapularis), the one on
the right engorged with a blood meal. I scapularis is the
vector for Lyme disease. Photograph: Courtesy of Ento-
mology Department, Walter Reed Army Institute of Re-
search, Washington, D.C.
EXHIBIT 8-1
INFECTIOUS DISEASES WITH TICKS
AS VECTORS
Adapted with permission from Alexander JO. Arthro-
pods and Human Skin. Berlin, Germany: Springer-Verlag;
1984: 364.
In addition to these infectious diseases, ticks may
cause two syndromes, tick-bite alopecia and tick
paralysis, both presumably due to secreted toxins.4
The former is a patchy alopecia at the site of tick
attachment that clinically resembles alopecia
areata.  The hair loss begins about 1 week after the
tick is removed and may take up to 2 months to
completely regrow.  Tick paralysis is an ascending
flaccid paralysis resembling Guillain-Barré syn-
drome.  The onset is heralded by leg weakness and
can progress to complete flaccid paralysis, result-
ing in dysarthria, dysphagia, respiratory failure,
and death.  The paralytic symptoms usually disap-
pear rapidly if the tick is found and removed from
the skin.  Residual neurological sequelae after re-
moval of the tick are very rare.  These two syn-
dromes are also discussed in Chapter 9, Arthropod
Infestations and Vectors of Disease.
The initial bite of the tick is usually painless but
becomes a pruritic, urticarial lesion in a few hours.
If undetected, the tick can remain attached to the
skin for over 1 week, becoming completely en-
gorged with blood.  While it feeds, the host may
develop fever, chills, headache, abdominal pain,
and vomiting (tick-bite pyrexia).7  These symptoms
resolve a day or two after the tick is removed.  The
cutaneous lesion is generally an erythematous pap-
ule with a red halo, but may become bullous or
ulcerated.  Firm, pruritic nodules lasting for months
to years have been observed after tick bites.  When
examined histologically, these nodules can show
worrisome features suggestive of cutaneous
lymphoma.  Patients may also develop persistent
gyrate (annular and polycyclic) erythemas after a
tick bite.
Initial treatment consists of finding and remov-
ing the tick.  This should be done with steady, gentle
traction so as not to leave any broken-off tick parts
in the skin.  As with other arthropod bites, the
pruritic skin lesion is treated with topical cortico-
steroids, antipruritic lotions, and systemic antihis-
tamines.  Persistent nodular lesions often require
intralesional corticosteroid injection or even surgi-
cal excision.  Protective clothing as well as an insect
repellent such as DEET should be used when expo-
sure to ticks is anticipated.  The history of a tick bite
should heighten the clinician’s awareness for early
signs and symptoms of associated infectious dis-
eases, allowing for prompt treatment.
Exhibit 8-1 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does not
include usage in electronic media. The current
user must apply to the publisher named in the
figure legend  for permission to use this illustra-
tion in any type of publication media.

Military Dermatology
172
Scabietic Mites
Scabies is an infestation with the eight-legged
human mite known as Sarcoptes scabiei.  The adult
scabietic mite is approximately 0.4 mm in length,
barely visible to the naked eye as a black speck.
Adult mites copulate on the skin, after which the
female will burrow, laying her eggs along the way.24
Six-legged larvae hatch and pass through several
nymphal stages before becoming adults.  This life
cycle takes 10 to 14 days.  Scabietic mites generally
will survive off the human body for only 2 to 3 days
under normal room conditions.  Initial infestation is
completely asymptomatic, and it is not until about
30 days later that an immune response develops to
the mites or their excrement (scybala).  At this point,
pruritus and cutaneous inflammation appear.  Al-
though widespread skin lesions may be present
with this infestation, it has been demonstrated that
the average number of mites per patient is 11.25
Mites are found most frequently on the hands, wrists,
elbows, axillae, breasts, umbilicus, and genitalia.
Scabies is usually spread by close personal contact
with an infested individual.  Although sexual inter-
course is probably the most frequent mode of trans-
mission among single adults, embracing, sharing a
bed, or even shaking hands may also transmit the
disease.  Fomites (eg, clothing) can also play a role
in the spread of scabies.
Two types of cutaneous lesions are seen with
scabies: intact or excoriated burrows, which are
produced by the adult female mite, and erythema-
tous papules, which are believed to represent the
host’s immune response to the parasite.  The bur-
rows are slightly elevated, linear lesions that are
best observed with a hand lens.  At one end of the
burrow, a black speck, vesicle, or pustule is some-
times observed, indicating the location of the fe-
male mite.  The burrows are frequently excoriated
and may become secondarily infected, resulting in
crusting, pustule formation, or furunculosis.  Bur-
rows are often found in the digital web spaces,
wrists, axillae, nipples, umbilicus, and genitalia.
The erythematous papules are usually found on the
trunk but may become widespread.  Eczematous
and urticarial lesions can also be seen as part of the
immune response to scabies infestation.  In adult
patients, the scalp and face are uninvolved, al-
though infants can develop lesions over the entire
cutaneous surface.7  The pruritus of scabies is gen-
erally severe and most noticeable at night.  Diagno-
sis of this infestation rests on demonstrating the
mites, eggs, larvae, or scybala on microscopical
examination of lesional skin scrapings (Figure 8-24).
Scraping is best accomplished with a number 15
surgical blade coated with mineral oil.  An intact
burrow, generally found in the locations listed
above, will provide the highest yield for identifying
organisms.
Two clinical variants of scabies exist: nodular
scabies and Norwegian scabies.  In the former, one
sees a few erythematous or violaceous, firm nod-
ules that persist for weeks to months after treat-
ment, long after the rest of the eruption has re-
solved.  These nodules are commonly found on the
male genitalia and axillary folds.  Norwegian sca-
bies is seen in immunocompromised or debilitated
patients.  Recently, it has been reported4 in associa-
tion with acquired immunodeficiency syndrome.
These patients present with thick, scaling, crusted
plaques that are found most commonly on the hands,
feet, and scalp but may be generalized in distribu-
tion.  Unlike those seen in common scabies, the
lesions on these patients are teeming with mites,
with one source4 estimating the total body load of
parasites and eggs to be 5 to 10 million!  Patients
with Norwegian scabies, often found in hospitals or
nursing homes, are therefore highly contagious and
can be responsible for local epidemics of scabies.
Treatment of scabies requires ridding the body of
mites, relieving symptoms, and treating secondary
infection.  A variety of medications are available as
scabicides, the most widely used being lindane
cream or lotion.  Neurotoxicity has been reported
Fig. 8-24. Microscopical examination of lesional skin
scrapings from a patient with scabies reveals a larval
mite form (with three pairs of legs) on the left and four
ova on the right. The adult mite (not shown) is about 2- to
3-fold larger than the larva and has four pairs of legs.
Photograph: Courtesy of Entomology Department, Walter
Reed Army Institute of Research, Washington, D.C.
OK to put on the Web

Arthropod and Other Animal Bites
173
when lindane is applied to the eczematous skin of
infants or when excessive amounts have been used
inappropriately (eg, ingesting the liquid); however,
lindane is generally safe.  The drug should be ap-
plied to dry skin, covering the entire cutaneous
surface from the neck down, and left on for 8 hours.
Re-treatment 2 to 7 days later is suggested to kill
any newly hatched nymphs.  Opinions vary on the
safety of lindane when used in children under the
age of 2 years.26  An alternative for this population,
as well as pregnant women, is 5% to 10% precipi-
tated sulfur in petrolatum applied nightly for 3
nights.  Elimite cream (5% permethrin, manufac-
tured by Herbert Laboratories, Irvine, Calif.) is a
recent addition to the scabicides.  Elimite (applied
topically from the neck down, left on for 8 h, then
reapplied in 48 h) is reported to be equal to or better
than lindane and safe in infants older than 2
months.27  Another agent, although less effective, is
Eurax cream (25% crotamiton, manufactured by
Westwood Pharmaceuticals, Buffalo, N.Y.), which
should be applied topically from the neck down
with a second application 24 h later.  It is important
to treat all close contacts and sexual partners of the
patient with the chosen scabicide, for reinfection is
a frequent problem.  Because the mites survive off hu-
mans for only 2 to 3 days, it is necessary to wash only
recently used bed linen and clothing in hot water.
Although killing the mites usually provides a
rather dramatic reduction in pruritus, individuals
with scabies may continue to itch for several weeks.
Pruritus is controlled with systemic antihistamines as
well as topical corticosteroids and antipruritics.  Nodu-
lar scabies may require a one-time intralesional injec-
tion of a corticosteroid such as triamcinolone acetonide,
2.5 to 10 mg/mL.  Any secondary skin infection should
be treated with the appropriate antibiotic.
Nonscabietic Mites
In general, the reaction caused by nonscabietic
mites is due to a combination of secreted toxins and
allergic sensitization.  The cutaneous primary le-
sion is typically a red papule with a central hemor-
rhagic punctum or vesicle.  However, due to their
pruritic nature, the lesions often become crusted,
eczematized, and secondarily infected.  Occasion-
ally, widespread eruptions develop, probably as an
allergic phenomenon.  These conditions include
urticaria, angioedema, erythema, eczematous der-
matitis, a varicelliform eruption, and an erythema
multiforme-like reaction.28  In most instances, the
causative mites cannot be demonstrated on the pa-
tients.  Unless indicated otherwise, the treatment of
bites from all these mites consists of topical corti-
costeroid creams and antipruritic lotions.
Variants of Sarcoptes scabiei can infest and pro-
duce cutaneous disease in many different animals
including dogs, cats, horses, goats, pigs, sheep, and
cattle.24  Humans are infested after coming in con-
tact with the host animal.  These mites are unable to
complete their life cycle on human skin and burrow
only a short distance into the skin.  Cutaneous
lesions, consisting of intact and excoriated papules,
occur on areas most closely in contact with the
animal such as the arms, wrists, and abdomen.  Skin
scrapings from humans are almost always negative
and the causative mite must be demonstrated in the
host animal.  The disease in humans is self-limited
and is treated symptomatically.  The infested ani-
mal should be treated by a veterinarian to prevent
reinfestation.
A variety of mites are blood-feeding parasites
(Sarcoptes scabiei feed on skin) that can prey on
humans.  Often the primary host is a bird, mammal,
reptile, or even another arthropod, and humans are
involved secondarily.28  The tropical rat mite,
Ornithonyssus bacoti, which commonly infests the
black rat, is found in both tropical and temperate
urban centers.  When the rodents are exterminated,
the mites seek alternative hosts and at this time
humans are often bitten.  The mites tend to accumu-
late in warm areas such as near appliances or heat-
ing systems.  The bite of the tropical rat mite is
characteristically painful and pruritic.  Lesions ap-
pear as small hemorrhagic papules, usually on the
arms and legs.  These papules can become
eczematized and secondarily infected after they
have been scratched.
Allodermanyssus sanguineus is a parasite of house
mice, rats, and other small rodents, and its distribu-
tion is worldwide.  This mite is medically important
as the vector of Rickettsia akari, the agent respon-
sible for rickettsialpox.  Within the mites, the rick-
ettsial organisms are transmitted transovarially from
adult to the next generation.  Adult mites transmit
the disease to humans.  The first lesion to appear is
a crusted papulovesicle at the site of the bite.  This
lesion is followed in about a week by fever, chills,
sweats, headache, backache, and generalized papu-
lovesicular eruption that may resemble varicella.7
Tetracycline (250 mg orally every 6 h for 14 d) is the
drug of choice for rickettsialpox.  For a detailed
discussion of rickettsialpox, see Chapter 11, Rick-
ettsial Diseases.
Several species of mites infest birds as their pri-
mary host.  The northern fowl mite, Ornithonyssus
sylviarum, is found in birds and domestic fowl of the

Military Dermatology
174
northern temperate areas.  Bird handlers are most
commonly bitten.  Two mites, Dermanyssus gallinae
and Ornithonyssus bursa, can infest domestic poul-
try.  Consequently, pruritic and painful bites may
be seen on individuals working in the poultry in-
dustry.  These two mites also parasitize a number of
wild birds including sparrows, starlings, and pi-
geons.  When these birds leave their nests, as in
times of migration, humans may be bitten.
The Pyemotidae family of mites have as their
hosts a variety of insects that in turn infest grain,
straw, seeds, other stored food products, timber,
and furniture.  The human victims of these mites
include farm workers at harvest time, animal feed
handlers, florists, and individuals exposed to in-
fested furniture.  Cutaneous lesions can be papular,
urticarial, vesicular, or pustular.
Cheyletiellidae are nonburrowing mites that com-
monly infest domestic animals including dogs, cats,
and rabbits.  Often the pet appears asymptomatic,
but on close inspection has “walking dandruff.”
Because of this, the pet is often overlooked as a
source of the bites.  Humans are bitten more com-
monly during the cold winter months when ani-
mals are brought indoors.  The skin lesions are
found on the forearms, thighs, chest, and abdomen
where pets are held.  They consist of small papules
or pustules, frequently with a characteristic ne-
crotic center.  Urticarial lesions and widespread
erythema may occur.  The eruption will disappear
when the pet is treated.
The final group of mites to be discussed are those
from the family Trombiculidae, commonly known
as chiggers, red bugs, or mower’s mites.  Only the
six-legged larval form parasitizes other animals
(Figure 8-25).  These red larvae, found on the ground
or in grass, will attach to a host, feed for 2 to 3 days,
molt to the nymphal stage, and then leave the host.
They feed through a tube called the stylostome,
which is inserted into the epidermis.  Bites are
commonly seen between May and October when
the larvae are active.  As the host walks through
infested vegetation, the larvae crawl up the legs
and usually stop to feed where the clothing
constricts, such as the ankles, thighs, or beltline.
The initial bites are not felt and the skin lesions
develop 3 to 24 hours later when an allergic reaction
to mite saliva develops.  These lesions appear as
highly pruritic red papules grouped about the waist,
thighs, and legs that can persist for several weeks.
Prevention of bites includes the use of a repellent
such as DEET and tucking long trouser legs into
stockings.
OK to put on the Web
Fig. 8-25. A chigger is the larval form of mites belonging
to the family Trombiculidae. It will attach to the host for
2 to 3 days, feeding on blood via a stylostome and pro-
ducing highly pruritic papules on the legs, thighs, and
waist. Some of the Trombiculidae are vectors for
tsutsugamushi fever. Photograph: Courtesy of Entomol-
ogy Department, Walter Reed Army Institute of Research,
Washington, D.C.
Some of the Trombiculidae are vectors for scrub
typhus or tsutsugamushi fever caused by Rickettsia
tsutsugamushi.  The primary host of these mites are
field rats and, although they are probably not a
reservoir of infection, the rats serve to maintain the
mite population.  As with the mite vector of
rickettsialpox, R tsutsugamushi are passed transo-
varially to the larvae.  The constitutional symptoms
of scrub typhus, namely fever, chills, and intense
headache, occur about 10 days after the bite.  These
symptoms are followed by an erythematous macu-
lar rash that starts on the trunk and extends periph-
erally, and a pneumonitis.  At the site of the original
bite, an indurated papule develops that becomes
necrotic.  Tetracycline (250 mg orally every 6 h for
14 d) is the treatment of choice.
Scorpions
Scorpions are large arachnids with an elongated
abdomen that terminates in a stinger (Figure 8-26).7
They have a pair of abdominal glands that release
both neurotoxic and hemolytic venom into the
stinger.  The distribution of scorpions is worldwide,
especially in the tropics.  In the United States, the
Centruroides sculpturatus, measuring 13 to 75 mm, is
the most common stinging scorpion and is found in

Arthropod and Other Animal Bites
175
OK to put on the Web
Fig. 8-26. Scorpions have pincer claws, four pairs of legs,
and an elongated abdomen that terminates in a stinger.
In the United States they range in length from 1.5 to 7.5
cm. Photograph: Courtesy of Entomology Department,
Walter Reed Army Institute of Research, Washington, D.C.
the Southwest.29  Scorpions are nocturnal and hide
during the daytime in dark places including closets,
shoes, and under rocks and logs.  They sting in self-
defense, as when they are unwittingly stepped on.
Immediately after the sting, the affected individual
experiences pain and swelling at the site.  The
hemolytic venom usually produces little else, al-
though in cases of severe envenomation, coagu-
lopathy and cardiovascular symptoms may result.
The neurotoxin, on the other hand, can cause a
variety of symptoms including localized numbness,
fasciculation, lacrimation, salivation, profuse sweat-
ing, urinary urgency, nausea, tongue paresthesia,
restlessness, convulsions, and an increase in ex-
traocular muscle activity.  Anaphylaxis and death
from cardiac or respiratory failure may occur, espe-
cially in children.  Treatment of scorpion stings
consists of first removing the stinger, then applying
a tourniquet and cooling the site with ice.  If avail-
able, specific antivenin should be administered.
Barbiturates or diazepam can be given to control
the central nervous system hyperactivity and con-
vulsions.  Atropine may be useful in blocking the
cholinergic side effects of the neurotoxin.  A variety
of pesticides such as malathion and diazinon have
been used to eradicate scorpions.
Spiders
Although spiders are notorious among the pub-
lic as fierce and dangerous creatures and are hence
feared (arachnephobia), in fact they are usually shy
and tend to avoid contact with humans.  Over
30,000 species of spiders have been identified, and
yet fewer than 60 are of medical importance in the
United States.30  In this country, only the black
widow spider (Lactrodectus mactans) and the brown
recluse spider (Loxosceles reclusa) are known to cause
death.31  Worldwide, other potentially lethal spi-
ders include the Australian funnel-web spider (Atrax
robustus and A formidabilis), the South American
banana spider (Phoneutria fera), and the South Afri-
can Harpactirella.4  Although almost all spiders are
venomous, the overwhelming majority are unable
even to penetrate human skin with their jaws.  Those
that can penetrate usually cause only minor local
injury.
All spiders have a cephalothorax from which
extend eight legs and an abdomen.  A pair of jaws
(chelicerae) are found at the anterior end of the
cephalothorax.  These jaws terminate in sharp,
chitinized fangs from which venom is ejected.  This
pair of fangs produces the characteristic set of two
small puncta found at the site of most spider bites.
The venomous glands as well as the spider’s mul-
tiple eyes (usually eight) are also located in the
cephalothorax.  On the ventral surface of the abdo-
men are the spinnerets, which release the web-
forming silk.  All spiders are carnivores, feeding
primarily on insects.
Spiders can adapt to their local environment and
live well in man-made structures and refuse.  Webs
may be found around old tires, garbage cans, out-
houses, and lampposts.32  Spiders are frequently
encountered in woodpiles, junkyards, and cluttered
attics and closets.  They tend to relocate indoors
when the weather becomes cold.  Simple measures
such as cleaning out closets and attics as well as
maintaining woodpiles and refuse areas can dis-
courage infestation by and contact with spiders.
Spiders can cause cutaneous and systemic injury
in humans through a variety of different mecha-
nisms.  Most important is their venom, which can be
either neurotoxic or dermonecrotic.  These two types
of venom are seen in the black widow and brown
recluse, respectively, and will be discussed in more

Military Dermatology
176
detail below.  Many species of tarantulas have hairs
that produce urticaria when in contact with skin.
Pet owners are the primary recipient of this derma-
tologic problem.  The bite of most spiders, although
inconsequential in terms of discomfort or cutane-
ous damage, may become secondarily infected, pro-
ducing pustular, impetigenous, or cellulitic lesions.
Finally, repeated spider bites can rarely cause aller-
gic reactions including anaphylactic shock.
Brown Recluse Spider
The brown recluse spider (Loxosceles reclusa) has
a yellow-to-brown cephalothorax and a tan abdo-
men.  The species is identified by a dark brown,
violin-shaped marking on the dorsal aspect of the
cephalothorax (Figure 8-27).  Its body ranges from 1
to 1.5 cm in length, with a leg span of over 2.5 cm.
These shy, nocturnal hunting spiders are found
throughout the continental United States, and a
closely related species, L laeta, is found in South
America.  Within the United States, they are in
greatest numbers in the south-central part of the
country, preferring a warm, dry climate.  They like
protected places such as beneath rocks and boards
or in animal burrows or caves where they spin
small matted webs.  In northern areas of the coun-
try, they are more frequently found indoors,
in closets, attics, and garages.  They avoid daylight
and are not aggressive toward humans,
attacking only when trapped or crushed against the
skin.
OK to put on the Web
Fig. 8-28. The bite of the brown recluse spider may
produce full-thickness skin necrosis. This is usually pre-
ceded by a central area of blue-gray discoloration, a
blanched halo from arterial spasm, and a large surround-
ing zone of reactive erythema. Photograph: Courtesy of
Entomology Department, Walter Reed Army Institute of
Research, Washington, D.C.
The venom from the brown recluse is more po-
tent than that of a rattlesnake.  Although different
analyses of its contents have yielded conflicting
results, the primary dermonecrotic factor appears
to be a phospholipase, sphingomyelinase D.  This
interacts with and damages the plasma membrane
of many cell types including erythrocytes, endothe-
lial cells, and platelets.  Other enzymes have been
identified in the venom, such as alkaline phos-
phatase, hyaluronidase, collagenase, 5'-ribonucle-
otide phosphohydrolase, deoxyribonuclease, ribo-
nuclease, and other proteases and esterases.  These
enzymes, as well as host factors including prostag-
landins, leukotrienes, and complement, probably
all play a role in the neutrophil chemotaxis, platelet
aggregation, and tissue necrosis that occur as a
result of the bite.
The clinical outcome of brown recluse spider
bites varies widely, ranging from minor, inconse-
quential, cutaneous reactions to full-thickness skin
necrosis and, in some instances, death (Figure 8-28).
Multiple factors including host susceptibility,
amount of venom injected, and location of the bite
play a role in determining the extent of the reaction.
Only 10% of patients develop a significant necrotic
wound.  The initial bite is often painless and unno-
ticed by the patient.  Therefore, the spider is usually
not seen and a brown recluse bite is suspected only
on clinical grounds.  Within 12 to 24 hours of the
OK to put on the Web
Fig. 8-27. The brown recluse spider (Loxosceles reclusa) is
1 to 1.5 cm in length with a 2.5-cm leg span. Photograph:
Courtesy of Entomology Department, Walter Reed Army
Institute of Research, Washington, D.C.

Arthropod and Other Animal Bites
177
bite, pain, erythema, violaceous mottling, swelling,
induration, and blister or pustule formation may
occur.  A characteristic trizonal response takes place,
with a central blue-gray area due to thrombosis, a
blanched halo from arterial spasm, and a large
surrounding area of reactive erythema.  In the ab-
sence of any of these changes, the patient usually
will not develop significant tissue necrosis.  Once
these changes are seen, however, there is often
progression to eschar formation, dermal necrosis,
and stellate ulceration.  Healing is slow, in severe
cases taking up to 6 months.  Systemic symptoms
include headache, fever, malaise, and arthralgias.
A generalized maculopapular rash may be associ-
ated with the cutaneous changes.  A much more
severe systemic reaction due to hemolysis is a rare
complication seen primarily in children, who may
present with disseminated intravascular coagula-
tion, hemoglobinuria with acute renal failure, con-
vulsions, coma, and death.  Patients with significant
cutaneous necrosis (> 1 cm) should be tested for
progressive hemolytic anemia.
The therapy for brown recluse spider bites has
evolved but still remains somewhat controversial.
Elements of immediate care include immobiliza-
tion and elevation of the affected site and the appli-
cation of ice compresses: the enzymes in the venom
are rendered less active with a decrease in tempera-
ture.  Tetanus toxoid should be administered, if
indicated, and analgesics may be necessary.
Intralesional injection of corticosteroid (triamcin-
olone, 25 mg) helps to relieve pain and reduce
inflammation.33  Early excision of the bite site was
previously recommended, but this procedure may
actually extend tissue damage and delay wound
healing.  Systemic corticosteroids do not seem to
prevent or lessen the cutaneous necrosis but may be
beneficial for the systemic manifestations.  Dapsone
(4,4'-diaminodiphenylsulfone), 100 mg daily, is ef-
fective in limiting the cutaneous necrosis; however,
this drug must be used with care because it causes
hemolysis, most notably in patients deficient in
glucose-6-phosphate dehydrogenase.  Wound exci-
sion and skin grafting should be considered only
after the eschar has delineated itself and the wound
is no longer enlarging.  Systemic antibiotics may be
necessary to treat secondary wound infection.
Black Widow Spider
Of the five species of Latrodectus found in the
United States, L mactans, or the black widow, is the
most common and has the widest distribution.  These
OK to put on the Web
Fig. 8-29. The black widow spider (Lactrodectus mactans)
has a body measuring up to 1.5 cm long, with a leg span
up to 4 cm. Its black abdomen has a red hourglasslike
marking on the ventral surface. Photograph: Courtesy of
Entomology Department, Walter Reed Army Institute of
Research, Washington, D.C.
spiders are found from the South to southern New
England.  Only the female of the species is capable
of envenomating humans.  They are jet black with a
globose abdomen that has the characteristic red
hourglasslike marking on the ventral surface (Fig-
ure 8-29).  Measuring up to 1.5 cm in length with a
4-cm leg span, black widow spiders prefer a warm,
dry environment and can be found both outdoors
and inside buildings.  The large, strong webs they
spin are generally placed close to the ground in
protected places like rodent burrows, under stones
and logs, in the angles of doors and windows, and
in cluttered areas such as dumps, garages, sheds,
and outhouses.  Although black widows will not
aggressively attack humans, they bite when a per-
son inadvertently comes in contact with the web.  A
notorious and not infrequent scenario is the biting
of male genitalia by a black widow spider whose
web is located beneath an outhouse seat.
The black widow’s venom is a potent neurotoxin
composed of proteins, lipids, and carbohydrates.
One or more components of this venom bind to the
synaptic membranes of nerve terminals, causing
the release of large amounts of acetylcholine, cat-
echolamines, or both at the neuromuscular junc-
tions.  Re-uptake of the neurotransmitters is also
blocked and they are subsequently depleted.  Motor
nerves, as well as sympathetic and parasympa-
thetic nerves, are affected by this toxin, explaining
most of the signs and symptoms of black widow
envenomation.  This venom, unlike that of the brown

Military Dermatology
178
recluse spider, causes little local damage and no
necrosis at the site of the bite.
The actual bite of the black widow is often per-
ceived as a sharp pinprick.  Two tiny red puncta are
usually visible at the site.  Mild erythema and edema
then ensue, accompanied by a dull ache and numb-
ness that spread from the inoculation site to the
torso and, in some cases, the entire body.  The
systemic symptoms begin within an hour, peak at 1
to 6 hours, and can last 1 to 2 days.  Severe myalgias
and muscle cramping develop, first regionally, then
in a general distribution.  In the majority of victims,
the abdominal musculature is involved and may
simulate an acute surgical abdomen.  Other sys-
temic signs and symptoms include headache, rest-
lessness, anxiety, fatigue, insomnia, diaphoresis,
salivation, lacrimation, nausea, vomiting, tremors,
fasciculation, paresthesias (burning of the plantar
surface is characteristic), respiratory distress, shock,
and coma.  Patients have a characteristic facies that
is grimaced, flushed, and diaphoretic, with accom-
panying blepharoconjunctivitis.34  Although death
from a black widow bite is extremely rare in an
adult, it can occur in up to 50% of young children if
left untreated.31
In the treatment of black widow spider bites,
hospitalization should be considered for children,
the elderly, those with underlying cardiac or pul-
monary disease, or victims displaying severe sys-
temic signs and symptoms.  If the patient has no
history of sensitivity to horse serum and exhibits
severe systemic involvement, L mactans antivenin
can be given.  One ampule containing 2.5 mL, given
intravenously or intramuscularly, will relieve most
symptoms within 1 to 2 hours.  Analgesia can some-
times be obtained with aspirin or acetaminophen,
but in severe cases requires narcotics.  Muscle relax-
ants and intravenous calcium gluconate have also
been advocated.
Tarantulas
Tarantulas are the largest of all spiders and be-
long to the family Theraphosidae (Figure 8-30).  The
name “tarantula” is actually a misnomer and prop-
erly belongs to the much smaller but equally hairy
wolf spider found in Europe.  In the United States,
tarantulas are found throughout the Southwest,
where they live in burrows during the day and hunt
at night.  Their leg span can reach 15 to 18 cm.
Although the appearance of these large, hairy spi-
OK to put on the Web
Fig. 8-30. Tarantulas are hairy spiders whose leg spans
can measure up to 18 cm. Despite their intimidating
appearance, they are usually not harmful to humans,
biting only after significant provocation. Photograph:
Courtesy of Entomology Department, Walter Reed Army
Institute of Research, Washington, D.C.
ders is formidable, they are usually not harmful to
humans.  They will bite only after significant provo-
cation.  Even then, their bite produces only tempo-
rary pain without accompanying tissue damage.
However, when threatened, tarantulas may flick
some of their hair toward an aggressor.  These hairs
can penetrate the skin and cause a pruritic urticarial
dermatitis that lasts several days.  This reaction can
be treated with topical corticosteroids and oral an-
tihistamines or, if severe, with a brief course of
systemic corticosteroids.
Chiracanthium
The genus Chiracanthium includes the common
garden spider and the common house spider.  These
spiders are green to brown and vary in length from
7 to 10 mm.  They possess a venom that is similar to
that of the brown recluse but inject a much smaller
volume and, therefore, produce much less tissue
damage.  Bites occur most frequently at night on
exposed parts of the body.  The initial bite is usually
painful, and a crusted, necrotic lesion can develop
within several days.  Surrounding erythema and
induration are often seen.  Occasionally, pain ex-
tends far beyond the site of the bite, suggesting a
neurotoxin.  Treatment includes immobilization and
elevation of the site, tetanus prophylaxis, and anal-
gesics.  Antibiotics may be necessary for secondary
infection.

Arthropod and Other Animal Bites
179
REPTILES
tourniquet tightened only enough to impede super-
ficial venous and lymphatic flow can be applied
proximally to the fang marks.  The use of local ice
packs should be avoided, for unlike brown recluse
spider bites, tissue damage can actually be increased
by this maneuver.  Incising the wound and attempt-
ing to remove venom by suction is also discouraged
because it does little more than delay prompt trans-
portation.  Every attempt should be made to iden-
tify the snake involved.
Once the snake-bitten patient is hospitalized, an
evaluation for hemolysis and myonecrosis should
include blood and platelet counts, coagulation stud-
ies, and urinalysis.  If there is symptomatology or
laboratory evidence of envenomation, Antivenin
Polyvalent (manufactured by Wyeth-Ayerst Labo-
ratories, Philadelphia, Pa.) should be administered
via intravenous drip.  Antivenin is available for
both pit viper and coral snake bites.  Antivenins for
some other species of poisonous snakes can be ob-
tained from the Oklahoma City Poison Control Cen-
ter (405-271-5454).  Prior to initiation of therapy, the
patient should be skin-tested for hypersensitivity to
horse serum because anaphylaxis may occur.  Other
adverse reactions include fever and serum sickness.
Tetanus prophylaxis, analgesics, and appropriate
antibiotic coverage for secondary infection are all
often indicated.  Surgical debridement of necrotic
tissue should be done only after the patient is stabi-
lized with normal coagulation parameters.
Gila Monsters
Gila monsters are venomous lizards found in the
southwestern United States.35,37  They are large, slug-
gish creatures that will bite humans only when
attempts are made to capture or handle them.  Once
provoked, however, their bite can be both strong
and tenacious.  Their venom contains phospholi-
pase A, protease, hyaluronidase, and a kinin-releas-
ing factor.  If envenomation occurs, the victim may
experience sharp local pain and accompanying
edema.  Other symptoms include weakness, dizzi-
ness, tinnitis, fasciculation, nausea, vomiting, and
hypotensive shock.  Therapy consists, foremost, of
removing the lizard from the victim.  The Gila
monster’s jaws are powerful, and a chisel or crow-
bar may be required to pry them open.  The wound
A number of reptiles are capable of inflict-
ing significant bite wounds if provoked, and some
species pose the additional threat of envenoma-
tion.  Among the dangerous reptiles that humans
may encounter are poisonous snakes and Gila
monsters.
Snakes
Venomous snakes can be encountered through-
out the world.  In the United States, the rattlesnake,
cottonmouth moccasin, and copperhead, all belong-
ing to the family Crotalidae, or pit vipers, account
for the vast majority of bites.  These pit vipers are
found most frequently in the Southeast and South-
west.  Other dangerous vipers found in Europe,
North Africa, the Middle East, and Asia include the
Leventine viper, the puff adder, and a variety of
horned desert vipers and carpet vipers.  Coral
snakes, found in the southern United States, are
members of the family Elapidae (including cobras,
mambas, and kraits), and are responsible for less
than 2% of all poisonous snake bites.35  Although an
estimated 45,000 people are bitten by snakes each
year in this country, only 20% of these bites involve
venomous snakes and fewer than 12 result in death.35
Most fatalities are caused by rattlesnakes.
All the pit vipers bite with hollow fangs through
which their venom is discharged.36  Snake venom
contains nearly 30 enzymes, most of which are
hydrolases.  An anticoagulant in the venom causes
hemolysis and capillary leakage.  Other compo-
nents include neurotoxic, myotoxic, and cardiotoxic
substances.
A wide variety of signs and symptoms may re-
sult from a snake bite and accompanying en-
venomation.  Pain, edema, ecchymosis, vesicula-
tion, petechiae, and tissue necrosis can develop at
the site of the bite.  Systemic manifestations include
weakness, diaphoresis, nausea, vomiting, diarrhea,
abdominal pain, dysesthesias, headache, fascicula-
tion, hemorrhage, myonecrosis, and shock.  Rarely,
allergic reactions may be seen in individuals who
handle and are repeatedly bitten by snakes.
Therapy for a venomous snake bite should ini-
tially consist of the first-aid measures of immobili-
zation, maintenance of vital signs, and prompt
transportation to a medical treatment facility.  A

Military Dermatology
180
sary.  The victim should be monitored for
hypotension and treated accordingly with intrave-
nous fluids.  No antivenin is available.
is then irrigated with lidocaine and probed for
broken tooth fragments.  Tetanus prophylaxis, an-
algesics, and antibiotic coverage may all be neces-
CATS AND DOGS
Every year, an estimated 1 to 2 million dog bites
and 400,000 cat bites are reported in the United
States.38  These injuries account for about 1% of all
emergency room visits.  Although most wounds are
trivial, requiring little or no medical care, serious
complications such as cellulitis, osteomyelitis, sep-
tic arthritis, and sepsis can occur.  The hands and
face are frequent sites for bites.  The wound inflicted
can be a scratch or puncture, but more severe
injuries such as avulsions or crush injuries with
tissue necrosis may be seen.  The risk of wound
infection increases with (a) victims older than 50
years of age, (b) immunosuppressed victims, (c)
puncture wounds or crush injury, (d) bites to de-
pendent areas, and (e) wounds that have not been
promptly irrigated.  Although approximately 85%
of bite wounds will contain pathogenic bacteria,
only 2% to 30% of patients with bites will develop
wound infections.  A wide variety of bacteria can be
involved in wound infections, including both aero-
bic and anaerobic organisms.  Pasteurella multocida
is found in 20% to 25% of dog-bite wounds and 50%
of cat-bite wounds.
Initially, a dog or cat bite should be promptly
cleansed, liberally irrigated, and debrided of any
devitalized tissue,39 and tetanus toxoid should be
administered.  The affected area should be ban-
daged, elevated, and immobilized.  Culturing the
initial wound is generally not helpful either in pre-
dicting subsequent infection or in identifying the
causative organism if infection should develop.
Rather, aerobic and anaerobic cultures should be
taken only after evidence of infection is present,
with definitive antibiotic therapy guided by in vitro
sensitivity assays.  Initial empirical therapy should
provide coverage against P multocida, Staphylococ-
cus aureus, streptococci, Centers for Disease Control
alphanumeric bacteria (eg, DF-2, EF-4), and anaero-
bic bacteria.  Although penicillin (250 mg orally
every 6 h for 10 d) has been the standard treatment,
it provides poor coverage of S aureus, and a broader-
spectrum agent such as amoxicillin-clavulanic acid
(250 mg orally every 8 h for 10 d) should be consid-
ered.  Doxycycline and minocycline (each at 100 mg
orally every 12 h for 10 d) are good alternatives for
penicillin-allergic individuals.  In the absence of
clinical infection, consideration should be given for
empirical antibiotic therapy of severe wounds, crush
injuries, puncture wounds, and wounds involving
the hands, joints, or bones.  Suturing of laceration
wounds is controversial and is probably best re-
served for clinically uninfected wounds treated less
than 12 hours after the bite.  Some authorities rec-
ommend initial approximation with adhesive strips
and delayed closure.38  Rabies vaccine (prophylac-
tic, not therapeutic) should be considered if the bite
is produced by an unknown domestic animal or a
wild animal in which rabies is endemic.
SUMMARY
Arthropods compose the largest phylum and
have a worldwide distribution.  Bites and stings
inflicted by arthropods may cause significant
morbidity in the military operational environment.
Any break in the skin may serve as a portal of
infection, especially in a humid tropical setting.
The scratching that follows many arthropod
bites further compromises the skin integrity; cuta-
neous pyodermas have been a significant cause of
hospitalization during past military conflicts.
Severe systemic reactions including anaphylaxis
may result from a bite or sting.  Arthropods
also serve as the vectors for a number of infec-
tious diseases, a topic covered in Chapter 9, Arthro-
pod Infestations and Vectors of Disease, and
Chapter 11, Rickettsial Diseases.  It therefore be-
hooves the medical officer to become familiar with
the arthropods found in his or her geographical
setting.
Specific therapy exists for those arthropods tak-
ing up residence on the human skin such as scabies
and lice.  Topically applied insecticides such as
1% lindane and 5% permethrin will eradicate the
organisms.  In the majority of cases where the ar-
thropod is only in contact with the skin long
enough to bite or sting, the treatment is symptom-
atic, aimed at relieving pain and pruritus.  A variety
of methods exist for preventing arthropod bites.

Arthropod and Other Animal Bites
181
General public health measures include separating
livestock, wood piles, and latrine and garbage sites
from living quarters.  Doors and windows may
be fitted with mesh netting and the floors elevated
from the ground.  Protective clothing reduces
exposed skin.  Insecticides such as malathion and
the pyrethroids may be sprayed or powdered in
living quarters and on furniture.  Finally, a number
of repellents are available for both topical applica-
tion and impregnation in clothing.  One of the
best repellent combinations appears to be topically
applied DEET and permethrin-impregnated
clothing.
Although most cat and dog bites are minor
and require little or no medical care, they are a
frequent cause of visits to the emergency room,
and infection can arise without prompt wound
cleaning and administration of antibiotics.
Wounds inflicted by poisonous reptiles, although
less common than cat and dog bites, can have
 serious consequences and require immediate first-
aid treatment.  Gila monsters have powerful jaws,
and sometimes a crowbar is required to pry them
from the victim; patients should then be monitored
for hypotension.  In the event of a poisonous
snake bite, it is important to identify the variety
of snake so that the proper antivenin can be
administered.
REFERENCES
1.
MacPherson WG, Horrocks WH, Beveridge WWO. History of the Great War, Medical Services, Hygiene of the War.
Vol 2. London, England: His Majesty’s Stationery Office, 1923: 327–340.
2.
Pillsbury DM, Livingood CS. Dermatology. In: Havens WP, ed. Infectious Diseases and General Medicine. In:
Havens WP, Anderson RS, eds. Internal Medicine in World War II. Vol 3. Washington, DC: Medical Department,
US Army, Office of The Surgeon General; 1968: 543–673.
3.
Allen AM. Skin Diseases in Vietnam, 1965–72. In: Ognibene AJ, ed. Internal Medicine in Vietnam. Vol 1. Washing-
ton, DC: Medical Department, US Army, Office of The Surgeon General and Center of Military History; 1977:
59–139.
4.
Alexander JO. Arthropods and Human Skin. Berlin, Germany: Springer-Verlag; 1984: 3–9, 117, 364, 399–408.
5.
Mellanby K. Man’s reaction to mosquito bites. Nature. 1946;158:554.
6.
Burnett JW, Calton GJ, Morgan RJ. Centipedes. Cutis. 1986;37:241.
7.
Arnold HL, Odom RB, James WD. Andrew’s Diseases of the Skin. Philadelphia, Pa: WB Saunders Company; 1990:
486–533.
8.
Burnett JW, Calton GJ, Morgan RJ. Caterpillar and moth dermatitis. Cutis. 1986;37:320.
9.
Rosen T. Caterpillar dermatitis. Dermatol Clinics. 1990; 8:245–252.
10.
Burnett JW, Calton GJ, Morgan RJ. Bedbugs. Cutis. 1986;38:20.
11.
Burnett JW, Calton GJ, Morgan RJ. Triatoma: The “kissing bug.” Cutis. 1987;39:399.
12.
Elgart ML. Pediculosis. Dermatol Clinics. 1990;8:219–228.
13.
Meinking TL, Taplin D, Kalter DC, et al. Comparative efficacy of treatments for pediculosis capitis infestations.
Arch Dermatol. 1986;122:267–271.
14.
Elgart ML. Flies and myiasis. Dermatol Clinics. 1990;8:237–244.
15.
Brown AWA. The attraction of mosquitoes to hosts. JAMA. 1966;196:159–162.
16.
Kurgansky D, Burnett JW. Diptera mosquitoes. Cutis. 1988;41:317–318.

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17.
Burnett JW. Myiasis. Cutis. 1990;46:51–52.
18.
Burnett JW, Calton GJ, Morgan RJ. Blister beetles: “Spanish fly.” Cutis. 1987;40:22.
19.
Gayer KD, Burnett JW. Hymenoptera stings. Cutis. 1988;41:93–94.
20.
Elgart GW. Ant, bee, and wasp stings. Dermatol Clinics. 1990;8:229–236.
21.
Schorr WF, Tauscheck AL, Dickson KB, Melski JW. Eosinophilic cellulitis (Wells’ syndrome): Histological and
clinical features of arthropod bite reactions. J Am Acad Dermatol. 1984;11:1043–1049.
22.
Ross EV, Badame AJ, Dale SE. Meat tenderizer in the acute treatment of imported fire ant stings. J Am Acad
Dermatol. 1987;16:1189–1192.
23.
Modly CE, Burnett JW. Tick-borne dermatologic diseases. Cutis. 1988;41:244–246.
24.
Elgart ML. Scabies. Dermatol Clinics. 1990;8:253–263.
25.
Mellanby K. Biology of the parasite. In: Orkin M, Maibach HI, Parish LC, Schwartzman RM, eds. Scabies and
Pediculosis. Philadelphia, Pa: JB Lippincott, 1977.
26.
Lindane, a prudent approach. Arch Dermatol. 1987;123:1008–1010. Editorial.
27.
Taplin D, Meinking TL, Porcelain SL, et al. Permethrin 5% dermal cream: A new treatment for scabies. J Am Acad
Dermatol. 1986;15:995–1001.
28.
Blankenship ML. Mite dermatitis other than scabies. Dermatol Clinics. 1990;8:265–275.
29.
 Burnett JW, Calton GJ, Morgan RJ. Scorpions. Cutis. 1986;36:393.
30.
Wilson DC, King LE. Spiders and spider bites. Dermatol Clinics. 1990;8:277–286.
31.
Wong RC, Hughes SE, Voorhees JJ. Spider bites. Arch Dermatol. 1987;123:98–104.
32.
Spider bites. Arch Dermatol. 1987;123:41–43. Editorial.
33.
Burnett JW, Calton GJ, Morgan RJ. Brown recluse spider. Cutis. 1985;36:197–198.
34.
Burnett JW, Calton GJ, Morgan RJ. Lactrodectism: Black widow spider bites. Cutis. 1985;36:121.
35.
McKoy KC, Moschella SL. Parasites, arthropods, hazardous animals, and tropical dermatology. In: Moschella
SL, Hurley HJ, eds. Dermatology. Philadelphia, Pa: WB Saunders Company; 1985: 1731–1820.
36.
Burnett JW, Calton GJ, Morgan RJ. Venomous snakebites. Cutis. 1986;38:299–300.
37.
Burnett JW, Calton GJ, Morgan RJ. Gila monster bites. Cutis. 1985;35:323.
38.
Goldstein EJC. Management of human and animal bite wounds. J Am Acad Dermatol. 1989:21:1275–1279.
39.
Burnett JW. Bite wounds. Cutis. 1990;45:287.

Arthropod Infestations and Vectors of Disease
183
Chapter 9
ARTHROPOD INFESTATIONS AND
VECTORS OF DISEASE
CURT P. SAMLASKA, M.D.*
INTRODUCTION
MITES AND TICKS
Lyme Disease
Relapsing Fever
Rickettsial Diseases
Tick Paralysis
Tick-Bite Alopecia
Tick-Bite Reactions
FLEAS
Plague
Flea Bites
Papular Urticaria
Tungiasis
OTHER INSECTS
Lice
Bedbugs
Biting Flies
SUMMARY
*Lieutenant Colonel, Medical Corps, U.S. Army; Chief, Dermatology Service, Tripler Army Medical Center, Honolulu, Hawaii  96859

Military Dermatology
184
INTRODUCTION
To an entomologist the word “insect” refers
to the class Insecta, a group of organisms with six
legs and three body segments: head, thorax, and
abdomen.  The layman and many in the medical
community would also include spiders and mites
(class Arachnida), both of which have eight legs
and two body segments: head and abdomen.  A
more precise and inclusive term than insect is ar-
thropod (phylum Arthropoda), comprising organ-
isms from both classes, Insecta and Arachnida; these
classes have as common features a hard, jointed
exoskeleton and paired, jointed legs (Table 9-1).
Some arthropods evolved into parasites, develop-
ing piercing-sucking mouth parts enabling them to
obtain blood meals.  Harwood and James1 believe
that in their evolution, arthropods began as scaven-
gers of vertebrate-lair detritus.  The host, in addi-
tion to providing a steady food source, provides
warmth and shelter.  Synanthropy, in contrast to
parasitism, is a loose form of dependence between
insects (eg, cockroaches, some fly and ant species)
and vertebrates in which direct host feeding does
not occur.1
Insects are estimated to have preceded human
existence by at least 400 million years.  Documenta-
tion of human afflictions with insects dates back to
prehistoric times.1  Legends, art, and speech have
preserved our earliest knowledge of these most
numerous pests.  Stoneware from Mexico (AD 1200)
and Peru (AD 400–900) display detailed depictions
of fleas and tungiasis.1  Variations of the story of
Pandora’s box attempt to explain human louse and
flea infestations.  In about AD 1200, Native American
potters depicted mosquitoes poised for attack.  In
Exodus 8:24, the Bible refers to “a grievous swarm
of flies into the house of Pharaoh, and into all the
TABLE 9-1
ARTHROPODS KNOWN TO BE VECTORS OF HUMAN INFECTIOUS DISEASES
Class
Order
Families
—Subclass
—Suborder
—Subfamilies
Common Names
Arachnida
—Acari
Acarina
Ixodidae
Hard ticks
Argasidae
Soft ticks
—Acari
Acarina
—Parasitiformis
Gamasidae
Mites
Insecta
Anoplura
Pediculidae
Head and body lice
Pthiridae
Crab louse
Siphonaptera
Pulicidae
Human flea
Leptopsyllidae
Mouse flea
Diptera
Muscidae
Tsetse fly
Culicidae
—Culicinae
Aedes mosquito
—Anophelinae
Anopheles mosquito
Psychodidae
—Phlebotominae
Sandflies
Simuliidae
Black flies
Diptera
—Brachycera
Tabanidae
Horse and deer flies
Hemiptera
Reduviidae
Kissing bug
Data sources: (1) Harwood RF, James MT, eds. Entomology in Human and Animal Health. 7th ed. New York, NY: Macmillan Publishing
Co; 1979: 117–392. (2) Alexander JO. Arthropods and Human Skin. Berlin, Germany: Springer-Verlag; 1984: 303.

Arthropod Infestations and Vectors of Disease
185
land of Egypt: the land was corrupted by reason of
the swarm of flies.”  That insects were vectors of
human disease was first suggested in 1577 by
Mercurialis, who believed that flies carried the “vi-
rus” of plague.1  Subsequent observations by nu-
merous investigators up to the early 1900s helped
better understand vector transmission of yaws,
Carrion’s disease, bubonic plague, malaria, and
yellow fever.  Medical entomology began in 1909
and was the direct result of the development of the
microscope, rejection of the spontaneous genera-
tion theory, formulation of the germ theory by Louis
Pasteur, and establishment of controlled experi-
mentation by Walter Reed.1,2
Diseases caused by insects and arachnids can be
the result of direct tissue injury, transmission of
intermediate host parasites, or vector transmission
of infectious and parasitic organisms.1  Human dis-
eases transmitted by insect vectors are some of the
most ancient and deadly of all infectious disorders.
During World War I, louse-borne typhus contrib-
uted to the collapse of the Russian and Balkan
fronts.1  Epidemics occurred also during World War
II in Naples, Italy, and Germany; however, use of
dichlorodiphenyltrichloroethane (DDT) greatly re-
duced the spread of disease.1  War and natural
disasters promote epidemics of these ancient disor-
ders, as exemplified by the concerns that wide-
spread epidemics would follow Operations Desert
Storm and Desert Shield, 1991–1992.
MITES AND TICKS
Three orders of medical importance are found
within the class Arachnida: mites and ticks (Aca-
rina), spiders (Araneida), and scorpions (Scorpi-
onida).3  Of these, only mites and ticks are signifi-
cant vectors of human disease.  Infestations by
gamasid mites have been suspected to transmit a
variety of rickettsial and viral diseases (Figure 9-
1).4  Ornithonyssus bacoti has been implicated in the
transmission of endemic typhus, rickettsialpox, and
Q fever (which are discussed in Chapter 11, Rick-
ettsial Diseases), as well as relapsing fever, St.
Louis encephalitis, and western equine encephali-
tis.  Ornithonyssus sylviarum can transmit western
equine encephalitis and St. Louis encephalitis.
Ornithonyssus bursa has been shown to transmit
western equine encephalitis and is suspected to be
a vector for Q fever.  Demanyssus gallinae is a vector
for the transmission of endemic typhus and St.
Louis encephalitis.  Rickettsialpox outbreaks in
New York have been reported to be transmitted
by Liponyssoides sanguineus (house mouse mite).5
Gamasid mites are parasitic for domestic and wild
birds, rats, and mice.  They have a worldwide distri-
bution and are known to attack humans.
Scabies is an infestation with Sarcoptes scabiei, an
eight-legged human mite.  The disease is most fre-
quently transmitted through sexual intercourse.
Chiggers, from the family Trombiculidae, are
nonscabietic mites found on the ground or in grass.
Their larvae can crawl up the legs as the host walks
through infested vegetation.  For a detailed discus-
sion of mites and the dermatoses they transmit, see
Chapter 8, Arthropod and Other Animal Bites.
Ticks are natural parasites of mammals, birds,
reptiles, and amphibians (Table 9-2).  Ticks consist
of two groups: (1) the Ixodidae, which have a hard,
chitinous, dorsal shield (ie, scutum), and (2) the
Argasidae, or soft tick, which lacks a scutum.  The
natural life cycle is dependent on longer feeding
cycles than those of other parasitic organisms such
as flies, and ticks will feed until engorged with
blood, reaching several times their original size
(Figure 9-2).
As a group, most ticks fast for long periods be-
cause they cannot live on vegetable matter.  A blood
meal is acquired mostly by chance.  Ticks climb to
the top of grass stems or shrubs and await the
passing of a suitable host.  Sensory response to
odor, vibration, air currents, interruption of inci-
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Fig. 9-1. Gamasid mites. These mites have a worldwide
distribution, are known to attack man, and are suspect
vectors of rickettsial and viral diseases.

Military Dermatology
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TABLE 9-2
TICKS AS VECTORS OF HUMAN INFECTIOUS DISEASES
Infectious Disease
Tick Vector
Distribution
Lyme disease
Ixodes ricinus, I pacificus, I scapularis
Worldwide
Relapsing fever
Ornithodoros spp
Africa, Asia, United States, Europe,
Near East, Mediterranean, Canada,
Central and South America
Tularemia
Dermacentor andersoni, Ixodes spp
Americas, Europe, Japan, Israel,
Africa
Arboviruses
Omsk hemorrhagic fever
Dermacentor pictus, D marginatus,
Siberia
 Ixodes persulcatus, I apronophorus
Russian spring-summer encephalitis
Ixodes persulcatus
Central Europe, former USSR
Louping ill
Ixodes ricinus
British Isles, Spain
Powassan
Dermacentor andersoni, Ixodes
United States, Canada
spinipalpis
Kyasanur forest disease
Haemaphysalis spp, Ixodes spp
India
Rhipicephalus turanicus
Crimean-Congo hemorrhagic fever
Hyalomma marginatum
Asia, Europe, former USSR,
Mediterranean, China, Middle
East, Africa
Colorado tick fever
Dermacentor andersoni, Ixodes spp
United States, Canada
Ungrouped or other viruses
Lymphocytic choriomeningitis*
Amblyomma variegatum, Rhipicephalus
Ethiopia, Canada
 sanguineus,Dermacentor andersoni
Rickettsia
Rocky Mountain spotted fever
Ixodes spp, Dermacentor andersoni
United States, Canada, Mexico,
South America
Siberian tick typhus
Ixodes spp
Former USSR, Japan, Far East
Boutonneuse fever
Rhipicephalus sanguineus,
Africa, Europe, Asia, Mediterranean,
Haemaphysalis spp, Ixodes spp,
Turkey, Crimea, Israel
Hyalomma spp, Amblyomma spp,
Boophilus spp, Dermacentor spp
Queensland tick typhus
Ixodes holocyclus
Queensland, Australia
Epidemic (louse-borne) typhus
Pediculus humanus corporis
Ethiopia
Q fever*
Hyalomma asiaticum
Europe, Mediterranean, Black Sea,
Asia, Africa, North America,
Australia
Tick-bite fever*
Haemaphysalis leachi
South Africa
Sennetsu fever*
Tick spp
Japan
Ehrlichiosis*
Tick spp
United States
Piroplasmosis
Human babeosis
Ixodes scapularis
Eastern and midwestern United
States
*Association with human transmission by tick vectors yet to be proven.
Data sources: (1) Harwood RF, James MT, eds. Entomology in Human and Animal Health. 7th ed. New York, NY: Macmillan Publishing Co; 1979: 371–
416. (2) Samlaska CP. Arthropod-borne virus infections and virus hemorrhagic fevers. In: Demis DJ, ed. Clinical Dermatology. New York, NY: JB
Lippincott; 1991: Unit 14-22; 1–15. (3) Gear JH, Wagner JM, Dyssel JC, et al. Severe tick-bite fever in children. S Afr Med J. 1990;77:84–87.

Arthropod Infestations and Vectors of Disease
187
risk of igniting hair.  Excisions or punch biopsies
under local anesthesia are quite successful but are
more invasive than other methods.
Because rapid deployment and high mobility are
required of today’s military, regional control of tick
vectors for military personnel in the field is unlikely
to prove effective.  Therefore, individual preven-
tive measures are most important.  Use of
permethrin-based repellents on clothing and appli-
cations of diethyltoluamide (DEET) on the skin are
helpful.  A recent study performed by the U.S.
Army Environmental Hygiene Agency8 clearly dem-
onstrated that military uniforms impregnated or
sprayed with permethrin more successfully con-
trolled tick infestations than DEET applied to uni-
forms or skin.  Duration of tick attachment has been
shown to correlate with the probability of disease
transmission; therefore, diligent daily searches for
ticks should be performed.9  In endemic areas, pro-
phylactic antibiotics can be administered to sol-
diers who have been bitten by a tick.9
Lyme Disease
Lyme disease is an inflammatory disorder caused
by the spirochete Borrelia burgdorferi and transmit-
ted by Ixodes ticks.  An early manifestation of the
disease is an annular cutaneous lesion known as
erythema chronicum migrans; however, the ner-
vous system, heart, and joints may also become
OK to put on the Web
Fig. 9-2. Normal (on left) and engorged (on right) eastern
wood ticks. When engorged with blood, ticks expand to
several times their normal size.
dent light, warmth, and even moisture signal the
presence of a potential host.  The tick lacerates the
host’s skin with rigid, toothed chelicerae.  Salivary
solutions soften the surrounding tissues.  As the
tick penetrates the skin, it assumes a more vertical
position (Figure 9-3).  A cementlike substance is
secreted into the wound, securing the hypostome
into place.  Frequently, hemorrhage takes place
around the hypostome due to the cytolytic and
anticoagulant action of secreted saliva.  Feeding is
usually complete within 6 to 7 days, but the tick can
remain attached to the host for an unspecified pe-
riod.  Some ticks can live for 15 to 16 years.3
Ticks require a blood meal before they can lay
eggs, with the number of eggs laid ranging from 300
to 7,000 depending on the species.  There are four
stages of development: egg, larva, nymph, and adult.
The interval of development between the various
stages can be considerable (66–359 d).
Caution should be exercised when removing ticks;
at no time should they be forcibly removed.  Force-
ful removal promotes breaking off of mouthparts
and the subsequent development of a foreign-body
granuloma.  The preferred method for tick removal
is by forceps.6,7  The forceps are pressed to the sides
of the tick’s mouth parts and with a levering and
lifting motion the tick is detached.  Care should be
taken to avoid squeezing the body of the tick.
Numerous other methods of tick removal are
available.3  Application of liquid paraffin to the tick
results in blocking tick respirations.  This technique
requires 2 or more hours to work.  Applying chloro-
form or ether to the tick results in quicker removal;
however, there is a distinct risk of burn injury if
unexpectedly ignited.  Application of a warm match
or match flame also works quickly, but has the same
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Fig. 9-3. Tick feeding on human subject. Note vertical
positioning of the engorged tick body.

Military Dermatology
188
involved.  For a detailed discussion of Lyme dis-
ease, see Chapter 13, Bacterial Skin Diseases.
Relapsing Fever
Relapsing fever is either endemic and transmit-
ted by ticks or epidemic and transmitted by lice.
Endemic tick-borne relapsing fever is caused by
many species of Borrelia and is transmitted to hu-
mans by the soft Ornithodoros ticks.  Relapsing fever
transmitted by ticks is endemic in the western United
States, where infected ticks reside in dead wood or
are carried by wild rodents and domestic animals.
Infection occurs during the summer months in the
United States.  Tick bites are often not recognized
because they are painless; moreover, Ornithodoros
ticks are night feeders and drop off quickly.  The
infective agents of tick-borne relapsing fever can
vary their major surface antigens and thus evade
the host’s immune response.10  Borrelia organisms
infesting tick vectors are maintained in nature
in the tick, which frequently has a long life (Orni-
thodoros ticks can live up to 13 y), by trans-ovarian
transmission in some tick species, and by transmis-
sion to rodent reservoir hosts.11
Epidemic louse-borne relapsing fever is caused
by Borrelia recurrentis and is transmitted to humans
by the body louse Pediculus corporis.10  Louse-borne
relapsing fever was associated with large epidem-
ics during World War II, with over 50,000 reported
deaths.9  Lice remain infective for their lifetime, and
have no apparent natural vertebrate hosts.
The clinical manifestations of tick-borne and
louse-borne relapsing fevers are the same.  After a
short incubation period of 3 to 10 days, the patient
presents with sudden onset of fever associated with
constitutional symptoms of cough, headache, leth-
argy, myalgias, and arthralgias.  The fever termi-
nates abruptly after a few days but is followed 3 to
10 days later by another febrile episode; this pattern
persists, particularly in the tick-borne form, as new
major surface antigens appear.  The organisms are
found in the blood and other bodily fluids during
these febrile episodes.  The severity and duration of
the attacks decrease with time.9,11
An erythematous papular or petechial eruption
may occur on the trunk during the last 1 to 2 days of
the initial febrile episode.  Up to 30% of patients
develop neurological complications including cra-
nial nerve palsies, meningitis, seizures, hemiplegia,
and coma.  Eye complications such as iritis and
iridocyclitis occur in 15% of reported cases.  Severe
involvement resulting in death from fulminant liver
failure and myocarditis have also been reported.9
The diagnosis of relapsing fever is confirmed on
demonstration of Borrelia organisms in blood smears
during febrile episodes.  Wright- or Giemsa-stained
dried blood smears, or dark-field examination of
wet blood smears, yield positive results in up to
70% of patients.  False-positive serologic tests for
syphilis occur in up to 5% to 10% of cases.9
Antibiotics are effective treatment modalities for
relapsing fever, including tetracycline (500 mg orally
twice a day for 10–21 d), penicillin G (0.5–5 mU
every 6 h intravenously for 10 d), erythromycin (250
mg orally 4 times a day for 10–21 d), and chloram-
phenicol (500 mg orally 4 times a day for 10–21 d).
Louse-borne disease can be treated with a single
500-mg dose of erythromycin or tetracycline.
Rickettsial Diseases
Rickettsia is a Gram-negative genus of bacteria
capable of causing a number of diseases in humans.
These disorders are reviewed in detail in Chapter
11, Rickettsial Diseases; however, some of the more
common human infections are worth mentioning
briefly here.
Tick-bite fever is caused by Rickettsia conorii and
is believed to be transmitted to humans by the dog
tick, Haemaphysalis leachi.  The disease affects pre-
dominantly children in South Africa and is usually
benign and self-limited.  In adults and some chil-
dren, however, the disease may be fulminant, with
a profuse maculopapular eruption, hepatitis, renal
failure, and a hemorrhagic diathesis manifested as
petechial hemorrhages, thrombocytopenia, and dis-
seminated intravascular coagulation.12
Ehrlichiae are members of the family Rickett-
siaceae, first isolated from infected dogs in 1935.6
Until recently, the only known human disease was
Sennetsu fever, caused by Ehrlichia sennetsu.  The
disease was first described and the organism first
isolated in the 1950s in Japan.  Characteristic fea-
tures of the illness include remittent fever, general-
ized lymphadenopathy, hepatosplenomegaly, and
increased circulating mononuclear cells and atypi-
cal lymphocytes similar to those observed in infec-
tious mononucleosis.  Other features of mononucleo-
sis, such as fatigue, anorexia, chills, headache, and
myalgias, have been reported.  Cutaneous erup-
tions are unusual for this disorder.  Although yet
unproven, the disease is believed to be transmitted
to humans through tick bites.6
During the Vietnam conflict in the late 1960s, a
fatal epizootic hemorrhagic illness (called tropical
canine pancytopenia) caused the deaths of many
dogs attached to U.S. forces in the region.13  The

Arthropod Infestations and Vectors of Disease
189
illness correlated with heavy infestations of the tick
Rhipicephalus sanguineus, and the causative organ-
ism was shown to be Ehrlichia canis.  In 1987, the first
case of human ehrlichiosis caused by E canis was
reported.14  Patient serum samples submitted for
evaluation for suspected Rocky Mountain spotted
fever are confirmed positive for Rickettsia rickettsii
only 10% to 20% of the time.6  Many of these serone-
gative cases are now believed to be due to Ehrlichiae.
The majority of human ehrlichiosis cases have been
reported in the southeastern, south central, and
mid-Atlantic United States.  The predominant clini-
cal findings include fever (85%–99%); headache
(83%–94%); myalgia (47%–82%); anorexia (81%–83%);
nausea, vomiting, or both (42%–60%); rash (0%–60%);
diarrhea (38%–50%); abdominal pain (19%–33%); con-
fusion (12%–33%); and lymphaden-opathy (0%–
19%).6,15  When present, the cutaneous eruption may
be petechial or macular and distributed over the trunk
or extremities.  Leukopenia, thrombo-cytopenia, ane-
mia, 
and 
elevated 
aminotransferase
levels may occur.  Currently, confirmation of
ehrlichiosis requires acute and convalescent sera for
indirect immunofluorescence.  Due to the retrospec-
tive nature of this form of confirmation, early diag-
nosis is based on clinical findings.  Tetracycline (250
mg orally four times a day for 10 d) and tetracycline
derivatives are the drugs of choice, although
chloram-phenicol (500 mg orally four times a day
for 10 d) has also been used successfully.6,15
Tick Paralysis
Tick paralysis in animals was first identified in
Australia in 1824.3  The first human case was re-
ported by Bancroft16 in 1884 in Queensland, Austra-
lia, and subsequent cases have been described in the
United States, British Columbia, South Africa,
France, Germany, Yugoslavia, and Crete (Table 9-
3).  The acute, ascending, lower-motor-neuron pa-
ralysis is due to a toxin produced by certain species
of ticks.  The toxin causes a conduction block at the
myoneural junction similar to that observed with
curare; it has been partially purified from the Aus-
tralian tick Ixodes holocyclus and is resistant to diges-
tion by pepsin, papain, and trypsin.3,17  Parenteral
injection into dogs results in paralysis within 48
hours.  Tick paralysis results only from the bite of
gravid female ticks.17
Children are more frequently afflicted with tick
paralysis than adults.  Although dark-haired indi-
viduals are said to be more susceptible, perhaps
dark hair only makes the tick more difficult to find,
and consequently the diagnosis is delayed.17  Pain
or numbness may precede the onset of motor weak-
ness and, in children, restlessness, irritability, mal-
aise, anorexia, and vomiting are not uncommon
presenting complaints.  Fever is not a feature of tick
paralysis.  The paralysis begins 2 or more days after
the tick attaches, with weakness of the lower ex-
tremities progressing in hours to falling episodes
and incoordination.  True ataxia is rarely observed,
and incoordination is attributed to motor weak-
ness.  Some cases of more proximal motor weakness
have been described.  Cranial nerve findings may
ensue, manifested as dysarthria and dysphagia pro-
gressing to bulbar paralysis.  Localized paralysis
can sometimes occur, resulting in facial paralysis
(tick attached to external auditory meatus), photo-
phobia or blurred vision (tick attached behind the
ear), or frontalis and orbicularis oculi paralysis (tick
attached to frontal region).3  The weakness is sym-
metrical and flaccid, and diffuse areflexia is present.
The pupils remain reactive and sensory examina-
tion is normal.  Patients usually succumb to respira-
tory failure.
Removal of the tick and supportive medical care,
including respiratory support, form the cornerstone
of therapy.  The tick is usually found in the scalp.
More than one tick may be present; therefore, a
thorough examination is imperative.  Clinical im-
provement usually begins within hours after tick
removal, and full recovery occurs in 3 to 11 days for
most patients.  At times, however, recovery may be
slower, requiring weeks to months.  Permanent
paralysis is exceedingly rare.
The differential diagnosis of tick paralysis in-
cludes Lyme disease, Guillain-Barré syndrome,
myasthenia gravis, porphyria, botulism, and trans-
verse myelitis.7  The most common disease in this
group is Guillain-Barré syndrome, which can be
TABLE 9-3
GEOGRAPHIC DISTRIBUTION OF TICK
VECTORS IMPLICATED IN HUMAN
TICK PARALYSIS
Geographic Location
Ticks
Australia
Ixodes holocyclus, I cornatus
British Columbia
Dermacentor andersoni
United States
Dermacentor andersoni
South Africa
Rhipicephalus evertsi evertsi
Data source: Kincaid JC. Tick bite paralysis. Semin Neurol.
1990;10:32–34.

Military Dermatology
190
differentiated from tick-bite paralysis by elevation
of spinal fluid protein and slowed nerve-conduc-
tion velocities.  Although Lyme disease may in-
volve similar neurological complaints, they occur
weeks to months after the tick bite.  A negative
enzyme-linked immunosorbent assay (ELISA) for
Borrelia burgdorferi would also be helpful in differ-
entiating the two diseases.
Tick-Bite Alopecia
Tick-bite alopecia has been well established in
the medical literature since Ross and Friede18 de-
scribed the first human case in 1955.  The condition
is believed to be due to direct toxic effects from tick
saliva.19  A history of tick bite is noted, or a tick may
be found in the center of the site of alopecia.  The
hair usually begins to fall out 1 week after the tick
bite, coinciding with induction of telogen hairs.3
Necrosis at the site of the tick bite is frequently
observed, surrounded by a 1- to 4-cm patch of
alopecia.20,21  Exclamation mark hairs similar to those
observed in patients with alopecia areata have been
reported.20  Regrowth begins within 2 weeks and is
complete within 2 months.3  Scarring centrally from
the original tick bite may result in residual scarring
alopecia.
Tick-Bite Reactions
The most frequent sites of tick-bite reactions in
children are the head and neck; in adults, the trunk
and legs.3  Local effects include swelling, erythema,
paresthesia, blistering, pruritus, ecchymosis, indu-
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Fig. 9-4. Tick-bite reaction. These lesions are character-
ized by a large zone of erythema.
ration, nodule formation (prurigo-like lesions), and
necrosis (Figure 9-4).  Ixodes racinus bites may cause
local gangrene, erysipelatoid swelling, generalized
erythema, generalized urticaria, or psoriasiform
eruptions.  Healing of tick bites usually occurs in 2
to 3 weeks but may take longer.  Systemic symp-
toms include nausea, vomiting, diarrhea, pulse ir-
regularities, dyspnea, fever, gastrointestinal irrita-
tion, restlessness, muscular weakness, drooping
eyelids, photophobia, delirium, hallucinations, and
generalized pain of tick typhus.  Some of these
symptoms overlap with those reported for tick pa-
ralysis.  Most of these complaints resolve with re-
moval of the tick.3
FLEAS
Fleas evolved as highly specialized, bloodsuck-
ing parasites at least 60 million years ago.22  Their
ancestors may originally have had wings, but these
would have inhibited movement through the host’s
fur; thus, jumping provided an alternative means of
locomotion.  Fleas are amazingly resilient: various
species can jump 150-fold their own length (verti-
cally or horizontally equivalent to a human’s jump-
ing 900 ft); survive months without feeding; accel-
erate 50-fold faster than the space shuttle; withstand
enormous pressure; and remain frozen for a year,
then revive.  The amazing ability of the flea to jump
so well is due to a superelastic protein located in the
thorax known as resilin.  The leg and thorax muscles
compress a tiny pad of resilin, which is suddenly
released, resulting in the explosive unleashing of
kinetic energy.22
More than 2,400 species and subspecies have
been described.  The order Siphonaptera contains
only 2 flea families of medical importance: Puli-
cidae (human, cat, dog, and bird fleas) and
Sarcopsylidae (also called Tungidae), the sand flea,
which causes tungiasis.22,23  The human flea is Pulex
irritans.  Fleas are wingless, laterally compressed in-
sects with a hard, shiny integument.  The body has 3
regions: the head, thorax, and abdomen.  Mouth parts
are modified (paired maxillary palpi) for piercing and
sucking.  The head is applied directly to the three-
segmented thorax (no neck).  A “comb” may be
present or absent at the posterior margin of the first
segment and is a major feature for classification
(Figure 9-5).  A pair of legs is attached to each thoracic

Arthropod Infestations and Vectors of Disease
191
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segment, resulting in 3 pairs of legs.  Each leg has 5
distinct parts.  The abdomen has 9 to 11 segments.23,24
Fleas require a blood meal to perpetuate their species.
In some cases the blood meal must be from a specific
host, but in others any suitable host is sufficient.  Eggs
are deposited on the ground.  In some species, such as
the rabbit flea (Sipilpsyllus cuniculi), the female flea
responds to hormonal changes in the pregnant rabbit
host, resulting in synchronized rabbit-flea procre-
ation cycles.  In animals with thick fur, fleas tend to
infest for long periods of time, utilizing the warmth
and protection of the fur.  In humans, however, the
flea is only a transient visitor for the purpose of
feeding.  The life cycle for adult fleas varies consid-
erably: the human flea, Pulex irritans, lives 4 to 6
weeks; Tunga penetrans lives about 17 days.  The
individual stages can be modified by adverse con-
ditions, extending the flea life cycle to beyond 200
days.  Likewise, the pupal stage can vary from 7
days to 1 year.  At all stages of development, the flea
can withstand starvation for long periods.  The
stimulus for sudden, famished flea activity may be
initiated by footstep vibrations.  Fleas jump, on
average, about 20 cm; however, when searching for
food or attempting to escape enemies, they can
reach a height of 2 m or more.23  Fleas are important
vectors of disease and transmit some of the most
deadly infectious diseases ever known (Table 9-4).
TABLE 9-4
FLEAS AS VECTORS OF HUMAN INFECTIOUS DISEASES
*Fleas are definite vectors.
†Fleas are possible vectors.
‡Ticks are usual vectors, but the infectious organism has been isolated from fleas.
Adapted with permission from Alexander JO. Arthropods and Human Skin. Berlin, Germany: Springer-Verlag; 1984: 159.
Fig. 9-5. Pulex irritans, the human flea. Note the comb at
the posterior margin of the first segment, a major feature
for classification.
Table 9-4 is not shown because the copyright permission granted to the Borden Institute, TMM, does not
allow the Borden Institute to grant permission to other users and/or does not include usage in electronic
media. The current user must apply to the publisher named in the figure legend  for permission to use
this illustration in any type of publication media.

Military Dermatology
192
Plague
Plague is a zoonotic disease caused by Yersinia
pestis and usually transmitted to humans by ro-
dents and their fleas.  The condition is characterized
by a bubo, a mass of lymph nodes that become
matted together and drain purulent material.  A
detailed discussion of plague can be found in Chap-
ter 13, Bacterial Skin Diseases.
Flea Bites
Flea bites are the most common arthropod bites
known.  One flea can bite two to three times over a
small area.  It is not uncommon to see three flea bites
in a row, described as breakfast, lunch, and dinner
(Figure 9-6).25  The bites produce irregular, pruritic,
red wheals up to 1 cm in diameter.  Some patients
may present with a surrounding halo with a central
papule, vesicle, or bulla.  Others react by forming
hemorrhagic macules, papules, vesicles, or bulla.
In individuals immune to flea bites, an evanescent
erythema with a central hemorrhagic punctum ap-
pears.  A purpuric halo that persists for 3 to 4 days
has also been observed.  The lesions usually subside
within 2 to 3 days.  Bites usually are seen at points
of access, such as the ankles or wrist; however, the
first meal may occur at any site.  The scalp and face
are rarely affected.23  Treatment is usually support-
ive with mild to moderate topical steroids.
Papular Urticaria
Chronic reinfestation by fleas may result in urti-
carial lesions that appear in irregular crops; these
lesions are frequently observed on the limbs and
OK to put on the Web
Fig. 9-6. These lesions resulted from flea bites. They display
the characteristic “breakfast, lunch, and dinner” pattern.
around the waist.  They have also been reported to
involve the trunk, buttocks, neck, hands, and feet.23
The distribution is characteristically bizarre, with
lesions exhibiting two features: (1) new lesions ap-
pear in small groups, all in the same stage as earlier
lesions, and (2) new lesions tend to cluster around
the waistline, where tight clothing prevents further
flea migration (Figure 9-7).23  Postinflammatory
changes and scarring from scratching are not un-
common.  Papular urticaria has also been reported23
to result from the bites of other arthropods, such as
mites.  Treatment involves removing the soldier
from the infested area.  In cases of severe pruritus,
systemic steroids may be required.
Tungiasis
Tunga penetrans, also called sand flea, chigoe, and
jigger flea, is the only member of the family Tungidae
known to attack humans.26  Tungiasis originated in
Central and South America and was reported to
infest sailors from Columbus’ voyage in 1492.23  It
spread to Africa, where it was first recorded in
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Fig. 9-7. Papular urticaria secondary to flea bites. These
lesions tend to cluster around the waistline.

Arthropod Infestations and Vectors of Disease
193
1634.23  A major outbreak occurred in Brazil in 1872,
and tungiasis was shortly thereafter introduced
into Angola.  It has been reported in Central and
East Africa, Madagascar, the west coast of Pakistan,
and India.27
Tungiasis is caused by the female sand flea, which
burrows into human skin at the point of contact,
usually the feet.  The larva, adult males, and virgin
females live in dry, sandy soil around pigsties,
poultry runs, and stables, where they feed on veg-
etable matter.  The sand flea is the smallest known
flea (1 mm long) and has a 3- to 4-week life cycle.
The male dies shortly after copulation.  The gravid
female jumps, reaching heights of 35 cm, in an attempt
to find a suitable host.  On contact with human or
animal skin, the flea penetrates with its pointed
head and burrows into the skin.  The female en-
larges to the size of a pea over a 7- to 14-day period.
After discharging up to 300 eggs through the skin’s
surface, the female flea collapses and dies.23,26
Tremendous flea burdens can incapacitate an
individual by causing pain and superinfection.  In-
dividual lesions consist of a firm, indurated, slightly
tender nodule with a flat surface of whitish-yellow
keratin (Figure 9-8).  A minute black spot in the
center (the posterior end of the flea abdomen) may
be noted.  Secondary infections may result in aden-
opathy, cellulitis, and erysipelas.  Thrombo-phlebi-
tis, bone necrosis, and autoamputation of toes have
been reported.23  Tetanus and gas gangrene are also
potentially life-threatening complications.
Treatment of tungiasis involves surgical removal
of the parasites.  During the first 48 hours after the
female imbeds herself, a sterile needle may be suf-
ficient.  Curettage and cautery frequently works for
intermediate stages of development.  However, the
entire flea that has been in place for 7 to 14 days
should be surgically removed.  Antibiotic treatment
may be required for secondary infections.23
Fig. 9-8. Primary cutaneous lesion caused by Tunga  penetrans.
Note the white circular area with central black dot. Re-
printed with permission from Zalar GL, Walther RR.
Infestation by Tunga penetrans. Arch Dermatol. 1980;116:81.
Copyright 1980, American Medical Association.
In areas where tungiasis is endemic, use of good
protective footwear should be encouraged, and for
the soldier in the field, boots are adequate.  Indi-
vidual cutaneous inspections should be encour-
aged.  Known infested sites should be treated with
lindane, dimethyl phthalate, or dimethyl carbam-
ate.  Use of flypaper low to the ground to collect
jumping fleas is another measure that may help to
curb disease, and also is a good test for determining
the effectiveness of the insecticide being used.23
Lice
Pediculosis, or lice infestation, is caused by three
types of lice: Pediculus humanus capitis (head louse),
Pthirus pubis (pubic or crab louse), and Pediculus
humanus corporis (body louse).  After attaching to
the skin, these flattened, wingless insects feed on
human blood and can cause intense itching.  For a
detailed discussion of pediculosis, see Chapter 8,
Arthropod and Other Animal Bites.
Bedbugs
Members of the insect order Hemiptera include
bedbugs, which are vectors for the transmission of
Trypanosoma cruzi, the infective agent for Chagas’
disease (also called South American trypanoso-
miasis), which is discussed in Chapter 12, Tropical
Parasitic Infections.28  Its best-known vectors are
the assassin bugs, family Reduviidae, including
Rhodnius prolixus (northeastern South America) and
OTHER INSECTS
Figure 9-8 is not shown because the copy-
right permission granted to the Borden
Institute, TMM, does not allow the Borden
Institute to grant permission to other users
and/or does not include usage in electronic
media. The current user must apply to the
publisher named in the figure legend  for
permission to use this illustration in any
type of publication media.

Military Dermatology
194
R pallescens (Brazil and Panama).  Other Hemiptera,
such as Triatoma infestans (Argentina and Brazil), T
barberi (Mexico), T dimidiata (Mexico, Ecuador, and
Central America), T maculata (Venezuela), and
Panstrongylus megistus (Brazil and Guyana) are also
important vectors of Chagas’ disease.29
Biting Flies
Infectious diseases may also be transmitted to
humans by dipterous insects, which include biting
flies and mosquitoes.  A detailed list of mosquitoes
as vectors of viral diseases is provided in Chapter
10, Viral Hemorrhagic Fevers.  Myiasis (infestation
with fly maggots) is discussed in Chapter 8, Arthro-
pod and Other Animal Bites.
Bartonellosis (Carrion’s disease), with its two
clinical forms, Oroya fever and verruga peruana, is
transmitted by sandflies, Lutzomyia verrucarum and
L colombiana (Figure 9-9).  The bacterial agent is
Bartonella bacilliformis, which is restricted to en-
demic areas.26  Both visceral (kala azar) and dermal
leishmaniasis are transmitted to humans by
sandflies, Phlebotomus species (Old World) and
Lutzomyia species (New World).  Leishmania organ-
isms are flagellate protozoa in the genus Leishmania
and are composed of two visceral forms (Leishmania
donovani and L infantum) and three cutaneous forms
(L tropica, L braziliensis, and L mexicana).30
The large collection of flies in the family Taban-
idae contains over 3,000 species.29  They are blood-
sucking flies and include horseflies, deerflies, clegs,
breeze flies, greenheads, and mango flies.25  Taban-
OK to put on the Web
Fig. 9-9. The sandfly is capable of transmitting
bartonellosis as well as dermal and visceral leishmaniasis.
idae are important vectors for the spread of the
microfilaria Loa loa (loiasis) in Africa, and the bacte-
rial pathogens of anthrax (Bacillus anthracis) and
tularemia (Francisella tularensis) in the United
States.25,4  They are also important vectors for the
spread of animal trypanosomiasis worldwide.
Glossinidae are composed of 22 species of the tsetse
fly, which is well known for transmission of African
trypanosomiasis.
SUMMARY
Organisms from the arthropod classes Arach-
nida and Insecta have a hard-jointed exoskeleton
and paired, jointed legs.  In most instances, arthro-
pod bites are nothing more than a nuisance, result-
ing in localized, cutaneous reactions and pruritus.
However, some of these organisms are medically
important: fleas, lice, and ticks can transmit lethal
epidemic disorders, such as bubonic plague,
typhus, Crimean-Congo hemorrhagic fever,
Rocky Mountain spotted fever, and boutonneuse
fever.
Many of these vector-transmitted diseases are
endemic in various regions of the world.  Medical
officers need to know which of these ancient afflic-
tions are endemic to the region and treat infected
troops appropriately.  Medical officers also need to
be aware of other medical complications of arthro-
pod bites, such as tick-bite alopecia and tick paraly-
sis.  Tick paralysis may be particularly challenging,
and when progressive, lower-extremity weakness
is present, a vigorous search should be undertaken
to find and remove the tick.  This simple procedure
can be lifesaving.
In a fast-moving wartime environment, regional
control with pesticides is unlikely to control insect
vectors.  It is thus up to the individual soldier to
minimize exposure.  Reducing exposure can be
accomplished through repeated use of permethrin-
based repellents or diethyltoluamide (DEET) ap-
plied to clothing or the skin.  In addition, permethrin-
impregnated uniforms are even more effective than
DEET applications to skin or uniforms.  Therefore,

Arthropod Infestations and Vectors of Disease
195
uniform impregnation with permethrin-based re-
pellents should be strongly considered in field en-
vironments where the risk of vector-transmitted
diseases is high.
REFERENCES
1.
Harwood RF, James MT, eds. Introduction. In: Entomology in Human and Animal Health. 7th ed. New York, NY:
Macmillan Publishing Co; 1979:1–14.
2.
Bean WB. Walter Reed and yellow fever. JAMA. 1983;250:659–662.
3.
Alexander JO. The effects of tick bites. In: Arthropods and Human Skin. Berlin, Germany: Springer-Verlag;
1984: 363–382.
4.
Harwood RF, James MT, eds. Horse flies, deer flies, and snipe flies. In: Entomology in Human and Animal Health.
7th ed. New York, NY: Macmillan Publishing Co; 1979: 234–247.
5.
Alexander JO, ed. Infestation with gamasid mites. In: Arthropods and Human Skin. Berlin, Germany: Springer-
Verlag; 1984: 303–315.
6.
Harkess JR. Ehrlichiosis. Infect Dis Clinics N Am. 1991;5:37–51.
7.
Tibbals J, Cooper SJ. Paralysis with Ixodes cornatus envenomation. Med J Aust. 1986;145:37–38.
8.
Evans SR, Korch GW Jr, Lawson MA. Comparative field evaluation of permethrin and DEET-treated military
uniforms for personal protection against ticks (Acari). J Med Entomol. 1990;27:829–834.
9
Abele DC, Anders KH. The many faces and phases of borreliosis. Part 1: Lyme disease. J Am Acad Dermatol.
1990;23:167–186.
10.
Horton JM, Blaser MJ. The spectrum of relapsing fever in the Rocky Mountains. Arch Intern Med. 1985;145:871–875.
11.
Harwood RF, James MT, eds. Ticks and tick-associated diseases. In: Entomology in Human and Animal Health. 7th
ed. New York, NY: Macmillan Publishing Co; 1979: 371–416.
12.
Gear JH, Wagner JM, Dyssel JC, et al. Severe tick-bite fever in young children. A report of 3 cases. S Afr Med J.
1990;77:84–87.
13.
Huxsoll DL, Hildebrandt PK, Nims RM, et al. Tropical canine pancytopenia. J Am Vet Med Assoc. 1970;157:1627–1632.
14.
Maeda K, Markowitz N, Hawley RC, et al. Human infection with Ehrlichia canis. N Engl J Med. 1987;316:853–856.
15.
Harkess JR, Ewing SA, Brumit T, Mettry CR. Ehrlichiosis in children. Pediatrics. 1991;87:199–203.
16.
Bancroft J. Queensland ticks and tick blindness. Aust Med Gaz. 1984;4:37–38.
17.
Kincaid JC. Tick bite paralysis. Seminars Neurol. 1990;10:32–4.
18.
Ross MS, Friede H. Alopecia due to tick bite. Arch Dermatol. 1955;71:524–525.
19.
Marshall J. Ticks and the human skin. Dermatologica. 1967;135:60–65.
20.
Heyl T. Tick bite alopecia. Clin Exp Dermatol. 1982;7:537–542.
21.
Piesman J, Mathier TN, Sinsky RJ, et al. Duration of tick attachment and Borrelia burgdorferi transmission. J Clin
Microbiol. 1987;25:557–558.

Military Dermatology
196
22.
Duplaix N. Fleas, the lethal leapers. National Geographic. 1988;173:672–694.
23.
Alexander JO. Flea bites and other diseases caused by fleas. In: Arthropods and Human Skin. Berlin, Germany:
Springer-Verlag; 1984: 159–176.
24.
Harwood RF, James MT, eds. Fleas. In: Entomology in Human and Animal Health. 7th ed. New York, NY: Macmillan
Publishing Co; 1979: 319–341.
25.
Rees RS, King LE. Arthropod bites and stings. In: Fitzpatrick TB, Wisen AZ, Wolff D, Freedberg IM, Austen KF,
eds. Dermatology in General Medicine. 3rd ed. New York, NY: McGraw-Hill; 1987: 2495–2506.
26.
Fimiani M, Reimann R, Alessandrini C, Miracco C. Ultrastructural findings in tungiasis. Int J Dermatol.
1990;29:220–222.
27.
Hoeppli R. Early references to the occurrence of Tunga penetrans in tropical Africa. Acta Trop (Basel). 1963;20:143–153.
28.
Alexander JO. Infestation by Hemiptera. In: Arthropods and Human Skin. Berlin, Germany: Springer-Verlag;
1984: 57–74.
29.
Alexander JO. Reactions to dipterous biting flies. In: Arthropods and Human Skin. Berlin, Germany: Springer-
Verlag; 1984: 115–133.
30.
Harwood RF, James MT, eds. Gnats, black flies, and related forms. In: Entomology in Human and Animal Health.
7th ed. New York, NY: Macmillan Publishing Co; 1979; 142–168.

Viral Hemorrhagic Fevers
197
VIRAL HEMORRHAGIC FEVERS
Chapter 10
CURT P. SAMLASKA, M.D.*
INTRODUCTION
HEMORRHAGIC FEVERS CAUSED BY FLAVIVIRIDAE
Dengue Hemorrhagic Fever
Yellow Fever
Kyasanur Forest Disease
Omsk Hemorrhagic Fever
HEMORRHAGIC FEVERS CAUSED BY BUNYAVIRIDAE
Rift Valley Fever
Crimean-Congo Hemorrhagic Fever
Hemorrhagic Fever with Renal Syndrome
HEMORRHAGIC FEVERS CAUSED BY ARENAVIRIDAE
Lassa Fever
Argentine Hemorrhagic Fever
Bolivian Hemorrhagic Fever
HEMORRHAGIC FEVERS CAUSED BY FILOVIRIDAE
Ebola Hemorrhagic Fever
Marburg Hemorrhagic Fever
SUPPORTIVE TREATMENT
PREVENTION
SUMMARY
*Lieutenant Colonel, Medical Corps, U.S. Army; Dermatology Service, Tripler Army Medical Center, Honolulu, Hawaii  96859

Military Dermatology
198
INTRODUCTION
The United States’ involvement in Operations
Desert Storm and Desert Shield (1990–1991) empha-
sizes the need for our armed forces to be ready for
worldwide deployment at a moment’s notice.  This
requirement often arouses much trepidation in mili-
tary medical personnel who suddenly find them-
selves in a hostile environment that demands ex-
pertise in areas of medicine that are little known to
most practicing physicians.  Unlike trauma and
surgical support of war wounds, which changes
little from region to region, the general medical
officer will need to know the infectious and para-
sitic diseases endemic in the region of conflict.  Few
of these diseases will be more challenging and po-
tentially more lethal than the hemorrhagic fever
viruses.
Hemorrhagic fever viruses are a diverse group of
infections in which a hemorrhagic diathesis can
result in significant morbidity and mortality.  Most
hemorrhagic fevers are zoonoses, with transmis-
sion to humans occurring through mosquito or tick
vectors or through aerosol from infected rodent
hosts (Table 10-1).  Twelve distinct viral groups are
associated with hemorrhagic fevers in humans and
are found in both temperate and tropical habitats.1
These viruses belong to four families: Flaviviridae,
Bunyaviridae, Arenaviridae, and Filoviridae.
The viral hemorrhagic fevers within each family
generally have similar epidemiological traits; how-
ever, the viruses are individually diverse and can be
grouped by other shared characteristics.  For ex-
ample, the African viral hemorrhagic fevers occur
mostly in southern Africa and consist of Rift Valley
fever, Marburg virus disease, and Crimean-Congo
hemorrhagic fever.2  Ebola hemorrhagic fever is not
included with the African viral hemorrhagic fevers
because it has not been isolated in southern Africa.
Significant outbreaks of hemorrhagic disease with
person-to-person transmission have been associ-
ated with Lassa, Marburg, Ebola, and Crimean-
Congo viral disease.3  This chapter will address the
hemorrhagic fevers by viral family.
HEMORRHAGIC FEVERS CAUSED BY FLAVIVIRIDAE
Flaviviruses are transmitted by mosquitoes or
ticks.  They can infect a multitude of vertebrate
hosts and cause primarily encephalitis and hemor-
rhagic fevers.4  Hemorrhagic fevers caused by
Flaviviridae include dengue hemorrhagic fever,
yellow fever, Kyasanur Forest disease, and Omsk
hemorrhagic fever.
Dengue Hemorrhagic Fever
Epidemic illnesses that clinically resemble den-
gue have been reported in tropical and subtropical
areas of the world since the 17th century.5  In 1635,
a disease was described in the West Indies that may
have been dengue.  Numerous outbreaks during the
18th and 19th centuries were described in Java, Egypt,
India, Spain, Caribbean Islands, Americas, Indochina,
and Southeast Asia.6  In 1906, Bancroft7 suggested
that transmission to man may be through mosquito
vectors.  This hypothesis was conclusively shown
by Cleland et al7 in 1916 and 1919 in Aedes aegypti.
Other vectors include A albopictus and Culex fatigans.8
Dengue, endemic to some areas in the Pacific dur-
ing World War II, was known to be a major threat to
nonindigenous troops.7  In 1944, for example, 24,079
cases were reported among U.S. troops in New
Guinea and 20,000 cases were reported among mili-
tary personnel on Saipan.5  Transportation of men
and supplies throughout the Pacific resulted in out-
breaks in Japan, Hawaii, Australia, and many other
Pacific islands.  During the Vietnam conflict, den-
gue was reported in Burma, Cambodia, Vietnam,
the Philippines, Indonesia, and India.5
Synonyms for dengue include dengue fever,
break-bone fever, dandy fever, denguero, bouquet
fever, giraffe fever, polka fever, 5-day fever, 7-day
fever, hemorrhagic dengue (dengue hemorrhagic
fever), and dengue shock syndrome (in the Philip-
pines and Thailand).6  Dengue hemorrhagic fever is
actually a more severe form of dengue with hemor-
rhagic manifestations.  The first reported outbreaks
of dengue hemorrhagic fever were observed in the
Philippines in 1953 and 1956.1  The disease is strongly
associated with urban environments and breeding
of A aegypti vectors in domestic water containers.
Dengue hemorrhagic fever has developed into a
major pediatric disease in Southeast Asia and the
Western Pacific, with over 600,000 hospital admis-
sions and over 20,000 deaths in these regions over
the past 20 years.1  An outbreak in Cuba in 1981

Viral Hemorrhagic Fevers
199
TABLE 10-1
HEMORRHAGIC FEVER VIRUSES ASSOCIATED WITH HUMAN DISEASE
*High viral antibody titers; viral isolation yet to be achieved
Adapted with permission from Samlaska CP. Arthropod-borne virus infections and virus hemorrhagic fevers. In: Demis, DJ, ed.
Clinical Dermatology. New York, NY: JB Lippincott; 1991: Unit 14-22; 6.
Table 10-1 is not shown because the copyright permission granted to the Borden Institute, TMM, does
not allow the Borden Institute to grant permission to other users and/or does not include usage in
electronic media. The current user must apply to the publisher named in the figure legend  for permis-
sion to use this illustration in any type of publication media.

Military Dermatology
200
resulted in over 340,000 cases and 156 deaths, the
first outbreak in the Americas of the disease in its
hemorrhagic form.  Recent epidemics have occurred
in China in 1978, 1980, and 1986, with hemorrhagic
disease involving both children and adults.8  All
four serotypes are associated with disease; how-
ever, they are not cross-protective.  Some authors9
believe that subsequent infection with a heterolo-
gous dengue virus results in a much greater risk of
developing life-threatening dengue hemorrhagic
fever.  Humans are considered to be the main reser-
voir for the virus.
Signs and Symptoms
Classic dengue begins abruptly after an incuba-
tion period of 5 to 6 days.  Fever may be of the
“saddleback” type, in which remission of all symp-
toms occurs after 2 to 3 days, followed by a second
phase of mild fever and less severe symptoms last-
ing 1 to 2 days.  The single-phase type is more
commonly observed in epidemics, with fevers last-
ing for 3 to 8 days, accompanied by dizziness, head-
ache, back pain, arthralgias, weakness, and eye
pain.  Flushing of the face and conjunctival injection
are common features.  An enanthem consisting of
tiny glistening vesicles on the soft palate may be
seen within 12 hours of onset.  Dengue can occur
with no obvious exanthem.  More often, a
morbilliform eruption begins on the third to fifth
day on the inner surfaces of the upper arms, the
lateral surface of the thorax, and in the lumbar area.
The macular or scarlatiniform rash spreads to the
face, neck, shoulders, and thorax (Figure 10-1).
Pruritus can occur if the hands and feet are in-
volved.  In some cases, a petechial eruption is noted
on the dorsa of the feet, legs, hands, and wrists.
Cervical lymphadenopathy is frequently observed.
Bradycardia may occur late in the illness and persist
through convalescence.  Recovery often requires 1
to 2 weeks and almost invariably is dominated by
neurasthenia, mental depression, insomnia, and
anorexia.
Hemorrhagic manifestations of dengue are seen
predominantly in children.  The symptoms are vari-
able and include petechiae, purpura, oozing from
venipuncture and injection sites, gingival bleeding,
epistaxis, hemoptysis, hematemesis, melena,
hematochezia, hematuria, uterine bleeding, and
intracranial hemorrhage.8  Shock can occur after
several days of symptoms and is characterized by
clinical and laboratory signs of hypovolemia.  Hem-
orrhagic manifestations have been reported with all
four serotypes.
OK to put on the Web
Fig. 10-1. Scarlatiniform eruption of dengue fever. Note
the “white islands within a sea of red,” a classic descrip-
tion for the cutaneous findings of dengue fever. Photo-
graph: Courtesy of Thomas P. Monath, M.D.; formerly,
Walter Reed Army Institute of Research, Washington, D.C.
Laboratory Findings and Treatment
Laboratory features of dengue include leukocy-
tosis, atypical lymphocytes, and thrombocyto-
penia.10  Dengue virus inhibits marrow prolifera-
tion early in the course of disease but not in later
stages.  Although laboratory evidence of dissemi-
nated intravascular coagulation can be detected in
severe cases of dengue hemorrhagic fever,
morphologic evidence is usually found only in ado-
lescents and adults.10  Coagulation defects include
prolongations of the partial thromboplastin time,
prothrombin time, and thrombin time, as well as
decreased factors II, V, VII, VIII, IX, and X.  Dissemi-
nated intravascular coagulation is not central to the
pathogenesis of dengue hemorrhagic fever, because
treatment with heparin has not proved successful.
Treatment of dengue hemorrhagic fever is sup-
portive.  Live attenuated vaccines are currently
being developed.  The need for vaccination against
all four known serotypes of dengue virus is depen-
dent on the relative risk of developing hemorrhagic
disease during subsequent infections with a differ-
ent serotype.9
Yellow Fever
Military medicine has provided significant con-
tributions to science and the understanding of hu-
man disease.  One of the most significant of these
contributions came from U.S. Army Major Walter
Reed and his studies on yellow fever in the late 1800s.
In 1878, Charles Finlay was the first to suggest that

Viral Hemorrhagic Fevers
201
yellow fever was spread by mosquito bites, particu-
larly A aegypti, instead of alkaline earth.11  Many
physicians were skeptical, and due to the lack of well-
planned experimental medicine as well as incorrect
assumptions, Finlay was unable to prove the associa-
tion over 20 years of work.  Through well-controlled
experiments, Walter Reed was able to show that
• the mosquito could pick up the “poison”
from an infected victim during the first 2 to
3 days of illness,
• the mosquito had to live for at least 12 days
before the disease could be transmitted to man,
• blood taken from an infected person could
produce infection in normal subjects if in-
jected into their bloodstream, and
• the offending agent was not bacterial be-
cause filtered blood failed to stop infection
of injected normal subjects.
Initiation of mosquito control measures in Ha-
vana subsequently resulted in a marked reduction
in the disease.  For his meticulous studies and
implementation of informed consent, Walter Reed
is known as the founder of modern and ethical
clinical experimentation.11
Although a safe and effective vaccine against
yellow fever has been available for 50 years, the
disease continues to occur in Africa and South
America.12  In the Americas, the disease remains
confined to the Amazon, Orinoco, Catatumbo,
Atrato, and Magdalena river basins.13  The virus is
sustained in Aedes mosquito vectors, monkeys, and
marmosets.  The Pan American Health Organiza-
tion received reports of 2,255 cases of sylvatic yel-
low fever between 1965 and 1983.  In Africa, yellow
fever occurs sporadically in forested areas and in
large outbreaks, usually in savanna regions; 2,840
cases of yellow fever were reported in Africa be-
tween 1965 and 1983.  Several large epidemics have
occurred in West Africa, Nigeria (1969, 1970, 1986),
Gambia (1978–1979), and Burkina Faso (1983).12  The
true incidence of the disease is grossly underesti-
mated, based on postmortem collections of liver
samples in Brazil.6,13
Signs and Symptoms
Yellow fever shares many of the clinical manifes-
tations observed in other hemorrhagic fevers; how-
ever, in yellow fever, severe hepatic involvement is
characteristic.  Three clinical phases are found in
patients with yellow fever: (1) infection, (2) remis-
sion, and (3) intoxication.  Infection begins abruptly
with fever, headache, generalized malaise and weak-
ness, lumbosacral pain, nausea, and vomiting.
During the 3 days of symptoms, the virus can easily
be isolated from blood.  Bradycardia, called Faget’s
sign when accompanied by fever, can be a signifi-
cant physical finding.  Remission may last as long as
24 hours, followed by intoxication, which can
progress to death 7 to 10 days after presentation.
Features of intoxication include jaundice and scleral
icterus (Figure 10-2), as well as albuminuria, oliguria,
cardiovascular instability, and hemorrhagic mani-
festations.  Neurological features include delirium,
stupor, convulsions, and coma.  The case-fatality
rate for severe yellow fever is 50%.13
Laboratory Findings and Treatment
Laboratory findings for yellow fever are diverse
and complex, reflecting fulminant hepatitis, dis-
OK to put on the Web
Fig. 10-2. Jaundice and scleral icterus in a patient with yellow
fever. Photograph: Courtesy of Thomas P. Monath, M.D.;
formerly, Walter Reed Army Institute of Research, Wash-
ington, D.C.

Military Dermatology
202
seminated intravascular coagulation, and renal fail-
ure.  Death is usually due to refractory hypoglycemia
and metabolic acidosis, although fulminant infec-
tions resulting in death within 2 to 3 days of onset
have been reported.  The diagnosis can be con-
firmed by use of an immunoglobulin (Ig) M-capture
enzyme-linked immunosorbent assay (ELISA) or
complement-fixation test.12  The differential diag-
nosis of yellow fever includes other forms of hem-
orrhagic fever, malignant malaria, leptospirosis,
and viral hepatitis.  Treatment is supportive and
may require intensive care.
Kyasanur Forest Disease
Kyasanur Forest disease was first reported in
1957 as a fatal epizootic disease in monkeys in the
Shimoga District, Karnataka State, India.14  Although
the virus has been isolated from ticks, major out-
breaks of the disease are usually related to exposure
to infected regions as a consequence of clearing
forested areas or shipping infected monkeys.15
The incubation period for Kyasanur Forest dis-
ease is 3 to 8 days and is followed by an acute onset
of fever, headache, and severe myalgias.  Diarrhea
and vomiting are frequently experienced by the
third or fourth day.  Significant early physical find-
ings include severe prostration, conjunctival suffu-
sion, photophobia, cervical and axillary adenopathy,
and, rarely, splenomegaly or hepatosplenomegaly.
Papulovesicular lesions involving the soft palate
are seen in most patients.  Bronchiolar involvement
can result in blood-tinged sputum and evidence of
pneumonia.  Although hemorrhagic manifestations
were commonly observed in initial patients, hemor-
rhagic involvement in more recent cases is rarely
observed.  This difference has been attributed to a
large number of individuals with secondary dis-
eases, such as tuberculosis and heavy helminthic
infections,15 in earlier series.  In addition, although
neurological manifestations were initially thought
to be rare, more recently documented infections
show clear evidence of neurological involvement.
The mortality rate is 5% to 10%.  An ELISA has been
developed for Kyasanur Forest disease virus.16  Treat-
ment is supportive.
Omsk Hemorrhagic Fever
Omsk hemorrhagic fever was first reported to
infect muskrat trappers and skinners in the Asian
portions of the Soviet Union during the 1940s and
1950s.1  Aerosol transmission and ticks have been
implicated in its spread.  The virus has virtually
disappeared and little is known about its current
reservoir status.
HEMORRHAGIC FEVERS CAUSED BY BUNYAVIRIDAE
Bunyaviridae is a family of arthropod-borne vi-
ruses composed of five genera: Phlebovirus (eg, Rift
Valley fever), Nairovirus (eg, Crimean-Congo hem-
orrhagic fever), Hantavirus (eg, hemorrhagic fever
with renal syndrome), Uukuvirus, and Bunyavirus.4
Bunyaviruses share several basic characteristics with
arenaviruses, such as having similar replication
cycles.  Bunyaviridae and Arenaviridae are not as
well studied as viruses in other families.17
Rift Valley Fever
The first reported outbreaks of Rift Valley fever
occurred in 1951 in South Africa when three veteri-
narians and two residents became ill after postmor-
tem examination of a berserk bull that suddenly
died.  The virus has subsequently been isolated
from cattle, sheep, and antelope.  Epidemics are
associated with these animal reservoirs and mos-
quito vectors, most commonly Aedes caballus and
Culex theileri.  Rift Valley fever virus can be main-
tained by mosquitoes alone through transovarial
transmission.1  Numerous cases have been associ-
ated with handling carcasses, meat, and internal
organs of infected animals.1,18  Recent epidemics
include the 1987 outbreak in Mauritania and the
1977 outbreak in Egypt.18  Currently, three antigenic
strains of Rift Valley fever virus have been identi-
fied.
Signs and Symptoms
The initial clinical manifestation of Rift Valley
fever is a biphasic fever, the first bout lasting 4 days.
After 1 or 2 days of normal temperatures, the sec-
ond fever spike occurs, lasting 2 to 4 days.  The most
common complication of Rift Valley fever (10% of
patients) is retinitis characterized by macular cot-
ton-wool exudates, which can permanently impair
vision if bilateral involvement is present.  Hemor-
rhagic features occur toward the end of the first
week of illness, manifested by epistaxis, hem-
atemesis, and/or melena.  Massive gastrointestinal
hemorrhage due to acute hepatic necrosis is often

Viral Hemorrhagic Fevers
203
fatal.  Additional clinical features include jaundice,
encephalitis, and disseminated intravascular co-
agulation.  Rift Valley fever virus has been associ-
ated with spontaneous abortions in ewes and may
be associated with human abortions and congenital
malformations.19
Laboratory Findings and Treatment
The laboratory features of Rift Valley fever are
similar to those found in other hemorrhagic fevers
and depend on the severity of disease.  Although an
IgM-capture ELISA is available for Rift Valley fever
virus, the assay has a low sensitivity, reported at
26%.20  Inoculation of sera into Aedes pseudoscutellaris
cells is the most sensitive method of confirming the
disease.  Inoculation intracerebrally into suckling
mice and detection of type IgM gamma globulins
can also be used.
Interferon21 and ribavirin (2 g intravenous [IV]
loading dose, followed by 1 g every 6 h for 4 d, then
0.5 g every 8 h for an additional 6 d)22 have been
shown in animal models to be effective therapeutic
agents.  A live attenuated vaccine is available; how-
ever, it should be used with caution in women of
childbearing age due to the reported association
with microcephaly and hydrops amnii.19
Crimean-Congo Hemorrhagic Fever
The first reported cases of Crimean-Congo hem-
orrhagic fever occurred in 1944 on the Crimean
peninsula.3  It has become a prominent pathogen in
Europe, Asia, and Africa.23  The tick vectors are
species of Hyalomma.  Natural reservoirs are cur-
rently unknown.
Signs and Symptoms
The incubation period of Crimean-Congo hem-
orrhagic fever is 2 to 7 days.2  Clinical features
include an abrupt onset with violent headaches,
lumbosacral muscle spasms, dizziness, sore eyes,
photophobia, fever, rigors, chills, leg pains, nausea,
vomiting, sore throat, abdominal pain, and diar-
rhea.  Patients often have injected and flushed con-
junctiva or chemosis.  Half the patients will have
hepatomegaly.  A petechial eruption is common.3
In severe cases, a hemorrhagic diathesis develops
by the third to fifth day, manifested by petechiae,
purpura (Figure 10-3), epistaxis, hemoptysis,
hematemesis, melena, and hematuria.  The disease
can progress to hepatorenal failure, resulting in
jaundice, mental obtundation, stupor and eventual
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Fig. 10-3. Crimean-Congo hemorrhagic fever with
purpura involving the axillae and arms. Photograph:
Courtesy of David I. H. Simpson, Department of Micro-
biology and Immunobiology, The Queen’s University of
Belfast.
coma, and death.  The mortality rate is reported to
range from 15% to 70%.3
Laboratory Findings and Treatment
Laboratory data reflect the degree of hepatorenal
dysfunction and coagulopathy caused by the dis-
ease.  Leukopenia, thrombocytopenia, and raised
serum transaminases are usually present.  Dissemi-
nated intravascular coagulation is an early and
prominent feature of Crimean-Congo hemorrhagic
fever.  The diagnosis can be confirmed by injecting
serum intracerebrally into day-old mice for virus
isolation, ELISA (the most sensitive), indirect im-
munofluorescence tests, and complement-fixation
tests.
Treatment is usually supportive.  Ribavirin (2 g
IV loading dose, followed by 1 g every 6 h for 4 d,
then 0.5 g every 8 h for an additional 6 d) may have
clinical utility.22
Hemorrhagic Fever with Renal Syndrome
Synonyms for hemorrhagic fever with renal syn-
drome include Korean hemorrhagic fever, Far East-
ern hemorrhagic fever, epidemic hemorrhagic fe-
ver, hemorrhagic nephrosonephritis, Songo fever,
epidemic nephritis, and neuropathia epidemica.
Korean hemorrhagic fever was first appreciated in
1951 during the Korean conflict, when United Na-
tions troops were afflicted with a hemorrhagic dis-
order previously unknown to Western medicine.24,25
By 1954, more than 3,200 cases were confirmed,

Military Dermatology
204
with 480 deaths.  The disease may have existed in
Asia for at least 1,000 years, documented in a Chi-
nese medical book written about AD 960.  The patho-
physiology of the disease was little known until
1976, when culturing of the prototype Hantaan vi-
rus resulted in the development of an immunofluo-
rescent antibody assay for serologic diagnosis.24
The subsequent 14 years have resulted in an explo-
sion of medical knowledge on Hantaan virus dis-
eases and their epidemiology.  We now know that
the Hantaan virus has a worldwide distribution
and is frequently found in healthy wild rodents.6
Three serotypes of Hantaan virus are associated
with hemorrhagic fever with renal syndrome and
can cause disease ranging from mild to severe.
Transmission to man occurs through the aerosol form
of urine, feces, and saliva from infected rodents.
• Hantaan virus serotype is associated with
the most severe forms of hemorrhagic fever
with renal syndrome and occurs in Korea,
China, and southeastern Siberia.26  The ro-
dent host is the field mouse Apodemus
agrarius.  In the Far East, two peaks of human
disease occur in the spring and summer.
• The Seoul serotype is associated with a less
severe form of hemorrhagic fever with renal
syndrome and causes urban outbreaks due
to infestation of rats: Rattus rattus and R
norvegicus.  Rat infestation has been docu-
mented worldwide, including in the United
States.
• Puumala virus infections result in the mild-
est form of the disease, called nephropathia
epidemica.27  It is most frequently docu-
mented in Europe and the western part of
the former USSR.  The natural host is the
bank vole, Clethrionomys glareolus.  The peak
incidence of disease is in the mid-to-late
summer.
Additional serotypes are being identified.  Pros-
pect Hill virus was isolated from a meadow vole on
Prospect Hill in Frederick, Maryland.  Another se-
rotype called Leakey virus has been isolated from
domestic mice in West Virginia.  Neither virus (Pros-
pect Hill or Leakey) has yet been proven to be
associated with human disease.  It should be noted
that a number of human infections have occurred in
Korea and Japan among personnel working in medi-
cal center animal rooms.24  The potential for trans-
mission of the disease by importing infected ani-
mals to research centers further underscores the
worldwide nature of this disease.
Signs and Symptoms
In the severe forms of hemorrhagic fever with
renal syndrome, five distinct clinical phases exist:
(1) febrile, (2) hypotensive, (3) oliguric, (4) diuretic,
and (5) convalescent.  The incubation period is 2 to
3 weeks but can range from 4 to 42 days.28  The
febrile phase begins abruptly and lasts 3 to 7 days.
Additional clinical features include chills, malaise,
weakness, myalgias, anorexia, dizziness, headache,
and eyeball pain.  A characteristic facial flushing
extending to the neck and chest is frequently ob-
served.  Conjunctival hemorrhage (Figure 10-4) and
fine petechiae distributed over the axillary folds,
face, neck, soft palate (Figure 10-5), and anterior
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Fig. 10-4. Conjunctival hemorrhage in a patient with
hemorrhagic fever with renal syndrome.
Fig. 10-5. Petechiae involving the palate in a patient with
hemorrhagic fever with renal syndrome.

Viral Hemorrhagic Fevers
205
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Fig. 10-7. Purpura involving the elbow in a patient with
hemorrhagic fever with renal syndrome.
Fig. 10-6. Purpura in a patient with hemorrhagic fever
with renal syndrome.
chest wall are frequently observed toward the end
of this phase, as is purpura (Figures 10-6 and 10-7).
The hypotensive phase begins abruptly and can
last for several hours to 2 days.  Clinical manifesta-
tions include depressed sensorium, confusion,
tachycardia, narrowed pulse pressure, hypotension,
and cardiac arrest.24  In severe disease, shock results
in death in one third of the cases.  In moderate
disease, recovery usually occurs within 1 to 3 days.
The oliguric phase lasts from 3 to 7 days, and up
to 60% of patients develop hypervolemia and hy-
pertension.  Symptoms and clinical features at this
time include nausea, vomiting, epistaxis, conjuncti-
val hemorrhage, cerebral hemorrhage, gastrointes-
tinal hemorrhage, central nervous system symp-
toms (severe cases), and pulmonary edema (severe
cases).  Approximately 50% of the fatalities occur
during the oliguric phase of the disease.
The onset of the diuretic phase is a good prognos-
tic sign; however, recovery can be delayed because
of marked dehydration, electrolyte imbalance, or
secondary infections.  The diuretic phase lasts for
days to weeks.
Frequently, 2 to 3 months are required for the
convalescent phase.  This period is noted for a
progressive increase in glomerular filtration rate
resulting in up to 70% return of renal function
within 6 months after the onset of disease.  Vertical
transmission from mother to child resulting in spon-
taneous abortion has been reported.28
Laboratory Findings and Treatment
Laboratory abnormalities reflect the degree of
renal dysfunction at each stage of the disease;
thrombocytopenia, anemia, azotemia, proteinuria,
hematuria, hyperkalemia, and rising creatinine are
typically observed toward the end of the hypotensive
phase and through most of the oliguric phase.  Many
types of tests are available for serologic confirma-
tion.  The most sensitive and easy to perform is the
ELISA; however, it can not distinguish between the
Hantaan and Seoul variants.28  Plaque-reduction
neutralization tests are more specific for the sero-
types.  The differential diagnosis includes other
forms of hemorrhagic disease, leptospirosis, scrub
typhus, viral hepatitis, hemorrhagic glomerulo-
nephritis, influenza, and many other disorders that
can cause thrombocytopenia and acute renal fail-
ure.28  Treatment is supportive, although ribavirin (2 g
IV loading dose, then 1 g every 6 h for 4 d, followed by
0.5 g every 8 h for 6 d) may have clinical utility.22
The Arenaviridae family includes several viruses
that cause often fatal hemorrhagic fevers (eg, Lassa,
Argentine, and Bolivian hemorrhagic fevers).4
Arenaviruses frequently use rodents as a reser-
voir.29
Lassa Fever
Due to the extremely contagious nature of the
virus, Lassa fever has a propensity for infecting medi-
cal personnel.  The first reported cases occurred in
HEMORRHAGIC FEVERS CAUSED BY ARENAVIRIDAE

Military Dermatology
206
northern Nigeria in 1969, when two of three nurses
afflicted with the disease died.3  Since then, numer-
ous laboratory personnel have been infected with
the Lassa virus.  Naturally occurring infections re-
sulting in nosocomial outbreaks have occurred in
Nigeria, Sierra Leone, Guinea, and Liberia.30  At
least 10 instances of imported Lassa fever have been
reported; however, none of these episodes has re-
sulted in human disease.3  The natural reservoir is
the rodent Mastomys natalensis, and transmission to
man is by aerosol.22  Person-to-person transmission
is important in nosocomial infections.  In areas
where the virus is endemic, Lassa fever occurs in
higher frequency during the dry season.
Signs and Symptoms
The clinical spectrum of disease in Lassa fever is
variable, with 9% to 26% of infections resulting in
illness.  The incubation period is between 1 and 3
weeks.  Onset is frequently insidious, with fever,
sore throat, weakness, and malaise followed by low
back pain, headache, and a nonproductive cough.
Additional variable features include retrosternal or
epigastric pain, vomiting, diarrhea, and abdominal
discomfort.  Physical findings include fever, exuda-
tive pharyngitis, conjunctival injection, and, rarely,
jaundice, petechiae, and cutaneous eruptions.  Pul-
monary manifestations can be significant, resulting
in rales, pleural and pericardial friction rubs, and
adult respiratory distress syndrome.3  In the most
severe form of the disease, patients can exhibit
facial and neck edema, conjunctival hemorrhages,
mucosal bleeding, melena, hematochezia, hema-
turia, vaginal bleeding, hematemesis, central
cyanosis, encephalopathy, shock, and death.
Women infected during pregnancy have the high-
est mortality rate, 16%.30  A high incidence of fetal
wastage also exists, particularly if the infection oc-
curs during the third trimester.3  Recovery usually
begins a week after onset and about 20% of indi-
viduals will develop sensorineural deafness.  The
overall case-fatality rate is 1% to 2%.3
Laboratory Findings and Treatment
Laboratory abnormalities in Lassa fever are often
nonspecific and include proteinuria, transient
thrombocytopenia, and elevated transaminases,
with aspartate aminotransferase values exceeding
those of alanine aminotransferase.  Although an
IgM-capture ELISA is available for the detection of
the disease, the indirect fluorescent antibody tech-
nique is the diagnostic test of choice.  The differen-
tial diagnosis includes other forms of hemorrhagic
fever, typhoid fever, gastroenteritis, pneumonia,
pyelonephritis, postpartum sepsis, septic abortion,
encephalitis, meningitis, and hepatitis.  Treatment
is supportive, although ribavirin (2 g IV loading
dose, then 1 g every 6 h for 4 d, followed by 0.5 g
every 8 h for 6 d) has been shown to be effective
treatment in animal studies if administered before
the seventh day of illness.22
Argentine Hemorrhagic Fever
Argentine hemorrhagic fever is caused by the
Junin virus, a single-stranded RNA virus.31  The
disease is endemic in agricultural and cattle-raising
areas of Argentina, with the first reported outbreaks
occurring in 1955 in Bragado city.  Annual epidem-
ics occur between January and August.1  The pri-
mary reservoir hosts are the rodents Calomys laucha
and C musculinus.  Transmission to man occurs
through aerosols from urine or feces.  Junin virus
can also infect through contact with abraded skin.31
Signs and Symptoms
The clinical manifestations of Argentine hemor-
rhagic fever range from subclinical to severe.  After
an 8- to 12-day incubation, an abrupt onset of fe-
vers, asthenia, dizziness, retroocular and muscular
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Fig. 10-8. Maculopapular eruption in a patient with Ar-
gentine hemorrhagic fever. Photograph: Courtesy of
David I. H. Simpson, Department of Microbiology and
Immunobiology, The Queen’s University of Belfast.

Viral Hemorrhagic Fevers
207
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Fig. 10-9. Petechiae in a patient with Argentine hemor-
rhagic fever. Photograph: Courtesy of David I. H.
Simpson, Department of Microbiology and Immunobi-
ology, The Queen’s University of Belfast.
Fig. 10-10. Conjunctival hemorrhage in a patient with
Argentine hemorrhagic fever. Photograph: Courtesy of
David I. H. Simpson, Department of Microbiology and
Immunobiology, The Queen’s University of Belfast.
pain, lymphadenopathy, maculopapular eruptions,
and cutaneous as well as pharyngeal petechiae takes
place (Figures 10-8 and 10-9).  Hemorrhagic mani-
festations are variable, resulting in conjunctival
hemorrhage (Figure 10-10), hemorrhagic gingivitis,
epistaxis, hematuria, metrorrhagia, and gastrointes-
tinal bleeding.32  In severe cases, bradycardia,
hypotension, and shock can be observed.  Neuro-
logical manifestations frequently occur, resulting
in tremor (including of the tongue), areflexia,
hyporeflexia, muscular hypotonia, ataxia, extrapy-
ramidal signs, mental depression, and coma.32  The
acute phase of the illness lasts for 10 days.  Approxi-
mately 10% to 16% of those infected die from their
disease, usually as a result of severe central nervous
system involvement.31
Laboratory Findings and Treatment
Laboratory abnormalities of Argentine hemor-
rhagic fever include leukopenia, thrombocytopenia,
and bone marrow suppression early in the disease.
Blood coagulation studies are variable; however,
no evidence of disseminated intravascular coagula-
tion has been found.32  Renal involvement results in
albuminuria, hyalin and granular casts, and Milani
cells.  Recent studies have demonstrated that the
ELISA is more specific than indirect immunofluo-
rescence tests.33
Treatment is supportive, although infusion of
antibody-rich convalescent plasma is reported to
decrease the mortality rate to 1% to 2%.31  Animal
studies suggest that ribavirin (2 g IV loading dose,
then 1 g every 6 h for 4 d, followed by 0.5 g every
8 h for 6 d) may be useful in treating Argentine
hemorrhagic fever.34
Bolivian Hemorrhagic Fever
In 1959, cases resembling Argentine hemorrhagic
fever were reported in Bolivia.  The causative agent
was determined to be the Machupo virus, and the
natural reservoir the rodent host Calomys callosus.1
Machupo virus is transmitted to man by aerosolized
rodent excreta, although person-to-person trans-
mission has been reported.  The virus is restricted to
Bolivia, and rodent-control measures have greatly
reduced the incidence of human disease.
The illness, known as Bolivian hemorrhagic fe-
ver, begins with 1 or 2 days of prodromal symptoms
that consist of malaise, fatigue, headaches, and
myalgias.35  The febrile phase lasts 7 to 10 days and
is characterized by severe headaches, excruciating
back pain, and diffuse joint and muscle aches.  A
cutaneous hyperesthesia similar to a sunburn can
be observed.  Additional clinical features include
upper-body flushing, conjunctivitis, cardiovascu-
lar lability, periorbital edema, gastrointestinal bleed-
ing, encephalopathy, and proteinuria.  Platelet counts
are frequently depressed.  Treatment is usually sup-
portive.  Clinically, little has been written about
Bolivian hemorrhagic fever since the early 1970s.

Military Dermatology
208
HEMORRHAGIC FEVERS CAUSED BY FILOVIRIDAE
The morphologic structure of filoviruses is
unique; they are the only mammalian viruses that
are filamentous.36  Ebola and Marburg viruses are
the only members of this family and are among the
most lethal of human viruses.4
Ebola Hemorrhagic Fever
Ebola virus is a single-stranded RNA virus named
after a small river in northwestern Zaire.  Ebola
hemorrhagic fever, also known as Yambuku hem-
orrhagic fever, was first identified in 1976 when two
epidemics occurred in southern Sudan and north-
western Zaire.3,37  In 284 cases in the Sudan epidemic,
the mortality rate was 53%.  In the hospital-based
Zaire epidemic, 88% of 318 infected patients died
(Figure 10-11).  Sporadic cases have been described in
Sudan and Zaire, and Ebola virus may also be en-
demic in other parts of eastern and central Africa.  The
mode of transmission and natural reservoir hosts are
unknown, although epidemiological studies suggest
that spread of the disease occurred through casual
contact or aerosol transmission.3
In November 1989 at Hazleton Research Prod-
ucts in Reston, Virginia, 16 imported cynomolgus
monkeys died from a hemorrhagic disorder.38  Viro-
logical analysis resulted in the identification of a
filovirus antigenically indistinct from Ebola virus.
The monkeys had been imported from the Philip-
pines, a previously unreported site for Ebola infec-
tions.  This incident marked the first time a filovirus
had been isolated from a nonhuman host not ex-
perimentally induced.  Epidemiological analysis
identified seven shipments of infected monkeys
from the Philippines.39  Four animal handlers were
seropositive for the filovirus; however, none could
identify an associated illness.  Although cross-reac-
tivity exists between this virus and Ebola, research-
ers at the Centers for Disease Control believe the
virus is antigenically and genetically distinguish-
able from Ebola virus.39  The lack of associated
human disease suggests that this hypothesis is cor-
rect.  Another possibility is that the virus is an
attenuated form of Ebola; one might speculate on its
possible use as a vaccine.
Signs and Symptoms
The incubation period of Ebola hemorrhagic fe-
ver ranges from 2 to 21 days.  The onset of disease is
abrupt, with symptoms resembling influenza,
including fever, headache, malaise, myalgias, joint
pains, sore throat, diarrhea, and abdominal pain.
A fleeting morbilliform eruption often appears
within the first week of illness, followed by desqua-
mation (Figure 10-12).  Additional physical
findings include pharyngitis, conjunctivitis, jaun-
dice, and edema (Figure 10-13).  Hemorrhagic
manifestations can develop after the third day of
illness, manifested by petechiae, ecchymosis, con-
junctival hemorrhage, gingival bleeding, oropha-
ryngeal bleeding ulcerations, vaginal bleeding,
bleeding from injection sites, hematemesis, and
melena.37
Laboratory Findings and Treatment
Laboratory findings for Ebola virus include
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Fig. 10-11. Ebola infection in African patient 24 hours
prior to death. Photograph: Courtesy of Thomas P.
Monath, M.D.; formerly, Walter Reed Army Institute of
Research, Washington, D.C.

Viral Hemorrhagic Fevers
209
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Fig. 10-12. Morbilliform eruption in a patient with Ebola
hemorrhagic fever. Photograph: Courtesy of Thomas P.
Monath, M.D.; formerly, Walter Reed Army Institute of
Research, Washington, D.C.
Fig. 10-13. Jaundice in a patient Ebola hemorrhagic fever.
Photograph: Courtesy of Thomas P. Monath, M.D.; formerly,
Walter Reed Army Institute of Research, Washington, D.C.
OK to put on the Web
Fig. 10-14. Hemorrhagic diathesis observed in a patient
with Marburg hemorrhagic fever. Photograph: Courtesy
of David I. H. Simpson, Department of Microbiology and
Immunobiology, The Queen’s University of Belfast.
ported in Kenya in 1987 and resulted in the death of
a boy.  The mode of primary transmission is un-
known.  Secondary spread of disease can occur
through close contact with infected persons includ-
ing sexual transmission.3
The incubation period of Marburg hemorrhagic
fever ranges from 3 to 10 days.  The clinical and
laboratory features are indistinguishable from those
of Ebola hemorrhagic fever (Figure 10-14).  The
diagnosis is confirmed by detecting IgG or IgM
antibodies to Marburg hemorrhagic fever antigens
by indirect immunofluorescence.  Treatment is the
same as for Ebola hemorrhagic fever.
proteinuria and elevated transaminases, with as-
partate aminotransferase values exceeding those of
alanine aminotransferase.3  The diagnosis is confirmed
on identification of IgM or rising IgG antibodies by
indirect immunofluorescence, Western blot analy-
sis, or ELISA, or any combination of the three.
Treatment is supportive and, as with all forms of
severe viral hemorrhagic disease, may require in-
tensive care.  In the hospital setting, extreme care
must be provided when handling any body secre-
tions or blood products.  The patient should be
isolated and strict barrier-nursing techniques
should be enforced.  Recent evidence in animal
models suggests that ribavirin (2 g IV loading dose,
then 1 g every 6 h for 4 d, followed by 0.5 g every 8
h for 6 d) may have clinical utility in treating the
disorder.3
Marburg Hemorrhagic Fever
Marburg is a single-stranded RNA virus that is
morphologically similar to Ebola virus but is anti-
genically distinct.  The virus is named after a small
German town where the first cases were described,
but the virus is found in nature in Zimbabwe, Kenya,
and South Africa.3  In Europe in 1967, 25 people
became acutely ill after handling material from
African green monkeys imported from Uganda.  An
Australian traveler died from Marburg hemorrhagic
fever in 1975 after exposure in South Africa; two
other patients survived.  A third outbreak occurred
in Kenya in 1980, resulting in one fatality and one
survivor.  Another isolated case occurred in South
Africa in 1982.  The most recent episode was re-

Military Dermatology
210
SUPPORTIVE TREATMENT
The severity of the various hemorrhagic fevers is
quite variable.  Many cases are initially categorized
as fevers of unknown etiology until additional clini-
cal findings become manifest.  For example, during
the Vietnam conflict, 3.4% to 28% of all patients
hospitalized for fever of unknown etiology were
eventually shown to have dengue.5
Intravascular volume should be maintained by
intravenous infusion of plasma expanders such as
normal saline.  Oral fluid support is also important;
however, protracted vomiting can be a clinical com-
plication, necessitating even more aggressive intra-
venous support.  Hemorrhagic manifestations and
thrombocytopenia should be treated with platelet
transfusions, intravenous plasma infusions, or both.
If bleeding is severe and fractionated blood compo-
nents are unavailable, whole blood should be trans-
fused.  Metabolic acidosis may require intravenous
sodium bicarbonate, and a rising hemoglobin is
treated with infusion of plasma.  Acute renal failure
should be treated with close monitoring of intravas-
cular volume, close monitoring of intake and out-
put with replacement of free water losses only (in-
cluding insensible losses), and avoidance of volume
expanders such as sodium-containing products.  In
severe cases, hemodialysis should be considered, if
available.
Patients with hemorrhagic fever with renal syn-
drome also experience a diuretic phase, necessitat-
ing aggressive intravenous support to maintain in-
travascular volume.  Antiviral therapy with ribavirin
(2 g IV loading dose, then 1 g every 6 h for 4 d,
followed by 0.5 g every 8 h for 6 d) may prove to
be good adjunct therapy for supportive medical
care in some viral hemorrhagic fevers.  Adrenocor-
tical steroids, antibiotics, and vasoactive agents
have not been shown to alter the clinical course of
disease.5
PREVENTION
The prevention of viral hemorrhagic fevers is
based on two possible plans of action: (1) develop-
ment of vaccines providing immunity and (2) con-
trol of the vectors or rodent hosts.  Many vaccines
are currently being developed; however, few are
available.  Control of mosquito vectors is an old
concept spawned from Dr. Walter Reed’s research
on yellow fever.  Because mosquitoes breed in open
water, elimination of standing water sites around
military installations helps to control regional dis-
ease.  Use of insecticides such as malathion is effec-
tive, reducing vector populations in limited areas.
Knowledge of vector feeding habits is also helpful;
for example, the mosquito A aegypti prefers to feed
indoors during daylight.  Therefore, insect nets
around beds are little protection against this vector,
and windows should be screened securely.5
These measures are good for established regional
areas; however, they cannot be implemented when
the soldier is in the field.  Most of the cases of
dengue experienced during the Vietnam conflict
were contracted by support troops who had contact
with civilian populations.5  The speed with which
modern warfare is undertaken, exemplified by
Operations Desert Storm and Desert Shield, also
results in a much higher risk of contracting disease
because of increased contact with civilians over
large regions and the lack of preventive vector-
control measures.  These facts emphasize the need
for development of effective vaccines that will es-
sentially remove the potential for disease in high-
risk areas.
SUMMARY
Hemorrhagic fever viruses are transmitted to
humans by arthropods and through rodent excreta.
The twelve viral groups producing hemorrhagic
fever in humans are found in both temperate and
tropical climates.  Some of the hemorrhagic fever
viruses are associated with large-scale epidemics.
All of them can cause life-threatening hemorrhagic
disease.
Although serologic tests such as ELISA are avail-
able, the diagnosis is dependent more on clinical
presentation because of the acute nature of these
diseases.  Treatment is supportive in most patients
and often requires intensive care.  Ribavirin may
have clinical utility in treating Rift Valley fever,
Crimean-Congo hemorrhagic fever, hemorrhagic
fever with renal syndrome, Lassa fever, and Argen-

Viral Hemorrhagic Fevers
211
tine, Ebola, and Marburg hemorrhagic fevers.
Prevention is based on development of vaccines
or control of the arthropod and animal vectors.
Because of the rapid mobility of modern warfare,
the best possible preventive measure is vaccination;
however, few vaccines are currently available.  The
medical officer in the field must be aware of the
potential risk of these frequently fatal viral infections.
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Bhamarapravati N. Hemostatic defects in dengue fever. Rev Infect Dis. 1989;2(suppl):S826–S829.
11.
Bean WB. Walter Reed and yellow fever. JAMA. 1983;250:659–662.
12.
De Cock KM, Naside A, Enriquez J, et al. Epidemic yellow fever in eastern Nigeria. Lancet. 1986;1:630–633.
13.
Monath TP. Yellow fever: A medically neglected disease. Report on a seminar. Rev Infect Dis. 1987;9:165–175.
14.
Pavri K. Clinical, clinicopathologic, and hematologic features of Kyasanur Forest disease. Rev Infect Dis.
1989;2(suppl):S854–S859.
15.
Rodrigues FM, Bhat HR, Prasad SR. A new focal outbreak of Kyasanur Forest disease in Belthangady Taluk,
South Kanara District, Karnataka State. NIV Bull. 1983;1:6–7.
16.
Geetha PB, Ghosh SN, Gupta NP, Shaikh BH. Enzyme-linked immunosorbent assay (ELISA) using beta-
lactamase for the detection of antibodies to KFD virus. Indian J Med Res. 1980;71:329–332.
17.
Joklik W. The virus multiplication cycle. In: Joklik W, Willett H, Amos D, Wilfert C, eds. Zinsser Microbiology.
20th ed. Norwalk, Conn: Appleton and Lange; 1992: 828.
18.
Saluzzo JF, Anderson GW Jr, Hodgson LA, Digoutte JR, Smith JF. Antigenic and biological properties of Rift
Valley fever virus isolated during the 1987 Mauritanian epidemic. Res Virol. 1989;140:155–164.
19.
Parsonson IM, Della-Porta AJ, Snowdon WA. Developmental disorders of the fetus in some arthropod-borne

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virus infections. Am J Trop Med Hyg. 1981;30:660–673.
20.
Digoutte JP, Jouan A, Le Guenno, et al. Isolation of the Rift Valley fever virus by inoculation into Aedes
pseudoscutellaris cells: Comparison with other diagnostic methods. Res Virol. 1989;140:31–41.
21.
Morrill JC, Jennings GB, Cosgriff TM, Gibbs PH, Peters CJ. Prevention of Rift Valley fever in rhesus monkeys
with interferon-alpha. Rev Infect Dis. 1989;2(suppl):S815–S825.
22.
Huggins JW. Prospects for treatment of viral hemorrhagic fevers with ribavirin, a broad-spectrum antiviral
drug. Rev Infect Dis. 1989;2(suppl):S750–S761.
23.
Swanepoel R, Gill DE, Shepherd AJ, Leman PA, Mynhardt JH, Harvey S. The clinical pathology of Crimean-
Congo hemorrhagic fever. Rev Infect Dis. 1989;2(suppl):S794–S800.
24.
Lee HW, van der Groen G. Hemorrhagic fever with renal syndrome. Prog Med Virol. 1989;36:62–102.
25.
Bruno P, Hassell H, Brown J, Tanner W, Lau A. The protean manifestations of hemorrhagic fever with renal
syndrome: A retrospective review of 26 cases from Korea. Ann Intern Med. 1990;113:385–391.
26.
Cosgriff TM. Hemorrhagic fever with renal syndrome: Four decades of research. Ann Intern Med. 1989;110:313–316.
27.
Bruno P, Hassell H, Quan J, Brown J. Hemorrhagic fever with renal syndrome imported to Hawaii from West
Germany. Am J Med. 1990;89:232–234.
28.
Lee HW. Hemorrhagic fever with renal syndrome in Korea. Rev Infect Dis. 1989;2(suppl):S864–S876.
29.
Johnson K. Lymphocytic choriomeningitis virus, Lassa virus (Lassa fever), and other arenaviruses. In: Mandell
G, Douglas R, Bennett J, eds. Principles and Practice of Infectious Diseases. 3rd ed. New York: Churchill
Livingstone; 1990: 1329–1330.
30.
Frame JD. Clinical features of Lassa fever in Liberia. Rev Infect Dis. 1989;2(suppl):S783–S789.
31.
Carballal G, Videla CM, Merani MS. Epidemiology of Argentine hemorrhagic fever. Eur J Epid. 1988:4:259–274.
32.
Molinas FC, de Bracco ME, Maiztegul JI. Hemostasis and the complement system in Argentine hemorrhagic
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33.
Garcia Franco S, Amrosio AM, Feuillade MR, Maiztegui JI. Evaluation of an enzyme-linked immunosorbent
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34.
McKee KT Jr, Huggins JW, Trahan CJ, Mahlandt BG. Ribavirin prophylaxis and therapy for experimental
Argentine hemorrhagic fever. Antimicrob Chemother. 1988;32:1304–1309.
35.
Stinebaugh BJ, Schloeder FX, Johnson KM, Mackenzie RB, Entwisle G, De Alba E. Bolivian hemorrhagic fever:
A report of four cases. Amer J Med. 1966;40:217–230.
36.
McCormick J. Rhabdoviruses and filoviruses. In: Joklik W, Willett H, Amos D, Wilfert C, eds. Zinsser Microbi-
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37.
Sureau PH. Firsthand clinical observations of hemorrhagic manifestations in Ebola hemorrhagic fever in Zaire.
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38.
Jahrling PB, Geisbert TW, Dalgard DW, et al. Preliminary report: Isolation of Ebola virus from monkeys
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Centers for Disease Control. Update: Filovirus infection in animal handlers. MMWR. 1990;39:221.

Rickettsial Diseases
213
Chapter 11
RICKETTSIAL DISEASES
VINCENT L. ANGELONI, M.D.*
INTRODUCTION
SPOTTED FEVER SEROGROUP
Rocky Mountain Spotted Fever
Boutonneuse Fever
Rickettsialpox
TYPHUS SEROGROUP
Epidemic Typhus
Recrudescent Typhus (Brill-Zinsser Disease)
Endemic (Murine) Typhus
SCRUB TYPHUS, TRENCH FEVER, AND Q FEVER SEROGROUPS
Scrub Typhus
Trench Fever
Q Fever
EHRLICHIOSIS SEROGROUP
Ehrlichiosis
Sennetsu Fever
SUMMARY
*Major, Medical Corps, U.S. Army; Staff Immunodermatologist, Dermatology Clinic, Brooke Army Medical Center, Fort Sam Houston,
Texas 78234-6200

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INTRODUCTION
Rickettsiae are pleomorphic, rod-to-coccoid–
shaped organisms that stain poorly with Gram’s
stain but are morphologically typical of Gram-nega-
tive bacteria.  They are unique in that, except for the
genus Rochalimaea, they are obligate intracellular
parasites.  Living cells are required for the culture of
all rickettsiae (with the exception of Rochalimaea
quintana, the rickettsia that causes trench fever).
This is a hazardous undertaking done by only a few
specially equipped laboratories.
Within the family Rickettsiaceae, four genera—
Rickettsia, Coxiella, Rochalimaea, and Ehrlichia—are
capable of producing disease in humans.  The rick-
ettsiae are grouped by the clinical infections they
induce, their etiologic agents, vectors, serologic re-
actions, and epidemiological factors.  Their anti-
genic differences have allowed these organisms to
be classified into genera, groups, and species.  The
pathogenic members of the family Rickettsiaceae
can be divided into six serogroups: spotted fever,
typhus, scrub typhus, trench fever, Q fever, and
ehrlichiosis (Table 11-1).  In the spotted fever group,
the typhus group, and in scrub typhus, rickettsiae
are found within the cytoplasm of the infected cell.
Spotted fever serogroup organisms may also grow
within the nucleoplasm of the cell.1  Ehrlichia species
exist within a phagosome in the host cell, and Coxiella
within a phagolysosome; Rochalimaea species are
epicellular parasites that cling to the exterior of cells.
The transmission of rickettsial diseases to hu-
mans usually requires an insect or arachnid vector,
and rickettsiae survive only briefly outside the host
or vector.  Human infection is incidental (except for
epidemic typhus) and is of no benefit to the infect-
ing rickettsial organism.  Rickettsiae do not pen-
etrate intact skin but can cause infection in abraded
skin or can be transferred by the fingers to mucosal
surfaces, which are readily infected.  In humans,
rickettsial diseases can be mild or life threatening
and are characterized by fever and skin rash.  The
genus Coxiella, however, is an exception to the above
generalizations.  Coxiella is extremely resistant to
desiccation and survives for long periods outside
the host; its spread does not involve a vector but
occurs via inhalation of the organism, and it is
usually not associated with a skin rash.  Rocky
Mountain spotted fever (RMSF), caused by R
rickettsii, is the most common rickettsial disease in
the United States2 and carries the threat of signifi-
cant morbidity and mortality if the diagnosis is not
made promptly.  Other rickettsial diseases that are
indigenous to the United States include murine
typhus, rickettsialpox, and R prowazekii infections
associated with flying squirrels.3,4  However, im-
ported cases of boutonneuse fever5 or scrub typhus6
are not unusual.
SPOTTED FEVER SEROGROUP
Rickettsiae in the spotted fever serogroup are
genetically related but differ in their surface anti-
gens.  There are several nonpathogenic members of
this group.  The spotted fever group organisms are
maintained in nature in Ixodid ticks and animals.
They induce a widespread vasculitis that involves
both skin and internal organs, producing the clini-
cal manifestations of rash and dysfunctions of brain,
heart, lungs, and kidneys.  The diseases produced
by the spotted fever serogroup include RMSF,
boutonneuse fever, and rickettsialpox.  RMSF is
generally the most severe infection of the group,
although fatalities may also occur with infections of
other spotted fever serogroup organisms.  These
other organisms produce diseases that induce head-
ache, myalgia, fever, and maculopapular eruptions
that may become petechial similar to RMSF, but the
diseases are usually milder and may have an eschar
at the site of tick attachment.
Rocky Mountain Spotted Fever
RMSF is an acute, severe, infectious disease.  It is
the most prevalent of the rickettsial diseases in the
United States and is identical to Sao Paulo fever,
Colombian spotted fever, fiebre maculosa, fiebre
petequial, and fiebre manchada of Mexico.  RMSF was
first described in the 1890s, when a series of cases
was described in the Bitterroot valley of Montana.
The first published account was by a U.S. Army
surgeon in 1896,7 although the impact of RMSF on
military campaigns has been insignificant.  From
1942 through 1945, only 135 cases were reported
among army personnel; all of these occurred in the

Rickettsial Diseases
215
TABLE 11-1
RICKETTSIAL DISEASES OF MEDICAL IMPORTANCE
Geographical
Serogroup
Disease
Organism
Vector
Reservoir
Location
Spotted Fever
Rocky Mountain
Rickettsia rickettsii
Tick
Ticks, rodents,
Western hemisphere
Spotted Fever
dogs
(Brazilian and Mexican
spotted fevers)
Boutonneuse Fever
R conorii
Tick
Ticks, rodents,
Europe, Africa, Asia
(Mediterranean fever,
dogs
South African Tick Bite
fever, Kenya tick typhus,
Indian tick typhus,
Marseilles fever)
Siberian Tick Typhus
R sibirica
Tick
Rodents, ticks
Siberia, Mongolia
North Asian tick-borne
rickettsial disease
Queensland Tick Typhus
R australis
Tick
Rodents,
Australia
marsupials
Rickettsialpox
R akari
Mouse mite
House mouse
North America, Europe,
former Soviet Union,
Korea
Typhus
Epidemic Typhus
R prowazekii
Body louse
Human
Worldwide (war, famine
associated), rare in the
United States
Recrudescent Typhus
R prowazekii
None
Human
Worldwide
(Brill-Zinsser Disease)
Endemic (Murine) Typhus
R typhi
Rat flea
Rat
Worldwide
Scrub Typhus
Scrub Typhus
R tsutsugamushi
Mite
Rodents,
Asia, Australia, Pacific
trombiculid
islands, Malaysia
mites
Trench Fever
Trench Fever
Rochalimaea quintana
Body louse
Human
Europe, Africa, Central
and South America
(war associated)
Q Fever
Q Fever
Coxiella burnetii
None
Ticks, sheep,
Worldwide
(airborne)
goats, cattle
Ehrlichiosis
Ehrlichiosis
Ehrlichia chaffeensis
Tick?
Unknown
Southeastern, south-
central United States
Sennetsu Fever
Sennetsu Fever
E sennetsu
Tick?
Unknown
Japan, Malaysia
continental United States.8  Several large military
bases (eg, Fort Sill, Oklahoma; Fort Bragg, North
Carolina) are located in areas of the United States
that have some of the highest rates reported for
RMSF.  Therefore, it is possible that medical officers
in these areas will see patients with this disease.
Microbiology
R rickettsii is a small (0.3 x 1 µm), pleomorphic,
coccobacillary organism and is an obligate intracel-
lular, bacterial parasite.  It may be stained with
Geimsa, Machiavello’s, or Castaneda’s stains.  Al-
though R rickettsii stains poorly with the Gram’s
stain, it is Gram-negative.  This fairly fragile organ-
ism is killed by drying, moist heat (50°C), formalin,
and phenol.  Freezing does not kill the organism,
and it may remain viable in the frozen state for long
periods. Because R rickettsii grows only in the cyto-
plasm or nucleoplasm of eukaryotic cells, culturing
is done in guinea pigs and mice, yolk sacs of em-
bryonated hen’s eggs, or tissue culture.  The organ-

Military Dermatology
216
isms grow directly in the cytoplasm of the host,
without being surrounded by a host cell membrane.
The outer membrane of the organism has a slime
layer, which is thought to play a role in virulence.
After the organism divides by binary fission a few
times within the cell, some of the rickettsiae exit the
cell to infect other cells.  In contrast, R prowazekii
replicates until the host cell finally bursts.9  Rickett-
sia species proliferate best at temperatures of 32°C
to 38°C, which may explain the accentuated rash on
the extremities and scrotum.10
Various tick species serve as the primary reser-
voir, hosts, and vectors.  Rickettsial growth in the
tick’s ovaries results in transovarial transmission to
at least some of the female tick’s offspring.11  Whether
the infection is obtained transovarially or through
feeding on an infected mammal, the infection per-
sists for the life of the tick.  This may be several
years.  Tick species harboring R rickettsii are charac-
terized by a life cycle with three stages: larva, nymph,
and adult.  Only the adult ticks feed on humans.
When the tick is attached to and feeding on a hu-
man, a “reactivation” process occurs in the rickett-
sial organism and it transforms from a dormant,
avirulent state to a highly pathogenic one.  This
reactivation requires several hours.  A certain inter-
val of time is also required for the organisms to be
inoculated into human skin after their release from
the tick’s salivary gland.12  In the tick, infection with
the organism begins in the gut wall, which is even-
tually penetrated and a generalized infection is
produced.  Transstadial transmission (ie, transmis-
sion of the organism from the larva to the nymph
and from the nymph to the adult) also occurs in
these ticks.
In humans, inoculated rickettsiae spread via the
blood and lymphatic system to infect endothelial
cells in all parts of the body.  The organisms prolif-
erate within the endothelial cells with some of the
organisms exiting the infected cells, causing infec-
tion in other endothelial cells or vascular smooth
muscle cells.  Infection in humans is a biological
dead end for the organism.
Epidemiology and Vectors
Humans are only incidentally involved with R
rickettsii.  Transmission of disease occurs when an
infected tick bites a human or the tick is crushed and
contaminates the skin with rickettsiae.  Rickettsiae
are present in the hemolymph and feces of infected
ticks.  Aerosol spread of the disease is unlikely
because the organism loses infectiousness rapidly in
such material,11 but this has been reported in labora-
tory accidents.13  In one case, RMSF was acquired
via blood transfusion when the infected donor was
phlebotomized 3 days prior to the onset of illness.14
When the tick attaches for its first meal after
hibernation, a reactivation process is initiated in the
rickettsial organism, which adds several hours to
the time needed for the transmission of the infec-
tion.15  Later in the season, only 6 to 10 hours of
attachment may be needed for transmission.16,17
Dermacentor andersoni (the wood tick) requires 10 to
24 hours of feeding to transmit the infection.11  In
endemic areas, screening children for ticks twice a
day is recommended to prevent infection.18,19
In the continental United States, several species
of ticks have been identified as carriers of RMSF.  D
andersoni is the primary vector in the West, while D
variabilis (the dog tick) is implicated in the South
and the East.  Amblyomma americanum (the Lone Star
tick) has been implicated as a possible vector in the
Southwest.  In Brazil and Colombia, Amblyomma
cajennense is the vector.  Rhipicephalus sanguineus
(brown dog tick) is a vector in southern regions of
Mexico and the United States.16,20  Most species of
vector ticks appear to have a low rate of infection.
The prevalence of R rickettsii infection among ticks
has been estimated at 1 in 1,000.12
Several other ticks have been found to be infected
with R rickettsii but, because they rarely attack hu-
mans, are not important as vectors.  These are
Hemaphysalis leporispalustris,12 Dermacentor parum-
apertus, Ixodes dentatus, I  brunneus, and I texanus.
Several species can be considered potential vectors,
however; they attack humans and have been found
to contain R rickettsii or a closely related organism,11
but they have not yet been documented as a cause of
RMSF (Exhibit 11-1).
R rickettsii has also been found in numerous small
mammals (eg, chipmunks, opossums, rabbits, squir-
rels, mice, and rats).  This is due largely to the
feeding habits of the various tick hosts.  Some of
these small mammals develop rickettsemia to a
degree that would allow them to cause new infec-
tions in uninfected ticks that feed on them.  These
mammals probably play an important role in main-
taining the organisms in nature.  Infection in ticks
tends to be limited in subsequent generations be-
cause the rickettsial infection may cause decreased
viability and fecundity in tick offspring after sev-
eral generations.  Thus, the presence of small mam-
mals provides a survival advantage for the organ-
ism by establishing new lines of infection, thereby
overcoming the limitation of the infection that would
be expected by the decreased reproductive ability
or survival of future tick generations.15,21

Rickettsial Diseases
217
EXHIBIT 11-1
VECTORS OF ROCKY MOUNTAIN
SPOTTED FEVER
Known Vectors
Dermacentor andersoni
D variabilis
Amblyomma cajennense
Rhipicephalus sanguineus
Potential Vectors
Amblyomma americanum
D maculatum
D occidentalis
Ixodes scapularis
I pacificus
Data source: Burgdorfer W. Ecological and epidemio-
logical considerations of Rocky Mountain spotted fever
and scrub typhus. In: Walker DH, ed. Biology of Rickett-
sial Diseases. Vol 1. Boca Raton, Fla: CRC Press; 1988: 33–50.
out the year, even in winter.25  July is typically the
month with the highest number of reported cases.
Even with effective antibiotics available, the fatality
rate for RMSF remains in the 3% to 7% range.2,10,16,22,26
Clinical Manifestations
The incubation period lasts 4 to 8 days (range 2–
14 d).  The prodromal period lasts 2 to 3 days and is
characterized by headache, malaise, anorexia,
photophobia, chills, fever, arthralgia, and myalgia.
Symptoms may appear gradually or rather sud-
denly with rigors, prostration, and severe head-
ache, backache, and abdominal pain.  At this point,
the observed symptoms are nonspecific and the
disease is difficult to distinguish from more com-
mon illnesses.  Asymptomatic infection has not
been conclusively demonstrated.12
Because RMSF causes widespread capillary dam-
age, the signs and symptoms of the disease are
protean.  Although the presence of the RMSF classic
triad (fever, rash, history of tick bite) would seem
to be very helpful, only 3% of patients will have
these findings during the first 3 days of illness.2
Fever, rash, and edema are common clinical find-
ings.  The fever is characterized by morning remis-
sions, may reach 106°F, and can last up to 3 weeks in
severe cases.  Restlessness, insomnia, and delirium
can be seen when the fever peaks.  The pulse rate
usually parallels the temperature and a sudden
elevation of pulse rate over a 24-hour period may
herald the appearance of circulatory failure.
Myalgia, hyperesthesia, slight nonproductive cough,
and epistaxis are also seen frequently.
The rash is an important, although not always a
completely reliable, diagnostic sign (Figure 11-1).  It
may appear from 2 to 14  days after onset, occurring
most often around the fourth day.  An eschar is not
typical of RMSF, although it has been described
rarely.27  The rash first appears on the cooler por-
tions of the body such as the distal extremities or
scrotum.19  Initially, it is macular and blanches with
pressure.  In some cases, it may appear first on the
trunk, but even in these patients it tends to become
accentuated on the extremities.18  The lesions spread
in a centripetal fashion with involvement of the
trunk, buttocks, neck, axilla, and face.  Within 2 to 3
days, the rash assumes a petechial or purpuric char-
acter.  At this time, while the rash is petechial, the
Rumpel-Leede phenomenon may be seen: when a
tourniquet or sphygmomanometer cuff is applied
to the extremity for 3 to 5 minutes, petechiae can be
seen below the site of compression.  The Rumpel-
Leede phenomenon is not specific for RMSF and
Although the name RMSF persists, it has become
a misnomer.  Prior to the 1940s, most cases were
reported from the western mountain states.  Now,
however, the most common sites in the United
States are the eastern, southeastern, and south-cen-
tral regions.22  The incidence appears to be highest
in areas characterized by eastern deciduous forests
made up largely of pine, oak, or hickory trees.18  The
disease may also occur in urban areas and, rarely,
urban endemic foci have been described.23  All states
in the United States except Maine, Alaska, and
Hawaii are considered endemic areas.24  States with
the highest rates of infection are Oklahoma, North
Carolina, and South Carolina.12,18  High incidences are
also seen in Maryland, Virginia, Georgia, Tennessee,
Ohio, Missouri, Arkansas, Texas, and Kansas.
Human males and females of all ages are suscep-
tible to RMSF.  The age distribution and gender of
patients tend to be related to the occupational or
recreational activities in the area.  Rural areas have
higher incidences of disease and in the West, infec-
tion seems to occur more often in persons following
outdoor occupations.  Adults are primarily affected
in the Rocky Mountain area, but in the southern
United States, children make up a large number of
cases, probably because the dog tick is the main
vector in that area.
Seasonal variations in the number of reported
cases are related to the responsible tick vector’s
periods of activity.  Most cases occur between April
and October although sporadic cases occur through-

Military Dermatology
218
OK to put on the Web
OK to put on the Web
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c
a
b
also can be seen in platelet disorders and sometimes
scarlet fever.  After the petechial stage, lesions may
coalesce and form ecchymotic areas.  Necrotic or
gangrenous changes may follow, occurring over
bony prominences, the scrotum, penis, vulva, ears,
and, in severe cases, the extremities.  In mild cases,
the rash may never become petechial and the
macules can disappear, especially after antibiotic
treatment has been initiated.  Estimates of the per-
centage of cases with petechial rashes are in the
range of 40% to 60%.  Only one third of patients will
have fever, headache, and petechial skin lesions.28
The rash may not involve the palms and soles in a
substantial number of cases.12,29
Unfortunately, the late appearance of the rash
often causes a delay in diagnosis that could have
catastrophic consequences.  In approximately 10%
of patients, the rash may be completely absent.22
“Spotless” spotted fever is seen more often in older
patients, fatal cases, and black people whose heavy
pigmentation obfuscates the rash.
Nonpitting edema occurs frequently.  It may be
generalized or strictly limited to the periorbital
region, face, or extremities.  This usually worsens as
the disease progresses and is a direct result of the
vascular damage caused by the organism.
Nonproductive cough may be noted.  Chest radi-
ography may reveal patchy interstitial infiltrates in
Fig. 11-1. (a) Macular, (b) petechial, and (c) purpuric
lesions in patients with Rocky Mountain spotted fe-
ver. Photographs: Courtesy of Walter Reed Army
Medical Center Dermatology Service, Washington, DC.

Rickettsial Diseases
219
approximately one third of patients.  The pulmo-
nary edema seen in severe cases is due to increased
permeability in the pulmonary vessels caused by rick-
ettsial infection of the endothelial cells.10  Severe pul-
monary edema and development of adult respiratory
distress syndrome is a life-threatening complication.
Eye findings include conjunctivitis (in 30%),
photophobia, and sometimes petechial lesions.  In
severe disease, ocular palsy, hemorrhage, venous
engorgement, vascular occlusion, and papilledema
may occur.  The latter is seen in 1.5% of patients, can
occur with normal cerebrospinal fluid pressure,2,29,30
and is thought to be due to vascular involvement of
the optic nerve head.
Electrocardiographic findings are usually non-
specific; however, myocarditis occurs and can trig-
ger arrhythmias in approximately 7% of patients.2
There have also been isolated reports of creatine
kinase–myocardial band elevations.29  In general,
the myocarditis is rather mild and often completely
overshadowed by pulmonary problems.29
Abdominal pain is not unusual and could be
severe enough to cause misdiagnosis and unneces-
sary laparotomy for suspected appendicitis,31 rup-
tured diverticula, or acute cholecystitis.12,32
Anorexia, nausea, vomiting, and diarrhea are the
most frequent gastrointestinal complaints.33  Prob-
ably the most common misdiagnosis is gastro-
enteritis.  Guaiac-positive stools and vomitus can
be seen in approximately 10% of patients.34  Fatal
gastrointestinal hemorrhages may occur.9  Spleno-
megaly can occur later in the first week of illness.
Jaundice is seen infrequently, and the liver is usu-
ally not severely damaged.  Hypotension due to
peripheral circulatory failure results in prerenal
azotemia that sometimes progresses to acute oliguric
renal failure.29,35
Neurological manifestations are common and
can mimic encephalitis or meningitis.  Mild nuchal
rigidity and Kernig’s sign may be present.  Early in
the disease, mental status changes consisting of
confusion, dulling of the senses, and restlessness
are possible.  Lethargy, delirium, and coma may
follow.  Loss of sphincter control and transient
deafness are rare complications.  Abnormal neu-
rological findings such as ankle clonus or a positive
Babinski sign can appear as the condition worsens.
Other neurological manifestations include tremor,
rigidity, meningismus, opisthotonus, central blind-
ness, convulsions, pyramidal tract signs, aphasia,
dysarthria, ataxia, unilateral corticospinal signs,
hemiplegia, paraplegia, neurogenic bladder, and
cerebral hemorrhage.18,28,29,36  Psychiatric symptoms
may complicate the picture; hallucinations, para-
noid behavior, and involuntary commitment have
been reported.28
Initially, the illness appears nonspecific and is
difficult to distinguish from other illnesses associ-
ated with fever, headache, and myalgia.  In RMSF,
however, symptoms usually progress.  Overwhelm-
ing infections may result in death within a few days,
especially in patients with glucose-6-phosphate
dehydrogenase (G6PD) deficiency.  In fatal cases,
patients are usually comatose and may show signs
of neurological embarassment, circulatory collapse,
and renal failure.
Severe disease may be associated with thrombo-
cytopenia resulting in various hemorrhagic phe-
nomena such as purpura or secondary hemorrhage
in the brain or lungs.  Necrotic gangrene may occur
in dependent areas such as the fingers, toes, scro-
tum, and earlobes.  Massive skin necrosis requiring
skin grafts has also been reported.37  Secondary
bacterial infection may also complicate the picture:
pneumonia, otitis media, and parotitis may occur.16
Convalescence is usually rather slow, requiring
weeks to months.
Most patients without complicated courses will
have no sequelae.28  Neurological sequelae include
symptoms ranging from “nervousness” to convul-
sions.  Abnormal electroencephalogram findings
may persist.  In children, the risk of learning disabil-
ity is increased.18  Deafness and impaired vision can
be permanent.  Severely ill patients may have im-
pairment of fine motor control, hypotonia,
hyperreflexia, ataxia, mental retardation, aphasia,
paraplegia, neurogenic bladder, transverse myeli-
tis, depression, learning disabilities, and decreased
intelligence.29
Laboratory Findings
There are no diagnostic laboratory findings in
RMSF.  Early in the disease, leukopenia or a normal
white blood cell count may be seen with increased
band forms that later evolve into a leukocytosis.18, 28
Mild, normocytic, normochromic anemia may also
be found.  Hemolysis occurs rarely, mainly in pa-
tients who are deficient in G6PD.26,38  Thrombo-
cytopenia may occur in 32% to 52% of patients16 and
may be related to an increased adherence and mar-
gination of platelets, to vascular endothelium at
foci of infection.39  Evidence of coagulation distur-
bances can be found.  Hypofibrinogenemia, elevated
fibrin degradation product levels, and prolonged
prothrombin and partial thromboplastin times can
occur and may not be associated with disseminated
intravascular coagulation (DIC) or bleeding.28  Al-

Military Dermatology
220
though laboratory findings are compatible with
intravascular coagulation, true DIC in RMSF prob-
ably occurs only rarely.  Normal or elevated plasma
fibrinogen levels can be seen in RMSF, an excep-
tional finding in cases of DIC.10  In true DIC, occlu-
sive thrombi occur in normal blood vessels and
heparin is effective therapy.  In RMSF, heparin
therapy may result in increased hemorrhage.40
Thrombi in RMSF are found only in vessels where
there is severe injury, and bleeding occurs more
often without coagulopathy.  The preferred treat-
ment is with antirickettsial antibiotics.9,12
Hyponatremia is common.  Abnormal liver func-
tion tests may be noted; aspartate aminotransferase,
alanine aminotransferase, and bilirubin may be in-
creased.29,33  Blood urea nitrogen may be increased.
The urine is usually normal except in cases where
renal failure is developing.  Inappropriate secretion
of antidiuretic hormone has been reported41; how-
ever, inappropriate secretion cannot be diagnosed
with certainty when hypotension, hypovolemia, or
edema are present.42  What appears to be elevated
may actually be appropriate secretion of antidiuretic
hormone followed by a dilutional hyponatremia.29
Cerebrospinal fluid findings are variable.  Mod-
erate lymphocytic pleocytosis is not uncommon
although cells may be absent.  Glucose is usually
normal and protein may be normal to moderately
elevated.28
In severe cases, elevation of creatine kinase and
aldolase enzymes may be noted, reflecting muscle
involvement.29
Prognostic Factors
Two important factors in the prognosis of RMSF
are the rapidity with which the diagnosis is made or
suspected and when treatment is started.  Typi-
cally, patients who are treated before the fifth day of
illness do well, whereas those who are not treated
until the sixth day have a 25% mortality.43  Factors
that result in delayed diagnoses include the late
appearance or absence of the rash, late reporting or
lack of tick-bite history, and an initial diagnosis
other than RMSF.
Age is also important: patients over 40 do signifi-
cantly worse than younger patients.  Mortality for
patients younger than 40 years of age is approxi-
mately 13%, whereas patients older than 40 have a
41% mortality.18  The presence of other underlying
diseases complicates management and adversely
affects prognosis.  The infective burden and the
virulence of the organisms also play a role.  This is
reflected by a short incubation period and increased
severity of symptoms.  Patients with G6PD defi-
ciency can have particularly fulminant courses.44
The need for mechanical ventilation, the pres-
ence of coma, or acute renal failure portend a poor
prognosis.  In one study, 9 of 10 patients who
needed mechanical ventilation died.30  Of patients
who lapse into coma, 86% have fatal outcomes.12
Acute renal failure complicates fluid management
and may require dialysis.12
Men tend to do worse than women.  Black men
also seem to have more severe illness, a finding that
is unrelated to skin color or socioeconomic class.29,38
When the role that dark pigmentation plays in de-
laying recognition of the RMSF rash, and therefore
delaying treatment, is eliminated, black men are
still found to have a significantly higher mortality.
Thus, in a study comparing mortality data in black
women to age-matched white women with RMSF,
the mortality rates are very similar.  However, when
black men are compared to an age-matched white
control population with RMSF, the black men have
a strikingly higher mortality rate than their white
counterparts.38  Case fatality rates for blacks are
more than 3-fold higher than for whites, with black
men over the age of 40 at high risk for a fatal
outcome.22,26
Diagnosis
Serologic Diagnosis.  Serology is the principal
diagnostic tool for rickettsial diseases used in most
laboratories.  It is, however, a retrospective method
that compares acute titers of antibodies to convales-
cent titers obtained weeks later.  Treatment should
not be withheld while waiting for antibody titers.
Because immunity to infection is lifelong, confirm-
ing the diagnosis of RMSF is important for both the
physician and the patient.  Samples should be col-
lected as early as possible in the illness, during the
second week, and again 4 to 6 weeks after the onset.
Serologic studies should be repeated even after
successful treatment, because negative results im-
ply that the patient does not have immunity.19
Diagnostic testing for RMSF includes commer-
cially available tests such as latex agglutination and
Proteus OX-19 and OX-2 agglutination (the Weil-
Felix test).  Indirect fluorescent antibody, indirect
hemagglutination, and complement fixation tests
are available through reference laboratories.  There
is cross-reactivity of the antibodies identified by
indirect hemagglutination, indirect fluorescent an-
tibody, and latex agglutination among other mem-

Rickettsial Diseases
221
bers of the spotted fever serogroup (R akari, R conori,
R sibirica, and R australis), typhus serogroup (R
prowazekii, R typhi), and scrub typhus serogroup (R
tsutsugamushi).  The indirect hemagglutination and
indirect fluorescent antibody tests appear to be the
most sensitive of those currently in use.45
The indirect fluorescent antibody test is the cur-
rent standard for serologic tests, with a sensitivity
of 94% to 100% and a specificity of 100%.  Antibody
titers of 1:64 or greater are considered to be diagnos-
tic when detected 7 to 10 days after the onset of
RMSF-like symptomatology.10  Indirect fluorescent
antibody titers tend to be more persistent, allowing
the test to be used to screen for disease prevalence.
In addition, the test can be used to quantitate the
immunoglobulin M and immunoglobulin G re-
sponse, which is necessary to distinguish epidemic
typhus from recrudescent typhus (Brill-Zinsser dis-
ease, which is discussed later in this chapter).16  The
main disadvantages of the indirect fluorescent anti-
body test are that it is technically difficult to per-
form and requires a fluorescent microscope.  Repro-
ducibility can also be a problem due to variations
induced by different fluorescent conjugates, light
sources, and optical systems.
Complement fixation testing is used less often
today, although previously it was the principal
serologic test with fairly high specificity.  However,
low sensitivity in early disease was a major problem
with this test.  The Centers for Disease Control and
Prevention have stopped providing rickettsial anti-
gen for this test.10  Complement fixation antibody
titers can persist at low levels for years.  Spotted
fever group and typhus group cross-reactions are
observed frequently.
The indirect hemagglutination test can detect
antibodies earliest in the disease, showing a sharp
rise in convalescent titers after days 7 through 9 of
illness.  However, few RMSF patients have diagnos-
tic titers in the acute stages of illness.12  Cross-
reactions are seen with RMSF, rickettsialpox, and
boutonneuse fever.  Sensitivity in convalescent sera
is very high but in the acute stages it is low.
Latex agglutination is a rapid, simple, commer-
cially available test that requires no special equip-
ment to perform.46  Titers fall below levels of signifi-
cance after approximately 2 months.  Only active
RMSF infections are detected and a single high titer
(1:128) is usually diagnostic.47,48  Specific latex agglu-
tination tests for murine typhus, epidemic typhus,49
and boutonneuse fever have also been developed.50
Proteus agglutination (Weil-Felix) tests were in-
itially described in 1916 and depend on cross-re-
acting antigens present on Proteus vulgaris strains.
These antibodies appear in the sera of patients 5 to
12 days after RMSF develops and cause agglutina-
tion with Proteus strains OX-19 and OX-2.  The Weil-
Felix test has also been used in the diagnosis of
murine typhus, epidemic typhus, boutonneuse fe-
ver, and other rickettsial diseases.  Patients with
rickettsialpox and recrudescent typhus fever do not
develop Weil-Felix antibodies.  The sensitivity and
specificity are low when compared to more current
serologic tests that detect specific rickettsial anti-
bodies.  False-positive results have been reported in
cases of leptospirosis, Proteus infections, brucellosis,
tularemia, enteric, relapsing, and rat bite fevers,16
atypical measles,51 and healthy people.12  Most
people who are found to have positive Weil-Felix
antibody titers early in the disease course are subse-
quently proven not to have RMSF.12  Weil-Felix
testing is no longer considered by the Centers for
Disease Control and Prevention as a criterion for
the laboratory diagnosis of RMSF, and some au-
thorities have recommended its abandonment.10,52
The Centers for Disease Control and Prevention
criteria for confirming the laboratory diagnosis of
RMSF, which were established in 1981, are the fol-
lowing45:
• a 4-fold increase in serum antibody titers
from the acute to the convalescent phase, as
determined by complement fixation, indi-
rect fluorescent antibody, indirect hemag-
glutination, latex agglutination, or micro-
agglutination tests;
• a single, high, acute-phase titer using latex
agglutination, which is confirmatory only
when acute and convalescent titers are not
available;
• a single convalescent titer of 1:16 or higher
by complement fixation or 1:64  or higher by
indirect fluorescent antibody testing in clini-
cally compatible cases;
• isolation of rickettsiae; and
• fluorescent antibody staining of biopsy of
autopsy specimens.
Notable is the absence of the Weil-Felix test in this
diagnostic scheme.  Weil-Felix positivity is only a
probable indicator of disease, and should be con-
firmed with more-specific tests.
Rickettsial Isolation.  Isolation of the rickettsial
organism is not feasible in most situations, as this
technique is practiced by only a few research labo-
ratories.  Rickettsiae may be grown in guinea

Military Dermatology
222
pigs and mice, cell culture, and yolk sacs of embry-
onated hen’s eggs.  Guinea pigs inoculated intra-
peritoneally develop fever, erythema, edema, and
sometimes hemorrhagic necrosis of the scrotum.
The animals are sacrificed on day 3 of fever, and
diagnosis may be attempted by staining smears of
tunica vaginalis, or frozen sections of epididymis or
spleen, with fluorescein-conjugated antibody.  Al-
ternatively, specimens may be frozen at –70°C and
sent to a reference laboratory for confirmation of
diagnosis.10
Identification of Rickettsiae in Tissue.  Attempts
to visualize rickettsiae in tissue using standard or
modified histochemical stains (eg, Giemsa, modi-
fied Brown-Hopps) have been made.  However,
because the number of organisms in tissue may be
small, using these techniques to identify organisms
is tedious and fraught with error.
A more-acceptable method is the use of 3-mm
punch biopsies of lesional skin, followed by stain-
ing with specific immunofluorescent antibodies or
indirect immunofluorescent techniques.  Sensitiv-
ity of the direct immunofluorescent technique is
70% and specificity is 100%.  The reliablility of
the results may directly correlate with the experi-
ence of the pathologist.  In any case, negative results
do not rule out the diagnosis.  Rickettsiae appear
to be most numerous in endothelial cells at the
center of the petechial lesion.  Therefore, step sec-
tions through the middle of the frozen specimen are
more likely to demonstrate the organisms.
Antirickettsial antibiotic treatment appears to have
little effect on the sensitivity of the biopsy if used for
less than 24 hours.  After 24 hours of antiobiotic
therapy, the number of organisms in the tissue
appears to be dramatically reduced, making the
biopsy unreliable.  Punch biopsy and immunofluo-
rescence can also be used to diagnose boutonneuse
fever, murine typhus, and epidemic typhus.10  The
disadvantages of the immunofluorescent technique
are the following:
• this technique is not widely available,
• a fluorescent microscope is necessary,
• the results may depend on the experience of
the pathologist, and
• a rash must be present and a biopsy of a
petechial lesion is the preferred specimen.
Rickettsiae can be demonstrated in formalin-
fixed, paraffin-embedded tissue.  This technique
can be employed to make a diagnosis the same day
or the next day, but it has not been routinely used as
of this time.53–55
Pathological Findings
There are no diagnostic histopathological find-
ings in RMSF and the pathological findings are
similar to those caused by other Rickettsia species.
The major sites of involvement are the capillaries
and venules.  The arteriolar damage may be more
prominent owing to the infiltration of the media by
R rickettsii.  Endothelial swelling and perivascular
and interstitial infiltration of lymphocytes, mac-
rophages, and a few neutrophils are seen.  Although
this may have the appearance of a leukocytoclastic
vasculitis, it is not the result of immune complexes.
Thrombi may be seen in a small number of vessels
and microinfarcts are found infrequently.10
Similar histopathological patterns are seen in
affected organs such as skin, kidney, heart, lung,
liver, muscle, esophagus, stomach, intestines, pan-
creas, testis, and epididymis.  The most characteris-
tic lesion is the glial or typhus nodule that occurs in
the central nervous system, where perivascular lym-
phocytes and macrophages infiltrate the subendo-
thelium and neuropil.  This lesion is not diagnostic
of rickettsial infection, as it is seen in various
encephalitides.10
Myocardial changes are typified by interstitial
inflammation with occasional necrosis of myocar-
dial cells.  Conduction fibers involvement may re-
sult in electrocardiographic abnormalities.56
Differential Diagnosis
The presumptive diagnosis of RMSF should be
entertained in a febrile patient with a recent history
of a tick bite or having crushed a tick.  Especially in
endemic areas, the absence of this history should
not decrease the medical officer’s index of suspi-
cion.  Because in some areas more than 50% of the
populace may have a history of tick bite, a positive
history may not be particularly helpful either.57
Problems arise when patients are initially misdiag-
nosed and are given an antibiotic that is ineffective
against rickettsiae.  When such patients return to
the physician because their symptoms have pro-
gressed and a rash has developed, the diagnosis of
drug eruption—rather than RMSF—is likely to be
made, further delaying treatment.  Inappropriate
antibiotic therapy is associated with a mortality of
20%.2  Within the first week of illness, finding a
marked left shift in the differential count with a
near-normal number of leukocytes should suggest
consideration of the diagnosis.  Biopsy of a skin
lesion (preferably petechial) for immunofluores-
cent staining could help in making a rapid diagno-

Rickettsial Diseases
223
sis if the results are positive but is not helpful if
negative.19
The rash may be a helpful clinical sign, but it is
not always classic or diagnostic in its presentation.
Other illnesses that present with fever and petechial
lesions must be considered: meningococcemia,
murine and epidemic typhus, typhoid fever, measles
(especially atypical measles), and enteroviral infec-
tion with an exanthem.
The rash of meningococcemia becomes purulent
or necrotic within a day or two of onset.  It is
additionally distinguished by abnormal cerebrospi-
nal fluid findings; positive culture of organisms
from the cerebrospinal fluid, blood, or skin lesions;
and positive countercurrent immunoelectrophore-
sis or latex agglutination of cerebrospinal fluid or
urine.43  If the diagnosis is in doubt, then treatment
to cover both RMSF and meningococcus infection
should be started using tetracycline with the addi-
tion of penicillin, or with chloramphenicol alone.
Measles usually has a distinctive prodrome with
coryza, respiratory symptoms, photophobia, and
Koplik’s spots.  Atypical measles can mimic RMSF
more closely with fever, myalgia, and headache,
followed by a rash and elevated Weil-Felix OX-19
titers.51  The rash is maculopapular and petechial,
starts on the extremities, and spreads centripetally.
Urticarial or vesicular lesions may be noted, differ-
ing from RMSF.  Koplik’s spots are absent and
pneumonia may occur.  Atypical measles is a diag-
nostic consideration only in adults: it depends on
the patient’s having received the inactivated measles
vaccine during the years 1963 through 1967.18
Enteroviral infections can be confusing owing
to their seasonal occurrence and the faint macu-
lopapular rash that may accompany them.  These
patients usually have a milder, self-limiting illness.
The rash usually
• starts on the trunk,
• may be petechial on occasion, and
• can involve the palms and soles.
The occurrence of aseptic meningitis can further
confuse the clinical picture.  When the diagnosis is
in doubt, treatment for RMSF is indicated.
Murine typhus, which is usually a milder dis-
ease, occurs more often during the winter and in
urban areas, and is rarely purpuric.  Epidemic ty-
phus can produce many of the same findings as
RMSF, but the rash is rarely seen on the palms,
soles, and face, and usually is first seen on the trunk,
spreading centrifugally to the arms and thighs.  The
individual lesions initially begin as pink, blanchable
macules but as the exanthem progresses, petechiae
are found.  As in RMSF, skin lesions may progress
to necrosis or gangrene.  Cases of RMSF that occur
during the winter should be scrutinized closely to
rule out epidemic typhus, although therapy for
these diseases is the same.58
In the western United States, Colorado tick fever
is more common than RMSF.  Caused by a virus that
is transmitted by D andersoni, Colorado tick fever is
characterized by fever, headache, backache, and
leukopenia, but it does not produce an exanthem.
Thus, it may be confused with RMSF early in the
disease, before the rash is seen.  Episodes of fever
followed by 2 to 3 afebrile days, with subsequent
return of fever, suggests Colorado tick fever.  This
is usually not a severe illness.59
Other diagnostic considerations include immune
complex vasculitis, idiopathic thrombocytopenic
purpura, thrombotic thrombocytopenic purpura,
disseminated gonococcal infection, secondary syph-
ilis, leptospirosis, rubella, and drug eruptions.
Treatment
The antibiotics tetracycline and chloramphenicol
are effective in treating RMSF.  These agents are
bacteriostatic, not bacteriocidal, and if adminis-
tered late in the course of disease, the infection may
still prove to be fatal.  Most patients who are treated
4 to 5 days after the onset of symptoms will survive,
with the exception of the rare patient with both
G6PD deficiency and RMSF.  Because G6PD defi-
ciency predisposes to severe infection, patients with
this history may require presumptive therapy with
doxycycline as soon as they present with signs and
symptoms even slightly suggestive of RMSF.19  Re-
sults are usually seen within days of initiating treat-
ment.  Therapy is generally continued until 4 days
after the patient becomes afebrile, or for a 7- to 10-
day course.  Sulfonamides are contraindicated if RMSF
is suspected because they enhance the infection.
Antibiotic therapy for patients older than 9 years
of age who are stable with mild disease and who do
not have significant nausea or vomiting should
consist of oral tetracycline or doxycycline.  The dose
of tetracycline should be 30 to 40 mg/kg/d, admin-
istered every 6 hours (the maximum dose is 2 g/d).
Doxycycline should be administered with a loading
dose of 4.4 mg/kg/d divided every 12 hours the
first day, followed by a maintenance dose of 2.2
mg/kg/d divided every 12 hours.  The maximum
dose of doxycycline is 300 mg/d.43  Doxycycline is
the recommended tetracycline if azotemia is
present.60

Military Dermatology
224
More severely ill patients who require hospital
care should be given intravenous antibiotics.  Tetra-
cycline is the drug of choice, especially in patients
with hematologic complications (ie, thrombo-
cytopenia).  The intravenous dose of tetracycline is
also 20 to 30 mg/kg/d in divided doses adminis-
tered every 12 hours.  Chloramphenicol is adminis-
tered intravenously or orally in a dose of 50 to 100
mg/kg/d, divided every 6 hours (the maximum
dose is 3 g/d).  Chloramphenicol has the advantage
of also covering meningococcal disease and is the
preferred drug for pregnant women.  Hematologic
parameters must be monitored with chlor-
amphenicol therapy to screen for the development
of blood dyscrasias.
Therapy for pediatric patients younger than 9
years of age is controversial.  Some authorities pre-
fer chloramphenicol because enamel hypoplasia can
occur with tetracycline therapy in this age group.61
However, the fact that chloramphenicol has been
associated with bone marrow aplasia causes some
experts to recommend tetracycline despite tooth
discoloration.61,62  Dental abnormalities associated
with tetracycline are more likely with repeated or
prolonged exposures to the drug.  Doxycycline may
be preferred over tetracycline because it binds less
to calcium, decreasing its potential to affect the
tooth enamel.  Whichever antibiotic is chosen, ad-
equate documentation should be included in the
patient’s record specifically addressing the discus-
sion of the side effects with the patient’s parents
(Figure 11-2).61
Ancillary and supportive care can be difficult in
some cases.  Fluid management can be a trouble-
some problem due to the vascular damage sus-
tained during the course of the illness.  Albumin or
plasma may be needed in addition to electrolyte
solutions.  Injudicious use of fluids may lead to
circulatory overload, increasing edema and car-
diopulmonary failure.  Hematologic parameters,
including platelets, should be monitored closely,
and transfusions may be needed in some cases.
Management of DIC is best handled by its preven-
tion, using appropriate antibiotic treatment early to
control the infection.  Standard heparin therapy for
DIC may be ineffective in patients with RMSF.1,16,62
Treatment with systemic corticosteroids is contro-
versial but may be useful in patients with widespread
vasculitis and encephalitis with cerebral edema.24,62
Prevention
Because a commercial vaccine for RMSF is not
currently available, preventive efforts are aimed at
avoiding or reducing contact with ticks.  Insecti-
cides such as dichlorodiphenyltrichloroethane
(DDT), dieldrin, chlordane, toxophene, and
malathion have been used succesfully in the past.
However, environmental concerns have limited the
use of residual insecticides such as chlordane or
dieldrin for tick control in large areas.  Dipping
domestic animals, rodent control, and clearing brush
may help control the tick population.
Avoidance of ticks is the primary personal pre-
ventive measure.  Repellents such as N,N-diethyl-
m-toluamide (DEET), dimethyl phthalate, or
permethrin should be applied to clothing and ex-
posed body parts and should be reapplied after
swimming or perspiring heavily.  Applying the
repellant to clothing may produce longer periods of
effectiveness.59  The acaricide permanone (ie, a syn-
thetic permethrin) is an effective repellent that may
be applied to clothing and remains effective for
several weeks, even after one or more washings.60
Ticks may be easier to detect on lighter-colored
apparel, and clothing should cover the legs and
arms.  Pants should remain tucked into socks.  Even
with these precautions, it is important to inspect the
entire body for ticks every 4 hours.63  It is not
uncommon for people to be totally unaware of ticks
crawling on their skin and biting.  Because ticks
must remain attached for several hours to transmit
the infection, periodic examination and removal of
attached ticks may prevent transmission.
Engorged ticks must be removed with care.  The
most successful method appears to be using fine-
tipped forceps to grasp the tick near the insertion of
the mouthparts into the skin.  Steady, gentle trac-
tion with the forceps is then applied in an attempt to
dislodge the tick.64  The site should then be disin-
fected with soap and water or alcohol.  Whether
using forceps or fingers, it is important not to crush
the tick since this could contaminate the skin with
rickettsiae.  A more-recent study suggests that a
twisting motion with forceps held as close to the
skin as possible is a more-effective and safer method
for removing the tick.65  If the fingers are used for
deticking, the skin should be protected with gloves,
cloth, or tissue that can be discarded.  The hands
should always be washed immediately after detick-
ing.
Dogs should be deticked and wear tick-repellent
collars.  Treating the baseboards and cracks in hu-
man and dog quarters with a residual insecticide
will help.
Prophylaxis is not a routine practice even after a
recognized tick bite.  Only 2% to 5% of ticks carry
rickettsiae,21 and only 1%12 of these rickettsiae are R

Rickettsial Diseases
225
Fig. 11-2. Rocky Mountain spotted fever treatment algorithm. RMSF: Rocky Mountain spotted fever; CSF: cerebrospinal fluid.
rickettsii.  Therefore, most patients with tick bites
would be treated unnecessarily.29  Experimental
work with guinea pigs also does not support pro-
phylaxis.66
Boutonneuse Fever
The boutonneuse group of spotted fevers (which
have various names wherever they occur) are caused
by R conorii.  The rash becomes maculopapular and
sometimes even nodular, resulting in the name
boutonneuse (ie, buttonlike).
Microbiology
R conorii, the most ubiquitous of the spotted fever
serogroup rickettsiae, is easily identified in ticks by
means of (a) the light microscope and Giemsa and
Stamp stains or (b) immunofluorescence.  R conorii
is antigenically distinct and is less virulent for ani-
Suspect RMSF
Draw acute serum specimen and freeze (assuming 
that a rapid diagnostic test is not available)
Memingococcemia possible?
Evaluate CSF; culture blood, 
CSF, skin lesions, etc.
Yes
Patient > 9 years of age?
Treat with either doxycycline or 
chloramphenicol after counselling 
parent/guardian about dental 
complications of tetracyclines and 
hematological complications of 
chloramphenicol
No
Yes
Treat for RMSF mild disease: 
by mouth, tetracycline  or doxy-
cycline
Severe disease: intravenous 
administration of tetracycline or 
chloramphenicol
Draw additional serum at 10–14 d and 4–6 wk after onset.  Elevated 
titers at 10–14 d may be diagnostic. Submit acute and “convalescent” 
sera together to minimize laboratory variations.
Increasing titer confirms diagnosis and implies 
immunity from further infection for the patient.
No
Meningococcemia possible?

Military Dermatology
226
TABLE 11-2
RICKETTSIAE OF SPOTTED FEVER GROUP DISEASES (EXCLUDING RMSF)
Organism
Disease
Tick
R australis
Queensland tick typhus
Ixodid ticks
R conorii
Boutonneuse fever
Ixodid: Rhipicephalus sanguineus
(Marseilles fever,
Mediterranean fever)
R conorii
East African tick typhus
Rhipicephalus simus or Hemaphysalis leachi
R conorii
Indian tick typhus
Ixodid ticks, especially Hemaphysalis
R conorii var pyperi
South African tick-bite fever
Ixodid: Rhipicephalus and Amblyomma  spp, and H leachi
R sibirica
North Asian tick typhus
Various Ixodid ticks of Hemaphysalis and Dermacentor spp
RMSF: Rocky Mountain spotted fever. Data source: Gear JHS. Other spotted fever group rickettsial diseases: Clinical signs,
symptoms, and pathophysiology. In: Walker DH, ed. Biology of Rickettsial Diseases. Vol 1. Boca Raton, Fla: CRC Press; 1988: 101–114.
mals and humans than R rickettsii.  Growth in cell
cultures is similar to other rickettsiae of the spotted
fever group, and it is cultivated in the same ways as
R rickettsii.  The various strains of R conorii isolated
throughout the world appear to be antigenically
identical.
Epidemiology, Vectors, and Hosts
Varieties of boutonneuse fever are found in al-
most every country.  The reservoirs are field ro-
dents or dogs.  The vector is the brown dog tick,
Rhipicephalus sanguineus.  African tick-bite fever is
seen in every region of southern Africa except semi-
desert environments.  The common veld ticks trans-
mit the disease in rural areas, whereas the dog tick
(Hemaphysalis leachi) transmits the disease in the
suburbs.  Other species may be more important in
certain geographical areas (Table 11-2).  The reser-
voirs are Rhabdomys pumilio (striped mouse), Otomys
irroratis (vlei rat), and Rattus rattus.67  Dogs and
humans acquire the infection incidentally.  Adult
ticks rarely transmit the infection because they are
(a) more host specific and (b) large enough to be felt
crawling on the skin, making it likely that they will
be removed before they have a chance to attach.
Larval ticks are almost invisible and are the primary
vectors of this disease, as they are not very host
specific and are too small to be felt crawling on the
skin.  Transovarian transmission occurs in these
ticks.68
Transmission to humans occurs either via a tick
bite or contamination of the conjunctiva with tick
juice or excretions.  The tache noire is the character-
istic lesion; it manifests as a raised red lesion with a
black central crust, but is not seen when the mode of
transmission is conjunctival contamination.  Typi-
cally, the tache noire causes regional lymph-
adenopathy, systemic manifestations, and rash.  The
illness lasts approximately 1 to 2 weeks in untreated
patients.
Patients can be from urban or rural areas and
often have had contact with dogs.69  In endemic
areas such as Sicily, as many as 20% of the populace
are serologically positive.  However, many of these
people do not have any history of boutonneuse
fever, making it possible that asymptomatic illness
is fairly common or that nonpathogenic strains of R
conorii exist.70  The peak period in which boutonneuse
fever occurs is June through October.
Clinical Findings
Most patients report that they have been in tick-
infested areas or that a tick may have been found
in their clothing or bed linen within the last few
weeks.  After an incubation period of approximately
7 days, the tick bite becomes a red papule progress-
ing to black and necrotic.  This lesion is completely
painless and only rarely pruritic; it may be seen
in 30% to 90% of patients and is usually pathogno-
monic when found with a compatible rash and
symptoms.  Multiple taches noires have also been
reported.69,71  Some patients with the disease will
have only a febrile illness lacking both the eschar
and the rash, while others have the tache noire
without other signs or symptoms.70  In adults, the
tache noire is usually found on the lower limbs,

Rickettsial Diseases
227
groin, or lower abdomen.  In infants, the scalp is a
common site.69  In patients who do not have a
clinically obvious tache noire, close examination of
the skin drained by enlarged nodes may reveal the
lesion.  Conjunctival transmission should be sus-
pected in patients with severe unilateral conjunct-
ivitis.  Edema of the eyelid may be severe enough to
cause chemosis.  Shallow ulcers may be apparent on
the conjunctiva, and the preauricular nodes on the
affected side may be enlarged.  One day after the
bite, some patients will experience malaise; chills,
anorexia, muscle and joint pain, headache, and fe-
ver follow.  The fever peaks on day 2 or 3 and
continues for approximately 10 days.  In mild cases,
fever may last only 1 to 7 days.  The rash appears on
days 3 through 5; it is first noted on the extremities,
then spreads to the trunk.  The rash appears in crops,
with new macules and papules noted approximately
every 1 to 3 days.  The papules tend to be rather
coarse and may feel like shotty nodules in the skin.
The lesions are pink at first, and later become darker.
Characteristically, the patient’s palms, soles, and
even face are involved.68  The profuseness of the
rash correlates to the severity of the illness.  In more-
severe cases, the rash may be petechial and dusky.
Usually, boutonneuse fever is a benign, uncom-
plicated disease with recovery the norm.  On occa-
sion it is severe—more often in elderly patients in
whom complications are common—and may be
fatal if untreated.  Adverse prognostic indicators in
addition to old age include chronic alcoholism,
underlying disease, generalized purpuric exan-
thema, abnormalities of serum electrolytes, renal
failure, and prolonged prothrombin time.71,72  The
most frequent complication is deep venous
thrombosis that may or may not be accompanied by
pulmonary embolus.  Thrombosis may occur in
other areas; vision changes may be due to involve-
ment of the retinal veins.  Myocarditis can occur, as
can electrocardiographic abnormalities, pericarditis,
and heart failure.69  Gangrene of the fingers and toes
may also be seen.  Severely ill patients may have
hypotension; a cyanotic, dusky appearance; and,
rarely, may develop a hemorrhagic state.  Epistaxis,
hemoptysis, hematemesis, melena, and petechial
hemorrhages in the skin may be manifestations of
this coagulopathy.  Jaundice can be seen in more-
severe cases.  Renal failure is more likely to occur in
patients with preexisting renal disease.  Death may
be due to a combination of severely increased vas-
cular permeability, shock, pulmonary embolism,
uremia, and hemorrhage.68
As occurs in patients with RMSF (and also in
murine typhus and scrub typhus, which are dis-
cussed later), G6PD deficiency may be associated
with increased severity of disease.73  The malignant
form of boutonneuse fever bears a clinical resem-
blance to RMSF with a petechial rash and neuro-
logic, renal, and cardiac involvement.74
In Israel, an endemic disease similar to bouton-
neuse fever is caused by R sharonii, which is anti-
genically distinct from R conorii.  The Israeli variant
is also characterized by fever and rash, but lacks a
tache noire.75
North Asian tick typhus (also called tick-borne
rickettsiosis) is caused by R sibirica.  This disease is
characterized by fever, eschar, regional adenitis,
and a macular and papular rash.  Some patients may
have petechial lesions.  Severe forms are uncommon.
Queensland tick typhus is caused by R australis
and is found only in Australia.  It is similar to
boutonneuse fever with an eschar seen in most
cases.  This illness is usually benign, although fa-
talities have been reported.76
Laboratory Findings
In mild cases of boutonneuse fever and similar
diseases, the hemoglobin and hematocrit are unaf-
fected.  Anemia can be seen in one third of patients
and severe anemia may be seen in patients with
underlying diseases or the malignant form of the
disease.  Leukocyte counts are usually near normal,
but neutrophilia may be noticed more often in the
elderly, and leukopenia with a relative lymphocy-
tosis is common in adolescents and children.  Plate-
lets may be slightly to severely decreased with a
decreased prothrombin time in some cases.  More
severely ill patients can have abnormal liver func-
tion tests, especially aspartate transferase and ala-
nine transferase or increased bilirubin.  Urinalysis
may reveal proteinuria and hematuria.  If renal
failure ensues, increased creatinine and blood urea
nitrogen, oliguria, and anuria may be found.
Hyponatremia is seen in roughly one fourth of
patients.77
Differential Diagnosis
Secondarily infected insect bites with local
adenopathy can cause confusion in making the dif-
ferential diagnosis.  Diseases to be considered, de-
pending on the geographical location, are anthrax,
bubonic plague, sporotrichosis, trypanosomiasis,
venereal disease (herpes simplex, lymphogran-
uloma venereum, chancroid, syphilis), coxsackie A
or echovirus infections in children, and arborvirus
infections.

Military Dermatology
228
Diagnostic Tests
The diagnosis of boutonneuse fever is usually
made clinically.  When available, direct immuno-
fluorescence of skin biopsy specimens can be used.
Rickettsiae can be demonstrated in the skin, us-
ing tissue obtained from the periphery of the tache
noire70 or macular elements of the rash.78  This
provides the earliest diagnosis but is usually only
available from reference labs.  Isolation of the or-
ganism may be attempted in guinea pigs.  Such
testing is useful before antibiotics are administered,
in more-severe cases, and in questionable cases that
lack the tache noire.79
Serologic diagnosis is accomplished using spe-
cific tests such as complement fixation, latex agglu-
tination,80 indirect fluorescent antibody,50 or
microimmunofluorescence.  Microimmunofluor-
escence is not readily available and is difficult and
time consuming to perform.  Antibody titers be-
come positive after 10 days and may persist for
years after the initial attack.68,81,82
Weil-Felix testing should be used for screening
purposes only.68  Equal titers of OX-19 and OX-2 are
usually found.  If OX-19 is found singly, or if the
titer of OX-2 is much greater than that of OX-19,
then the diagnosis of tick typhus is probable.  If OX-
19 titer is much higher than OX-2, then both epi-
demic and murine typhuses would be more likely
considerations (epidemic and endemic typhuses
are discussed later in this chapter).  The Weil-Felix
test is not specific and should not be relied on for
diagnosis.  Low titers are often seen in healthy
people in areas where this infection is common.
Therapy
Quarantine of patients is unnecessary.  Ironing all
clothing and bed linens will kill any remaining larvae.
Most patients will respond promptly to antibiotic
therapy and show improvement within 48 hours.
Tetracycline is the antibiotic of choice and chloram-
phenicol is a useful alternative.  Treatment with two
200-mg doses of doxycycline may be as effective as the
usual 10-day treatment with tetracycline.72
Prevention
Control measures for these tick-borne diseases
are the same as those for RMSF.  Infested dogs, cats,
and rats should not be allowed inside dwellings.
Tick repellents and proper clothing are also helpful.
Vaccines have been developed and may be consid-
ered for military operations.
Rickettsialpox
Rickettsialpox is a febrile illness that is character-
ized by cutaneous eschar followed by a papulo-
vesicular exanthem.  This disease was not discov-
ered until after World War II, so there are no figures
regarding its occurrence among troops.83
Microbiology
R akari, which causes rickettsialpox, is a
coccobacillary organism that is morphologically
similar to R rickettsii.  It is serologically cross-reac-
tive with other spotted fever organisms due to the
presence of a group-specific antigen.  The R akari
organism is a small, coccobacillary, obligate intrac-
ellular parasite that stains with Giemsa and
Machiavello’s stains.  It is infective for mice and
guinea pigs and grows in the developing chick
embryo.  The mouse is highly susceptible to infec-
tion and is considered to be the animal of choice for
isolation.
Epidemiology, Vectors, and Hosts
The vector for rickettsialpox is the mouse mite,
Allodermanyssus sanguineus.  The host is the house
mouse, Mus musculus.  The disease is transmitted to
humans by the bite of the mite.  This illness is rarely
seen outside cities in the United States, where im-
provements in housing have limited the scope of
the house mouse and its mites.  Rickettsialpox has
become a disease of the inner city, with most cases
now seen in New York City.59  All ages and both
sexes are equally susceptible to infection.
Clinical Findings
Estimates on the incubation period are difficult
because the bite of the vector, Allodermanyssus
sanguineus, is painless and the mite is microscopic,
so it cannot be felt on the skin.  Laboratory accidents
and cases that have been well documented after
exposure suggest that the incubation period is 7 to
14 days.84
A papule at the bite site may appear within 1 to
2 days. This lesion is usually asymptomatic al-
though some patients will complain of pruritus.  A
vesicle develops over the papule, which subse-
quently dries and forms a crust or eschar.  Indura-
tion surrounds the lesion and there is regional
lymphadenopathy.  The eschar can appear any-
where, but areas covered with clothing seem to be
preferred by the mite.84

Rickettsial Diseases
229
Fever and malaise are common, with tempera-
ture elevation as high as 106°F reported.  Morning
remissions are common.  Headache, stiff neck, back-
ache, myalgias, and photophobia may also be seen.
Occasionally, cough, nausea, vomiting, and abdomi-
nal pain are reported.84
The rash usually appears 2 to 3 days after sys-
temic symptoms are seen.  The typical morphology
of the early lesions is a firm, erythematous,
nonpruritic papule.  A small vesicle or pustule will
be present in some of the lesions, although not all
will vesiculate.  Rarely, the lesions may resemble
“rose spots” of typhoid, presenting as faint macules.
The vesicular lesions resolve without scarring.  The
lesions are seen on the face, trunk, and extremities
most commonly, but palms, soles, and mucous
membranes may also be involved.84
Laboratory Findings
Routine laboratory findings are nonspecific in this
disease.  Leukopenia is common in the early stages.
Histological examination of the eschar will show
swollen endothelial cells, capillary fibrin thrombi,
and a dense perivascular infiltrate of lymphocytes,
mononuclear cells, and a few polymorphonuclear
cells.  Rickettsial organisms have not been identi-
fied in cutaneous lesions.  Histologically, the vesicles
show a mononuclear infiltrate along the subepider-
mal region, with vacuolar changes in the basal cells.
The vesicle seems to form subepidermally,9 but
intraepidermal locations have been described.84
Differential Diagnosis and Treatment
Other rickettsial diseases with eschars (taches
noires) should be considered; scrub typhus, tick
typhus (Siberian or Queensland), and boutonneuse
fever may have eschars that cannot be distinguished
from that of rickettsialpox.  Chickenpox is com-
monly confused, but the lack of an eschar and the
finding of multinucleated giant cells on the Tzanck
preparation should make this diagnosis.  Direct
fluorescent antibody staining for varicella-zoster
virus could also be used to confirm varicella.
Complement fixation or indirect fluorescent an-
tibody testing can be used to identify this infection.
Cross-reactions with other spotted fever group rick-
ettsiae occur.  A cross-absorption technique using R
rickettsii and R akari antigens can be performed to
allow more-accurate diagnosis.85  In most cases, the
clinical syndrome and a rise in group-specific indi-
rect fluorescent antibody titers will make the diag-
nosis.  Weil-Felix antibodies do not develop in this
disease.
This is a mild illness from which even untreated
patients recover without difficulty.  Treatment with
tetracycline will speed defervescence and recovery.
TYPHUS SEROGROUP
Typhus serogroup organisms are responsible for
epidemic typhus, the recrudescent form of epidemic
typhus called Brill-Zinsser disease, and endemic
(murine) typhus.  The organisms are characterized
by a common, group-specific antigen and intracyto-
plasmic growth.  The pathology of these diseases is
also that of a vasculitis, as in spotted fever group
infections.  Both epidemic and endemic typhuses
have a rash that begins on the trunk and spreads to
the extremities, in contrast to the rash of RMSF,
which is found first on the extremities.
Epidemic Typhus
Epidemic typhus has many common names:
louse-borne typhus, classic typhus, typhus
exanthematicus, tarbardillo, fleckfieber, and jail fe-
ver.  Both the primary disease and its recrudescent
form (Brill-Zinsser disease) are caused by R
prowazekii.  Clinically, epidemic typhus is quite
similar to murine typhus except that it tends to be
more severe.  Epidemic typhus can also be similar to
RMSF, except that the truncal distribution of the
rash characterizes epidemic typhus.  Mortality rates
for this disease vary from 10% to 40% in untreated
patients.86  Epidemic typhus associated with flying
squirrels (ie, sylvatic typhus) generally tends to be
a milder disease.
Several important investigators perished while
studying this disease, the most notable being
Howard T. Ricketts, who died in 1910 while study-
ing typhus in Mexico,87,88 and Stanislaus von
Prowazek, who died in 1915 while studying typhus
in Siberia and Turkey.86,89
Military Significance
Although typhus infections have played an im-
portant role in every major European military cam-
paign since the 16th century, epidemic typhus has
never been a serious problem for the U.S. military.90
Early accounts of the disease are difficult to classify

Military Dermatology
230
definitively as typhus.  In 1492, a malignant spotted
fever in Spain killed 17,000 troops during the con-
quest of Granada.  This number is roughly 5-fold
greater than the number of battlefield casualties.
Typhus was also a major factor in Napoleon I’s
invasion of Russia in 1812.  In a period of approxi-
mately 7 weeks, more than 60,000 Russian troops
died, mostly from typhus.  The disease was then
spread throughout Europe by French and Russian
prisoners of war.  In Germany during 1813 and
1814, 2 million people are estimated to have con-
tracted the disease and 250,000 died.88
During the American revolution, a typhuslike
illness forced continental forces in New York to
retreat from the British, prolonging the war by an
estimated 2 years.91  There was little typhus noted
among the soldiers in the Civil War; however, well-
described cases underscore the difficulties of medi-
cal practice in the preantibiotic era.  The commonly
used medications included quinine, turpentine
emulsion, brandy, whiskey, tannin, and beef soup.92
The toll extracted by typhus during World War I
was great.  An epidemic of typhus in Serbia claimed
an estimated 180,000 to 210,000 lives in 1915, in-
cluding one third of the Serbian physicians.93  In
1909, the body louse was discovered to be the vector
of the disease.88  This discovery led to the quaran-
tine of louse-infested patients and the burning of
infested clothing.  However, 3 million deaths and 25
million cases of typhus were reported in Russia
from 1917 through 1925.88  Surprisingly, little or no
typhus was reported among U.S. military person-
nel despite widespread lousiness (pediculosis)
among the troops.83
Significant advances were made in the control of
rickettsial diseases, especially epidemic typhus,
during World War II.  (The mild, recrudescent form
of typhus, Brill-Zinsser disease, had no effect on
military operations.83)  DDT was first used as a
dusting agent on the clothes of infested persons
during the winter of 1943 and 1944, when an epi-
demic in Naples, Italy, was suppressed with its
use.83  Scrub typhus was similarly controlled in the
Pacific using miticidal dusting agents.18  Much of
this progress resulted from investigations done
under the auspices of the U.S. Typhus Commission,
which was established in 1942.  Contributions made
by this commission led to a better understanding of
the disease and resulted in improved louse control,
personal hygiene, treatment, and vaccines.  U.S.
Army research played a key role in these accom-
plishments, especially in the development of the
vaccine and purifying the antigen, which allowed
the diagnostic serologic test to be developed.94  Vac-
cinations started in January of 1942.83 During 1942
alone, there were 23,000 civilian cases of typhus in
Egypt and 77,000 cases in French North Africa.
From 1942 through 1945, U.S. troops had only 30
cases, none of which was fatal.88,93,95  These numbers
are truly amazing, considering that when the Allied
forces undertook the North African invasion, there
were estimates that the unreported cases of typhus
may have totalled over 500,000.83
During World War II, Polish physicians used
their knowledge of immunology to keep German
authorities away from several villages.  Knowing
that the Germans did not wish to have their person-
nel in an epidemic area, the Polish physicians ad-
ministered Proteus OX-19 antigen to persons in
these villages who showed symptoms that might be
compatible with typhus.  German health authorities
were then given sera from these patients to test, and
they found high titers against OX-19, suggesting
louse-borne typhus.  Due to the number of positive
sera the Germans tested, they considered the vil-
lages to be epidemic areas.  Fortunately for the
Poles, the Germans never examined any of the pa-
tients, nor were they suspicious of the uniformly
high initial titers in all the patients.96,97
German concentration camps reportedly had
thousands of cases of typhus.  When camps were
liberated, extensive delousing efforts were neces-
sary to prevent spread of the infection throughout
Europe.  These efforts were complicated by the fact
that many of the prisoners fled the camps and
scattered throughout the countryside.83
The U.S. Army was not affected by typhus during
the Korean and Vietnam conflicts.93
Microbiology
R prowazekii is an obligate intracellular bacterium
that appears antigenically to be closely related to R
typhi.  It is classically described as a coccobacillary
form measuring approximately 0.25 x 0.35 µm, al-
though it is the most pleomorphic of the rickettsiae.
It also stains with Geimsa and Machiavello’s stains.
The organism is infective for mice, guinea pigs, and
embryonated eggs.  Stored at –70°C, R prowazekii
may remain viable for years, but it is destroyed by
phenol, formalin, merthiolate, and other antisep-
tics.98
Epidemiology, Hosts, and Vectors
Epidemic typhus is a disease of the colder months,
poor sanitation, wars, and times of social upheaval.
These conditions favor poor hygiene and crowding,

Rickettsial Diseases
231
factors conducive to the spread of louse infestation.
The last reported epidemic of louse-borne typhus
occurred in the United States in 1922.  Sporadic cases
of the disease have occurred since then, as have cases
of the recrudescent type (Brill-Zinsser disease) or
typhus associated with flying squirrels.99
Hosts for R prowazekii include humans, the flying
squirrel (Glaucomys volans),3 and the body louse
(Pediculus humanus corporis).
Lice are very host specific; usually they remain
on the same host and do not leave voluntarily un-
less the host’s temperature changes significantly.
Thus, lice tend to leave hosts who are febrile and
those who have died.  Transfer between humans
occurs during conditions of close contact, poor sani-
tation, and overcrowding.  Both the human body
louse (Pediculus humanus humanus) and the head
louse (P humanus capitis) can be infected with R
prowazekii.  The head louse has not been implicated
in the transmission of typhus, leaving the body
louse as the main vector for humans.  The louse
acquires the infection from feeding on an infected
human and becomes infective itself in 5 to 7 days.
The infected louse then feeds on an uninfected
human, defecating while feeding.  Transmission to
humans occurs by contamination of the bite site
with the infected feces, not from the bite itself.
Transmission may also occur when infective louse
feces contaminate the conjunctiva or mucous mem-
branes or when the louse is crushed.  Aerosolized
spread is possible if infected louse feces become
airborne when clothing is shaken.100
Lice feed approximately every 5 hours.  They will
acquire R prowazekii 60% to 80% of the time after a
single feeding, so the ultimate rate of acquisition of
infection is near 100%.  However, patients with
Brill-Zinsser disease will infect lice with R prowazekii
only 1% to 5% of the time.101
Once R prowazekii enters the louse, infection is
limited to the gut epithelial cells, which eventually
become full of rickettsiae and rupture, discharging
the organisms into the feces.  The feces remain
infective for up to 100 days.  Infected lice die within
14 days.101
In the flying squirrel, the infection is transmitted
by the squirrel louse, Neohaematopinus sciuropteri
and, to a lesser degree, by the squirrel flea, Orchopeas
howardii.  Most cases of human infection occur in the
eastern United States when flying squirrels enter
attics in the winter months.  The exact mechanism of
transmission of the disease is unknown but could
involve the squirrel flea, which has been reported to
parasitize humans.99  The squirrel louse does not
feed on humans and is unlikely to be involved.
Ground squirrels (eg, chipmunks, prairie dogs) or
tree squirrels (ie, gray squirrels) are not hosts for R
prowazekii.  When infections due to flying squirrels
are encountered, they are not associated with hu-
man-to-human spread, because pediculosis is not a
major health problem in the eastern United States.4,99
Several cases of epidemic typhus thought to involve
the flying squirrel have been reported.4,102,103
Clinical Findings
The incubation period is usually approximately
7 days (range 3–11 d).  Compared with murine
typhus (which is discussed later), the onset of epi-
demic typhus is more dramatic; prostration occurs
early with more-severe symptoms noted.  The tem-
perature rises rapidly over the next 1 to 2 days, and
the rash may appear on approximately day 5 of the
illness.  The rash is first seen on the trunk and
axillary folds as erythematous macules (Figure 11-
3).  These become petechial in a day or so.  During
the second week of illness, the lesions tend to be-
come confluent, hemorrhagic, and occasionally ne-
crotic.  The lesions spread in a centrifugal pattern
from the trunk to the extremities, but they are only
rarely seen on the palms, soles, or face.  As in RMSF,
the eruption may be absent in 10% of patients.98
Neurological involvement can be significant.
Severe delirium, maniacal episodes, or coma can
occur.  Respiratory involvement is fairly common,
with a hacking, nonproductive cough.  Hemoptysis
may occur secondary to bronchial erosion.  Rales
Fig. 11-3. The petechial lesions seen on the trunk are
characteristic of epidemic typhus, which developed in
this patient during World War II. Photographs: Courtesy
of Walter Reed Army Medical Center Dermatology Ser-
vice, Washington, DC.
OK to put on the Web

Military Dermatology
232
may be appreciated in the lower lung fields, usually
during the second week of illness.  Cardiovascular
involvement characteristically produces hypoten-
sion with a weak, rapid pulse.  Peripheral cyanosis
and cold sweats occur, as they do in murine typhus.
Abnormalities may be found on the electrocardio-
gram.  Photophobia, eye suffusion, conjunctival
injection, and deep eye pain may be present.  Tran-
sient partial deafness is common in patients with
epidemic typhus.  Gastrointestinal findings include
nausea, vomiting, abdominal pain, constipation, and
splenomegaly.  The liver is usually not enlarged.104
Otitis media, parotitis, and pneumonia can occur
due to secondary bacterial infections.  In addition,
bronchiolitis, vascular collapse and shock, gangrene,
and azotemia may be observed in untreated indi-
viduals.  With treatment, mortality from epidemic
typhus is essentially zero.105
Laboratory Findings
Leukopenia can be found early in the illness; the
leukoyte count is normal late in the disease.  Uri-
nalysis findings include albuminuria and, rarely,
hematuria.  Serum chemistry may be remarkable
for hypochloridemia and hypoalbuminemia.
Azotemia may also be noted.
Differential Diagnosis
Typhoid, meningococcemia, boutonneuse fever
(without eschar), malaria, measles, yellow fever,
relapsing fever, and epidemic typhus acquired from
flying squirrels all may need to be considered in the
differential diagnosis.  Suspicion regarding epi-
demic typhus should be raised when medical offic-
ers encounter patients who seem to have atypical
cases of RMSF or murine typhus.  When diseases
resembling RMSF occur during an unusual season
(ie, winter) or in an area with an extremely low
incidence of RMSF, serologic data should be closely
scrutinized.  Additionally, patients (a) with com-
patible symptoms who lack a history of tick bite or
exposure, (b) without a rash, or (c) who have a
centrifugally spreading rash should also be sus-
pected of having epidemic typhus.4
Laboratory Diagnosis
Immunofluorescent staining can detect R
prowazekii in the gut of lice that have been collected
from patients suspected of having classic epidemic
typhus.  This could allow the diagnosis to be made
within a matter of hours.106
Serologic testing using either complement fixa-
tion or the indirect immunofluorescent test will also
confirm this diagnosis.  Note that cross-reactions
with murine typhus and spotted fever serogroup
organisms are possible; the toxin neutralization test
can help distinguish cross-reactions to murine ty-
phus.4  Titers for R rickettsii are usually much lower
than those to R prowazekii.  The same tests are also
used for diagnosing epidemic typhus associated
with flying squirrels.
Weil-Felix testing shows positive titers for only
OX-19, usually after 10 to 14 days.  False-positive
reactions may make interpretation difficult in cer-
tain areas (see the previous discussion of the sero-
logic diagnosis of RMSF).
Isolation of the organism should be attempted
only by experienced personnel with the proper fa-
cilities.  Storing clotted blood from an infected pa-
tient at –70°C will maintain the viability of the
organisms for years.  Refrigerated clots must be
used for isolation attempts within a few days.
Treatment
Tetracycline or chloramphenicol in appropriate
doses should be continued until the patient is afe-
brile for more than 24 to 48 hours.  Relapses may
occur, especially when treatment is started early in
the course.  Because antibiotic resistance does not
develop, relapses usually respond to continuation
of the antibiotic.  In some situations (eg, natural
disasters, refugee populations), single-dose therapy
with doxycycline (100–200 mg) is an effective
therapy that may be preferable if medical supplies
are limited.  The severe headache does not respond
to the usual drugs.  Severely toxic patients may
require treatment with systemic steroids.107
Control Measures
Where conditions favor lousiness, an effective
residual insecticide should be applied to the body
and clothing.  Personal hygiene should be main-
tained at adequate levels.  Typhus vaccine that
prevents or attenuates the disease is available but is
not routinely administered to military person-
nel.105,107
Epidemic typhus is a reportable illness and local
health authorities must be notified.  Isolation of
patients is not necessary; however, the patient
should be deloused as should the patient’s clothing,
quarters, and close contacts.  Disinfection should
include insecticide powder and treatment of nits
using pyrethrin shampoo or lindane.  Even the

Rickettsial Diseases
233
corpses of patients who die before delousing should
be deloused appropriately.
Louse-infested persons who are both susceptible
and exposed to typhus fever should be deloused
with residual insecticides and observed for 15 days.
All immediate contacts should be deloused, if nec-
essary, and observed for 2 weeks.63,98
Recrudescent Typhus (Brill-Zinsser Disease)
Brill-Zinsser disease, the recurrent form of epi-
demic typhus, appears years after the original in-
fection.  Brill-Zinsser disease is not related to louse
infestation and has been reported only sporadically
in the United States.  It should be suspected in
patients with a previous history of epidemic ty-
phus, especially among survivors of concentration
camps or immigrants from eastern Europe.108  The
disease is caused by the reactivation of R prowazekii
that remains in the lymphoid tissue of previously
infected persons.  Thus, humans act as a reservoir
for epidemic typhus, since infected patients may be
responsible for transmitting the infection to
uninfected body lice.  Clinically, Brill-Zinsser dis-
ease is much milder than the original illness and the
rash is usually absent.  Serologic testing will reveal
extremely high immunoglobulin G titers for R
prowazekii because the recrudescence is an amnestic
antibody response.  Titers of immunoglobulin M
antibody will be low or absent.  Weil-Felix testing is
negative in patients who have Brill-Zinsser disease.
Endemic (Murine) Typhus
Murine typhus is a phylogenetically older and
milder disease than epidemic typhus.  Both the
vector (the rat flea) and the reservoir (the rat) sur-
vive the infection by R typhi without ill effects,
whereas infection with R prowazekii causes the death
of the louse and more severe illness in humans.
Murine typhus usually occurs sporadically rather
than in epidemics.  Prior to 1940, all forms of typhus
were considered together in U.S. Army medical
statistics.  During World War II, 787 cases of typhus
were reported, with 15 deaths.93,109  Troops on ma-
neuvers in the southern United States at this time
accounted for 497 of these patients.  Troops sta-
tioned in the Hawaiian Islands accounted for 123
cases during 1942 through 1945.83
Data on the incidence of murine typhus during
the Korean conflict are not available, but murine
typhus was the second-most-common cause of fe-
brile illness in U.S. Army personnel in Vietnam.110
Murine typhus can also be a major cause of fe-
brile illnesses in refugee camps.  One study of adults
in a camp in Thailand for displaced Khmers (Cam-
bodians) found the 1-month attack rate for adults to
be 185 per 100,000.111
Microbiology
R typhi (R mooseri) measures 0.4  by 1.3 µm, and is
a Gram-negative, obligate intracellular parasite.  It
is less pleomorphic than R prowazekii and shares
common soluble antigens with that organism.  R
typhi is destroyed by formalin, phenol, and tem-
peratures greater than 56°C for 30 minutes.  R typhi
is infective for rats, mice, guinea pigs, and yolk sacs
of embryonated eggs98 and is more virulent than R
prowazekii for guinea pigs and mice.
Epidemiology, Vectors, and Hosts
Murine typhus is common in the United States,
and this disease has the highest worldwide preva-
lence of all the rickettsial diseases.  It is seen on
every continent except Antarctica.110
The hosts in this disease include a large spectrum
of animals.  Rats (Rattus norvegicus and Rattus rattus)
are the animal reservoir.  Shrews, skunks, opos-
sums, mice, and cats are fed on by various arthro-
pod vectors and can serve as hosts.110,112  In rats,
infection is nonfatal and rickettsemia lasts only 1 to
2 weeks.101  The infection is spread when fleas feed
on infected rats.  R typhi infects the gut epithelial
cells and is excreted in the feces.  Infection is not
fatal for the flea and persists for life without affect-
ing life span.  Transmission to humans occurs when
the skin, respiratory tract, or conjunctiva are con-
taminated with infected flea feces.  Xenopsylla cheopis
(the oriental rat flea) is the major vector.  Leptopsylla
segnis (the mouse flea), Ctenocephalide felis (the cat
flea), and Pulex irritans  ( the human flea) are also
implicated as potential vectors based on laboratory
data.  L segnis fleas are not thought to be an impor-
tant vector in the United States, owing to their
semisessile nature, but they may be more important
in locations where X cheopis  fleas are absent.101
Transmission is thought to occur when infected
feces are rubbed into the bite, but recent investiga-
tors have shown that the organism can be transmit-
ted by flea bites alone.110  Infection via inhalation of
dust from rat-infested buildings may occur.110  In
the wild, however, fecal contamination remains the
most important means of transmission.  The infec-
tion may be transmitted transovarially in fleas, sug-
gesting that fleas may also serve as reservoirs for
the disease.113

Military Dermatology
234
Most cases are reported between late spring and
early autumn when X cheopis is abundant.  Endemic
areas are primarily urban settings associated with
commensal rats and their fleas.  Rural areas may
also be affected, however.  Sea ports and coastal areas
are favored.  People whose occupation or living condi-
tions bring them into close contact with rats or rat runs
are primarily affected, especially in food-storage ar-
eas or granaries.  Most human cases are acquired
indoors where rats are present.  Areas with higher
incidences of this disease include South America,
Mexico, Ethiopia, Malaya, Australia,98 Thailand,
India, Pakistan, and the southern United States.112
Clinical Manifestations
The typical incubation period is approximately
11 days (range 8–16 d).  Prodromal symptoms begin
with frontal headache, severe backache, and
arthralgias approximately 4 to 6 days after expo-
sure.104  Usually, the patient notes a sudden, shak-
ing chill but may have only a chilly sensation.  Head-
ache, fever, nausea, and vomiting are seen in nearly
all patients.  The patient’s temperature increases
steadily over the first few days and may become
intermittent when the rash appears, with the morn-
ing temperature tending to be normal.  Children
may have fevers as high as 106°F, while that of
adults peaks at 103°F to 104°F.  Fever usually lasts
approximately 12 days.
The rash makes its appearance after approxi-
mately 5 days of illness.  It is seen first in the axillae
and inner arms.  Dull, red macules develop rapidly
on the abdomen, shoulders, chest, arms, and thighs.
The earlier lesions tend to be macular while older
lesions are slightly raised.  Approximately 20% of
patients will lack the rash.104  The spread of this rash
is from trunk to extremities, the opposite of that
seen in patients with RMSF.  Only rarely will the
rash involve the palms, soles, or face.  Petechiae
may develop in some cases, and the lesions may
become hemorrhagic.114
Of the neurological findings, headache usually
predominates.  Patients with more severe illness
may progress to stupor, prostration, and lethargy.
Some may have neck stiffness, but Kernig’s sign is
usually not present.  Transient, partial deafness and
weakness have been reported.104
A hacking, nonproductive cough is not uncom-
mon.  Rales may be appreciated in the lower lung
fields.  Hypotension occurs, especially in the early
stages.  Clinical evidence of cardiac failure is un-
usual, however.  Minimal electrocardiographic ab-
normalities, peripheral cyanosis, and cold sweating
can be seen.  Nausea, vomiting, abdominal pain,
constipation, and splenomegaly are fairly common
findings.
Although secondary bacterial infections leading
to otitis media, parotitis, and pneumonia can com-
plicate the illness, murine typhus is a benign dis-
ease for most, with complete recovery the norm.
Laboratory Findings
Laboratory findings are nonspecific for murine
typhus.  Moderate leukopenia may be noted ini-
tially, with a normal leukocyte count later in the
illness (except when secondary bacterial infection
occurs).  Urinalysis may show albuminuria and,
rarely, hematuria.  Hypochloridemia and azotemia
can occur.
Differential Diagnosis
Other diseases to be considered are typhoid,
meningococcemia, boutonneuse fever (when lack-
ing an eschar), mild epidemic typhus, flying squir-
rel–associated epidemic typhus, RMSF, and scrub
typhus.
Diagnosis
Indirect fluorescent antibody can be used to di-
agnose murine typhus, but it requires cross-absorp-
tion with homologous and heterologous antigens to
distinguish murine from epidemic typhus.  Patients
who have been previously vaccinated against epi-
demic typhus respond to murine typhus with anti-
bodies that react in higher titers with R prowazekii.50
Clotted blood obtained prior to antibiotic therapy
can be used for attempted isolation of the organism.
After the blood has clotted and the serum has been
removed, the clot may be stored at –70°C.115
Treatment
Tetracycline or chloramphenicol are administered
in appropriate doses until the patient is afebrile for
longer than 24 hours.  For critically ill patients who
do not present until late in the illness, systemic
steroids administered for 2 or 3 days may be a
useful additional therapy; however, this regimen is
not recommended for mild or moderately ill pa-
tients.104  After recovery, permanent immunity to
murine typhus exists, with cross-immunity to epi-
demic typhus.

Rickettsial Diseases
235
Control Measures
Flea populations should be reduced, using insec-
ticides to prevent additional exposure to fleas.  Af-
ter this is accomplished, insecticide powders with
residual action should be used on rat runs and
burrows.  Attempts to treat rat-infested areas before
the flea population is controlled will result in addi-
tional cases of disease when hungry fleas turn to
humans in the absence of their usual host.112  Isola-
tion or quarantine are not necessary for the patient
or his or her contacts.63
SCRUB TYPHUS, TRENCH FEVER, AND Q FEVER SEROGROUPS
Scrub typhus, trench fever, and Q fever each
comprise a separate serogroup.  These diseases are
distinct from each other and from other rickettsial
diseases; they are grouped together in this chapter
for convenience only.
Scrub Typhus
Scrub typhus, caused by R tsutsugamushi, is in a
distinct serogroup separate from the typhus and
spotted fever serogroups.  The disease is also known
as tsutsugamushi disease, tropical typhus, rural
typhus, Japanese river fever, and Kendani fever.95
The mortality rate varies in untreated patients, rang-
ing from 1% to 60%; with treatment, however, the
mortality is less than 5%.98  Aside from the antigenic
differences that were discussed earlier in this chap-
ter, this organism possesses a distinctive cell wall
structure when compared to other rickettsiae.  In
addition, scrub typhus is transmitted by the larval
form of trombiculid mites, which are commonly
called chiggers.  Trombiculid mites also serve as a
reservoir for this disease.
Military Significance
Scrub typhus affects not only military personnel
but also indigenous rural populations.  The chigger
that is the vector for this disease is found in south-
east Asia, Japan, Malaysia, China, eastern Russia,
Australia, Sri Lanka, Indonesia, Korea, India, and
the Philippines.  The term “scrub typhus” was used
by Allied troops to describe the vegetation where
the mites are usually found.  Scrub typhus was
feared by military personnel during World War II
because there was no effective therapy and death
was possible.  Full convalescence often took more
than 2 months and had significant impact on af-
fected units.
Among Allied troops in World War II, 18,000
cases of this disease were reported, with a fatality
rate that varied from 1% to 35%.  According to U.S.
Army statistics, 5,718 cases occurred in the south-
west Pacific area.90  In some areas the attack rate was
quite high, with 25% to 33% of two U.S. Army Air
Force squadrons in this region hospitalized in 1944.88
Cases of scrub typhus were also reported from the
Philippines and the India-Burma theater.95  During
this time, scientists from the United States and
Britain investigated this disease and advanced our
knowledge of the epidemiology and treatment of
scrub typhus.  In 1948, a U.S. Army–sponsored
investigative team working at Walter Reed Army
Institute of Research (WRAIR), Washington, D. C.,
and Kuala Lampur, Malaya, discovered that
chloramphenicol was an effective treatment for scrub
typhus.  Joseph E. Smadel and his colleagues at
WRAIR and the University of Maryland showed
that this drug also cured murine typhus and RMSF.94
Scrub typhus had little effect on military opera-
tions in Korea.93  During the Vietnam conflict, the
incidence of scrub typhus was dwarfed by the inci-
dence of malaria and diarrheal illnesses in this
region.116  Still, a 6% incidence of scrub typhus was
found in patients hospitalized for malaria.90  The
actual number of reported cases is probably under-
estimated because the Weil-Felix test was positive
only half the time with scrub typhus, and many
cases were diagnosed and treated without serologic
confirmation or even hospitalization.  No deaths
were reported from this disease.90  The use of a
repellent seems to have helped prevent chigger infes-
tation, but sometimes soldiers did not use repellents
for fear that the enemy would detect the odor.117
Microbiology
Several strains of R tsutsugamushi are antigeni-
cally similar, producing short-lived cross-immu-
nity.  Three major serotypes (ie, Karp, Gilliam, and
Kato) have a sufficient degree of cross-reactivity
with other strains to allow the indirect microim-
munofluorescent test to be used diagnostically.  This
obligate intracellular parasite is distinguished from
other rickettsiae by its growth in the cytoplasm
without a surrounding vacuolar membrane.  In

Military Dermatology
236
addition, the outer layers of R tsutsugamushi are
significantly different from those of other rickett-
siae.  The outer leaflet is very thick with a thin inner
layer, the opposite of other rickettsiae.  R
tsutsugamushi can be stained with Giemsa’s stain or
by using the modified Gimenez procedure that is
used for other rickettsiae.
Epidemiology and Vectors
Several mites of the genus Leptotrombidium are
vectors of scrub typhus: L akamushi, L arenicola, L
deliense, L fletcheri, L pallidum, L pavlovskyi, and L
scutellare.  The mites are parasitic for humans only
as larvae.  They do not exhibit specific host-seeking
behavior.  Instead, they wait patiently on grass
stems or leaves for a host to walk by.  They tend to
congregate in small areas, creating “mite islands.”
Shrubs or transitional vegetation are their preferred
environment.  In particular, overgrown fields, bor-
der areas at the edges of forests, and margins of
streams are areas where the mites may be found in
great numbers.  Two days after hatching, the mites
feed on tissue juices of the host for 2 to 12 days, then
drop off the host and enter a pupalike stage that
lasts for 5 to 7 days.  Then they become nymphs and
enter a second pupalike stage, after which they
emerge as adults.  The nymphs and adults are
scavengers of the forest floor and do not feed on
humans.11
The host for R tsutsugamushi is the genus Rattus,
in which long-lasting infection is produced.  Chig-
gers also feed on pigs, rabbits, shrews, and birds;
these animals can also carry the organism.
Infection in the larva is acquired as an egg in the
infected female; the larval is the only stage capable
of transmission, and the larva feeds on a host only
once.  Transovarial transmission seems to be the
only mechanism for the maintenance of the the
organism in nature.
Scrub typhus is a disease of the Far East that has
not been found in the western hemisphere.  People
whose occupations place them in contact with in-
fected mites remain the most susceptible group for
this infection.
Clinical Findings
An eschar, which is seen in scrub typhus, tick
typhus, and rickettsialpox, begins as a red papule
and becomes a punched-out ulcer that develops a
hard crust (Figure 11-4).  The crust may be lacking
in moist intertriginous areas.116  This lesion is pain-
less and is seen in 95% of patients with rickettsialpox
but only in approximately 50% of patients with
scrub typhus.104
The rash—a maculopapular eruption that is nei-
ther hemorrhagic nor petechial—may be prominent
or completely absent; it was reported in fewer than
40% of Americans in Vietnam.117  However, the rash
is uncommon when the disease occurs in the indig-
enous population.
A prodrome of headache, chills, and anorexia
begins insidiously.  Later, fever, cough, and gener-
alized lymphadenopathy are seen.  Characteristic
clinical findings in patients without eschars are
lacking, making this disease difficult to diagnose in
such cases.118
Laboratory Findings
Routine laboratory findings are not helpful diag-
nostically.  Lymphocytosis is common, with atypi-
cal lymphocytes seen somewhat frequently.  There
may be mild elevations of the liver function tests.
Differential Diagnosis
Other diseases to be considered and ruled out are
murine typhus, leptospirosis, arborviral infection,
typhoid, and malaria.  When the rash is absent,
generalized lymphadenopathy and the presence of
atypical lymphocytes may suggest the diagnosis of
infectious mononucleosis.116
OK to put on the Web
Fig. 11-4. Characteristic eschar (tache noire) of scrub
typhus. Similar lesions are seen in tick typhus,
boutonneuse fever, and rickettsialpox. Photographs:
Courtesy of Walter Reed Army Medical Center Derma-
tology Service, Washington, DC.

Rickettsial Diseases
237
Diagnosis
An indirect fluorescent antibody titer of 1 to 400
or greater is 96% specific and 48% sensitive for the
diagnosis of scrub typhus.50  In poorer regions that
lack funds for fluorescent microscopes, an alterna-
tive test, the indirect immunoperoxidase kit, is avail-
able.  This kit has been in use in the Malaysian
region since 1986 and has been shown to have
acceptable sensitivity and specificity as well as a
long shelf life.119  The indirect immunoperoxidase
kit and the indirect fluorescent antibody test were
the recommended tests endorsed by the World
Health Organization, which specifically advised
against the use of the Weil-Felix reaction when
other, more sensitive tests are available.120
Weil-Felix tests in patients with scrub typhus
will reveal positive OX-K agglutinins in some, but
in general, the sensitivity is rather low; positive
results are seen in only 40% to 60% of patients.6,116
However, because it is a simple test to perform, the
Weil-Felix test is still the main test used in some
areas of the world.
Treatment
Chloramphenicol can be given in a dose of 500
mg every 6 hours for 7 days, and has the advantage
of covering both typhoid and meningococcus infec-
tions.  Tetracycline seems to be more efficacious and
is given in a dose of 500 mg every 6 hours for 7 days.
Doxycycline has been used successfully as a single,
oral dose in treating both louse-borne and scrub
typhus.121,122
Recrudescence is likely when the patient is treated
within the first 3 days of illness; a second course of
antibiotics may be required.  Recrudescence may
also occur with single-dose therapy under similar
circumstances.63,116,123
Control Measures
Effective chigger repellents that can be applied to
the body include diethyltoluamide and dimethyl-
phthalate.  Clothing and bed linen should be im-
pregnated with permethrin and benzyl benzoate,
which are miticidal.  Mite-infested areas may be
treated with lindane, dieldrin, or chlordane.63  Ex-
perimental evidence indicates that chiggers may
need to remain attached to humans for 6 to 8 hours
before R tsutsugamushi is transmitted.124  Therefore,
bathing after exposure may be helpful in prevent-
ing the disease.  Chemoprophylaxis against scrub
typhus and leptospirosis is possible using doxy-
cycline in weekly doses of 200 mg.  This prophylac-
tic regimen is not used routinely for indigenous
populations but would be beneficial for soldiers
engaged in military operations.124  Due to the exist-
ence of numerous antigenically different strains of R
tsutsugamushi, an effective vaccine is not yet available.
Trench Fever
Except during outbreaks associated with wars,
trench fever is a rarely reported disease.  It has also
been known as Wolhynian fever, Meuse fever, His-
Werner disease, shin bone fever, shank fever, and
quintan or 5-day fever.125  Rochalimaea quintana, the
rickettsia that is the causative agent, has also been
identified as one of the etiologic agents in bacillary
angiomatosis, a disease that was first described in
patients with acquired immunodeficiency syn-
drome.126
In modern times, this disease was first recog-
nized and described in 1915 as “trench fever” and
“5-day fever.”  Epidemics were seen among sol-
diers of all armies along the western, eastern, and
Balkan fronts with at least 1 million men stricken in
western Europe.127  Although the disease is rela-
tively mild, trench fever accounted for more lost
man-days for the U.S. armed forces than any other
disease except influenza.125  Each affected person
was unfit for duty an average of 60 to 70 days.
Fatalities were low, but many individuals experi-
enced one or several relapses of the disease.93  In
peacetime, the disease is reported only sporadically
in minor outbreaks.  During World War II, epidem-
ics again appeared with 80,000 cases in eastern
Europe.127
Microbiology
Rochalimaea quintana is a short rod (0.5–1.5 µm)
that resembles other rickettsiae in morphology and
staining properties.  It is unusual in that it can be
cultured in host cell-free media.  The organism can
be cultured in axenic media and the yolk sac of
chicken embryos.  Laboratory animals are not sus-
ceptible to infection.
Epidemiology, Vectors, and Host
Rochalimaea quintana is still considered to be a
member of the family Rickettsiaceae, although it is
now classified in the genus Rochalimaea.  Trench
fever is distributed worldwide, although it is pri-

Military Dermatology
238
marily associated with wars, overcrowded condi-
tions, and poor sanitation.  Humans are the reser-
voir and body lice are the vectors.  As with epidemic
typhus, when the gut epithelium of the louse is
infected, R quintana are excreted in the louse’s feces.
Humans acquire the organism when the feces are
scratched into the bite wound.
Clinical Findings
The onset of trench fever is often sudden and a
prodromal period is usually lacking.  The incuba-
tion period varies from 3 to 38 days and the illness
begins with chills followed by fever.  The fever has
three clinical forms: abortive, periodic, and con-
tinuous.  Some patients will lack fever or show only
rudimentary febrile episodes.  Abortive fever is
typified by continuous fever for approximately 4 to
5 days.  Periodic fever is typified by paroxysms of
fever alternating with normal temperatures at in-
tervals of 5 days.  There may be 3 to 8 cycles of this
pattern, which is the characteristic febrile pattern
for the disease.  Continuous fever is uninterrupted
for 2 to 3 weeks or longer.  This type is associated
with more severe symptoms.127
Chills, tachycardia, headache, retroorbital pain,
vertigo, nystagmus, myalgia, exanthem, and
hepatosplenomegaly can be seen.  The rash is com-
posed of erythematous macules and papules that
are seen on the chest, abdomen, and back.125  Char-
acteristically, the disease will relapse days, weeks,
months, or even years after the initial infection.
Symptoms during these relapses are generally
milder than those previously experienced.  Leuko-
cytosis and albuminuria may be present during the
relapse.
Diagnosis and Treatment
Influenza, malaria, relapsing fever, typhus, rat
bite fever, enteric fever, brucellosis, and other dis-
eases may need to be considered.  The characteristic
fever pattern is helpful in making the diagnosis.
Serologic testing using complement fixation,
microagglutination, or indirect immunofluorescence
are helpful in confirming the clinical diagnosis.  An
indirect hemagglutination test has also been devel-
oped that has a specificity greater than 99% and
does not cross-react with other rickettsiae.50
Tetracycline and doxycycline are effective drugs
for treatment of trench fever.  As with other rickett-
sial diseases, chloramphenicol is an acceptable al-
ternative.
Prevention and Control
Residual insecticides should be dusted on cloth-
ing and bedding.  In areas where DDT resistance is
encountered, lindane or malathion is recommended;
however, these chemicals will not kill organisms in
louse feces.  Clothing and bedding should be steril-
ized at 100°C for at least 30 minutes.127  Sputum and
urine have been reported to contain viable organ-
isms and should be disposed of as infective waste.98
Q Fever
Q fever, the sole member of the Q fever serogroup,
was first described in 1937 and was designated “Q”
for query.128  At that time, the infectious particle was
tentatively identified as a rickettsial organism, which
is now known as Coxiella burnetii.129  This is the only
rickettsial disease that does not typically produce a
rash.  Most commonly, Q fever is a self-limited,
mild, febrile illness.  Other manifestations, in de-
scending order of frequency, are pneumonia,
endocarditis, and granulomatous hepatitis.  Rarely,
the disease may present with unusual manifesta-
tions (Exhibit 11-2).130
Q fever was called “Balkan grippe” when it oc-
curred in British paratroops in Greece during World
War II.93  The disease occurred during the winter of
1944 and spring of 1945 in the North Apennine
region of Italy, which is endemic for the disease.131,132
An epidemic also affected five squadrons of the
449th Bomb Group in Italy; troops returning home
to the United States from Italy had an attack rate of
38%.133  In the process of isolating the organism
from these soldiers, outbreaks of the disease oc-
curred among laboratory personnel.134
Microbiology
C burnetii is a well-adapted organism that grows
within the phagolysosome of the cell, requiring an
acid pH.  A sporelike form has been described,
which accounts for the organism’s longevity after
dessication.135  C burnetii is a highly infectious or-
ganism; a single organism may initiate the disease
in humans.  It is well adapted to survive harsh
conditions, remaining viable after dessication on
wool at 15°C to 20°C for 7 to 10 months, cold storage
on fresh meat for 1 month, and after 40 months in
skim milk at room temperature.  The organism can
be isolated from infected tissues stored in formalde-
hyde after 4 to 5 months and even from fixed paraf-
fin-embedded tissue, although it is destroyed by 2%

Rickettsial Diseases
239
formaldehyde.136  There is no genotypic relation-
ship and very little phenotypic similarity between
Rickettsia and Coxiella.  Essentially, Coxiella remains
in the genus as a matter of history and convenience.
Epidemiology
Q fever is a zoonosis whose reservoirs are prima-
rily cattle, sheep, and goats.  The organism is shed
in the animals’ urine, feces, milk, and birth prod-
ucts and is extremely resistant to dessication.  Evi-
dence of C burnetii infection has also been found in
horses, swine, water buffalo, dogs, camels, pigeons,
chickens, ducks, geese, turkey, and several species
of wild birds.136  Cats and rabbits may be the most
important vectors in some areas.  Squirrels, meadow
mice, deer mice, harvest mice, and deer may also
harbor the organism.  Infected domestic animals
rarely show signs of infection.  C burnetii is a hearty,
widespread organism that has been isolated in 39
species and 10 genera of Ixodidae (hard ticks) and
Argasidae (soft ticks).  Q fever has been reported in
51 countries on five continents.136  Arthropods main-
tain the organism in nature.
The placenta of infected animals is heavily con-
taminated with C burnetii, and after the placenta
dessicates, the organisms are aerosolized.  Viable
organisms can be detected in the soil for 150 days.
Humans are infected when they inhale the
aerosolized organism, ingest raw milk, or handle
contaminated straw or manure.  Contaminated cloth-
ing may also be a source of exposure.130  This disease
usually affects those who are in contact with in-
fected animals such as farmers, veterinarians, and
abattoir workers.  However, outbreaks may be seen
in others through ingestion of contaminated raw
milk, skinning infected wild animals, blood trans-
fusion, or exposure to parturient cats,136  Outbreaks
of infection among laboratory workers are not un-
usual with this organism.33  Rarely, cases of human-to-
human transmission have been reported.98
Clinical Findings
The self-limited form of Q fever is similar to
influenza with fever, myalgia, anorexia, headache,
and retroorbital pain.  The pneumonic form can
present as an atypical pneumonia, a rapidly pro-
gressive pneumonia, or a febrile illness with pneu-
monia found only incidentally.  Included in the
differential diagnosis of atypical pneumonias are
Mycoplasma pneumoniae, Legionella pneumophila,
Chlamydia psittaci, pneumonic tularemia, and cy-
tomegalovirus and other viral pneumonias, as well
as Q fever.  The incubation period is 9 to 17 days.
A clue to the diagnosis is often the severe head-
ache, which may be overrepresented as a symptom.
Cough, fatigue, nausea, anorexia, myalgia, sweats,
retroorbital pain, and pleuritic chest pain are com-
mon findings.  One third of patients have vomiting
and diarrhea.  Rarely, sore throat may be a com-
plaint.  The physical exam may reveal inspiratory
rales or may lack auscultatory findings completely.
Although Q fever characteristically produces no
rash, an erythematous macular eruption on the trunk
has been described in a few patients.137
Hepatomegaly or splenomegaly may affect ap-
proximately 5% of patients.  Nuchal rigidity or con-
fusion is reported in a small number of patients.
Rapidly progressive pneumonia is seen in approxi-
mately 20% of patients.  These patients are usually
extremely ill and hypoxemic.  The chest radiograph
may show multiple round opacities, pleural effu-
EXHIBIT 11-2
RARE PRESENTATIONS OF Q FEVER
Arteritis
Arthritis
Aseptic meningitis
Dementia
Encephalitis
Epididymitis
Extrapyramidal disease
Fetal infection
Manic psychosis
Myocarditis
Nephritis
Orchitis
Osteomyelitis
Parotitis
Pericarditis
Thrombophlebitis
Thyroiditis
Toxic confusional states
Data source: Marrie TJ. Q fever: Clinical signs, symp-
toms, and pathophysiology. In: Walker DH, ed. Biology
of Rickettsial Diseases. Vol 2. Boca Raton, Fla: CRC Press;
1988: 1–16.

Military Dermatology
240
sions, or increased interstitial markings.  The eryth-
rocyte count may be elevated in one third of pa-
tients, but most are normal.  Hepatic transaminases
increase in almost all patients and the syndrome of
inappropriate antidiuretic hormone secretion may
occur.130
Some patients with Q fever present with an ill-
ness resembling typical hepatitis, or possibly with a
fever of unknown origin with mild liver function
test elevations.  Hypercalcemia may be seen.  Liver
biopsy reveals a “doughnut granuloma” (a dense
fibrin ring surrounding a central lipid vacuole),
which can also be seen in patients with Hodgkin’s
disease or infectious mononucleosis.
Endocarditis usually involves previously abnor-
mal valves and patients may present with a fever of
unknown origin or with culture-negative endo-
carditis.  This very serious manifestation of Q fever
is the most common manifestation of chronic Q
fever.  Fever, clubbing (50%), cardiac murmur,
purpuric rash (22%), and arterial emboli (35%) oc-
cur.130  Histologically, the rash is a leukocytoclastic
vasculitis, which is thought to be due to the ex-
tremely high levels of circulating immune com-
plexes that characterize the disease.  Prosthetic
valves and the aortic and mitral valves are the usual
sites of Q fever endocarditis.  Thrombocytopenia
and increased hepatic transferases and alkaline
phosphatase are common.130
Definitive Diagnosis
Coxiella undergoes a phase variation.  In the natu-
ral state and in the laboratory, it exists in what
is called phase I, in which C burnetii cells react
strongly with late (45-d) convalescent guinea pig
sera and weakly with early (21-d) guinea pig conva-
lescent sera.  Phase II organisms are produced when
the organism is passed repeatedly in embryonated
chicken eggs. The phase II form is avirulent and
differs from the phase I organism in the sugar com-
position of its lipopolysaccharide and several other
characteristics.136  The diagnosis of chronic Q fever
culture-negative endocarditis is made when phase
I titers are markedly higher than phase II titers.136,138
This is the opposite of what one would see in acute
Q fever infections.
Various serologic tests such as complement fixa-
tion, microimmunofluorescence, and the enzyme-
linked immunosorbent assay are used to diagnose
Q fever.138  As it has in other diseases where organ-
isms are difficult or dangerous to isolate, the poly-
merase chain reaction may find future application
in the diagnosis of Q fever.139
Treatment
Tetracycline is the drug of choice, although
trimethoprim-sulfamethoxazole and rifampin have
been used successfully.  Erythromycin with rifampin
is the preferred regimen for patients in whom the
diagnosis of atypical pneumonia caused by Q fever
is considered.140  Patients with rapidly progressive
pneumonia should be treated with tetracycline.
For endocarditis, the combination of tetracycline
and clotrimazole is effective.  Rifampin is also use-
ful.  Some authorities recommend indefinite treat-
ment because relapses are common and replace-
ment of the valve may be necessary.136  If and when
treatment is discontinued, the patient’s comple-
ment fixation titers should be followed carefully
every 6 months.130
Q fever hepatitis usually responds to a 2-week
course of therapy with tetracycline.
Prevention
Australian abattoirs have long had problems with
Q fever.  Trials there have proven a vaccine effective
in preventing disease with a minimum of adverse
reactions.141–143  A purified preparation of C burnetii is
currently being tested by U.S. Army researchers.140
Ehrlichiae are bacteria grouped within the fam-
ily Rickettsiaceae; ehrlichial diseases are catego-
rized in the ehrlichiosis serogroup.  Ehrlichiae are
presumed to be tick-borne and are well known as
veterinary pathogens.  Until recently, Ehrlichia
sennetsu and E canis were thought to be the only
species of Ehrlichia causing human disease; how-
ever, E chaffeensis has recently been identified as the
sole etiologic agent of ehrlichiosis in the United
States (Table 11-3).  Other species cause infections
in horses, dogs, sheep, cattle, bison, and deer.
Ehrlichiae differ from other rickettsiae antigeni-
cally and in their preference for infecting leuko-
cytes over vascular endothelial cells.  They also
grow and replicate within a phagosomal vacuole in
the host cell.  With the exception of Coxiella and
Ehrlichia, rickettsiae grow in the cell without a sur-
rounding membrane or vacuole.
EHRLICHIOSIS SEROGROUP

Rickettsial Diseases
241
TABLE 11-3
EHRLICHIOSES OF MEDICAL AND VETERINARY IMPORTANCE
Organism
Host
Vector
Disease
E equi
Horse
Unknown
Equine ehrlichiosis
E canis
Dog
Rhipicephalus sanguineus
Canine ehrlichiosis (tropical canine
 pancytopenia)
E chaffeensis
Unknown
Tick*
Human ehrlichiosis
E phagocytophila
Sheep, cattle, bison, deer
Ixodes ricinus
Tick-borne fever
E risticii
Cat,* horse
Unknown
Potomac horse fever
E sennetsu
Human*
Tick*
Sennetsu fever
Ehrlichiosis
Clinically, ehrlichial diseases range from
asymptomatic or mild to severe or fatal.  Diagnosis
presently relies on detection of antibodies, which
takes weeks.  In the future, more rapid diagnosis of
ehrlichial infections may be accomplished through
the use of the polymerase chain reaction once ap-
propriate probes are sequenced.  Although still only a
research procedure, this has already been done for
E risticii, the agent of Potomac horse fever.144
Ehrlichiae have not been reported to have a sig-
nificant impact on military campaigns.  However,
in 1968, sentry dogs used by U.S. troops in Vietnam
developed an epizootic of a fatal disease called
tropical canine pancytopenia.145,146  This was charac-
terized by debilitation, fever, anemia, and
leukopenia, and hemorrhage.  The disease is more
severe in German shepherds; 200 to 300 dogs were
lost to this disease during the war.147  The cost of the
dogs alone was estimated to be a minimum of $1
million.147  Military units that relied on these ani-
mals were also compromised.  During 1969, many
units (usually military police) had more than one-
half their dogs classified as possibly infected, re-
sulting in loss of the units’ operational capabili-
ties.147  The etiologic agent was postulated by
investigators at WRAIR to be an ehrlichia-like or-
ganism,148,149 and the organism was subsequently
proven to be E canis.150  The illness was responsive to
tetracycline therapy.151
Microbiology
Ehrlichiae are obligate intracellular, bacterial
parasites.  They are small, Gram-negative organ-
isms that preferentially infect mononuclear cells or
polymorphonuclear leukocytes and grow within a
phagosome in the cell cytoplasm.  Their develop-
ment within the cell is similar to that of chlamydiae,
with three stages described (Figure 11-5).
Based on serologic testing of infected patients, E
canis was originally believed to be the pathogen
causing human ehrlichiosis.  Because serology does
not specifically identify the causative agent because
of the possibility of cross-reactions with an anti-
genically related organsim, E canis was character-
ized as a tentative etiologic agent.  However, E
chaffeensis, a newly described ehrlichia that is closely
related to E canis, was identified in 1991 as the
causative agent of human erhlichiosis in the United
States.  The organism was named for Fort Chaffee,
Arkansas, where it was isolated from a U.S. Army
recruit with human erhlichiosis.152
Vectors and Reservoirs
Rhipicephalus sanguineus, the brown dog tick, is
the vector of canine ehrlichiosis, but it is not a
reservoir for the organism.  Larval and nymph
forms of the tick acquire the infection after feeding
on chronically infected dogs and later, as adults,
transmit the infection to uninfected dogs.  Recent
studies have failed to document transovarial trans-
mission.153,154  The most likely reservoir for canine
ehrlichiosis would seem to be chronically infected
canids, although this has not been proven.  Other
vertebrates or ticks may eventually be shown to be
reservoirs.153
No specific tick has been identified as the vector
for human ehrlichiosis.  Epidemiological data that
were generated when E canis was the suspected
pathogen indicate that the disease is not acquired
from dogs directly.  In the United States, serologic
*Not proven

Military Dermatology
242
Morula
Elementary body
Initial body
Fig. 11-5. In the first stage of the development of erlichia,
elementary bodies (individual organisms) are phagocy-
tized by host monocytes. Fusion of the phagosome with
a lysosome does not occur, however. Elementary bodies
grow within the phagosome and replicate by binary
fission. After 3 to 5 days, the elementary bodies packed
into the phagosome are (a) approximately 1.0 to 2.5 mµ in
size, (b) recognizable as pleomorphic inclusions within
the cell, and (c) called initial bodies. With additional growth
over the next 7 to 12 days, morulae (mature inclusions)
form and can be visualized via light microscopy. Each
infected monocyte contains several morulae, which break
up into initial bodies when the cell ruptures, allowing the
infectious cycle to be repeated. Illustration source:
Adapted from McDade JE. Ehrlichiosis—a disease of
animals and humans. J Infect Dis. 1990;161(4):609–617.
Legend source: Nyindo MBA, Ristic M, Huxsoll DL,
Smith AR. Tropical canine pancytopenia: In vitro cultiva-
tion of the causative agent—Ehrlichia canis. Am J Vet Res.
1971;32:1651–1658.
evidence of E canis infection has been found in dogs
in all geographical areas.155,156  The geographical
distribution of human cases corresponds to the dis-
tribution of the Lone Star tick, Amblyomma
americanum.  Additionally, the onset of cases in
spring and early summer corresponds to the time of
greatest activity for A americanum and for the dog
tick, Dermacentor variabilis.157  R sanguineus is more
widely distributed than A americanum and bites
humans less often.158  However, evidence of R
sanguineus bites have been documented in Texas,
suggesting the possibility of an increasing
anthropophilicity in these ticks.159  The vector and
reservoir for E chaffeensis are yet to be definitively
determined; however, E chaffeensis has been found
in a single D variabilis tick from an opossum.  This
evidence awaits confirmation and studies to docu-
ment that D variabilis can transmit the infection.152
Epidemiology
Most cases of human ehrlichiosis are reported in
rural areas from the spring to fall.  As a group,
patients tend to be older than those with RMSF.
Cases appear to be most common in the months of
May through June.  Most patients report either an
actual tick bite or exposure to ticks within a few
weeks of infection.160,161
This may be a disease that is actually more com-
mon than would be suspected from the number of
cases reported.  In some areas, the incidence of
ehrlichiosis may match or exceed that of RMSF.161
Approximately 10% to 12% of specimens submitted
with the tentative diagnosis of RMSF and that tested
negatively for RMSF were found to be positive for E
canis (the agent implicated serologically when these
studies were done).160,162  In a study of hospitalized,
febrile patients in southeast Georgia, 10.7% of the
patients were found to have a 4-fold rise or fall in
titers to E canis.161
Currently, the predominant regions where
ehrlichiosis has been reported include the south-
central, southeastern, and mid-Atlantic states.
States with high incidences are Oklahoma, Arkansas,
Missouri, Virginia, and Tennessee.158
People in older age groups are at higher risk for
ehrlichial infections in general and also have higher
rates of serious complications and hospitalization.158
Human ehrlichiosis can be rather mild in many
cases.  Of 74 U.S. Army reservists who were ex-
posed to ticks, 12% had serologic evidence of
ehrlichial infection.  None required hospitalization
and most experienced only mild symptoms.  Two
patients were asymptomatic.163  Investigation of
ehrlichiosis in Oklahoma revealed that fewer than
half the patients required hospitalization160; how-
ever, hospitalization rates of up to 88% have been
reported.164  In cases reported in 1988, 6% of patients
died.164
Ehrlichial infections in dogs appear to be wide-
spread in both the size of the population affected
(11%-58%)165 and the geographical area.  Cats have
also been found to have infections with ehrlichia-
like organisms.166

Rickettsial Diseases
243
Clinical Findings
More than 80% of patients will recall exposure to
ticks during the 3-week period before the onset of
illness.158  The incubation period averages approxi-
mately 9 days (range 4–33 d).164
Clinical manifestations tend to be nonspecific.
Fever, chills, headache, myalgias, anorexia, and
nausea and vomiting may appear abruptly or sub-
acutely.  A rash may occur 4 to 13 days after the
onset of illness but is seen within the first week in
only a minority of patients.  The rash may be
maculopapular or petechial and may involve vari-
ous aspects of the body.  Most children will develop
the rash, whereas only one third of adult patients
do.  The rash does not appear to be a reliable marker
for this disease because it is so variable in location
and appearance.158,167
Serious complications may occur.  Meningitis
was reported in a pediatric patient.168  Pulmonary
complications may necessitate intubation and me-
chanical ventilation.  Encephalopathy, mental sta-
tus changes, coma, and acute renal failure can oc-
cur.  Death may occur, especially in those with
preexisting medical problems.158
Laboratory Findings
In studies of hospitalized patients, lympho-
cytopenia, leukopenia, and thrombocytopenia were
fairly common.  Although the hematologic findings
may be characterized as a transient pancytopenia,
leukopenia is noted first because of the shorter life
span of these cells.  Over one half the patients
developed anemia at some time during their hospi-
talization, but usually not within the first
week.158,161,162  Various abnormalities of the bone
marrow have been described158,162,169,170 but the mar-
row of many patients is normal.  The findings of
normal bone marrows suggest sequestration or pe-
ripheral destruction as etiologies for the hemato-
logic abnormalities.171  Studies of dogs reveal a
paucity of infected cells in the marrow, supporting
this contention.172
Inclusion bodies may rarely be noted in the pa-
tients’ leukocytes.  Animals infected with E canis
usually lack leukocyte inclusions.162  Geimsa-stained,
buffy-coat preparations may be helpful in finding
inclusions, which can be found in lymphocytes,
atypical lymphocytes, band neutrophils, segmented
neutrophils, and monocytes.  However, only 1% to
2% of cells will contain inclusions.  The inclusions
are purple, round, or ovoid structures 2 to 5 µm in
size.  Usually only one inclusion is seen, although
up to four may be present in the cell.  With electron
microscopy, the inclusions are seen to be made up
of numerous electron-dense organisms surrounded
by a vacuolar membrane.173  Because demonstrating
inclusions is not dependable, serologic testing is
more important in confirming this diagnosis.
Serum transaminase levels are elevated in most
patients during the acute phase of the illness.  El-
evations of alkaline phosphatase, bilirubin, creati-
nine, and blood urea nitrogen are less common.
Cerebrospinal fluid pleocytosis, with predominant
lymphocytes and elevated protein, has been re-
ported.158,174
Differential Diagnosis
Other febrile illnesses associated with ticks should
be considered.  These include Lyme disease, tulare-
mia, babesiosis, and RMSF.  Babesiosis is distin-
guished by the presence of parasites in erythrocytes
on blood-smear examinations.  Tularemia and Lyme
disease should be distinguishable on a clinical ba-
sis.  RMSF can be difficult to distinguish in early
cases, especially those without a rash.
Diagnostic Testing
An indirect fluorescent antibody test for detect-
ing E canis in dogs has been adapted for use in
humans.160  Positive results are indicated by at least
a 4-fold rise or fall in acute and convalescent titers.
In one series, 24% of patients with positive tests for
E canis had confirmed diagnoses which were incon-
sistent with ehrlichiosis.  False-positive results were
seen in patients with streptococcal pharyngitis,
mononucleosis, hepatic cirrhosis, urosepsis, tulare-
mia,160 and hepatitis A.175  The CDC no longer uses
E canis as the antigen for the indirect immunofluo-
rescent antibody assay, but now uses E chaffeensis
instead.176
Antibody titers rise sharply during the first 3
weeks of illness and peak at approximately 6 weeks.
Acute-phase samples should be collected as early as
possible in the course of the illness and convales-
cent titers should be drawn 3 to 4 weeks later.  If the
initial serum sample is not obtained until after the
third week of illness, attempts to demonstrate a 4-
fold decrease in titer can provide confirmatory evi-
dence of infection.  Serum must be collected during
weeks 4 through 7 after onset of illness and again 6
weeks later.  Other tick-borne illnesses should also
be excluded serologically to confirm the diagnosis
of ehrlichiosis.  Most patients will seroconvert only
to E canis, but some will show cross-reactions with

Military Dermatology
244
other rickettsiae (R typhi, R rickettsii, C burnetii).177
Simultaneous infection with other tick-borne ill-
ness is possible, as exemplified by patients with
ehrlichiosis and Lyme disease.178,179
Treatment
Therapy for human erlichiosis is similar to that
for RMSF, with tetracycline being the drug of choice.
It has proven efficacy in ehrlichiosis in dogs151 and
appears to be efficacious in humans also.  Although
no formal controlled studies have been done, some
patients treated with chloramphenicol appear to do
as well as those treated with doxycycline, but some
adult patients have gotten worse or died with
chloramphenicol.173,180  A recent in vitro study
showed that E chaffeensis is resistant to chlor-
amphenicol, bringing into question the usefulness
of this agent.181  This same study found that E
chaffeensis was susceptible in vitro to rifampin, which
offers a possible alternative therapy.  Confirmatory
studies are needed to define the role of chlor-
amphenicol and rifampin in the treatment of this
infection.  In patients who have prominent
thrombocytopenia and leukopenia, tetracycline is a
better alternative.  Treatment should be instituted
as early as possible.  As it is in the treatment of
children with RMSF, the use of these antibiotics in
children under 9 years of age who have erlichiosis is
controversial.
Sennetsu Fever
The causative agent of Sennetsu fever, Ehrlichia
sennetsu, was originally isolated in 1953 from the
peripheral blood, lymph nodes, and bone marrow
of a patient with infectious mononucleosis–like
symptoms.  At the time, it was thought to be a new
rickettsia.  Subsequent studies revealed it to be
related to E canis both antigenically and morpho-
logically.  A significant difference is that E sennetsu
is readily propagated in mice, primary cell cultures,
and several continous cell lines, whereas E canis
propagates in canine monocytic cell lines only.153  E
sennetsu seems to grow in human monocytes in a
manner similar to that of E canis in canine mono-
cytes.  Morulae and individual organisms are ob-
served within cells in membrane-lined vacuoles.182
Western Japan and Malaysia are the most com-
monly reported areas affected by Sennetsu fe-
ver.183,184  The actual geographical area involved
may be more extensive than this, as serologic test-
ing for this agent is usually not attempted else-
where in the world.  The vector of Sennetsu fever is
presumed to be a tick, although this has not been
conclusively proven.
Senettsu fever appears to be a rather mild, mono-
nucleosis-like disease.  Patients may present with
fever, postauricular and posterior cervical lymph-
adenopathy, malaise, and anorexia.  An exanthem
is rarely seen, but generalized erythematous or lo-
calized petechial lesions have been described.
Hepatosplenomegaly is seen in one third of pa-
tients.  Fatalities have not been reported.183
Leukopenia with increased numbers of neutro-
phils is reported early in the disease.  Later,
lymphocytosis and atypical lymphocytes are seen.
The diagnosis may be confirmed using the
complement fixation or indirect fluorescent anti-
body tests.
Sennetsu fever is treated with tetracycline.  Im-
provement is prompt, with defervescence noted in
2 to 3 days and resolution of other symptoms shortly
thereafter.
SUMMARY
The rickettsiae are grouped taxonomically in a
unique family of bacteria that can cause diseases
with a spectrum of effects ranging from rather be-
nign to rapidly fatal.  Because military personnel
may be deployed to parts of the world that are
endemic for some rickettsial diseases, these dis-
eases pose particular challenges for medical offic-
ers.  Diseases such as epidemic typhus have played
crucial roles in military history.  Although most
military physicians have had no previous experi-
ence with this disease, it is one that is commonly
associated with wartime conditions so we must be
familiar with its presentation, treatment, preven-
tion, and control.  Some military bases are located in
regions of the world where rickettsial diseases that
are not seen in the United States (eg, boutonneuse
fever and scrub typhus) are endemic.  RMSF and
ehrlichiosis are threats to soldiers who are training
at bases in the continental United States that are in
areas endemic for these diseases.  In-depth knowl-
edge and understanding of the diagnosis, treat-
ment, and prevention of rickettsial diseases will
allow medical officers to deal competently with
these illnesses.

Rickettsial Diseases
245
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Sci. 1990;590:148–156.
173.
Maeda K, Markowitz N, Hawley RC, et al. Human infection with Ehrlichia canis, a leukocytic rickettsia. N Engl
J Med. 1987;316(14):853–856.
174.
Dimmitt DC, Fishbein DB, Dawson JE. Human ehrlichiosis associated with cerebrospinal fluid pleocytosis: A
case report. Am J Med. 1989;87:677–678.
175.
Rohrbach BW, Harkess JR, Ewing SA, et al. Epidemiologic and clinical characteristics of persons with serologic
evidence of E. canis infection. Am J Public Health. 1990;80(4):442–445.
176.
Spach DH, Liles WC, Campbell GL, Quick RE, Anderson DE, Fritsche TR. Tick-borne diseases in the United
States. N Eng J Med. 1993;329:936–947.
177.
Dawson JE, Fishbein DB, Eng TR, Redus MA, Green NR. Diagnosis of human ehrlichiosis with the indirect
fluorescent antibody test: Kinetics and specificity. J Infect Dis. 1990;162(1):91–95.
178.
Barton LL, Luisiri A, Dawson JE, Letson GW, Quan TJ. Simultaneous infection with an Ehrlichia and Borrelia
burgdorferi in a child. Ann N Y Acad Sci. 1990;590:68–69.
179.
Raad I, Singh V, Quan TJ. Concurrent positive serology for ehrlichiosis and Lyme disease. J Infect Dis.
1989;160(4):727–728.

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180.
Dumler JS, Brouqui P, Aronson J, Taylor JP, Walker DH. Identification of ehrlichia in human tissue. N Eng J Med.
325:1109–1110.
181.
Brouqui P, Raoult D. In vitro antiobiotic susceptibility of the newly recognized agent of ehrlichiosis in humans,
Ehrlichia chaffeensis. Antimicrobial Agents and Chemotherapy.. 1992;36:2799–2803.
182.
Hoilien CA, Ristic M, Huxsoll DL, Rapmund G. Rickettsia sennetsu in human blood monocyte cultures:
Similarities to the growth cycle of Ehrlichia canis. Infect Immun. 1982;35(1):314–319.
183.
Tachibana N. Sennetsu fever: The disease, diagnosis, and treatment. In: Leive L, Bonzentree PS, Morello JA,
Silver SD, Wu H. Microbiology—1986. Washington, DC: American Society for Microbiology; 1986: 205–208.
184.
Ristic M. Pertinent characteristics of leukocytic rickettsiae of humans and animals. In: Leive L, Bonzentree PS,
Morello JA, Silver SD, Wu H. Microbiology—1986. Washington, DC: American Society for Microbiology; 1986:
182–187.

Tropical Parasitic Infections
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TROPICAL PARASITIC INFECTIONS
Chapter 12
JAMES H. KEELING III, M.D.*
INTRODUCTION
PROTOZOAL INFECTIONS
Leishmaniasis
South American Trypanosomiasis
African Trypanosomiasis
Amebiasis
HELMINTHIC INFECTIONS
Human Hookworm Disease
Strongyloidiasis
Filariasis
Dracunculiasis
Trichinosis
Schistosomiasis
SUMMARY
*Colonel, Medical Corps, U.S. Army; Residency Program Director, Dermatology Service, Brooke Army Medical Center, Fort Sam Houston,
Texas 78234-6263

Military Dermatology
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INTRODUCTION
A parasite is an organism that lives on or within
another organism.  The organism on which or within
which it lives is referred to as the host.  While a
parasite–host relationship may be one of mutual
benefit (mutualism) or one in which the host de-
rives no benefit but is not injured by the relation-
ship (commensalism), the term parasitism is used in
this chapter to mean that the parasite is afforded
physical protection or nourishment to the detri-
ment of its human host.
The life cycles of parasites may be complex.  In a
definitive host, the parasite becomes sexually ma-
ture and undergoes reproduction.  Reservoir hosts
are those in which parasites that are pathogenic to
other animals or to humans reside.  An animal
reservoir confers a survival benefit to the parasite,
for it is often difficult to track and eliminate the
organism from the larger pool of animals in which
it is carried.  When humans intrude into the wild
and interrupt the zoonotic life cycle, they may be
incidentally infected and thus become incidental (or
accidental) hosts.  In an intermediate host, the para-
site exists in larval or asexual forms pending trans-
mission to a definitive host.1
Often, the means by which a parasite is transmit-
ted to the host involves an agent (eg, arthropod,
mollusk), which is referred to as the vector of disease
transmission.  In a biological vector, the parasite
undergoes development or multiplication prior to
transmission.  On the other hand, a mechanical
vector carries or transmits the organism without
any biological modification of its life cycle.1
Because they are deployed worldwide, U.S. armed
forces are often in tropical locales where parasitic
organisms produce diseases that may be truly foreign
to the clinical experience of many military physicians.
Although the historical record suggests that bacte-
rial and fungal infections and immersion syndromes
produce the bulk of cutaneous disease, the record
also shows that parasites can cause considerable
morbidity in war.2  Tropical parasitic diseases that
manifest with distinctive cutaneous signs offer a
unique opportunity for early diagnosis and treat-
ment.  To reduce morbidity and thus increase troop
effectiveness and morale, medical officers must know
the cutaneous signs, methods of diagnosis, epide-
miology, and effective treatment of these diseases.
Furthermore, members of the local populace, in
whom the incidence and prevalence of these dis-
eases is much greater, are often treated at military
medical treatment facilities.  During peacetime hu-
manitarian missions, this is expected; however, it
also often occurs during wartime.  During the Viet-
nam conflict, medical teams were sent to treat na-
tives in nearby villages.  The l8th Surgical Hospital
(Mobile), located south of the border with North
Vietnam at Quang Tri, Republic of Vietnam, had 20
to 30 beds added to its normal configuration to care
for pediatric patients.3  During Operation Desert
Storm in Southwest Asia, physicians who were at-
tached to hospitals that were deployed forward into
Iraq, providing medical and surgical support to
forces engaged in active combat, also provided
medical and surgical care to civilians caught within
the theater of operations.  An understanding of the
tropical parasitic diseases in the civilian populace,
then, becomes important not only in delivering
proper medical care but also in limiting the possi-
bility of spread of disease from these civilians, who
may also serve as disease reservoirs.4
Diseases common to the tropics are discussed in
other chapters in this textbook.  This chapter fo-
cuses on the characteristic cutaneous manifesta-
tions of protozoan and helminthic diseases that
medical officers might expect to encounter during
troop deployments.
the characteristic means of locomotion) or in sub-
phylum Sarcodina (in which pseudopodia [ie, creep-
ing protoplasmic flow] are the basis of movement).1,5
Leishmaniasis
While reporting on a case of Delhi boil in 1885,
British Surgeon-Major D. D. Cunningham is cred-
Parasitic protozoa that are infectious to humans
are generally unicellular organisms that have
nuclear structures separated from the cytoplasm by
a membrane.  Because these organisms can replicate
in human tissue, single exposures can result in
massive infections.1  Those most likely to be associ-
ated with cutaneous manifestations are to be found
in subphylum Mastigophora (in which flagella are
PROTOZOAL INFECTIONS

Tropical Parasitic Infections
257
ited with making the first scientific observation of
leishmanial organisms.  Subsequently, Borovsky
and Wright, working independently, concluded that
the parasite was probably protozoan.  In 1903, two
British Army medical officers, Colonel W. B.
Leishman (of the Royal Army Medical College) and
Colonel C. Donovan (of the Indian Medical Service,
working at Madras, India) discovered that the para-
site is the cause of visceral leishmaniasis; hence-
forth, the organism has been referred to as a
Leishman-Donovan body in tissue.6
Although in 1913 the British Army reported only
53 cases of “oriental sore,” the numbers increased
during World War I to an estimated 10,000 in its
Mesopotamia Force.7  During World War II, U.S.
forces experienced 1,000 to 1,500 cases of cutaneous
leishmaniasis, most of which originated in the Per-
sian Gulf Command between October 1943 and
August 1945.  Because all these soldiers were treated
as outpatients, manpower was little affected.  Fifty
to 75 cases of visceral leishmaniasis were estimated
to have occurred in the Mediterranean Theater of
Operations and India.8
To standardize therapy, the treatment of
leishmaniasis in U.S. military personnel has been
done on protocol at Walter Reed Army Medical
Center, Washington, D. C.  Between 1957 and 1981,
approximately 288 patients diagnosed as having
leishmaniasis were treated—most having contracted
the disease in Central or South America.  (Because
the leishmanial species from this region have
the potential to cause mucocutaneous disease,
treatment takes on added importance.)  By 1994, the
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Fig. 12-2. Promastigotes of leishmaniasis obtained from
an infected sandfly. The flagellum, large central nucleus,
and kinetoplast are apparent.
total number of cases had increased to more than
440.9  A number of patients (including several cases
of systemic disease that were documented by bone
marrow examination) were diagnosed following
Operations Desert Shield and Desert Storm in
1990 and 1991.10  Given the fact that the primary
lesion of leishmaniasis from Southwest Asia tends
to be of short duration and often is a self-limited
disease, it is likely that a number of cases of
cutaneous leishmaniasis have gone unreported or
undiagnosed.
The life cycle of leishmaniasis begins in nature
with a variety of animals (eg, dogs, sloths, rodents),
as well as humans, serving as reservoirs for infec-
tion.11  Located within reticuloendothelial cells of
infected tissues, leishmania exist in an amastigote
(nonflagellate) form, which is round or oval in shape
and approximately 2 to 5 µm in its greatest dimen-
sion (Figure 12-1).  Feeding on a reservoir animal’s
infected tissues, female sandflies of the genera
Phlebotomus or Lutzomyia ingest the parasitized cells.
In the gut of the vector, the leishmania transform to
the promastigote (or flagellate) form (Figure 12-2).
The promastigote is a slender organism with a fla-
gellum, undulating membrane, nucleus, and termi-
nal kinetoplast; it can measure 28 µm (including the
flagellum) in length.  After replicating, the leishma-
nia promastigotes migrate to the sandfly’s probos-
cis, from which they are regurgitated into the next
host as the sandfly feeds (Figure 12-3).
Although the adult sandfly lives only a few weeks,
it is able to transmit disease within 7 to 10 days after
feeding on an infected reservoir host.11  In some
cases, the number of promastigotes is so great that
they may physically obstruct the proboscis and
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Fig. 12-1. Intracellular amastigotes of cutaneous
leishmaniasis. Photograph: Courtesy of Lieutenant Colo-
nel Martha L. McCollough, Medical Corps, U.S. Army,
San Antonio, Tex.

Military Dermatology
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Fig. 12-3. (a) An adult sandfly, the vector of leishmaniasis. (b) The sandfly, seen in close-up. Photographs: Courtesy
of Jorge Molina, M.D., Honduras, Central America.
prevent feeding.12  Thus, the sandfly may make
several attempts before successfully feeding.  As a
result, multiple primary inoculations, resulting in
multiple primary lesions, can occur in a single hu-
man host; in other cases, single abortive feeding
attempts on different persons may cause several
individuals to become infected.
Once introduced into human skin, promastigotes
activate complement, bind C3, and become inter-
nalized by means of complement receptors on ma-
ture macrophages.13,14  Assuming the amastigote
form, the leishmania replicate, causing the cell to
rupture, which releases amastigotes that then infect
other cells.  Thus, infection (as defined by the pres-
ence of organisms) may be widespread, although
the obvious manifestations of disease are limited.
Control of disease by eliminating the parasite is
thought to be mediated by (a) a cellular oxidative
burst or (b) lymphocyte-mediated cytotoxicity.
When the cellular immune response is adequate,
the parasite is eliminated and species-specific im-
munity results.  Also, limited cross-immunity with
other Leishmania species develops in some cases.
Immunity, however, is not absolute, as reinfection
with the same species of organism can occur.13
The taxonomy of the genus Leishmania has been
complicated by the inclusion of complexes, subgen-
era, species, and subspecies identification based on
a variety of clinical, biological, epidemiological,
immunological, and biochemical criteria.15  For a
number of years, the standard procedure has been
to classify organisms as members of complexes: L
mexicana complex, L braziliensis complex, L tropica
complex, or L donovani  complex.  A recently pro-
posed change in the classification is that all mam-
malian leishmania that develop in the foregut or
midgut of the vector be placed into subgenus Leish-
mania, and those with hindgut development into
subgenus Viannia.  Because a consensus has yet to
be developed, many authorities have adopted the
simplified nomenclature used in Table 12-1.16,17
Cutaneous Manifestations
Clinically, it is convenient (although immuno-
logically simplistic) to think of leishmaniasis in
three forms: cutaneous, mucocutaneous, and vis-
ceral.  Because of clinical differences, the disease is
often classified as Old World (Africa, the Mediter-
ranean littoral, the Middle East, India, Southwest
Asia, and Asia) or New World (Central America
and South America) leishmaniasis.  Old World
leishmaniasis tends to produce either cutaneous or
visceral disease, while New World leishmaniasis
may be cutaneous, mucocutaneous, or visceral.
Morphologically, the initial cutaneous lesions of
both Old World and New World disease are similar
(Figures 12-4, 12-5, and 12-6).13,18–23  In the Old World,
these lesions are called Baghdad sore, Aleppo boil,
Delhi boil, or oriental sore.  Synonyms for cutane-
ous New World disease include American leish-
maniasis, South American leishmaniasis, uta, pian
bois, and Chiclero’s ulcer.  Generally occurring on
exposed areas of the body (ie, face, ears, arms, legs),
single or multiple erythematous papules develop
weeks to months after the bite of an infected sandfly.
The papules enlarge (> 1–5 cm) to form indurated
nodules or plaques.  Satellite lesions are not uncom-
mon.  These lesions may have overlying scale or
they may ulcerate, leaving a central crater.  The
extensive differential diagnosis includes pyoderma,
kerion, deep fungal infection, tuberculosis, atypical
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b

Tropical Parasitic Infections
259
TABLE 12-1
NAMES, GEOGRAPHICAL DISTRIBUTION, AND DISEASE MANIFESTATION OF LEISHMANIA
SPECIES THAT INFECT HUMANS
*rare manifestation
†taxa not recognized by all authorities
CL: cutaneous leishmaniasis
DCL: disseminated cutaneous leishmaniasis
MCL: mucocutaneous leishmaniasis
PKADL:  post–kala-azar dermal leishmaniasis
VL: visceral leishmaniasis
Reprinted with permission from Walton BC. Leishmaniasis: A worldwide problem. Int J Dermatol. 1989;28:307.
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Fig. 12-4. An ulcerated nodule of cutaneous leishmaniasis
in an active-duty soldier. The lesion appeared during
Operation Desert Shield in Saudi Arabia. Clinical resolu-
tion occurred spontaneously after 6 to 7 months.
Fig. 12-5. An ulcerated nodule of leishmaniasis in a
patient from Panama.
Table 12-1 is not shown because the copyright permission granted to the Borden Institute, TMM, does
not allow the Borden Institute to grant permission to other users and/or does not include usage in
electronic media. The current user must apply to the publisher named in the figure legend  for permis-
sion to use this illustration in any type of publication media.

Military Dermatology
260
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Fig. 12-6. A cutaneous ulcer of leishmaniasis. Photo-
graph: Courtesy of Colonel Alfred K. Cheng, Medical
Corps, U.S. Air Force (ret), San Antonio, Tex.
mycobacteria, sarcoidosis, foreign body reaction,
squamous cell carcinoma, or granuloma faciale.
Extension of disease may be manifest as subcutane-
ous nodules following the lymphatic drainage,
which occurs in both Old World and New World
disease (Figure 12-7).24  Gradually the lesions begin
to flatten and develop dermal fibrosis, leaving
an irregular, sometimes disfiguring, scar.  Disease
due to L tropica or L major (Old World) generally
resolves within a few months to a year.  Leish-
maniasis occurring in Central America or South
America may produce cutaneous lesions that per-
sist for much longer periods of time.21
A form of leishmaniasis associated with specific
immunological unresponsiveness is disseminated
anergic cutaneous leishmaniasis, often called dif-
fuse cutaneous leishmaniasis.18,19  In patients with
this disease, hundreds of nonulcerating nodules
and plaques develop and may become confluent.
The facial involvement may become extensive and
create the appearance of leonine facies.  Macroph-
ages within the lesions teem with amastigotes
and the skin test reaction to leishmanial antigen is
negative.  Visceral involvement is thought not to
occur.19  The differential diagnosis includes
lepromatous leprosy.
Mucocutaneous Manifestations
Seemingly unique to the spectrum of New World
disease, espundia (mucocutaneous leishmaniasis)
is caused by infection with L braziliensis or L
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Fig. 12-7. (a) Plaque with satellite papules of Leishmania panamensis in a U.S. Army soldier on active duty in Panama,
Central America. (b) The soldier’s inner arm shows the array of papules and nodules occurring along lymphatic
drainage that is known as sporotrichoid lymphatic involvement. (c) Close-up of the lesions along the pathway of
lymphatic drainage.
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a
b
c

Tropical Parasitic Infections
261
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a
b
Fig. 12-8. Mucocutaneous leishmaniasis (espundia) of (a)
the nose and (b) the nose, malar region, and upper lip in
two patients from Central America. Photographs: Courtesy
of Colonel Eric W. Kraus, Medical Corps, U.S. Army (ret).
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Fig. 12-9. Mucocutaneous leishmaniasis. A friable plaque
(arrow) in the patient’s posterior pharynx. Photograph:
Courtesy of Colonel Alfred K. Cheng, Medical Corps,
U.S. Air Force (ret), San Antonio, Tex.
panamensis.17  Recurrent leishmaniasis involving the
upper respiratory system may develop 3 to 10 years
after the primary lesion—often at a distant site—
has apparently healed.21  Symptoms frequently be-
gin with epistaxis or coryza, with subsequent exten-
sive destruction of the nasal cartilage (Figure 12-8).
The resulting overhanging nasal deformity coupled
with infiltration is said to make the patient re-
semble a tapir.19  Espundia’s further progression to
the palate, tongue, floor of the mouth, and pharynx
may create an extensive midline facial defect (Fig-
ure 12-9).  Untreated, inanition with aspiration pneu-
monia and death may occur (Figure 12-10).  The
differential diagnosis of espundia includes deep
fungal infections, lethal midline granuloma, malig-
nant tumors, rhinoscleroma, syphilis, tuberculosis,
and leprosy.
Visceral Manifestations
Visceral leishmaniasis is caused by organisms of
both the Old World and the New World (see Table
12-1).  Viscerotropic species cause a systemic dis-
ease that may have fever, malaise, abdominal swell-
ing, pain, anorexia, hepatosplenomegaly, and ane-
mia.  The earth-gray pigmentation of the face, hands,
and feet gives this disease its common name, kala

Military Dermatology
262
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Fig. 12-10. Mucocutaneous leishmaniasis. Autopsy speci-
men showing tracheal involvement. The patient died
after aspirating a portion of the plaque. Photograph:
Courtesy of Colonel Alfred K. Cheng, Medical Corps,
U.S. Air Force (ret), San Antonio, Tex.
• needle aspiration at the elevated edge away
from the scar, or
• biopsy and subsequent touch preparation.
All of these preparations are stained by Giemsa or
Wright’s stain and the investigator should look for
the amastigote within the cell.  Demonstrating or-
ganisms in tissue by this method is difficult, espe-
cially when numbers of parasites are low; thus,
cultures of tissue specimens are often prepared.
Results of cultures, however, are dependent on
the numbers of organisms inoculated and the skill
of the laboratory.  The culture is usually grown
on Novy-MacNeal medium, modified by Nicolle
(ie, NNN medium), overlaid with Schneider’s
Drosophila medium and fetal bovine serum.
Promastigotes are demonstrated in positive cul-
tures.  The Montenegro intradermal skin test is
produced from promastigotes but is not commer-
cially available in the United States.28  This skin test
is of limited usefulness in endemic areas because (a)
a high percentage of the population may have been
exposed to leishmania and (b) diffuse cutaneous
disease tests negative.  Serologic tests, in particular
indirect fluorescent antibody tests and enzyme
immunosorbent assays, have been developed but
may be negative in 20% to 30% of cases.23,28  Indirect
immunofluorescent studies using monoclonal anti-
bodies directed against leishmanial antigens are
more sensitive than either Giemsa stains or culture
and hold great promise in facilitating diagnosis.10,29
Therapy
Comprehensive reviews of therapy are avail-
able.30,31  Medical officers must keep in mind that
strictly cutaneous Old World leishmaniasis is often
self-healing, generally does not presage the devel-
opment of kala azar, and thus may not require
treatment.  However, in addition to those patients
having visceral disease, those whose cutaneous dis-
ease manifests as multiple lesions, facial lesions, or
lesions occurring over a joint where motion might
be limited by scar formation warrant consideration
for therapy.  Primary cutaneous lesions of New
World leishmaniasis also show self-healing.  How-
ever, because (a) cutaneous disease of New World
leishmaniasis has a longer duration and (b) subse-
quent mucocutaneous disease is a possibility, pa-
tients with New World leishmaniasis are treated.  L
tropica, L major, L donovani, L mexicana, and L
braziliensis are treated with stibogluconate sodium
(20 mg Sb [antimony, the active ingredient]/kg/d,
administered intravenously or intramuscularly for
azar (ie, black sickness).25  No pigmentary changes
were noted in the cases of visceral disease that
occurred among U.S. military personnel during
World War II.26  Either during the course of treat-
ment or years after their apparent cure, an eruption
of hypopigmented macules, butterfly erythema,
and diffuse nodules develop in some patients in
Kenya and India with visceral leishmaniasis.25,26
The disorder is known as post–kala azar dermal
leishmaniasis.
Diagnosis
Diagnosis of leishmaniasis is generally accom-
plished by demonstrating the organism.22,23,27,28
Methods of directly visualizing leishmania that are
infecting tissue include the following:
• scraping of the primary lesion,
• a nonbloody slit smear of a nodule,

Tropical Parasitic Infections
263
20–28 d) or meglumine antimonate (20 mg Sb/kg/
d, for 20–28 d, route of administration not speci-
fied).32  Adequate treatment of cutaneous disease
due to L braziliensis may markedly diminish the risk
of espundia.33  Because pentavalent antimonials are
not always effective and drug resistance has been
documented, the quest for new therapies contin-
ues.34,35  Investigational treatments include the use
of amphotericin B, pentamidine isethionate,
ketoconazole, recombinant human gamma inter-
feron, and heat.22,32
South American Trypanosomiasis
Trypanosoma cruzi causes a disease encountered
in Central America and South America known as
South American trypanosomiasis or Chagas’ dis-
ease.  Over a period of years, the disease may evolve
from an acute stage, which includes cutaneous mani-
festations, through a clinically silent latent stage, to
a chronic phase characterized by cardiac and gas-
trointestinal disease.
The life cycle of the parasite causing human dis-
ease typically begins with a wide variety of domes-
tic (eg, dogs, cats, pigs) and wild (eg, rodents, mar-
supials) animals, which serve as reservoirs for
infection.36–38  The trypomastigote form circulates in
the blood stream as a slender, spindle-shaped form,
15 to 20 µm in length (in humans), having a nucleus,
terminal kinetoplast, undulating membrane, and a
long flagellum (Figure 12-11).  While feeding on in-
fected animals, true bugs (of the suborder Hemiptera)
from the insect family Reduviidae (subfamily
Triatomidae) ingest the trypomastigote.  Dividing
and transforming in the gut of the bug, the T cruzi
appear in the hindgut as metacyclic trypomastigotes,
which are infective to humans.  Once infected, the
bug remains so for life.  Although many species of
triatomid bugs exist, those that are adapted to liv-
ing in human habitats serve as vectors of trypano-
somiasis: Rhodnius prolixus in Central America,
Colombia, and Venezuela (Figure 12-12); Triatoma
infestans throughout much of South America; and
Panstrongylus megistus in Brazil.  Hiding within the
cracks and crevices of mud and thatch homes dur-
ing the day, the bug ventures out at night to feed on
exposed skin (typically the face, hence the name
“kissing bug”) of sleeping humans.  While feeding,
the bug defecates, thus depositing the infective
metacyclic trypomastigotes on the skin surface.
Although the insect is undetected while feeding, a
short time later the victim develops pruritus, which
elicits a rubbing or scratching response, which then
inoculates the organism from the fecal deposit into
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Fig. 12-11. A peripheral blood smear of Trypanosoma
cruzi. The flagellum, undulating membrane, nucleus,
and large terminal kinetoplast are obvious. The C-shape
is characteristic. Photograph: Courtesy of Armed Forces
Institute of Pathology. Negative 73-1150.
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Fig. 12-12. A reduviid bug, the vector of South American
trypanosomiasis. Photograph: Courtesy of Colonel Alfred
K. Cheng, Medical Corps, U.S. Air Force (ret), San Anto-
nio, Tex.
the victim’s skin or mucous membrane.  Invading
tissue macrophages, the organisms transform to
rounded, nonflagellate amastigote forms of approxi-
mately 3 µm in diameter.

Military Dermatology
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a
Fig. 12-13. (a) Amastigotes of Trypanosoma cruzi within a cardiac muscle fiber. (b) Inflammatory response elicited by
the rupture of cardiac muscle fiber releasing trypanosomes. Photographs: Courtesy of Colonel Alfred K. Cheng,
Medical Corps, U.S. Air Force (ret), San Antonio, Tex.
Multiplying by binary fission, the T cruzi burst
from the macrophages as trypomastigotes and dis-
seminate widely to invade most human tissues in-
cluding cardiac and skeletal muscle, parasympa-
thetic ganglion cells, the central nervous system
(CNS), and the reticuloendothelial system, where
the cycle is repeated (Figure 12-13).39,40  In addition
to being vector-borne, the disease can also be trans-
mitted transplacentally, by transfusion, transplan-
tation, and in laboratory accidents.41
The circulating trypomastigotes produce a gly-
coprotein that may protect them from destruction
by the alternate complement pathway.38,40  Thus,
parasites are relatively numerous initially and eas-
ily demonstrable on peripheral blood smear.  With
time, however, the human body produces neutral-
izing antibodies that permit complement-mediated
destruction.  Binding to fibronectin receptors on
monocytes and macrophages, the T cruzi are inter-
nalized to the cytoplasm, where they are protected
from the cellular oxidative burst as well as from the
hostile extracellular milieu.  This phase of immu-
nologically diminished but, importantly, life-long
parasitemia corresponds to latent and chronic phases
of disease and creates a reservoir of disease.  Al-
though the parasite persists in the human body, an
autoimmune response to the parasite may magnify
the extent of parasite-induced disease—especially
in the chronic stages.42
Clinical Manifestations
While infection may occur at any age, often only
in children is clinical disease detected acutely.39,40,43–45
Rupturing from infected macrophages about 5 days
after infection, the T cruzi precipitate an inflamma-
tory response at the site of inoculation.  This pro-
duces an erythematous, edematous, indurated le-
sion, known as a chagoma, which is only minimally
tender.  A chagoma occurring on the eyelid and
conjunctivae is known as Romana’s sign and is
often associated with bipalpebral edema and en-
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Fig. 12-14. A child manifesting Romana’s sign of South
American trypanosomiasis. Photograph: Courtesy of
Colonel Alfred K. Cheng, Medical Corps, U.S. Air Force
(ret), San Antonio, Tex.
b

Tropical Parasitic Infections
265
larged preauricular nodes (Figure 12-14).  The
chagoma lasts only a few days to a couple of weeks.
However, the hematogenous dissemination and
subsequent widespread tissue invasion may pre-
cipitate an acute systemic illness with fever to 104°F,
vomiting, diarrhea, cough, hepatosplenomegaly,
edema, myocarditis, seizures, and meningoen-
cephalitis.  Occasionally, a transient morbilliform,
urticarial, or erythema multiforme-like eruption
precedes the hepatosplenomegaly.39,40  Ninety per-
cent or more of patients survive the acute stage,40,44
which subsides in 1 to 3 months.40
Patients then enter a latent phase of disease dur-
ing which they are relatively asymptomatic, and
parasitemia is difficult to detect on a peripheral blood
smear.  Estimates vary, but after years or decades, 10%
to 20% of patients46 or 10% to 30% of patients41
develop chronic symptomatic disease.  Myocardial
heart disease, with fibrosis, conduction defects,
cardiomegaly, failure, and an apical ventricular
aneurysm, is characteristic (Figures 12-15 and 12-
16).38,43–45,47  Local denervation is believed to be im-
portant in the pathogenesis of cardiac disease.41
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Fig. 12-16. This markedly thinned cardiac ventricular
wall is due to chronic disease with Trypanosoma cruzi.
Photograph: Courtesy of Colonel Alfred K. Cheng, Medi-
cal Corps, U.S. Air Force (ret), San Antonio, Tex.
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Fig. 12-15. Cardiomegaly of South American trypano-
somiasis. Photograph: Courtesy of Colonel Alfred K. Cheng,
Medical Corps, U.S. Air Force (ret), San Antonio, Tex.
Destruction of the parasympathetic ganglion leads
to dilation of portions of the gastrointestinal tract,
typically the esophagus and colon, which is known
as mega syndrome.38,40,44,48  Dysphagia, aperistalsis,
regurgitation, and constipation may result.
Diagnosis and Treatment
In acute disease, diagnosis is established by find-
ing trypomastigotes in the patient’s blood.  Comple-
ment fixation, indirect immunofluorescence, hemag-
glutination, and enzyme-linked immunosorbent
assays (ELISAs) have been used for serologic diag-
nosis of chronic disease.  However, because the
tests lack specificity, it has been recommended that
two different, positive assays be used to establish a
diagnosis.41  Organisms can be detected in about
50% of patients who have positive complement-
fixation tests by allowing laboratory-raised redu-
viid bugs to feed on the individual and then identi-
fying trypomastigotes in the bug—a technique
known as xenodiagnosis.44
Nifurtimox (adult dose: 8–10 mg/kg/d, divided
and administered orally 4 times daily for 120 days;
the pediatric dosage is discussed elsewhere32) or
benznidazole (5–7 mg/kg/d for 30–120 d, mode of
administration not specified) are useful but toxic in
the parasitemic phase of disease.32,38,41  The
amastigotes in tissue, however, are not eradicated
by medication so the chronic disease persists de-
spite treatment.38,41,44,47  Therefore, control of the
vector in the domestic setting is the key to prevent-
ing the disease.

Military Dermatology
266
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Fig. 12-17. This smear of peripheral blood shows the
trypomastigotes of Trypanosoma (T) b rhodesiense. The
flagellum, undulating membrane, large nucleus, and small
terminal kinetoplast are apparent. Photograph: Courtesy of
Armed Forces Institute of Pathology. Negative 74-19698.
Fig. 12-18. A tseste fly—the vector of African trypano-
somiasis. This specimen is Glossina morsitans, the vector
of East African (rhodesiense) disease. Photograph:
Courtesy of Armed Forces Institute of Pathology.
Negative 75-14469.
human habitation.51  In an endemic area, however,
less than 1% of the flies are infected; the number
increases to perhaps 5% in epidemic areas.49  Once
infected, the fly remains so for life.
In the production of human disease, the life cycle
begins when the tsetse fly (Glossina) feeds on an
infected reservoir animal.49,50  The tsetse fly ingests
trypomastigotes, which multiply by binary fission
in the fly’s midgut.  Then moving to the fly’s sali-
vary gland, the trypomastigotes transform in stages
to become infective metacyclic trypomastigotes.  In
those flies capable of transmitting disease, the time
from ingestion to the development of infective try-
panosomes is about 3 weeks.  When the fly next
feeds on human blood, it injects the trypanosomes
into the human.  Initially multiplying at the site of
the bite and later in the victim’s bloodstream and
lymphatics, the organisms ultimately gain access,
through the blood–brain barrier, to the CNS.  These
trypanosomes do not become internalized within
the tissue cells, but do elicit an inflammatory re-
sponse in many organs.37  The organisms are diffi-
cult to identify in biopsy material.50
Trypanosomes shift their antigenic surface coat,
with the result that effective immunological con-
tainment may not be achieved.49  Because immunity
is only type-specific, new antigenic strains of trypa-
nosomes constantly appear in the infected host.
There is an initial lymphatic and plasma cell re-
sponse with a nonspecific elevation of immunoglo-
bulin (Ig) M; later, though, a state of relative cellular
and humoral immunosuppression develops.
African Trypanosomiasis
In sub-Saharan Africa, trypanosomes produce a
disease known as African trypanosomiasis (sleep-
ing sickness).  Two morphologically similar organ-
isms produce diseases with cutaneous, cardiac, and
CNS manifestations that are ultimately fatal if not
treated.46  Geographical restrictions, rapidity of dis-
ease progression, and drug response are some fea-
tures used to distinguish the two.49
Taxonomically, the organisms are placed in the
genus Trypanosoma (subgenus Trypanozoon) and
species brucei; rhodesiense is the subspecies in East
Africa and gambiense in West Africa.  The organisms
are long and slender, measuring up to 30 x 3.5 µm,
and each has a nucleus, kinetoplast, undulating
membrane, and long flagellum (Figure 12-17).  In
East Africa, the reservoir is animal, while in West
Africa, it is human.49
Hematophagous tsetse flies of the genus Glossina
are the vectors of disease: G morsitans is the most
important in East Africa (Figure 12-18) and G palpalis
in West Africa.49  G morsitans is found in savanna
and woodland areas, while G palpalis is found in the
thickets along rivers and lakes.49,50  The flies have a
painful bite, will follow moving objects, and will
bite through thin clothing.49  They are, however,
susceptible to becoming desiccated; thus, brief ex-
posures to light are potentially lethal.50  Because the
tsetse fly’s distribution is widespread and the po-
tential for resulting epidemics is great, one fourth of
the African continent is effectively unavailable for

Tropical Parasitic Infections
267
Clinical Manifestations
The signs and symptoms of the disease vary
somewhat according to the area in which the dis-
ease was contracted.40,46,49,50,52  Within 1 to 2 weeks
after the bite, a dusky red nodule, which can reach
5 cm in size, develops and lasts approximately 2
weeks.  This lesion, the primary chancre, may
be painful and often is located on the lower
extremities.  The lesion is reported more often
in nonindigenous persons, who have no partial
immunity, and in disease caused by T (T) b
rhodesiense.49,51,52
The appearance of fever marks the beginning of
the parasitemic phase of the disease; it may occur
within a week in East African disease or, in West
African disease, in the immunologically naive.51,52
Then the patient may experience intermittent fe-
vers, headache, dizziness, joint pain, hepatosplen-
omegaly, lymphadenopathy, malaise, anorexia, ir-
ritability, personality change, and insomnia.
Posterior cervical lymphadenopathy (ie, Winter-
bottom’s sign) is thought to be characteristic of the
disease caused by T (T) b gambiense (Figure 12-
19).49,50  About 10 days after the initial fever, a
cutaneous eruption occurs in almost 50% of the
cases.49  The asymptomatic, circinate or oval,
erythematous macules with clear centers may sug-
gest an erythema multiforme-like eruption on the
trunk.40,49,52  Kerandel’s sign, variously described as
a delayed sensation to pain or as a sensation of
hyperesthesia, may be frequent.37,46,49  Pancarditis
and arrhythmias may develop, particularly in pa-
tients with East African (rhodesiense) disease.  Pre-
sumably because of partial immunity, months or
years may elapse before infected individuals who
are long-term inhabitants of endemic West African
areas experience clinical symptoms.49,51
The patient entering a late or chronic phase of
disease develops signs of meningoencephalitis.
Somnolence, lassitude, indifference, seizures,
and personality changes may develop and, with fur-
ther deterioration, coma ensues.  These CNS changes
may be more likely to develop in patients with West
African (gambiense) disease because of its more
gradual progression.49  East African (rhodesiense)
disease may be more acute and fulminant, with
patients dying of cardiac disease sometimes within
a few months of contracting the infection.
Diagnosis
Nonspecific abnormal laboratory findings include
elevated erythrocyte sedimentation rate, markedly
elevated IgM, moderately elevated IgG, cryo-
globulinemia, anemia, thrombocytopenia, dissemi-
nated intravascular coagulation, and abnormal liver
function tests.46,49  Many of these are found more
commonly in disease due to T (T) b rhodesiense.
Because of the greater degree of parasitemia,
demonstration of T (T) b rhodesiense on thick and
thin smears is easier than with T (T) b gambiense.
Examination of aspirated fluid from a chancre or
node, as well as bone marrow or cerebral spinal
fluid, is useful in these situations.  Increased leuko-
cytes (> 5/mm3) and protein (> 25 mg/dL), and/or
increased IgM in the cerebral spinal fluid suggests
a CNS invasion.49  Serologic tests become positive 2
to 4 weeks after the onset of disease, which may be
too late to be useful for diagnosing a patient with
fulminant East African disease.  Further, the anti-
genic variability of the trypanosomes makes stan-
dardizing immunofluorescence, hemagglutination,
and ELISAs difficult.46
Therapy
Suramin, which does not cross the blood–brain
barrier, is very effective in destroying trypanosomes
and effecting a cure when there is no CNS dis-
ease.34,50  The adult dose is 100 to 200 mg adminis-
tered intravenously (as a test dose), then 1 g admin-
istered intravenously on days 1, 3, 7, 14, and 21.32
The pediatric dose is 200 mg/kg administered on
days 1, 3, 7, 14, and 21.
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Fig. 12-19. Enlarged posterior cervical nodes—Winter-
bottom’s sign of West African (gambiense) trypanoso-
miasis. Photograph: Courtesy of Armed Forces Institute
of Pathology. Negative 74-8337.

Military Dermatology
268
Melarsoprol is effective in all stages of sleeping
sickness, including CNS involvement; but, because
of its toxicity (the drug can produce a fatal reactive
encephalopathy), it is used only when the CNS
is involved or when other drugs fail.  The adult
dose is 2.0 to 3.6 mg/kg/d, administered intrave-
nously for 3 days; after 1 week, the dose is 3.5 to 4.5
mg/kg/d, for 3 days; 7 days later, 5.0 mg/kg/d is
given for 3 days.  The pediatric dosage is discussed
elsewhere.32
Amebiasis
Infection with the ameba Entamoeba histolytica is
known as amebiasis.  The spectrum of clinical pre-
sentation includes an acute dysenteric form and a
less symptomatic, nondysenteric, intestinal form;
some people with amebiasis are asymptomatic
cyst passers.  From these presentations, a variety
of mechanisms have been proposed to explain the
development of cutaneous lesions.  In 1986, it
was estimated that 480,000,000 people (slightly > 10%
of the global population) were infected, with the ma-
jority (> 80%) asymptomatic.53  Amebiasis causes
40,000 to 75,000 or more deaths per year and may be
the third-leading parasitic cause of death.53,54
Significant numbers of U.S. military personnel
were exposed to amebiasis during World War I,
World War II, and the Korean conflict.  During
World War II, at least 1.2 million man-days of duty
may have been lost to this disease.  Unfortunately,
no reliable statistics are available to reflect the num-
bers or types of extraintestinal amebiasis cases.
Cutaneous amebic disease was rarely seen in the
Vietnam conflict.55
Although the organism has been identified in
insects and other animals, humans are considered
to be the reservoir of disease.53,56  Infection is ac-
quired when cysts from fecally contaminated sources
(usually food or water) are ingested.40,53,56–58  Cysts
may survive for months in a warm, moist environ-
ment outside the host; further, they are resistant to
chlorine concentrations that are usually used for
water purification.56  The spherical cysts (5–25 µm
in diameter) have a thick wall that provides protec-
tion in the acidic gastric milieu.  When they reach
small intestine, excystation and division occur; each
quadrinucleate cyst produces eight trophozoites
that vary in size from 15 to 60 µm.  Trophozoites are
carried to the large intestine where various hosts or
amebic factors (discussed below) determine whether
tissue invasion or simple colonization of the bowel
by trophozoites will occur.  The cycle is established
when trophozoites divide and form quadrinucleate
cysts that are then passed in the stool.  In patients
who are experiencing diarrhea, trophozoites may
be passed prior to becoming encysted.
Intestinal and Extraintestinal Manifestations
Symptomatic amebiasis is produced when the
host’s tissues are invaded.  Bacterial flora in the gut,
nutritional status, and cellular immune responses
may be important host parameters; while amebic
strains, adhesins, cytotoxins, and contact-depen-
dent cytolysis are considered to be the parasitic
determinants of tissue damage.58,59
Asymptomatic infections—detected only by the
presence of cysts in screening examinations—
account for most human infection.  Acute disease
may develop suddenly 1 to 3 weeks after the cysts
are ingested.  Abdominal cramps, fever, chills,
headaches, tenesmus, and diarrheal stools with
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Fig. 12-20. Cutaneous amebiasis of the anterior portion of
the external genitalia in a female child. Photograph:
Courtesy of Jorge Molina, M.D., Honduras, Central
America.

Tropical Parasitic Infections
269
Diagnosis
The diagnosis of cutaneous disease is established
by finding trophozoites in scrapings or biopsy of
the skin lesion.  The presence of phagocytized eryth-
rocytes or the use of special stains may be helpful in
distinguishing trophozoites from histiocytes in tis-
sue sections.57  Thus, cutaneous amebiasis may be
more amenable to direct diagnosis than intestinal or
liver amebiasis, with their attendant difficulties of
demonstrating the trophozoites or cysts.  Indirect
hemagglutination, immunofluorescence, and
ELISAs are usually positive in patients with
amebiasis, but these tests are variably sensitive in
detecting asymptomatic carriers.64
Therapy
A variety of drugs are available to treat amebiasis
of intestinal and extraintestinal sites.32  Cutaneous
disease seems to respond well to metronidazole;
but emetine, dihydroemetine, and hydroxyquin-
olone have also been reported successful.61,62  Be-
cause metronidazole is well absorbed, iodoquinol
or paromomycin, which achieve higher luminal
concentrations, should be used to eradicate
noninvasive amebae in the intestine.32,56  The doses
are, for metronidazole, 750 mg administered three
times daily for 10 days; for iodoquinol, 650 mg
administered three times daily for 20 days (not to
exceed 2 g/d and not to exceed 20 d); and for
paromomycin, 25 to 30 mg/kg/d, divided and  ad-
ministered in three doses for 7 days.  The pediatric
dosage is discussed elsewhere.32
bloody mucus and fewer leukocytes than are
characteristic of bacterial dysentery may develop.
Nondysenteric intestinal disease may be character-
ized by intermittent constipation, watery or
mushy stools, flatulence, abdominal cramps, fa-
tigue, and weight loss.  Extraintestinal disease,
most often in the form of liver abscesses, can de-
velop in patients who might not have manifested
intestinal symptoms.56
Cutaneous Manifestation
Cutaneous lesions of amebiasis seem to be ex-
tremely rare and are reported in literature as iso-
lated cases.60–62  A review of 5,000 South African
cases found only two patients with cutaneous dis-
ease.63  Proposed mechanisms of cutaneous involve-
ment include direct extension of intestinal disease
onto the skin, extension of liver abscess to the skin,
direct inoculation during anal intercourse, and, in
young children, trophozoites retained in direct con-
tact with the skin under diapers.57,62  Hematog-
enous and lymphatic spread is controversial.  Pa-
tients with lesions, which are most commonly
located in the anogenital region, present with pain-
ful ulcerations that may enlarge rapidly (Figure 12-
20).  The border may be red or violaceous, and the
edges may be verrucous or undermined.  The base
can have granulation tissue and may have a puru-
lent exudate.  The differential diagnosis includes
syphilis, granuloma inguinale, leishmania, deep
fungal infections, tuberculosis, condyloma, inflam-
matory bowel disease, pyoderma gangrenosum,
pemphigus vegetans, and carcinoma.
HELMINTHIC INFECTIONS
Helminth is derived from the Greek word helmins,
meaning worm.  For practical medical purposes, the
helminths are categorized as annelids (ie, phylum
Annelida, the segmented worms), nematodes (ie,
phylum Nematoda, the roundworms), and platy-
helminths (ie, phylum Platyhelminthes, the flat-
worms). The platyhelminths are further subdivided
into trematodes (ie, flukes) and cestodes (ie, tape-
worms) (Exhibit 12-1).  While almost any worm
infestation may elicit nonspecific cutaneous find-
ings (eg, urticaria) or laboratory abnormalities (eg,
eosinophilia), only the characteristic findings that
would suggest skin penetration are emphasized.
Thus, this discussion focuses on nematodes and
trematodes; cestodes are not discussed.
Although sanitary and combat conditions ame-
nable to the acquisition of helminthic infections
existed in many of the theaters of operations in
World War II, it was from the Pacific that infections
were reported in significant numbers.4,65–67  Preva-
lence surveys revealed that 10% to 40% of U.S. troops
had human hookworm infection, perhaps in excess
of 10,000 had filariasis, and more that 1,300 had
schistosomiasis.65–67  Strongyloidiasis was diagnosed
in groups of U.S. military personnel who had been
prisoners of war and who had worked on the Burma–
Thailand Railroad during World War II.68  Outbreaks
of human hookworm disease were documented in the
Vietnam conflict, and in one small study of 75 return-
ing servicemen, the prevalence of human hook-

Military Dermatology
270
EXHIBIT 12-1
HELMINTHS THAT PRODUCE
CUTANEOUS DISEASE
Nematodes (phylum Nematoda: Roundworms)
Hookworms
Human
Animal
Strongyloides stercoralis
Filaria
Dracuncula
Trichinella
Platyhelminths (phylum Platyhelminthes: Flatworms)
Trematodes (flukes)
Schistosomes
Cestodes (tapeworms)
human waste is poor and the proper conditions of
shade, sandy soil, warm temperature, and relatively
high humidity prevail, the eggs hatch in the soil.
Larvae emerge, develop through a series of stages,
and become infective filariform larvae.  On contact
with human skin (eg, bare feet), the larvae penetrate
the skin, pass into the venous circulation, and are
carried to the lung where they rupture into the alveoli.
Then moving up the victim’s respiratory tree to the
pharynx, the larvae are swallowed and come to rest in
the host’s gut, where the larvae mature without in-
vading tissue.  Adult females tend to be larger than
males and may be 9 to 13 mm in length; adult worms
may live 6 years or longer.  Hookworm eggs begin to
appear in human feces within approximately 2
months after the skin was penetrated.71
Cutaneous Manifestations
Manifestations of human hookworm infection
may occur (a) coincident with larval migration to
other tissues or (b) as a result of chronic parasitic
infection of the bowel.  Cutaneous disease develops
when penetration of the skin occurs and is fre-
quently described as “ground itch.”  Most often,
disease develops among people who go into con-
taminated areas without wearing shoes; however,
contaminated soil may come in contact with the
skin by passing through the vents or eyelets in boots
or through holes in torn uniforms, or by being flung
about by troops actively engaged in digging.55  Ex-
perimental studies showed that a first exposure to
the larvae of N americanus produces erythematous
patches 24 hours later at the site of penetration
(Figure 12-21).72  By 48 hours after penetration,
Fig. 12-21. (a) Erythematous patches apparent 24 hours after larvae of Necator americanus have penetrated the skin of
a volunteer. (b) Punctate, petechial papules that developed 48 hours after larvae of Necator americanus penetrated the
skin of a volunteer. Photographs reprinted by permision of Cline BL. Am. J. Trop. Med. Hyg. 1984;33:390.
b
a
worm disease or strongyloidiasis or both ranged from
15% to 55%.56  Although filariasis was endemic, few
cases were ever documented among U.S. troops.55
Finally, an outbreak of human hookworm disease
involving over 200 soldiers who participated in
military operations in Grenada has been reported.69
Human Hookworm Disease
Human hookworm disease is caused by the
roundworms Ancylostoma duodenale and Necator
americanus, both of which are found worldwide.
The life cycle begins when female worms, residing
in the host’s small intestine, release eggs that are
passed in the feces.70,71  When the management of
Figure 12-21 is not shown because the copyright permission granted to the Borden Institute, TMM,
does not allow the Borden Institute to grant permission to other users and/or does not include
usage in electronic media. The current user must apply to the publisher named in the figure legend
for permission to use this illustration in any type of publication media.

Tropical Parasitic Infections
271
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Fig. 12-22. These threadlike, meandering burrows are
caused by Necator americanus. Known as cutaneous larva
migrans, this lesion is typical in patients who are immu-
nologically sensitized to the organism. Photograph: Cour-
tesy of Paul C. Beaver, PhD, Tulane University, New
Orleans, La.
discrete, punctate, erythematous papules are fre-
quently present.  Pruritus is common.  If rechal-
lenged with larvae several weeks after the initial
exposure, the host develops pruritic, erythematous,
edematous, linear, threadlike tracts marking larval
migration in the skin (Figure 12-22).  This burrow is
referred to as cutaneous larva migrans (also called
creeping eruption), a finding also noted in other
parasitic helminthic infections (Table 12-2).  The
tract progresses for approximately 1 week.  With
long intervals between recurrent exposure, the in-
tensity of the cutaneous reaction wanes.73
Pulmonary and Gastrointestinal Manifestations
Pulmonary symptoms attributed to larval migra-
tion through the lung include cough and wheezing,
and radiography may show associated pulmonary
infiltrates.  Gastrointestinal symptoms include ab-
dominal pain, flatulence, nausea, vomiting, and
diarrhea.  Iron deficiency anemia is a characteristic
finding, although it is dependent on the species,
total worm burden, duration of infection, and nutri-
TABLE 12-2
PARASITES THAT PRODUCE A CUTANEOUS LARVA MIGRANS–LIKE ERUPTION
Reprinted with permission from Neafie RC, Meyers WM. Cutaneous larva migrans. In: Strickland GT, ed. Hunter’s Tropical Medicine.
7th ed. Philadelphia, Pa: WB Saunders Company; 1991: 773.
Table 12-2 is not shown because the copyright permission granted to the Borden Institute, TMM, does not
allow the Borden Institute to grant permission to other users and/or does not include usage in electronic
media. The current user must apply to the publisher named in the figure legend  for permission to use
this illustration in any type of publication media.

Military Dermatology
272
tional status of the host.  Eosinophilia may also be
present.69,71,74
Diagnosis and Treatment
Diagnosis of human hookworm disease is made
by finding hookworm ova in stool specimens.  The
current recommended treatment regimen for adults
and pediatric patients is 100 mg of mebendazole
administered orally twice daily for 3 days.  A single,
400-mg dose of albendazole is an alternative.32
Animal Hookworm
Worldwide, Ancylostoma braziliense, the dog or
cat hookworm, is the most common cause of cutane-
ous larva migrans (see Table 12-2 and Figure 12-
23).75  Eggs passed in the feces of infected dogs or
cats hatch in the soil and develop into infective
filariform larvae.  After they penetrate human
skin, these larvae lack the ability to invade further
and complete their life cycle.  Thus, they meander
erratically through the epidermis producing
raised, threadlike, serpiginous, pruritic, erythema-
tous tracks that extend a few centimeters a
day.  Attempts to demonstrate the worm by biopsy
are usually futile because the cutaneous change
develops after the larva’s passage.  Because the
human is a “dead-end” host, the parasite usually
dies.  However, one study has shown that if un-
treated, 64% of patients continued to have lesions
after 4 weeks, although the total number of lesions
was markedly decreased.76  Pulmonary and gas-
trointestinal symptoms do not develop because sys-
temic invasion of and infection with these parasites
do not occur.
The cutaneous lesions of dog or cat hookworm
may be treated topically with 10% thiabendazole
suspension four times daily for 7 days, or until 1 or
2 days after the last tracks have resolved, is effec-
tive.77,78  Thiabendazole (50 mg/kg/d, divided and
administered in two doses, maximum 3 g/d, for 2–
5 d) may be used if oral treatment is elected.  Toxic-
ity may require dose reduction.32
Strongyloidiasis
After penetrating the skin, Strongyloides stercoralis
(commonly known as threadworm) takes a migra-
tory pathway virtually identical to that of the hu-
man hookworm.  Eggs generally hatch in the bowel
mucosa, and thus the larval form rather than eggs
are found most often in the feces.  However, once
the mature female worm (approximately 1 mm in
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a
b
Fig. 12-23. (a) Thread-like serpiginous, meandering bur-
row of cutaneous larva migrans. (b) Multiple serpiginous
burrows of cutaneous larva migrans of the back of a
patient. Photograph b: Courtesy of Jorge Molina, M.D.,
Honduras, Central America.

Tropical Parasitic Infections
273
size) starts producing eggs, propagation takes one
of three forms79:
1.
Passed in the feces, the larvae develop to an
infectious stage, which finds another hu-
man host to penetrate.
2.
Alternatively, under ideal climatic condi-
tions, the larvae may develop into adults in
the soil and thus propagate outside the
host.
3.
Finally, in the autoinfection cycle, the in-
fectious larvae develop in the bowel of an
infected host.  Instead of passing in the
feces, these infectious larvae penetrate the
bowel mucosa or perianal skin and migrate
back to the lung to resume the migratory
cycle and perpetuate the infection in the
same host.
Just as with human hookworm, the three phases
of clinical manifestations of strongyloidiasis, which
correspond to the migratory pathway, are the cuta-
neous, pulmonary, and gastrointestinal.71,79
Cutaneous Manifestations
Penetration of the skin and tissue migration
are associated with parasitic secretion of a
metalloprotease, which degrades the elastin
and the dermal extracellular matrix.80  Most
often seen in the autoinfection cycle, the distinctive
cutaneous eruption is that of a migratory linear
or serpiginous, pruritic, erythematous, urticarial
band (Figure 12-24), which may move as much
as 10 cm or more per day.  Because of its rapid
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Fig. 12-24. (a) A serpiginous, urticarial track of Strongyloides stercoralis. (b) In the same patient, the eruption that was
present on initial examination at 1130 hours was traced using a surgical marking pen. The unmarked portion shows
how far the burrow had progressed in only 30 minutes (ie, by 1200 hours on the same day).
movement, this eruption is often referred to as larva
currens.
Pulmonary, Gastrointestinal, and Hematological
Manifestations
Pulmonary symptoms or findings may include
cough, hemoptysis, shortness of breath, wheezing,
and transient pulmonary infiltrates.  Gastrointesti-
nal symptoms include abdominal pain, vomiting,
bloating, and diarrhea.  Weight loss and eosinophilia
are common findings.  Of particular significance is
the fact that up to 40 years later the infection may
persist.68,81–85  Persistent infection, when combined
with suppression of the immune system, may result
in an overwhelming, potentially fatal, infection as-
sociated with multiorgan larval invasion and
bacteremia.86–88  In these patients, the multiple lin-
ear burrows of strongyloides may have a hemor-
rhagic or petechial component.89
Diagnosis and Treatment
The cutaneous eruption is diagnostic of stron-
gyloidiasis, and in its absence the diagnosis can be
quite difficult.  Finding larvae or, rarely, eggs in
feces is a tedious and time-consuming task.  Sero-
logic tests by means of ELISA or indirect immuno-
fluorescence may be helpful.90,91  Treatment for both
children and adults is with thiabendazole 50 mg/
kg/d, divided and administered in two doses (maxi-
mum 3 g/d) for 2 days.  Patients with disseminated
strongyloidiasis may require a 5-day course of therapy;
treatment of patients who are immunocompromised
may require further modification.32
b
a

Military Dermatology
274
Filariasis
Eight species of roundworm belonging to the
family Filarioidea (hence the name filariasis) de-
velop to adulthood in humans; of them, six are
generally accepted as being pathogenic (Table 12-
3).92  The life cycles of the filariae are similar.92,93
Microfilarial larvae in the blood of the human host
are ingested when the insect vectors feed on in-
fected humans.  Within the vector, the microfilariae
migrate to specific sites and develop from first-
stage larvae into infective third-stage larvae.  Then,
when feeding, the vector transmits the infective
larvae into a human, where the organism molts
twice more to become an adult worm.  The adult
worm may be found in the lymphatic vessels, lymph
nodes, or subcutaneous tissue.
The following observations have been made re-
garding the host–parasite interaction94:
• In endemic areas, a large percentage of the
populace may have microfilaremia but little
detectable disease.
• Individuals immigrating to areas of ende-
micity may experience symptoms due to in-
fection with adult worms and yet not have
demonstrable microfilaremia.
• Symptoms may vary markedly among those
who develop overt infection.
It is the interplay of humoral and cellular im-
mune responses that determines the manifestation
of disease.95  Most individuals in endemic areas
seem to develop a humoral antifilarial IgE response.
Effector immunological responses (eg, lymphocyte
proliferative response, gamma interferon genera-
tion, or IgE and IgG production) to microfilariae
seem to be specifically and actively suppressed in
those patients without clinical disease.  In endemic
areas, the effector responses are enhanced in a small
percentage of individuals, who develop the clinical
manifestations of the disease.  Tolerance to parasitic
infection (ie, there is no overt clinical disease) may
be prenatally determined by exposure to filarial
antigens.  The mechanisms that cause a shift from
tolerance (with suppression of specific immune re-
sponses) to responsiveness (with expression of ef-
fector immune responses) are unknown.  Individu-
als from nonendemic areas develop characteristic
inflammatory responses typical of the diseases by
virtue of intact effector immune responses when
they move into endemic areas.  Thus, the vast ma-
jority of these individuals are without detectable
microfilaremia.66
TABLE 12-3
FILARIAE OF MEDICAL SIGNIFICANCE
Organism
Vector
Wuchereria bancrofti
Mosquito
Brugia malayi
Mosquito
Brugia timori
Mosquito
Loa loa
Deerfly (Chrysops)
Onchocerca volvulus
Blackfly (Simulium)
Mansonella streptocerca
Midge (Culicoides)
Bancroftian Filariasis
Bancroftian filariasis is due to filarial infection
with Wuchereria bancrofti, which is found focally in
tropical and subtropical regions throughout the
world: sub-Saharan Africa, Asia, the South Pacific
and western areas of the Pacific, the Caribbean
region, the eastern coastal plains of South America,
and portions of Central America.96–98  The adult
worms are found in the patient’s lymphatic vessels
and nodes and may produce microfilariae over a 2-
to 4-year period.  Female worms measure approxi-
mately 100 mm x 0.3 mm; males are about one half
that size.  Microfilariae generally are absent from
the bloodstream during the day and are found in
greatest numbers during the 4-hour period before
and after midnight (ie, nocturnal periodicity)—cor-
responding to the feeding habits of the mosquito.  In
contrast is the diurnal periodicity seen in the South
Pacific—a phenomenon that is an adaptation to the
day-feeding habits of the local mosquitoes.  The
vectors of disease are mosquito species of the gen-
era Anopheles, Culex, and Aedes.  Marked variation
exists with regard to efficiency of transmission:
in Rangoon, Burma (now known as Yangon,
Myanmar), 16,000 bites of infected mosquitoes pro-
duced but one overt case of Bancroftian filariasis;
whereas in rural Tanzania, 200 bites per person per
year maintained infection within the population.96
Clinical Manifestations.  In individuals from
nonendemic areas, manifestations of Bancroftian
filariasis begin within 5 to 18 months of being bitten
and are localized to the genitalia (42%), arms (25%),
and legs (11%).96  Genital disease includes edema of
scrotal skin, funiculitis, epididymitis, orchitis, and
hydrocele.  A distinctive lymphangitis of the arms
or legs develops in many patients and is character-
ized by a unique retrograde spread or extension.

Tropical Parasitic Infections
275
Starting in a single node, erythematous patches of
subcutaneous edema, or diffuse erythema and
edema, develop and progress distally.  Although
the nodes and lymphangitis are tender, pain is not
significant.  Constitutional signs and symptoms
may vary from no symptoms at all to headache,
backache, fatigue, and, in some cases, fever, chills,
and malaise.96,98,99  The onset of genital and
adenolymphangitis is often acute, lasts a few days,
and is recurrent.  Increased heat, physical activity,
and fatigue seem to precipitate relapses.
The inflammatory histological response to the
adult and, more importantly, dead or dying filariae
may result in the clinical manifestations of filariasis.96
Yet, in a small study that spanned 16 years after
World War II, while the percentages of infected
servicemen who experienced recurring attacks of
disease increased, none developed elephantiasis or
chronic disabling disease.100  This favorable out-
come was attributed to rapid evacuation of service-
men with acute filariasis.  For it is repeated, acute
attacks from repeated infection that are thought to
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Fig. 12-25. This patient’s unilateral elephantiasis is caused
by filariasis. Photograph: Courtesy of Armed Forces In-
stitute of Pathology. Negative 78873.
produce lymphatic scarring severe enough to ob-
struct the lymphatics, producing elephantiasis (Fig-
ure 12-25).
Diagnosis.  Diagnosis of Bancroftian filariasis is
made by associating signs and symptoms with a
history of travel to endemic areas.  Eosinophilia
may be present in acute disease.  Identification of
microfilariae (among residents in endemic areas in
whom this is typical) in peripheral blood smears
 is the best means to establish the diagnosis.
Immunodiagnostic assays to detect infection are
being actively pursued with deoxyribonucleic acid
(DNA) probes showing great promise; ELISAs are
available in some laboratories.95,96
Treatment.  Diethylcarbamazine, which has been
the standard of treatment for years, kills microfi-
lariae and is toxic to adult worms when adminis-
tered in the following adult doses32,96:
• Day 1: 50 mg, administered orally after a
meal
• Day 2: 50 mg, administered orally three times
per day
• Day 3: 100 mg, administered orally three
times per day
• Days 4 through 21: 6 mg/kg/d, adminis-
tered orally in three doses
However, in a study of asymptomatic patients with
microfilaremia, ivermectin in single doses seems
to be effective in long-term suppression of
microfilaremia.101,102  Ivermectin’s effect on the adult
parasite is unknown.  Nevertheless, eradicating the
microfilariae is the key to stopping vector-borne
transmission.
Malayan Filariasis and Timorian Filariasis
Malayan filariasis and Timorian filariasis are due
to Brugia malayi and Brugia timori, respectively, and
are more limited in their geographical distribution
than is Bancroftian filariasis.96  Both diseases are
found in or near Indonesia; B malayi is found in
Malaysia and the Philippines as well.  Humans still
serve as the primary reservoir hosts; however, ani-
mals may also serve as reservoirs for B malayi.  In
both diseases, axillary or inguinal lymphadenitis,
lymphangitis, and fever are common.  Lymphatic
abscesses and resultant scarring are common.  In
areas where Malayan filariasis is endemic,
elephantiasis is uncommon; when it does occur, it
tends to involve the distal portions of the extremity.
Lymphedema of the leg frequently progresses to
elephantiasis in Timorian disease.

Military Dermatology
276
OK to put on the Web
Fig. 12-26. Microfilaria of Loa loa. Photograph: Courtesy
of Armed Forces Institute of Pathology. Negative 75-
6618.
Loiasis
Loiasis is caused by infection with Loa loa and is
found in the rain forests of central and West Af-
rica.103  The adult female worm measures 50 to 70 mm
x 0.55 mm; the male is approximately one half the
size.  Both can be found in the subcutaneous tissue
of the skin.  In patients with microfilaremia, mi-
crofilariae are found in the bloodstream in highest
numbers during the day, thus showing what is
termed diurnal periodicity (Figure 12-26).  Deerflies,
large flies of the genus Chrysops, are the vectors of
disease (Figure 12-27).  The flies live under the rain
forest canopy near streams and are attracted by the
movement of people or vehicles below.
OK to put on the Web
Fig. 12-27. A deerfly of the genus Chrysops—the usual
vector of Loa loa. Photograph: Courtesy of Armed Forces
Institute of Pathology. Negative 72-4516.
OK to put on the Web
Fig. 12-28. An adult Loa loa being removed from a patient’s
eye. Photograph: Courtesy of Armed Forces Institute of
Pathology. Negative 75-1789-4.
Clinical Manifestations.  A study of 20 individu-
als from nonendemic areas who visited an endemic
area found that generalized or localized pruritus
(75%); transient, nontender areas of angioedema
(70%); and urticaria (55%) were the major signs and
symptoms.104  Ocular involvement, manifested as a
worm migrating subconjunctivally, was noted in
only one patient (Figure 12-28).  Five of the 20
patients were asymptomatic and their disease was
detected only by virtue of eosinophilia.  Laboratory
abnormalities include marked eosinophilia, elevated
IgE, and hematuria.
The transient sites of angioedema, known as Cala-
bar swellings, are thought to represent allergic reac-
tions to antigenic substances that are produced by
the migrating adult worm.103,104  These swellings
persist for hours to days and 1 to 150 days can elapse
between recurrences.  Of the 14 patients with Cala-
bar swellings, 8 had more than six episodes in the
11-month (on average) interval between the onset
of symptoms and treatment.104
Diagnosis.  Definitive diagnosis is made by re-
covering a worm, either one migrating under the
conjunctiva or one from a subcutaneous nodule.  In
natives of endemic areas, diagnosis may be made by
identifying microfilariae in the blood.  Otherwise,
clinical symptoms and findings, laboratory find-
ings, and response to treatment are the means of
diagnosis.103,104
Treatment.  Treatment is with diethylcarbamazine
in the following adult doses32:
• Day 1: 50 mg administered orally after a meal
• Day 2: 50 mg administered orally three times
per day

Tropical Parasitic Infections
277
• Day 3: 100 mg administered orally three
times per day
• Days 4 through 21: 9 mg/kg/d administered
orally in three doses
However, in patients with marked microfilaremia,
corticosteroid treatment (or even plasmapheresis)
may be necessary to prevent iatrogenic meningo-
encephalitis, which may occur even when very low
initial doses (ie, 10 mg) are used.105  The appearance
of subcutaneous nodules containing the worm
and hematuria may be associated with treatment,
as well.105
Onchocerciasis
Onchocerciasis develops in response to infection
with Onchocerca volvulus.  In 1985, it was estimated
that 86 million people lived in endemic areas and of
these, 17.8 million were infected.106  More than 99%
of infected individuals live in tropical Africa; the
remainder are found in Yemen, Mexico, and coun-
tries in Central America and South America.  Adult
worms are often found encapsulated within fibrous
nodules in the dermis and subcutaneous tissues
near the bony prominences (Figure 12-29).  Female
worms, measuring 20 to 50 cm in length and 0.45 to
0.5 mm in width, may live up to 15 years, producing
1 million or more microfilariae per year.  Microfi-
lariae, which may live 6 months to 2 years, concen-
trate in the dermis, eyes, and regional lymph nodes
(Figure 12-30).106,107  In addition to the nodules
formed in response to the adult worm, the disease
manifestations are determined by the inflamma-
tory response elicited by the migration or degenera-
OK to put on the Web
Fig. 12-29. Coiled worms can be seen in this fibrous
nodule of onchocerciasis. Photograph: Courtesy of Armed
Forces Institute of Pathology. Negative 69-3639.
OK to put on the Web
Fig. 12-30. A biopsy from a patient infected with
Onchocerca volvulus. Numerous microfilariae (arrow) can
be seen in the dermis. Photograph: Courtesy of Armed
Forces Institute of Pathology. Negative 73-5681.
tion of microfilariae.108  Furthermore, there are dif-
ferences in the clinical presentations of the disease
in different geographical locales.107  Blackflies of the
genus Simulium are the vectors of disease (Figure
12-31).108  Because the flies favor habitats along
rapidly moving streams or rivers, the disease tends
to be focally distributed.
Clinical Manifestations.  Dermatitis is one of the
first signs of onchocerciasis.106–109  In the typical
African patient who is developing an immunologi-
cal response to microfilariae, a symmetrical, pru-
ritic, papular dermatitis of the lower trunk and
extremities develops.107,109  Chronic dermatitis sec-
ondary to the response to a heavy microfilarial load
is associated with scaling, hypopigmentation (leop-
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Fig. 12-31. A specimen of Simulium damnosum, the blackfly
vector of onchocerciasis in Africa. Photograph: Courtesy of
Armed Forces Institute of Pathology. Negative 72-4519-E.

Military Dermatology
278
ard skin), edema, and lichenification (elephant skin),
ultimately followed by the appearance of atrophy
(lizard skin) (Figure 12-32).106,107,109  In Yemen, in-
fected patients who mount a brisk immune response
(with concomitant marked decrease or absence of
microfilaremia) develop sowda: edema, hyperpig-
mentation, a pruritic papular eruption, and
adenopathy; the condition is generally confined to
one anatomical quarter or one limb.109  In travelers
who immigrate to endemic areas, sowda is the dis-
ease manifestation that commonly develops.106  Early
in the course of onchocerciasis, the differential di-
agnosis includes contact dermatitis, scabies, and
miliaria; later manifestations of chronic disease
might suggest vitiligo, pinta, yaws, streptocerciasis,
or leprosy.
Dermal and subcutaneous fibrotic nodules en-
close adult worms and tend to be located over bony
prominences in the skin.107  In Africa, these are
found around the pelvis and lower extremities,
whereas in Guatemala and Mexico, the head and
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OK to put on the Web
upper part of the body are the more common sites
(Figure 12-33).  Microfilariae may accumulate in
nodes that drain the areas of dermatitis.  In some
African patients, the inflammation and subsequent
fibrosis and atrophy may cause lymph nodes or
portions of bowel to hang in pockets of skin—the
“hanging groin” of onchocerciasis (Figure
12-34).106,107,110
In heavily infected endemic areas, up to 15% of
the community may be blind as the result of the
inflammatory reaction to onchocercal microfilariae
in the eye.107  Patients who are acutely ill with
onchocerciasis may have corneal opacites, while
individuals who are chronically heavily infected
may develop sclerosing keratitis, uveitis, and
chorioretinitis.
Diagnosis.  The diagnosis is usually established
by obtaining bloodless skin snips taken over bony
prominences or at sites of clinical manifestations.107
Several hours after the specimens have been placed
in saline or culture media, microscopical examina-
Fig. 12-33. Onchocercal nodules on the scalp of a child
from Central America. Photograph: Courtesy of Captain
Kenneth F. Wagner, Medical Corps, U.S. Navy (ret),
Bethesda, Md.
Fig. 12-32. The depigmentation found in chronic
onchocerciasis. Note also the onchocercal nodule at the
patient’s left knee. Photograph: Courtesy of Armed Forces
Institute of Pathology. Negative 72-17223.

Tropical Parasitic Infections
279
OK to put on the Web
Fig. 12-34. These bilateral inguinal and femoral adeno-
lymphoceles are the “hanging groins” of onchocerciasis.
Photograph: Courtesy of Armed Forces Institute of Pa-
thology. Negative 73-6655.
ted by the midge Culicoides grahami.  Adult worms
are found in the dermis of the patient’s upper trunk.
The microfilariae are found in the dermis and lymph
nodes but have not been found in the eye.  Pruritus,
hypopigmented macules, axillary or inguinal
adenopathy, and occasionally a few papules com-
prise the cutaneous manifestations.  Diethyl-
carbamazine kills both the adult worm and microfi-
lariae and prompts an exacerbation of cutaneous
symptoms analogous to a Mazzotti reaction.111
Dracunculiasis
Dracunculiasis, also called Guinea worm or
Medina worm, is caused by the nematode Dracun-
culus medinensis and is found focally in Africa, In-
dia, and Pakistan.112,113  Of the 160 million people at
risk, 10 to 15 million may be infected annually.113
The cycle of human infection begins when the fe-
male worm discharges larvae into fresh-water
sources.  Copepods (microcrustaceans approxi-
mately 1–3 mm in length) of the genus Cyclops
ingest the larvae, becoming the intermediate host.
Copepods are found in bodies of standing (rather
than flowing) water.  Within this intermediate host,
the larval parasite develops into an infective larva;
humans become infected when they drink water
containing the infected copepods.  In the gastric
milieu, the larva is freed from the copepod and
proceeds to penetrate the human host’s small intes-
tine to reach the peritoneum, where it matures.  The
worm (measuring 70–120 cm x 0.17 cm) migrates to
the skin where, when the human host is in contact
with water, it ruptures through the skin to release
the larvae into fresh water.  The cycle from inges-
tion of filariae to release of filariae takes approxi-
mately 8 to 12 months.
Clinical Manifestations.  Signs and symptoms of
dracunculiasis are generally associated with the
presence of the adult worm in the subcutaneous
tissue.112–114  In general, the site of eruption is on the
lower extremity and is signified by the presence of
a painful, erythematous nodule up to 7 cm in diam-
eter, a pruritic blister, or both.  At about the same
time, constitutional symptoms such as urticaria,
nausea, vomiting, diarrhea, syncope, and fever may
occur.  Eosinophilia is common and may be marked.
Worms that migrate to aberrant locations (other
than to the skin of a lower extremity) die and form
abscesses that may resolve with calcification.
Diagnosis.  Diagnosis may be readily obvious if
the worm is carefully examined as it emerges from
the nodule or blister (Figure 12-35).  Slowly extract-
ing the worm by wrapping it around a small stick
tion of the fluid will reveal microfilariae.  Biopsy of
a nodule will reveal an adult worm.  Slitlamp ex-
amination of the eye may reveal microfilariae.
Eosinophilia is a characteristic, nonspecific finding.
Serologic testing is hampered by false-positive cross-
reactions with other helminths; however, more spe-
cific tests are being developed.
Treatment.  Ivermectin 150 µg/kg administered
orally once every 6 to 12 months is the treatment of
choice for onchocerciasis.32  Ivermectin is a well-
tolerated drug that is toxic to microfilariae.  Because
it has no effect on the adult worms, it is given at
regular intervals to destroy or stop the release of
microfilariae.32,106,107  Ivermectin is not used to treat
disease in children under 5 years of age, pregnant or
lactating women, or patients who are otherwise ill.
In the past, diethylcarbamazine was employed in
the treatment, but such treatment was fraught with
problems.107  When given to acutely ill patients, it
caused a flare of the cutaneous symptoms; in heavily
infected individuals, it caused severe constitutional
symptoms, including marked worsening of the eye
lesion.  Administering doses small enough to elicit
a mild exacerbation of symptoms was the basis of a
potentially dangerous, indirect method of diagno-
sis known as the Mazzotti test, which has fallen into
disfavor.
Streptocerciasis
The filarial disease streptocerciasis is caused by
infection with Mansonella streptocerca.  The disease
is found in central and West Africa and is transmit-

Military Dermatology
280
released.  Attaching to the luminal wall, the larvae
mature into adults, with the female measuring 3 to
4 mm in length x 60 µm in width and the male one
half that size.  Before the adults are expelled from
the gut about 2 weeks later, they produce larvae
that penetrate the gut and disseminate through the
venous and lymphatic circulation.  The larvae pref-
erentially invade skeletal muscle and encyst, where
they remain viable for years.  The animal sources of
human infection acquire the disease by feeding on
the raw flesh of infected prey or carrion or on
uncooked household meat scraps.
Clinical Manifestations.  Signs and symptoms of
infection develop 2 to 12 days following infection;
the severity is influenced by the number of cysts
ingested as well as the immunological response,
which is determined by previous infection.116  Most
infections are asymptomatic.  While adult worms
inhabit the intestine, patients may experience diar-
rhea, constipation, abdominal pain, and anorexia or
vomiting as a result of mucosal irritation.115–117  The
phase of muscle invasion is associated with
myalgias, fever, and periorbital edema.  Splinter
hemorrhages, conjunctival hemorrhages, and
maculopapular eruptions may also be found.116
Severely infected patients may develop encephali-
tis, meningitis, myocarditis, bronchopneumonia,
and nephritis.115,117  Eosinophilia is a characteristic
finding, although it may not occur during the first
week of disease.
Diagnosis.  The larvae may be found by incision
biopsy of an infected muscle.  However, serologic
tests such as the bentonite flocculation test, the
fluorescent antibody test, or the ELISA can detect
the disease 2 to 3 weeks after the infection occurs.
Treatment.  The disease is usually self-limited
and requires no treatment.  Corticosteroids have
been used to reduce severe inflammation.  Addi-
tionally, patients experiencing prolonged or severe
illness, may be given mebendazole in the following
adult dose: 200 to 400 mg three times daily for 3 days,
then 400 to 500 mg three times daily for 10 days.32
Schistosomiasis
The phylum Platyhelminthes contains the dorso-
ventrally flattened worms; of these parasites, blood
flukes (schistosomes) belonging to the class
Trematoda and genus Schistosoma are the most im-
portant producers of disease in humans.  Schisto-
somiasis is the term generally reserved for disease
produced in humans by the schistosomes Schistosoma
mansoni, S haematobium, S japonicum, S mekongi, and
S intercalatum.
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Fig. 12-35. Dracunculus medinensis that has been removed
from its resting site at the surface of the patient’s skin.
Photograph: Courtesy of Armed Forces Institute of Pa-
thology. Negative 67-1563-3.
has been tried, but excision of the nodule may be a
better removal technique because it is less likely to
incite inflammation.112
Treatment.  Treatment is with metronidazole (for
adults: 250 mg administered three times daily for 10
days; the dosage for children is discussed else-
where) or thiabendazole (adult and pediatric doses:
50 mg/kg/d, divided and administered in two doses
for 3 d).32
Neither metronidazole, which is the drug of
choice, nor thiabendazole kills either the worm or
the larvae, but both drugs may be useful in reducing
inflammation caused by the emerging worm.32,113
Development of safe water supplies may be the best
method of eradicating the disease.  Until water
supplies are safe, water suspected of being contami-
nated should be avoided, and infected individuals
should stay physically removed from the water
supply source.
Trichinosis
Trichinosis develops when humans ingest inad-
equately cooked meat containing Trichinella
spiralis.115–117  Although traditionally pork is cited as
the source of infection, any meat-eating animal may
harbor infective larval cysts.  T spiralis in pork is
killed if the meat is fully cooked for 4 minutes at
135°F; however, 170°F is recommended to provide
a margin for error.  Refrigeration is another means
for killing cysts.115
The acidity and enzymatic activity of the human
digestive system disrupt the cyst and the larvae are

Tropical Parasitic Infections
281
Of the estimated 1 billion people worldwide at
risk for schistosomiasis, 200 million living in 75
countries are thought to be infected.118  S mansoni
occurs throughout much of sub-Saharan Africa,
portions of the Arabian peninsula, countries along
the eastern coast of South America, and in the Car-
ibbean.  S haematobium is found in Africa and the
Middle East, while S japonicum is restricted to China,
Indonesia, and the Philippines.119,120  Of these three,
schistosomiasis produced by S japonicum is the most
pathogenic, due to the greater number of eggs pro-
duced, and the most widespread.  Two other spe-
cies of limited geographical distribution also pro-
duce disease: S mekongi in Southeast Asia and S
intercalatum in central Africa.120
During World War II, approximately 1,300 to
2,000 servicemen developed acute schistosomiasis
in the Philippines.67,121  Outbreaks of an acute sys-
temic illness were reported from Vietnam; how-
ever, investigations suggested they were caused by
schistosomes that typically do not parasitize hu-
mans.122  Although no large-scale infections of
schistosomiasis have been reported recently among
U.S. military forces, outbreaks with high rates of
infection among groups traveling in endemic areas
emphasize the significant potential risk.123
The life cycle of the parasite begins with the
production of eggs by an adult pair of flukes, which
live in the venous plexus of the bladder or mesen-
teric plexus of the human host.118  The species of
schistosomes differ in their rate of egg production.
The egg contains a miracidium (a larval form) that
secretes enzymes that allow the egg to pass through
the blood vessel and into the lumen of the bowel or
bladder, from which it is then expelled.  On reach-
ing fresh standing or slowly moving water, and
with correct conditions of light and temperature,
the egg hatches, releasing the miracidium.  First, the
miracidium finds and penetrates one of the specific
snails that serve as intermediate hosts; then each
miracidium undergoes extensive asexual multipli-
cation, with the result that a multitude of cercariae
(final-stage larvae) are produced within the snail.
With proper conditions of light, the cercariae, which
have a head and a Y-shaped tail, are released into
the water.  Then, encountering humans, individual
cercaria attach and release proteolytic enzymes that
enable the cercaria to penetrate human skin.  At the
same time, the cercaria’s tail is lost.  Now known as
a schistosomulum, it penetrates the dermis and passes
to the lungs.  From the lung, by mechanisms that are
unclear, the schistosomulum passes to the host’s
liver, where it matures in the portal circulation to an
adult schistosome.  Adult worms then migrate to
specific venous plexuses, where they produce eggs
that are either (a) excreted to repeat the cycle or (b)
pass in the venous system to other organs.
Humans are thought to be the main reservoir
host for S mansoni and S haematobium.121  On the
other hand, S japonicum has been shown to infect a
wide variety of domestic animals (eg, dogs, cats,
goats, pigs, horses, water buffalo, cattle) and ro-
dents, which then serve as additional reservoirs.119,121
The host–parasite interaction in the production
of disease is complex.119,124  By acquiring host anti-
gens, the adult worm may effectively disguise itself
and not incite a host immunological response.  Thus,
an adult fluke (measuring 12–26 mm x 0.3–0.6 mm)
may reside in vessels of the venous plexus for 3 to 7
years, on average.118  However, penetration of the
schistosomulum elicits a brisk cell-mediated cyto-
toxic response, in which IgE and eosinophils are
important components.  A reaction similar to that
elicited by an immune complex formation is pre-
cipitated by worm migration, the initial reaction to
egg production by mature female worms, or both.
The granulomatous response to the eggs, which
results in obstruction of vessels, is thought to be
the major determinant of pathological manifesta-
tions of chronic disease.  Acute schistosomiasis is a
disease usually limited to travelers entering
 endemic areas and being exposed for the first time.
In endemic areas, most of those infected are
asymptomatic and major disease manifestations
develop only in a small percentage of heavily in-
fected individuals.119
Clinical Manifestations.  When the cercariae
contact the skin and begin their penetration, a tran-
sient pruritus or burning and erythematous macules
or urticarial papules may develop.119,125,126  Over the
next 3 days, a punctate hemorrhagic component
followed by crusting develops at the site.  After
several weeks, the eruption resolves, leaving
postinflammatory hyperpigmentation.  In humans,
this cercarial dermatitis is known as schistosomal
dermatitis, is less severe than that produced by
nonhuman schistosomes, and may be more severe
in individuals who have been sensitized by previ-
ous exposure.119
An acute syndrome that begins suddenly occurs
in infected individuals and seems to be related to
either migration of the worm or the initial release of
eggs by the mature worm.119,121,125–127  The acute
syndrome, known as Katayama fever, occurs 2 to 6
weeks after penetration by cercariae and may last 1
to 2 months.  Manifestations include spiking after-
noon fevers, chills, bronchitis, pneumonitis, head-
ache, lymphadenopathy, hepatosplenomegaly, joint

Military Dermatology
282
pain, diarrhea, urticaria, eosinophilia, leukocyto-
sis, and an elevated erythrocyte sedimentation rate.
Katayama fever is thought to be due to immune
complex formation, but, interestingly, proteinuria
and glomerulonephritis are not features of this stage
of disease.124
A late hypersensitivity reaction characterized by
generalized urticaria, pruritus, lichenified papules,
or dermatographism occasionally develops (Figure
12-36).  This may be due to a nonspecific reaction to
egg deposition.126
Chronic schistosomiasis is due to a granu-
lomatous response to egg deposition in target tis-
sues.  Localized in the venous plexus of the host’s
bladder, S haematobium releases its eggs, resulting
in a characteristic urogenital syndrome in which
hematuria, obstructive uropathy, and bladder can-
cer figure prominently.  The other schistosomes
that cause disease in humans are found in the venous
plexus of the bowel: S japonicum in the superior
mesenteric plexus and S mansoni in the inferior
mesenteric plexus.119  Egg granulomas in portal
presinusoidal vessels result in hepatomegaly,
splenomegaly, varices, ascites, and fibrosis
(Symmers’ clay pipestem); those in the mesenteric
distribution produce protein-losing enteropathies,
malabsorption anemias, hemorrhagic intestinal
polyps, and fibrosis.
Aberrant or embolic lodgment of eggs may pro-
duce lesions in a variety of other tissues, including
the kidney, lung, CNS, and, rarely, the skin.119  When
skin lesions occur, they are most commonly due to
S haematobium; genital and perigenital sites are more
frequent and periumbilical less frequent sites of
involvement.119,125–132  The lesions may be papules,
macules, or, especially in the female genitalia, warty
tumors.  Cutaneous lesions may be asymptomatic,
pruritic, or painful.  Complications of disease may
include ulcerations, fissures, multiple sinuses, fis-
tulae, and fibrosis.
Diagnosis.  It is systemic illness rather than cuta-
neous disease that leads the patient to seek treat-
ment.125  The diagnosis of Katayama fever is consid-
ered when patients who recently have been in an
endemic area present with fever, headache, fatigue,
diarrhea, or eosinophilia.123  Chronic illness due to
complications of egg granulomas is suspected more
readily because patients are in endemic areas.  Dif-
ficulties may arise, though, when such patients
present in nonendemic areas to physicians who
may be less familiar with the disease.
Finding ova in the feces or urine is the standard
method of diagnosis: S haematobium is an oval egg
OK to put on the Web
Fig. 12-36. This African patient developed these hyper-
pigmented nodules of cutaneous schistosomiasis on his
abdomen as a manifestation of his infection with
Schistosoma mansoni. Photograph: Courtesy of Armed
Forces Institute of Pathology. Negative 78-3500-1.
with a terminal spine, while the spine of S mansoni
is lateral, and that of S japonicum is small and rudi-
mentary. In acute schistosomiasis, egg production
may not be detectable.  Biopsy of specific (ie, egg-
induced) cutaneous lesions may well reveal granu-
lomas.  Reliable serologic diagnosis is currently
limited to a few research laboratories; a sensitive
ELISA seems to be the most promising.119
Treatment.  Treatment of all human schisto-
somiasis is with praziquantel.  One schedule calls
for 40 mg/kg/d administered orally in two doses
for 1 day, except for S japonicum and S mekongi,
which are treated by administering 60 mg/kg/d in
three doses for 1 day.32
Because of water-control measures, bodies of
water in which snails, the fluke’s intermediate host,

Tropical Parasitic Infections
283
thrive are increasing.  With population migration,
then, schistosomiasis is actually spreading.  In en-
demic areas, all fresh water should be considered
contaminated.  When using such water for bathing
purposes, pretreatment by heating to 122°F for 5
minutes or by using chlorine or iodine in concentra-
tions similar to those used for treatment of drinking
water should be used.  Also, vigorous toweling or
application of rubbing alcohol after potential expo-
sure may prevent cercarial penetration.123  Studies
are ongoing to develop barrier substances that would
limit skin penetration and subsequent infection.
SUMMARY
Medical support of U.S. armed forces is critical to
soldiers’ health and effectiveness.  The failure to
provide timely diagnoses and effective treatment of
cutaneous diseases may cause a serious degrada-
tion in the individual’s physical condition and, there-
fore, effectiveness.  Further, the psychological im-
pediment that can develop in soldiers so afflicted
should not be denigrated.  Thus, the medical officer
should never forget the maxim that common dis-
eases are common.  While this generally is con-
strued to mean that bacterial and, perhaps, fungal
diseases will cause the bulk of cutaneous disease, in
the tropics we should not underestimate the mor-
bidity that indigenous diseases can cause.
Tropical regions are host to a number of diseases
with which physicians trained in the United States
have little practical experience.  With proper cloth-
ing, appropriate use of insect repellents, proper
food handling, and good training in sanitation and
hygiene, soldiers may be able to avoid some of these
diseases.  Nevertheless, the wary medical officer
must remain alert to the possibility that these con-
ditions may develop among the troops; the physi-
cian will certainly encounter them in the population
native to the area.  Medical personnel who live in
these areas are excellent and important sources of
information about local health risks.  The Armed
Forces Medical Intelligence Center at Fort Detrick,
Frederick, Maryland, can provide information about
regional risks.  Coupled with that information,
knowledge of the cutaneous manifestations that are
often keys to the diagnosis should provide the medi-
cal officer the opportunity to diagnose accurately
and to initiate effective treatment in a timely fash-
ion.
Finally, medical officers should make every ef-
fort to consult regularly published periodicals for
the latest treatment update, as treatments for these
diseases are evolving.  The doses listed in this chap-
ter generally apply to adults.  It is important to note
that treatment of debilitated, frail patients; the eld-
erly; children; and pregnant women may vary from
the drugs and schedules listed in this chapter.  The
Medical Letter on Drugs and Therapeutics publishes a
regular update of the drugs used for treatment of
parasitic infection.
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Connor DH, Gibson DW, Neafie RC, Merighi B, Buck AA. Sowda–onchocerciasis in North Yemen: A clinico-
pathologic study of 18 patients. Am J Trop Med Hyg. 1983;32:123–137.
110.
Nelson GS. “Hanging groin” and hernia, complications of onchocerciasis. Trans Roy Soc Trop Med Hyg.
1958;52:272–275.
111.
Meyers WM, Neafie RC. Streptocerciasis. In: Strickland GT, ed. Hunter’s Tropical Medicine. 7th ed. Philadelphia,
Pa: WB Saunders Company; 1991: 746–748.
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Neafie RC, Connor DH, Meyers WM. Dracunculiasis. In: Binford CH, Connor DH, eds. Pathology of Tropical and
Extraordinary Diseases. Vol 2. Washington, DC: Armed Forces Institute of Pathology; 1976: 397–401.
113.
Spencer HC. Dracunculiasis. In: Strickland GT, ed. Hunter’s Tropical Medicine. 7th ed. Philadelphia, Pa: WB
Saunders Company; 1991: 750–756.
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Beaver PC, Jung RC, Cupp EW. The spirurida: Dracunculus and others. In: Clinical Parasitology. 9th ed.
Philadelphia, Pa: Lea & Febiger; 1984: 335–349.
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Murrell KD. Trichinosis. In: Strickland GT, ed. Hunter’s Tropical Medicine. 7th ed. Philadelphia, Pa: WB Saunders
Company; 1991: 756–761.
116.
Chaudhry AZ, Longworth DL. Cutaneous manifestations of intestinal helminthic infections. Dermatologic
Clinics. 1989;7:275–290.
117.
Neafie RC, Connor DH. Trichinosis. In: Binford CH, Connor DH, eds. Pathology of Tropical and Extraordinary
Diseases. Vol 2. Washington, DC: Armed Forces Institute of Pathology; 1976: 409–414.
118.
Sturrock RF. Biology and ecology of human schistosomes. Clin Trop Med Comm Dis. 1987;2:249–266.
119.
Strickland GT, Abdel-Wahab MF. Schistosomiasis. In: Strickland GT, ed. Hunter’s Tropical Medicine. 7th ed.
Philadelphia, Pa: WB Saunders Company; 1991: 781–809.
120.
Gilles HM. Schistosomiasis update. Int J Dermatol. 1988;27:400–401.
121.
McCully RA, Barron CN, Cheever AW. Schistosomes (Bilharziasis). In: Binford CH, Connor DH, eds. Pathology
of Tropical and Extraordinary Diseases. Vol 2. Washington, DC: Armed Forces Institute of Pathology; 1976:
482–508.
122.
Allen AM, Taplin D, Legters LJ, Ferguson JA. Schistosomes in Vietnam. Lancet. 1974;1:1075–1076.
123.
Centers for Disease Control. Acute schistosomiasis in US travelers returning from Africa. MMWR. 1990;39:141–
142, 147–148.
124.
Nash TE, Cheever AW, Ottesen EA, Cook JA. Schistosome infections in humans: Perspectives and recent
findings. Ann Int Med. 1982;97:740–754.
125.
Amer M. Cutaneous schistosomiasis. Int J Dermatol. 1982;21:44–46.
126.
Gonzalez E. Schistosomiasis, cercarial dermatitis and marine dermatitis. Dermatologic Clinics. 1989;7:291–300.
127.
Garcia-Palmieri MR, Marcial-Rojas RA. The protean manifestations of schistosomiasis mansoni: A
clinicopathologic correlation. Ann Int Med. 1962;57:763–775.
128.
Bittencourt AL, Pinho O, Lenzi HL, Costa IMC. Extragenital cutaneous lesions of schistosomiasis mansoni. Am
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Jacyk WK, Lawande RV, Tulpule SS. Unusual presentation of extragenital cutaneous schistosomiasis mansoni.
Br J Dermatol. 1980;103:205–208.
130.
Attili VR, Hira SK, Dube MK. Schistosomal genital granulomas: A report of 10 cases. Br J Vener Dis. 1983;59:269–
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131.
Obasi OE. Cutaneous schistosomiasis in Nigeria: An update. Br J Dermatol. 1986;114:597–602.
132.
Milligan A, Burns DP. Ectopic cutaneous schistosomiasis and schistosomal ocular inflammatory disease. Br J
Dermatol. 1988;119:793–798.

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291
Chapter 13
BACTERIAL SKIN DISEASES
RICHARD H. GENTRY, M.D.*
*Colonel, Medical Corps, U.S. Army; Department of Dermatology, Fitzsimons Army Medical Center, Aurora, Colorado 80045-5001
INTRODUCTION
PYODERMAS
Etiology
Clinical Features
Prognosis
Treatment
PLAGUE
Etiology
Epidemiology
Clinical Features
Laboratory Findings
Diagnosis
Treatment
TULAREMIA
Etiology
Epidemiology
Clinical Manifestations
Diagnosis
Treatment
DIPHTHERIA
Etiology
Epidemiology
Clinical Manifestations
Diagnosis
Treatment
Immunization
MENINGOCOCCAL INFECTIONS
Etiology
Epidemiology
Clinical Manifestations
Diagnosis
Treatment
Chemoprophylaxis of Carriers
Vaccines
LYME DISEASE
Epidemiology
Clinical Manifestations
Diagnosis
Treatment
SUMMARY

Military Dermatology
292
INTRODUCTION
Bacterial pyodermas are among the most com-
mon disabling skin conditions that occur in
wartime.  Secondary infections of various superfi-
cial wounds may lead to cellulitis, abscess forma-
tion, or lymphangitis.  Cuts from coral in the Pacific
Ocean during World War II1 and fungal infections
in Vietnam2 were common precursors to pyodermas.
Other bacterial diseases such as plague, meningo-
coccemia, and diphtheria can occur in epidemic
forms during wartime because of crowding
and common exposures to insect vectors.  These
diseases have had major influences on military
conflicts.3–5
Lyme disease is relatively newly recognized.  It is
not uncommon for present-day U.S. military troops
to develop erythema chronicum migrans, the early
skin manifestation of Lyme disease, after maneu-
vers in Germany.
Pyodermas due to Staphylococcus aureus and Strep-
tococcus pyogenes are common in army troops.  There
are several reasons for this: irregular bathing hab-
its, poor access to facilities for personal hygiene,
irritation of the skin by rough clothing and equip-
ment, minor traumatic abrasions, scabies, insect
bites, mingling with native populations, and
crowded living conditions for large numbers of
troops.
These infections have played a major part in
combat ineffectiveness among troops.  During World
War I, bacterial infections (furuncles, abscesses,
and cellulitis) and secondarily infected scabies were
by far the two most common causes for hospital
admission for skin disease among U.S. troops: as
the primary diagnosis, they comprised almost two
thirds of all hospital admissions of U.S. troops in the
Great War.6  During World War II, bacterial skin
infections were the most common source of morbid-
ity in a check of representative hospitals1:
• In a 3-week spot check of three American
divisions in 1944, cutaneous bacterial infec-
tions were found to be responsible for 70% of
lost man-days.
• In the Mediterranean theater, two chief
groups, cellulitis and furunculosis, com-
prised most of the bacterial skin infections.
• In the Pacific theater, pyodermas were more
common.  For example, in the Philippines,
excluding combat injuries, 70% to 80% of
troops attending sick call complained of
ecthyma.  Impetigo was also common in the
Pacific theater.
Although most of these lesions were likely due to
Staphylococcus aureus or Streptococcus pyogenes  or
both, some were culture-positive for Corynebacte-
rium diphtheriae.1
During the Vietnam conflict, bacterial skin infec-
tions were second only to fungal infections in their
frequency of occurrence and the disability they
produced for U.S. troops.  These were primarily
ecthymatous ulcers due to Streptococcus pyogenes
and were frequently referred to as “jungle sores.”
The importance of recognizing and treating these
infections was documented in the U.S. Army Medi-
cal Department’s official history, Skin Diseases in
Vietnam, 1965–72:
With respect to pyoderma, the most important ad-
vance made during the Vietnam war was the recog-
nition that these apparently trivial infections are a
major military problem in the Tropics.  Those who
attempted to prevent and treat pyoderma found
that simplistic solutions were of little avail and that
lesions tended to grow in size and number despite
the most strenuous efforts at control.  Progress was
made not only in recognizing the problem but also
in better defining these infections both clinically
and epidemiologically.2(pp89–90)
Pyodermas such as impetigo and ecthyma were
more frequent and more severe in infantrymen than
they were in support troops in Vietnam.  This was
explained by increased exposure to environmental
stresses (eg, insect bites, cuts, and scratches) among
infantrymen.  Black soldiers had fewer pyodermas
than white soldiers.2
Etiology
For years, it has been dogma that most bacterial
pyodermas were due to Streptococcus pyogenes occa-
sionally complicated by Staphylococcus aureus infec-
PYODERMAS

Bacterial Skin Diseases
293
tion.  In a study of pyoderma in Vietnam,2 60 of 86
cases (70%) grew both S aureus and β-hemolytic
streptococci.  An additional 14% of cases cultured
pure β-hemolytic streptococci, and another 10%,
pure S aureus.2  Within the past 10 years, most
studies7–9 of pyodermas show S aureus to be their
primary cause.
It is not uncommon for tropical ulcers to contain
several organisms of interest.  A recent report on
tropical ulcers in civilians found S aureus in only 2%
and streptococci in only 15%.  Coliform bacteria
were found in 60%, fusobacteria in 35%, and
bacteroides in 20%.  All specimens grew a mixture
of organisms.10
Folliculitis, furuncles, and carbuncles represent
a continuum of severity of an infection centered
about a hair follicle.11  Although usually attributed
to S aureus, one study12 found this organism in only
24% of cutaneous abscesses.  Another study13 found
S aureus in only 19% of vulvar furuncles; it sug-
gested that although S aureus was usually believed
to be the cause of furunculosis, it was not the only
cause, especially if the lesion was around the geni-
tals or the perianal region.
Erysipelas is almost always due to infection with
β-hemolytic streptococci.  Cellulitis is usually due
to infection with β-hemolytic streptococci or S
aureus.14
Clinical Features
The characteristic sign of impetigo is superficial,
stuck-on–appearing, honey-colored crusts (Figure
13-1).  This is dried exudate from the underlying
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Fig. 13-2. In bullous impetigo, the vesicles and bullae
quickly rupture and form a thin, dry, varnishlike veneer.
Annular lesions are not uncommon. These were positive
on culture for Staphylococcus aureus.
eroded tissue.  While impetigo often occurs on the
face, any break in the skin can become secondarily
infected.  In the field, exposed skin of the arms and
legs will be involved frequently, as most insect
bites, dermatophytoses, allergic contact derma-
titides, and traumatic sores commonly become sec-
ondarily infected.  Impetigo heals without scarring
because it does not penetrate the epidermis.
Bullous impetigo is usually due to pure S aureus,
which manufactures a toxin, exfoliatin, that pro-
duces a subcorneal split in the epidermis.15  Bullous
impetigo is characterized by a flaccid blister that
rapidly ruptures and makes the lesion appear var-
nished (Figure 13-2).  Often a collarette of scale is
also seen.  Lesions tend to occur in the axillae or
groin in adults  (Figure 13-3).
Ecthyma presents as a punched-out ulceration,
which may not be noted until a thick, overlying
crust is removed (Figure 13-4).  The condition is
often tender or painful.  Ecthyma was the most
common pyoderma noted among U.S. troops in
Vietnam2 and was seen primarily on the hands,
ankles, or lower extremities.  There was often a zone
of induration or erythema surrounding the ulcer,
and multiple lesions were common.  It heals with
scarring because the epidermis is penetrated by the
infection.
Furunculosis is an infection of the hair follicle
that forms an inflammatory nodule with a pustular
center (Figure 13-5).15  Cellulitis is a more serious
lesion that usually affects the lower extremities
(Figure 13-6), face, or ear.  It is red, painful or tender,
and warm to the touch.  If a palpable edge is present,
the term erysipelas is used.  Diagnosis is based on
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Fig. 13-1. This thick yellow crust is typical of impetigo.
Exudate from underlying denuded tissue dries, and pa-
tients present with this characteristic clinical sign.

Military Dermatology
294
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Fig. 13-6. This erythematous lesion above the ankle has
been slowly worsening for several days. It is hot to touch.
No raised, palpable edge is noted. In severe cases, such as
this one, scaling is often seen over the surface. This
location is classic for cellulitis.
Fig. 13-5. This erythematous papule with a pustular
center is centered about a hair follicle. A furuncle is best
treated with local heat and drainage.
Fig. 13-3. A superficial pustule is noted anterior to the
axilla. A Gram’s stain of the contents revealed neutro-
phils and Gram-positive cocci in clusters. Culture was
positive for Staphylococcus aureus. In the axillary vault,
the pustules have ruptured, leaving collarettes of scale,
which are characteristic of bullous impetigo.
Fig. 13-4. This punched-out ulceration above the ankle is
typical of the “jungle sores” seen in Vietnam and the
South Pacific during World War II. It had been present for
several weeks without change. A culture was positive for
β-hemolytic streptococci, group A. This lesion of ecthyma
rapidly responded to appropriate antibiotics.

Bacterial Skin Diseases
295
physical examination.  Both entities may be associ-
ated with rigors, fever, leukocytosis, and malaise.
Prognosis
Under combat conditions, ecthyma can last for
weeks unless properly treated.  In Vietnam, it was
not uncommon to find soldiers on light duty for a
month or more due to these skin ulcerations.  Fre-
quently, a new crop of lesions appeared as the old
lesions healed.  Cellulitis, erysipelas, and lymph-
angitis are well-known complications of impetigo
and ecthyma.  Acute glomerulonephritis can also
complicate skin infections caused by Streptococcus
pyogenes, but this was uncommon in Vietnam.2
Treatment
The treatment of choice for pyodermas is an
antistaphylococcal penicillin such as dicloxacillin
given in a dose of 250 mg orally four times daily for
10 days.  The dose is often doubled the first 3 days
in more severe infections.  Erythromycin and
clindamycin are suitable alternatives if the patient
is allergic to penicillin.  Cephalosporins or combi-
nations of amoxicillin and clavulanate may also be
used, but are much more expensive and seldom offer
an advantage over antistaphylococcal penicillins.
Topical antibiotics are generally not helpful or
necessary when appropriate oral antibiotics are
given.  Mupirocin is an exception to this.16  Applied
thrice daily for 1 week, it will heal most simple
pyodermas and may avoid the need for systemic
antibiotics.  Debridement of the lesions is helpful
but soaking in hexachlorophene or other antibacte-
rial soaks retards rather than enhances healing.
Treatment of pyoderma in a combat situation
remains a problem.  For most of these drugs to
work, they must be given four times daily, which is
impossible in combat.  The combination of
amoxicillin and clavulanate requires dosing thrice
daily as does topical mupirocin, but in combat even
this may be too much.  Benzathine penicillin may
be helpful as a single dose of 1.2 million units,
administered intramuscularly.  No further therapy
for Streptococcus pyogenes would be required;
however, this is poor coverage for Staphylococcus
aureus.
Furuncles are best treated with local heat.  When
there is superficial fluctuance, they can be drained.
Antibiotics are usually not required unless sys-
temic symptoms are present.13
Cellulitis and erysipelas are more serious infec-
tions.  Intravenous antibiotics are usually the best
therapy.  Penicillin is usually adequate for erysi-
pelas, but coverage with an antistaphylococcal peni-
cillin is indicated for cellulitis.  If the patient is
allergic to penicillin, intravenous vancomycin or
erythromycin may be used.  Elevation is important
if a lower leg is involved.14
PLAGUE
Plague is a zoonotic disease caused by the bacte-
rium Yersinia pestis, which is usually transmitted to
humans by rodents and their fleas but can also be
transmitted via the respiratory route.  When trans-
mitted by a flea bite, the disease is characterized by
an early sign known as a bubo (ie, a mass of lymph
nodes in the groin, axilla, or neck that become
matted together and drain purulent material).  Three
days after these buboes appear, the patients de-
velop high fever and delirium.  Black splotches
develop due to hemorrhages into the skin.  It is
these black areas that gave this disease its common
name: Black Death.  Systemic and pneumonic forms
of plague can also occur; these forms of the disease
and their transmission, which are discussed later in
this section, are far rarer than bubonic plague.
Plague is a disease of antiquity.  During the
second millennium BC, the Philistines were smitten
with plague after capturing the Ark of the Covenant
from the Israelites.  During the 6th century AD, the
Justinian plague (ie, the first plague pandemic) was
described in the area of Constantinople.3  During
the 14th century, 70% to 80% of those who con-
tracted the disease died from it.  During the year
1346, Europe and the lands around the Mediterra-
nean had a population of approximately 100 million
people.  An outbreak of plague lasting from 1346 to
1352 and known as the Great Dying or the Great
Pestilence (ie, the second pandemic) killed approxi-
mately one fourth of this population.  Europe alone
sustained a loss of approximately 20 million people.17
After the second great pandemic, plague recurred
in Europe over the next few centuries.  London’s
last experience with plague ended with the Great
Fire of 1666.17  The disease was subsequently seen in
the armies of Frederick the Great, Catherine the
Great, and Napoleon’s troops in Egypt.3
The third pandemic began in China and rapidly
spread to most of Asia during the period 1894
through 1920.  In India alone, an estimated 12 mil-

Military Dermatology
296
lion people died.  Several important epidemiologi-
cal discoveries were made during this period3:
• During 1894, Kitasato and Yersin indepen-
dently isolated and described the plague
bacillus.
• From 1903 to 1905, Liston of the Indian Plague
Commission demonstrated the association
with rats and fleas.  The vital concepts of rat
and flea control emerged from this commis-
sion.
• Haffkine, working in Bombay during this
same period, developed an effective plague
vaccine.
• Territorial spread of this disease was re-
duced by the development of rat-proof ships,
together with fumigation of premises and
vessels.
During World War II, a killed plague vaccine was
developed and administered to U.S. troops in en-
demic areas.  Dichlorodiphenyltrichloroethane
(DDT) was developed and introduced during the
war, and plague control became synonymous with
flea control.  Plague was not a significant problem
for U.S. troops during World War II.  Following the
war, plague control rapidly improved.  The sul-
fonamides and, especially, streptomycin and tetra-
cycline proved effective in the treatment of all clini-
cal forms of the disease.  Plague foci were found in
both commensal and wild rodents via improved
bacteriological and serologic techniques.  These foci
were reduced by new insecticides and rodenticides.
Promising new vaccines were introduced.3
Plague has never been a significant problem to
the U.S. military, thanks to an understanding of the
epidemiology of the disease.  Effective control mea-
sures have been rapidly incorporated into preventive
medicine programs.  Plague is endemic in Vietnam,
and during the conflict in the 1960s and 1970s, more
than 10,000 cases occurred per year in the Vietnam-
ese population.18  Still, there were relatively few
cases of this disease in American servicemen.3
Etiology
Yersinia pestis is a plump, Gram-negative, pleomo-
rphic bacillus (0.8 x 1.5 µm; range 0.5–2.0 µm).  A
bipolar (ie, safety-pin) appearance is best demon-
strated in smears of infected animal tissues stained
by either the Giemsa or the Wayson method.  Prepa-
rations stained with Gram’s stain do not depend-
ably render this classic appearance.  It does not
ferment lactose.19
Plague bacilli are aerobic and facultatively anaero-
bic.  They are not fastidious and grow readily in
most bacteriological culture mediums.  Growth is
satisfactory at 35°C to 37°C, but slow.  Even at the
optimum growth temperature of 28°C, about 48
hours are necessary before colonies are readily dis-
cernible on plain agar.19
The fluorescent antibody test is used for rapid
identification of this bacterium.  It tests for bacterial
envelope fraction 1, which is produced most readily
at 37°C but not at temperatures below 28°C.  This
test is best used on smears of animal tissues, aspi-
rates of exudates from buboes or other tissues, spu-
tum specimens, and cultures incubated at 37°C.
Clinical specimens that were frozen or refrigerated
after collection are suitable for immediate fluores-
cent antibody testing.  Cross-reactions with Y
pseudotuberculosis may occur, and occasional strains
of Y pestis exhibit weak or no staining.  A positive
fluorescent antibody test supported by epidemio-
logical and clinical evidence is good evidence for
this diagnosis.19
Epidemiology
The ecology of plague is complex.  Infection
occurs primarily in rodents and is usually spread to
people and pets by the bite of an infected rodent
flea.  The oriental rat flea, Xenopsylla cheopsis, has
been considered the traditional vector in urban
outbreaks; however, multiple species of fleas have
been associated with plague.20
In the X cheopsis flea, Y pestis infection leads to a
blockage of the midgut by fibrinoid material and
masses of these bacilli.  The flea, in effect, cannot
ingest a blood meal, and it makes repeated attempts
to feed.  Unable to pass the meal through the block-
age, it regurgitates several thousand bacilli onto the
bite site with each attempt.  If infected X cheopsis is
maintained at temperatures over 27°C, this block-
age will spontaneously clear.  Plague epidemics
have long been known to subside spontaneously
when ambient temperatures remain above 27°C to
30°C, probably due to this phenomenon.20  Epidem-
ics of plague are distinctly seasonal: bubonic plague
is a disease of the cooler months in hot climates and
of the warmer months in cool climates.3
Typical Mode of Transmission
The two most important reservoirs of plague
bacillus throughout the world are two commensal
rodents, Rattus rattus (the domestic rat) and Rattus
norvegicus (the urban rat).  Throughout history,

Bacterial Skin Diseases
297
plague epidemics have occurred when huge num-
bers of susceptible rats died, which forced their
infected fleas to seek other hosts.  Rats are not the
only host, however: more than 200 species of ro-
dents are susceptible,20 including prairie dogs, chip-
munks, marmots, and deer mice.  In the Rocky
Mountain states, where plague is endemic, epizoot-
ics among rock squirrels are often the source of
infection in humans.  The infected fleas can seek out
humans who are hunting, camping, or living in
these areas.19  The fleas can also be transported to
humans through pets such as dogs and cats.
Other Modes of Transmission
Pets can also acquire the disease via the
ingestional route, by devouring the sick animals,
which are easy prey.  Although in dogs plague is
usually a mild illness, it causes a higher than 50%
mortality in cats.20  Cats can transmit the disease to
humans by bite or scratch21 as well as via fleas.  Cats
have also been associated with the transmission of
pneumonic plague.22  Exposure to domestic cats
was associated with 3% of plague in the United
States during the 1970s, ranking third behind bites
of infected fleas (82%) and direct exposure to wild
animals (15%).23
Plague can also be rapidly spread through the
air, and about 5% of bubonic plague patients will
develop the potential for airborne transmission.
Most severe epidemics have occurred in areas where
the climate is relatively cool.  Y pestis cannot survive
in aerosol clouds at high temperature and humid-
ity.  Hence, primary plague pneumonia is rare in the
tropics.  Conversely, low humidity is also associ-
ated with rapid death of the plague bacillus in the
air.  Epidemics of primary plague pneumonia are
favored by cool weather, moderate humidity, and
close personal contact between individuals.3
The transportation of infected rodents and fleas
from endemic areas may introduce the disease into
new areas.  The rat-proofing of ships has greatly
reduced the risk of transporting infected rats and
fleas to distant seaports.  The technique of shipping
by containers, however, may present a special haz-
ard because the containers can harbor rats.3
Clinical Features
Plague begins abruptly and, unless early therapy
is initiated, can cause death in hours to a few days
in 60% to 90% of cases.  Only cholera and
meningococcemia can overwhelm a previously
healthy body’s defenses so rapidly.3  Plague usually
occurs in three forms: bubonic, septicemic, and
pneumonic.  Complications such as meningitis and
endophthalmitis can arise from hematogenous
spread of Y pestis.
Bubonic Plague
The bubonic form of plague is the most common.
After the flea bite, the organisms proliferate in the
lymph nodes.  After an incubation period of 2 to 8
days, the typical patient has the sudden onset of
chills, fever, weakness, and headache.  At the same
time or by the next day, the patient notices the
bubo.18  Intense pain usually heralds the onset of a
bubo with the lesion itself becoming visible or pal-
pable within 24 hours.  Buboes may occur anywhere
there are lymph nodes.  Occasionally, intraabdomi-
nal buboes have presented as acute surgical abdo-
mens, and operations for this have occurred on
numerous occasions.  The most common location,
accounting for over half of all buboes, is in the
groin.  Involvement in this location is felt to be
secondary to a flea bite on the leg.  Buboes are also
common in the axillae (Figure 13-7) and then the
OK to put on the Web
Fig. 13-7. This painful, swollen axillary lymph node oc-
curred in a prostrate, febrile patient with bubonic plague.
Buboes most frequently occur in the groin, as flea bites
are most common on the legs.

Military Dermatology
298
neck.  Intense pain is characteristic of these buboes.3
The patient is typically prostrate and lethargic in
uncomplicated bubonic plague.  The temperature is
in the range of 38.5°C to 40°C, with a pulse rate of
110 to 140 beats per minute and a low blood pres-
sure of approximately 100/60.  The liver and spleen
are often palpable and tender.18
Early bubonic plague is typically not associated
with skin lesions.24  In Vietnam, about 25% of pa-
tients had papules, pustules, vesicles, or eschars
near the bubo or in an anatomical area that drained
to the bubo.  Presumably, these were the sites of flea
bites.  White blood cells and plague bacilli were
found on opening these lesions.  Systemic disease
may also lead to purpura and gangrene of the distal
extremities.15
Septicemic Plague
Plague also has a septicemic form in which buboes
do not occur.  In this small subset (about 10%) of
patients, the mode of transmission is the same as in
the bubonic form; however, blood stream invasion
occurs prior to regional lymph node involvement.
Older patients, who seem to be particularly suscep-
tible to this aggressive form of plague, become
acutely ill.  In fact, there may be so many bacteria in
the blood that they are readily seen on a blood
smear.  This is a grave prognostic sign.19
Pneumonic Plague
One of the feared complications of bubonic plague
is secondary pneumonia, which occurs by spread of
the plague bacillus through the blood stream to the
lungs.  Intermittent bacteremia is common in plague.
Single blood cultures taken at the time of admission
of Vietnamese patients were positive in 27% of
cases.18  Plague pneumonia presents with cough,
chest pain, hemoptysis, and purulent sputum loaded
with bacilli.  It is highly contagious with an incuba-
tion period of less than 3 days in new patients.19  In
fact, healthy patients have reportedly been exposed,
become ill, and died on the same day.  Pneumonic
plague is invariably fatal when treatment is delayed
more than 1 day after the onset of the illness.18
Patients with plague may also present with
pharyngitis.18
Laboratory Findings
The white blood cell count is typically elevated in
the range of 10,000 to 20,000/mm3.  Severely ill
patients tend to have higher counts.  Platelet counts
are normal to low.  Disseminated intravascular co-
agulation is common, with the laboratory abnor-
malities typical for this.  Liver function tests are
often elevated, as are renal function tests.18
Diagnosis
Plague should be considered in all patients who
present with buboes.  It should also be seriously
considered in febrile patients who have been ex-
posed to rodents and fleas in endemic areas of the
world.  When a patient presents with a bubo, the
best way to make the diagnosis is by needle aspira-
tion.  (It may be necessary to inject a small amount
of saline to get an adequate specimen.)  The specimen
is sent for culture, but a small amount is air-dried
and stained with Gram’s and Wayson or Giemsa
stains.  The Gram’s stain reveals pleomorphic, Gram-
negative bacilli and coccobacilli.  The typical safety-
pin appearance is seen on either the Wayson or
Giemsa stain.  The fluorescent antibody test will
give rapid confirmation.18
Blood, purulent sputum, and skin lesions (if
present) should all be inoculated onto blood,
MacConkey agar plates, and infusion broth.  Ap-
propriate stains should also be done on these speci-
mens.18
For definitive identification, cultures can be
mailed in double containers to the Centers for Dis-
ease Control and Prevention Plague Branch, P.O.
Box 2087, Fort Collins, Colorado 80522 (telephone
303-221-6450).  This laboratory can also perform
acute and convalescent serologic testing to confirm
the diagnosis.18  The differential diagnosis should
include tularemia, staphylococcal and streptococ-
cal infections, lymphogranuloma venereum, and
chancroid.19
Treatment
Untreated, the case-fatality rate of bubonic plague
is about 60%.  In septicemic or pneumonic plague, it
is probably 100%.  The prognosis in pneumonic
plague is poor if therapy is delayed more than 1 day
after the onset of the symptoms.  With early therapy,
the fatality rate in bubonic plague should approach
zero, but recently it was listed at 16%.19
All patients with bubonic plague should be iso-
lated until 48 hours after specific therapy has been
instituted because of the possibility of secondary
plague pneumonia.  Purulent discharges should be
handled with rubber gloves.  Face masks, including

Bacterial Skin Diseases
299
eye protection, are indispensable in caring for pa-
tients with pulmonary plague.  Nonspecific therapy
includes management of shock, dehydration, high
fever, and convulsions.19
Antibiotic therapy should be started promptly,
without awaiting laboratory confirmation, after
specimens have been obtained for diagnosis.  The
drug of choice, intramuscular streptomycin, was
first demonstrated in 1948.25  No drug investigated
since then has proved more efficacious or less toxic.
It is injected at a dose of 30 mg/kg/d in two18 or
four19 equal portions for 10 days.  Most patients
improve rapidly and become afebrile within 3 days.
The drug should be used cautiously in pregnant
women.  The risk of hearing loss and vestibular
dysfunction is minimal, but this should be consid-
ered in patients with preexisting hearing loss and in
the elderly.  In such patients, the course could be
reduced to 3 days following the disappearance of
fever.  Renal injury due to streptomycin is rare, but
renal function should be monitored.18  Gentamicin
has also been reported to be effective and has the
advantage that it can be given intravenously.  Mo-
bilization of intramuscular streptomycin may be
compromised in hypotensive patients.24
Tetracycline is a satisfactory alternative, to be
given orally in a daily dose of 2 to 4 g/d in four
divided doses for 10 days.  This drug is contra-
indicated in young children, pregnant women, and
in patients with renal failure.  Tetracycline has also
been used to complete a 10-day course after 5 days
of intramuscular streptomycin, to minimize the side
effects of the latter.18
Chloramphenicol is especially good for the treat-
ment of plague meningitis or endophthalmitis be-
cause of its excellent penetration in these areas.  It
is also good in patients with hypotension, in
whom intramuscular injections would be poorly
absorbed.  The drug is given intravenously in the
above cases, but it can also be given orally.  The
intravenous loading dose is 25 mg/kg, followed by
60 mg/kg/d in four divided doses.  After clinical
improvement, the drug may be given orally to com-
plete 10 days of therapy.  The dose may be reduced
to 30 mg/kg/d in four divided doses to lessen the
effects of bone marrow suppression, which should
be monitored.18
Co-trimoxazole, a combination of trimethoprim
and sulfamethoxazole, has also been effective in the
treatment of plague,26,27 but it does not appear to be
as effective as the aforementioned drugs.
In an asymptomatic person who has had close (ie,
within 2 m or less) or face-to-face contact with a
patient with pneumonic plague, prophylaxis should
be considered.  Oral tetracycline (30 mg/kg/d in
divided doses every 6 h) is the best choice of
drugs.18,28  If the asymptomatic patient (a) cannot
tolerate tetracycline, (b) is a child, or (c) is pregnant,
then oral co-trimoxazole is recommended, although
it is not optimal therapy for treating active disease.
Reliable contacts who are not placed on drug pro-
phylaxis can be instructed to take their temperature
twice daily.  They are to seek medical attention
immediately if they develop fever or respiratory
symptoms, including a sore throat, as this could be
a manifestation of plaque pharyngitis.29  In such
cases, hospitalization, isolation, and more aggres-
sive therapy are indicated.  A 4-fold rise in titer of Y
pestis–specific antibody when comparing acute and
convalescent sera may establish whether actual in-
fection has occurred.19
There is a vaccine available for those who might
come in contact with plague.  Two injections are
given initially with an interval of 1 to 3 months
between them.  Thereafter, it must be given every 6
months.18  This vaccine is given to members of the
U.S. armed forces who are to deploy to regions
where plague is endemic (eg, Southeast Asia).
TULAREMIA
Tularemia (also called deer fly fever and rabbit
fever) is a disease caused by the bacterium Francisella
tularensis, which is usually transmitted to humans
by exposure to rabbits and ticks (direct inocula-
tion), but which can also be transmitted via infec-
tious aerosol.  Soldiers can be exposed to tularemia
while on maneuvers in areas where the disease
is prevalent.  The typical ulceroglandular form
of the disease is characterized by a cutaneous
ulcer, regional lymphadenopathy, fever, and
constitutional symptoms; however, tularemia also
takes typhoidal, oropharyngeal, and oculogland-
ular forms.
In 1911, McCoy described a plaguelike illness of
rodents while studying plague among California
ground squirrels.30  Subsequently, he recovered the
organism from rodents in Tulare County, Califor-
nia31 (rabbits, now classified zoologically as mem-
bers of the order Lagomorpha, were at that time
classified with the Rodentia).  In 1914, Wherry and

Military Dermatology
300
Lamb described the first bacteriologically confirmed
case of tularemia in a human patient.32
Etiology
F tularensis is a small, Gram-negative coccobacil-
lus.  It tends to be pleomorphic in culture.  On most
ordinary culture media, it grows poorly or not at all.
It does grow well on glucose cysteine blood
agar, thioglycolate broth, and in other media
containing enough cysteine (specifically, sulfhy-
dryl groups).  Optimal growth occurs at 37°C
under aerobic conditions, with small colonies oc-
curring at 24 to 48 hours.  The organism is identified
on the basis of its growth requirements, morphol-
ogy, fluorescent staining, and agglutinins with spe-
cific antisera.33
There are two types of F tularensis.  Type A is
distributed solely in North America and is virulent
for humans and rabbits.  It is also positive for
citrulline ureidase, and it ferments glycerol.  Type B
is found in North America, Europe, and Asia.  It
causes a milder form of disease in humans and is
avirulent for rabbits.  It is negative for citrulline
ureidase and does not ferment glycerol.34
Epidemiology
F tularensis is distributed throughout the north-
ern hemisphere between 30° and 71° north latitude.
It has been recovered from numerous wild and
domestic animals.  Outbreaks are generally attrib-
uted to rabbits, hares, and muskrats.  It has also
been isolated from fish, amphibians, birds, ticks,
deerflies, mud, and water.33  Large outbreaks of
gastroenteritis, which were traced to contaminated
water, occurred in Europe during World War II.35
Humans most commonly acquire the disease via
direct inoculation from a tick bite, or after exposure
to the bite, body fluids, tissues, or pelt of an infected
animal (eg, a rabbit).  F tularensis has been reported
able to penetrate intact skin but probably enters via
small, open skin lesions—or, of course, via the bite.
Most rabbit exposure cases have occurred in the
winter, while most tick-bite cases occur in the spring
or summer.33
Tularemia is an occupational hazard for rabbit
hunters, butchers, cooks, those who process frozen
rabbit meat and pelts, and laboratory technicians.34
Laboratory workers can acquire the disease via
two mechanisms: (1) direct inoculation and
(2) aerosolization of F tularensis from cultured
organisms.
Clinical Manifestations
The incubation period is usually 3 to 5 days.  A
skin papule develops at the site of entry and within
2 to 4 days, an ulcer forms.  The patient experiences
an abrupt onset of fever, chills, headache, malaise,
and fatigue.  Painful regional lymphadenopathy
follows, and buboes can occur.  This is the typical
ulceroglandular form of tularemia, which occurs in
more than 75% of cases.  In rabbit-associated cases,
the ulcer is located on the patient’s hand or fingers
in more than 90% of cases (Figure 13-8).  In tick-
associated ulcers, the lesions tend to occur on the
patient’s lower extremities, perineum, or trunk.
Multiple ulcers may occur in patients who came in
contact with many infected animals.33
Of rabbit-associated cases of tularemia, 80% to
90% of patients have axillary or epitrochlear
adenopathy; of tick-borne cases, 60% to 70% have
inguinal or femoral adenopathy.  Glandular tulare-
mia occurs in 5% to 15% of cases and is character-
ized by lymphadenopathy without skin ulceration.
In the typhoidal form (approximately 5% of cases),
fever, weight loss, and prostration occur without
lymphadenopathy.  The protean manifestations of
tularemia, including oropharyngeal and oculogland-
ular forms, and the often-negative history make
diagnosis difficult.33
OK to put on the Web
Fig. 13-8. This ulceration on the hand is typical of tulare-
mia in a rabbit hunter, one who skinned an infected
rabbit and in so doing, infected his hand. He will subse-
quently develop distal nodes in his axilla that will likely
suppurate. He will also develop profound malaise, chills,
and fever. Cultures are typically negative, even if special
media are used. Diagnosis is usually made on the basis of
serologic testing.

Bacterial Skin Diseases
301
Pleuropulmonary complications are not infre-
quent in tularemia.  Pneumonia is seen in 30% to
80% of the typhoidal cases and in 10% to 15% of the
ulceroglandular cases.  It is characterized by non-
productive cough, few findings on physical exam,
and ill-defined infiltrates in one or more lobes on
chest radiographs.33
A nonspecific skin eruption has been reported in
about 20% of cases.  In a few cases, erythema
nodosum and, less commonly, erythema multi-
forme have been reported.  Some patients develop
hepatomegaly and elevated liver function test
values.  Transient renal failure, rhabdomyolysis,
pericarditis, peritonitis, meningitis, and osteomy-
elitis rarely occur.33
Diagnosis
Tularemia may be immediately suspected in the
typical case of ulceroglandular tularemia with a
characteristic skin lesion, lymphadenopathy, fever,
and a history of exposure to rabbits or ticks.  The
diagnosis is much more difficult when other forms
of the disease are seen and when the history is
negative, as is frequently the case.  F tularensis is
seldom seen on Gram’s stain of sputum, skin ulcer-
ations, or node aspiration.  Because the organism
does not grow on most ordinary media, cultures are
usually negative.  Many laboratories are reluctant
to grow this organism because infectious aerosols
can be created.33
Most cases of tularemia are diagnosed serologi-
cally.  A 4-fold rise in the tube agglutination or
microagglutination titer is diagnostic of infection.
A single convalescent titer of 1:160 or greater is
diagnostic of past or current infection.  Titers are
usually negative in the first week of illness but are
positive in 50% to 70% of cases after 2 weeks of
illness.  Maximum titers are reached in 4 to 8 weeks
and may remain elevated at diagnostic levels for
many years.33
Treatment
Before the introduction of streptomycin therapy
in 1947, the natural course of tularemia was a pro-
longed illness with most patients unable to work for
the first month of illness; many could work only
part time for 3 months after the disease began.
Some illnesses lasted 14 to 15 months.35  Untreated,
the mortality of tularemia has been low, cited at 5%
to 7%.36  With antibiotics, mortality is about 2%.33  If the
patient has a serious underlying medical disorder or
if treatment is delayed, mortality may rise to 6%.36
The drug of choice is streptomycin, administered
intramuscularly in an adult dose of 0.5 g (15–20 mg/
kg/d in divided doses) twice daily for 7 to 14  days.33
In those with more severe infections (eg, pneu-
monic involvement or the typhoidal form), it may
be wise to double the dose for the first 2 to 3 days.34
Most patients’ fevers decrease during the first 48
hours.  Relapses are uncommon.35
Gentamicin is an acceptable alternative to strep-
tomycin.  The dose is 3 to 5 mg/kg/d in three
divided doses every 8 hours, administered intra-
muscularly.  (This dose may require adjustment
depending on the patient’s serum creatinine.)
Gentamicin is a particularly useful drug when the
diagnosis is unknown and additional Gram-nega-
tive coverage is desired.33
Tetracycline has also been used, but relapses are
more common.  A loading dose is given: 30 mg/kg,
administered orally, followed by 30 mg/kg/d in
divided doses for 14 days.33  Tetracycline should not
be given to pregnant or lactating women, young chil-
dren, or patients with renal or hepatic insufficiency.
A live attenuated vaccine is available.  It does not
provide complete protection but does ameliorate
the course of the disease.  Candidates for receiving
the vaccine include laboratory workers who are
routinely exposed to F tularensis and persons whose
vocations require repeated exposure to rabbits.33  Sol-
diers are not routinely vaccinated against tularemia.
DIPHTHERIA
Diphtheria, a disease of the pharyngeal mucous
membranes, is caused by a toxin produced by the
bacterium Corynebacterium diphtheriae.  Locally, this
toxin produces a tough pseudomembrane, which
can cause death by asphyxiation.  This same toxin
can profoundly affect distal targets—especially the
heart and nerves.  In the United States, infection
more commonly causes skin lesions than upper–
respiratory tract involvement.37
Early in the 1700s in New England, an epidemic
of diphtheria killed 2.5% of the population, includ-
ing one third of the children.  Thereafter, epidemics
occurred about every 25 years throughout the 18th
and 19th centuries.4
In France in 1821, Bretonneau first described the
unique clinical characteristics of diphtheria, nam-

Military Dermatology
302
ing it for the Greek word for leather, after its tough
pseudomembrane.  In 1883, Klebs described the
bacillus in diphtheritic membranes.  In Berlin in
1884, Loeffler first isolated the organism in pure
culture.  He then reproduced the disease in guinea
pigs.  He also demonstrated that healthy persons
could carry the disease in an asymptomatic fashion.
In 1888, Roux and Yersin demonstrated that bacte-
ria-free filtrates of the organism could kill guinea
pigs, thus demonstrating the production of a toxin.
In 1890, Von Behring showed that antiserum against
this toxin protected infected animals from death.
Horses were found in 1894 to be the most efficient
producers of antiserum.4
In 1913, Schick demonstrated that a person’s
susceptibility to diphtheria could be proven by in-
jecting toxin into his skin.  A positive reaction indi-
cated the absence of protective antibodies.  In 1923,
Ramon found that the toxin could be rendered non-
toxic by exposing it to formalin and heat, yet the
nontoxic form could induce an antibody response.
Between 1930 and 1945, most western countries
introduced large-scale childhood immunization
against diphtheria.4
About 5,700 cases of diphtheria occurred in the
U.S. Army from 1942 to 1945.  (In comparison,
150,000 cases of diphtheria, with nearly 14,000
deaths, had occurred in 41 states in 1920.  And
30,000 cases of diphtheria, with 2,600 deaths, oc-
curred in the entire United States in 1938.)  The
British Royal Army had recognized that cutaneous
diphtheria was common in the desert sores of their
troops in Palestine and Egypt during  World War I,
and this lesson was relearned later with the jungle
ulcers of the Pacific and the China, India, and Burma
theaters.  There was no widespread immunization
of U.S. troops during World War II because (a) the
number of cases was relatively low and (b) reactions
to the vaccine were feared.  An important consider-
ation in the decision not to immunize troops rou-
tinely was based on the knowledge that injection of
diphtheria toxoid would be followed by moderate-
to-severe reactions in an appreciable number of
cases: 10% of those injected developed incapacitat-
ing febrile reactions.38
After World War II, during the occupation of
Germany, the incidence of nasopharyngeal diph-
theria increased tremendously among the civilian
population living in bombed-out areas, often in
association with overcrowding.  As rules against
fraternization with the civilian population were
relaxed, diphtheria increased among the military
population.  During 1945, there were 2,240 cases
of diphtheria, with 67 deaths, among U.S. troops
in Europe.38  In April 1946, all susceptible military
personnel under the age of 35 were required to
be immunized before traveling to the European
theater.39
Etiology
C diphtheriae is an irregularly staining, pleomor-
phic, Gram-positive bacillus with clubbed ends.  In
Loeffler’s medium (consisting of a heat-coagulated
mixture of 75% serum and 25% broth), it initially
outgrows other throat flora.  The agar plates should
be inspected for growth at 12 to 18 hours.  Direct
smears from clinical exudates do not demonstrate
the characteristic metachromatic granules and “Chi-
nese character” palisading morphology as well as
smears that are taken from colonies grown on
Loeffler’s medium.  Tellurite medium inhibits much
of the normal throat flora and identifies C diphtheriae
as gray-black colonies, subdivided into gravis,
intermedius, and mitis, based on their hemolytic
potential, fermentation reactions, and differing co-
lonial morphology.4
C diphtheriae is not a very invasive organism,
tending to remain in the superficial portion of the
skin or mucous membranes.  Its major virulence is
due to the production of a potent exotoxin that
inhibits protein synthesis in mammalian, but not
bacterial, cells.  The toxin affects all cells in the body
but especially the heart, nerves, and kidney.  This is
an extremely potent toxin, in that one molecule
causes cessation of protein synthesis in one cell
within several hours.  Exotoxin production is de-
pendent on the presence of a lysogenic β phage,
which may or may not be present in C diphtheriae.
Antitoxin can neutralize the toxin before it reaches
its target, but antitoxin is useless once the toxin is
inside the cell.4
Epidemiology
Humans are the only known reservoir of C
diphtheriae.  The organism can be spread by means
of airborne droplets or from infected skin lesions.
Most upper respiratory infections occur in the colder
months in temperate climates and are associated
with overcrowding.  Convalescent or healthy carri-
ers and those incubating the disease are most im-
portant in spreading the disease.40
In endemic conditions, C diphtheriae can be found
in 3% to 5% of the population,4 but in North America
and Europe, the bacterium has recently become
very rare.  This is curious because in many parts of
the United States, a large proportion of the popula-

Bacterial Skin Diseases
303
tion is susceptible to the toxin.  For example, among
183 urban adults in Minnesota, only 26% of men and
21% of women showed an overall protective level of
antibody.41  Despite this, the disease is quite rare in
the United States at present.
Person-to-person spread from skin infections is
more efficient than from the respiratory tract.  Skin
infections were once thought to occur primarily in
the tropics, but several recent outbreaks have oc-
curred in Europe and North America among alco-
holics and poverty-stricken groups.4,37
Clinical Manifestations
The incubation period for C diphtheriae is usually
2 to 4 days.  Pharyngitis is the most common presen-
tation of diphtheria and is characterized by abrupt
onset, fever (usually < 103°F), mild pharyngeal in-
jection, pharyngeal pain, a uniquely fetid breath,
and the development of a membrane.  This mem-
brane may be on one or both tonsils, but it may also
extend to involve the posterior pharynx, soft palate,
larynx, and nasopharynx, which indicates more
severe disease (Figure 13-9).  Initially white, the
membrane evolves into a dirty gray color with
patches of necrosis.  Cervical adenopathy and swell-
ing may cause the patient to have a “bull-neck”
appearance, with respiratory stridor.  Involvement
of the larynx, trachea, and bronchi may produce
airway obstruction.  This may require intubation
and mechanical removal of the membrane, or the
patient may rapidly become exhausted and die.
Indeed, in the late 19th century, the most common
OK to put on the Web
Fig. 13-9. This febrile patient with pharyngeal diphtheria
has erythema, edema, and a gray membrane on the ton-
sils and posterior pharynx.
OK to put on the Web
Fig. 13-10. Hemorrhagic pustules on the digits are often
indicative of septicemia with Candida albicans or Gram-
negative organisms. In this patient, Corynebacterium
diphtheriae was the cause.
cause of death in children was suffocation.  Strepto-
coccus pyogenes is a common cause of secondary
infection, which is usually manifested by a bright
red pharynx and fever above 103°F.4,40
Cutaneous diphtheria occurs in patients of low
socioeconomic status who have poor personal hy-
giene.  Hemorrhagic pustules lead to ulcerations,
which are frequently slow to heal (Figures 13-10
and 13-11).  They are often infected with Staphylo-
coccus aureus and Streptococcus pyogenes as well as C
diphtheriae.  Systemic toxicity is unusual, as is heart
and nerve involvement.4  Other sites for diphtheria
infection include the ear, the conjunctiva, and the
genitalia.40
Systemic complications of respiratory diphthe-
ria are secondary to C diphtheriae’s production of
toxin.  The toxin may affect all tissues but is particu-
larly toxic to the heart and nerves.  Characteristi-
cally, myocarditis (a) is noticed when the respira-
tory disease is improving, usually 1 to 2 weeks after
the onset of the disease and (b) is responsible for
about half the mortality of diphtheria.  Clinically
significant cardiac abnormalities occur in about 20%
of cases.40  The onset of myocarditis may be acute or
gradual.  It is important to routinely monitor all
diphtheria patients with electrocardiograms.  The
patient may appear clinically well, but the electro-
cardiogram may show significant abnormalities.
Patients with electrocardiographic evidence of
myocarditis have a mortality rate 3- to 4-fold higher
than those with normal tracings.  Patients with
atrioventricular dissociation and left bundle branch
block have a mortality of 60% to 90%; survivors may

Military Dermatology
304
OK to put on the Web
Fig. 13-11. Diphtherial ulcerations characteristically have
a purplish rolled border and involve the feet or legs.
placed in appropriate media (ie, tellurite and
Loeffler’s).  An immunofluorescence test can rap-
idly identify C diphtheriae, but it will not establish
toxicogenicity.  This determination requires either
guinea pig inoculation or an agar gel–diffusion
technique.40
The presence of the pharyngeal membrane, elec-
trocardiographic abnormalities, and cranial nerve
palsies all point to the diagnosis of diphtheria.
Diagnosis is most difficult in mild cases.40
Treatment
For nearly a century, the cornerstone of treat-
ment has been diphtheria antitoxin.  Diphtheria
was the first disease in which treatment with spe-
cific antibody was shown to be of therapeutic value.
Diphtheria antitoxin only neutralizes toxin before it
enters the cell, so it is crucial to give it as soon as a
presumptive diagnosis is made.  Recommendations
by the Committee on Infectious Disease by the
American Academy of Pediatrics include the fol-
lowing:
• 20,000 to 40,000 units of diphtheria antitoxin
for pharyngeal or laryngeal infection of 48
hours’ duration,
• 40,000 to 60,000 units for nasopharyngeal
disease, and
• 80,000 to 100,000 for extensive disease of 3 or
more days’ duration or brawny edema of the
neck.
Intravenous administration is recommended to rap-
idly inactivate toxin.  Before systemic doses are
given, the patient must be tested for sensitivity with
1:10 antitoxin solution (for conjunctival testing) or
1:100 dilution (for intradermal testing).  Antitoxin is
probably of no value for cutaneous disease, but
some authorities use 20,000 to 40,000 units of anti-
toxin because toxic sequelae have been reported.37,42
The diphtheria antitoxin is produced in horses
and up to 10% of patients will show some allergy to
horse protein.  The patient must be questioned
about sensitivity to horse protein prior to starting
therapy.  Epinephrine should be available for im-
mediate administration.  If an immediate reaction
occurs, the patient should be desensitized with pro-
gressively increasing doses of diphtheria antitoxin.42
Antibacterial therapy serves three purposes:
1.
It shuts down toxin production.
2.
It treats the local infection and covers a
have permanent conduction defects.  The serum
aspartate aminotransferase level closely parallels
the intensity of the myocarditis and may be used to
follow its course.4
Neurological abnormalities occur more com-
monly in those patients with severe disease.  They
usually occur late, often a month after the onset of
the disease.  Cranial nerves are usually affected
first.  Paralysis of the soft palate and posterior
pharyngeal wall may lead to regurgitation of in-
gested fluids through the nose.  Aspiration may also
occur.  Neurological involvement can affect the
peripheral motor nerves, beginning proximally and
advancing distally; it especially affects the
dorsiflexors of the feet.  Involvement varies from
weakness to total paralysis.4  Slow, but complete,
recovery of neurological function is the norm.40
Diagnosis
The diagnosis of diphtheria is based on cultural
isolation and bacterial identification of the organ-
ism with laboratory proof of the toxicogenicity.  The
laboratory must be notified of the possibility of
diphtheria so that the culture specimens may be

Bacterial Skin Diseases
305
possible secondary infection with Strepto-
coccus pyogenes.
3.
It curtails the spread of the disease to other
persons.
Untreated, 1% to 15% of persons recovering from
diphtheria become carriers.40
The drug of choice in diphtheria for active infec-
tion is erythromycin, with an adult dose of 500 mg
every 6 hours by mouth for 2 weeks.  If the patient
cannot swallow, erythromycin may be given intra-
venously as 30 mg/kg/d in three divided doses
every 8 hours.  Thrombophlebitis is common with
intravenous usage.40
Penicillin is usually effective in active diphtheria
but is not as effective in carriers as erythromycin.
The adult dose of penicillin is 600,000
units (given in the procaine form) administered
intramuscularly every 12 hours for 2 weeks.  Clinda-
mycin and rifampin have also been effective,37 but
generally only erythromycin and penicillin are
recommended.40
The patient should be maintained in strict isola-
tion during therapy and should have three consecu-
tive negative cultures at 24-hour intervals at the
conclusion of therapy to document eradication of
the organism.  This is to assess for the carrier state.4
Regarding cutaneous diphtheria, the patient
should be placed in contact isolation until two cul-
tures of skin lesions, taken at 24-hour intervals, are
negative.42
The treatment of choice for the carrier state is 7
days of oral erythromycin.4  However, in one study,43
21% of patients treated with erythromycin cultured
positive for C diphtheriae 2 weeks after the conclu-
sion of therapy.  An alternative for adults is 2,400,000
units of benzathine penicillin G, administered in-
tramuscularly in one dose.  Carriers should also be
cultured for C diphtheriae 2 weeks after chemo-
therapy is concluded.40
Supportive care is also important.  Airway and
cardiac complications may occur early.  The mem-
brane can extend into the larynx or break off and
occlude the airway, causing breathing difficulties
or death by asphyxiation.  Many experts recom-
mend intubation or tracheostomy early, particu-
larly if the membrane involves the larynx.  This allows
access so that the membrane can be mechanically
removed.  Cardiac monitoring is also important.4
Immunization
Diphtheria is prevented by active immunization
using toxoid (formalin-detoxified diphtherial toxin).
Preschool immunization is undoubtedly effective,
but this protection wanes with age.  When
toxicogenic diphtheria was common, reinforcement
of immunization was also common owing to over-
crowding and high carrier rates.  In the United
States, reinforcement no longer occurs, and large
numbers of women and the elderly are now be-
lieved to be at risk.  Hence, it is now recommended
that adults be reimmunized every 10 years.41  This is
done usually with the highly purified tetanus-diph-
theria toxoid for adults.  Diphtheria immunization
is the standard practice in the U.S. Army, and con-
sequently, diphtheria should not be a problem for
soldiers; however, diphtheria may well be a prob-
lem in local populations where overcrowding and
poor hygiene are the rule.
Meningococcal infections usually begin with the
growth of Neisseria meningitidis in the human
oropharynx.  Occasionally, this proliferation will
give rise to systemic infection, usually meningitis
and bacteremia (ie, meningococcemia).
In 1805, Vieusseaux described epidemic cere-
brospinal fever (meningococcal meningitis) in
Geneva.  Weichselbaum isolated meningococcal
organisms from cerebrospinal fluid in 1887.  Healthy
persons were noted to be carriers of the organism by
Kiefer in 1896 and Albrecht and Ghon in 1901.  In
1909, Dopter first recognized serotypes of meningo-
coccus.  This laid the basis for Flexner’s serum
therapy of infection  in 1913.  Sulfonamides were
found to be effective in 1937.  Sulfonamides also
eradicated the carrier state and were given as pro-
phylaxis to prevent epidemics in areas of crowded
living conditions.  Subsequently, other antibiotics were
found to be more effective in treating meningococcal
infections, and mortality and morbidity declined fur-
ther.  In 1963, the resistance of N meningitidis to sul-
fonamide became a clinically significant problem.
This has lead to the development of safe and effective
vaccines against serogroups A, C, Y, and W-135.44
Military records indicate that the U.S. Army has
had significant outbreaks of meningococcal disease
in the War of 1812, the Mexican War, the Civil War,
World War I, and World War II.5  Hospital admis-
MENINGOCOCCAL INFECTIONS

Military Dermatology
306
sion rates have always been negligible except dur-
ing periods of rapid mobilization of new personnel.
During World War II, the Board for the Investiga-
tion and Control of Influenza and Other Epidemic
Diseases in the Army issued an interim report,
which contained this statement from its Commis-
sion on Meningococcal Meningitis:
[A] field laboratory was set up on September 28,
1942, [at Jefferson Barracks, Missouri].  The pur-
pose of the study [was] to determine if possible the
factors influencing the continued occurrence of
meningitis at this station.…  [The report empha-
sized] the three factors which aid the occurrence of
meningococcal meningitis: crowded quarters, a high
meningococcus carrier rate, and the continued ad-
dition of susceptibles (unseasoned recruits).45(p36)
Of 5,000 cases reported to the Commission on
Meningococcal Meningitis during World War II,
67% of the soldiers had been in service less than 3
months and 93% in service less than 1 year.5
The incidence of this disease is low compared
with that of other respiratory diseases.  During
World War I, meningococcal disease ranked only
76th as a cause of admission to a hospital; however,
40% of the cases were fatal and the disease ranked
sixth as a cause of death.5  Meningococcal disease is
one of the few that can kill a healthy young adult in
a matter of hours to a few days.
Etiology
N meningitidis appears as a Gram-negative diplo-
coccus with the adjacent sides flattened.  It is oxi-
dase positive and typically metabolizes both glu-
cose and maltose.  N gonorrhea, in contrast, does not
metabolize maltose.44
The organism is fastidious in terms of growth
media and conditions.  It is aerobic, grows best at
temperatures of 35°C to 37°C with a 5% to 10%
atmosphere of carbon dioxide, and requires en-
riched media such as chocolate agar.
44
Meningococci are surrounded by a polysaccharide
capsule and are divided into serogroups on the basis
of differences in their capsular polysaccharides.
Groups A, B, C, W, and Y cause the most serious
disease.46
Epidemiology
There is no known reservoir for meningococci other
than humans.  The bacteria are usually spread from
person to person by respiratory droplets from the
nasopharynx of asymptomatic carriers.  Usually this
gives rise to immunity that is serospecific for the
organism; serious infection will occasionally result.46
The carrier rate in the United States is estimated
to be 5% to 10%.  High carriage rates also consis-
tently develop in military recruits whether or not
actual disease has occurred.  In this situation, the
prevalence of meningococcal carriage has ranged
from 40% to 80%.  In household contacts of a case of
meningococcal meningitis, 17% to 50% are found to
carry the same strain as the index case.47
Major outbreaks of meningococcal disease have
been documented at 7- to 10-year intervals in the
United States during the 20th century, and large
epidemics (in both the indigenous population and
in the military) occurred during World War I, World
War II, and the Korean and Vietnam conflicts.  Sig-
nificant outbreaks, usually of the group A serotype,
are regularly reported in Africa and South America.48
Most epidemic disease in the United States was
also caused by the group A serotype until the 1960s.48
Then group B emerged and has remained the pre-
dominant serotype since: the B serotype currently
causes more than 50% of the meningococcal menin-
gitis in the United States.47  Group C is the second-
most-common serotype and is especially common
in closed populations (eg, military training centers).
Increasingly, Groups Y and W-135 are being reported
in Western Europe and the United States.  Group Y is
also commonly associated with pneumonia.48
Most meningococcal disease in the United States
occurs in two populations: infants and children
under the age of 4, and military recruits, but spo-
radic disease may occur in any age group.48  The
highest frequency of cases is in the winter and early
spring; the lowest in the summer.46
Several factors predispose to meningococcal
disease:
• prior viral respiratory disease,
• complement defects in C5, C6, C7 and C8,49
• properdin deficiencies,50 and
• immunoglobulin deficiencies.46
In addition,
• patients with a terminal complement defi-
ciency frequently have recurrent disease in
association with low mortality, a high inci-
dence of group-Y disease, and initial infec-
tion during the teenage years49; and
• properdin deficiency predisposes to fatal
disease.50

Bacterial Skin Diseases
307
Clinical Manifestations
The signs and symptoms of meningococcal dis-
ease can vary from bacteremia and transient fever
to death within a matter of hours.  Of patients with
meningococcal disease, 90% to 95% present with
either meningococcemia or meningitis or both.  The
typical patient has nonspecific prodromal symp-
toms of headache, cough, and sore throat followed
by the sudden development of spiking fever, chills,
myalgias, and arthralgias.46
Although a transient maculopapular eruption
associated with generalized myalgias has been de-
scribed in meningococcal disease, the more typical
eruption is petechial.  It may remain sparse or
progress to widespread purpura (Figure 13-12).  The
petechial eruption is manifested as 1- to 2-mm le-
sions on the trunk, lower extremities, and conjunc-
tivae.  They commonly occur on the skin where
elastic from underwear or stockings applies pres-
sure to the skin.  Petechiae correlate with the extent
of thrombocytopenia.  Increasing numbers and en-
larging lesions indicate progression of the bleeding
complications due to disseminated intravascular
coagulation.44
Postmortem studies44 have found varying de-
grees of myocarditis in over 50% of patients who
die of meningococcal disease.  There may be clin-
ical evidence of heart failure, which cardiac glyco-
sides have successfully reversed.
Fulminant Meningococcemia
Fulminant meningococcemia, also known as the
Waterhouse-Friderichsen syndrome, is meningo-
coccemia associated with shock and vasomotor col-
lapse.  The onset is abrupt, and profound prostra-
tion occurs within hours.  Extensive ecchymoses are
common.  With the onset of shock, the blood pres-
sure falls, mentation decreases, and coma may de-
velop.46  Global mortality for all meningococcal
disease among civilians has remained constant at
10% to 19% for the past few decades, but the mortal-
ity for fulminant meningococcemia is 40% to 57%.51
Recovering patients may have extensive sloughing
of skin or loss of digits due to gangrene.46
Arthritis–Dermatitis Syndrome
The arthritis–dermatitis syndrome consists of
fever, rash, and joint pain (or any combination) in a
young, sexually active patient.  This syndrome has
primarily been caused by Neisseria gonorrhea.  How-
ever, a recent report of 62 such patients noted blood or
synovial cultures, or both, positive for gonococci in 9
and meningococci in 5.  This suggests that N mening-
itidis should be given more consideration in the differ-
ential diagnosis of arthritis–dermatitis syndrome in
the future, although N gonorrhea still predominates.52
Meningitis
The other common form of meningococcal disease
is meningitis.  This occurs primarily in children aged
6 months to 10 years with symptoms of vomiting,
fever, headache, and confusion or lethargy.  Typically,
the patient has signs of an upper respiratory infec-
tion followed by an illness that progresses over a few
days.  Onset may also be sudden and rapidly progres-
sive.  A presumptive diagnosis of meningococcal dis-
ease should be made whenever meningitis occurs in
association with a petechial or purpuric erup-
tion because this is rarely seen in other infections.46
Signs of meningeal irritation are common except
in the very young or very old, but focal signs and
seizures are less common than in infections due to
Haemophilus influenza or pneumococcus.  The levels
of consciousness are about the same in all three
diseases.44
Meningococcal Pneumonia
Meningococcal pneumonia has been recognized
for decades.  This type of infection usually has no
OK to put on the Web
Fig. 13-12. This patient, a young man with meningo-
coccemia, developed a stiff neck and fever several days
before these purpuric macules developed. These lesions
progress by coalescence into angulated, confluent, re-
ticulated patches with central necrosis.

Military Dermatology
308
associated skin findings.  It is most commonly caused
by group Y.  A study of U.S. Air Force recruits
reported that a history of cough, chest pain, chills,
and previous respiratory infection occurred in
more than half of the cases.  Rales and fever oc-
curred in almost all patients, and pharyngitis
occurred in over 80%.  Forty-two percent of the
patients had involvement of more than one lobe,
and 29% had pleural involvement.  Bacteremia is
uncommon, so blood cultures are usually not
helpful.  Transtracheal cultures appear to be the
best way of making the diagnosis in meningococcal
pneumonia.53
Diagnosis
The diagnosis of meningococcal disease is usu-
ally made from positive blood and cerebrospinal
fluid cultures.  About half of patients with menin-
gococcal disease have positive blood cultures, and
58% to 94% of patients have positive cerebrospinal
fluid cultures or positive Gram’s stains for Gram-
negative diplococci in the cerebrospinal fluid.  Sev-
eral cases of meningococcemia with no evidence of
meningitis have had positive cerebrospinal fluid
cultures.  The cerebrospinal fluid in meningococcal
meningitis has elevated leukocytes (predominantly
neutrophils), low glucose, and elevated protein.44
Counterimmunoelectrophoresis and latex agglu-
tination assays may also be helpful, especially early
in the course of the disease or when the patient has
been treated with antibiotics before cultures were
obtained.46
Treatment
The current recommended treatment for menin-
gococcal meningitis, meningococcemia, and chronic
meningococcemia is penicillin G, administered in-
travenously at a dose ranging from 300,000 units
per kg per day to 24 million units per day in divided
doses.  If the patient is allergic to penicillin, the
second drug of choice is chloramphenicol, adminis-
tered intravenously at a dose of 100 mg/kg/d up to
4 g/d in divided doses.  A 7- to 10-day course of
therapy is usually adequate.44
Penicillin-resistant N meningitidis has recently
been reported in Europe.54  These bacteria were
sensitive to third-generation cephalosporins such
as ceftriaxone and cefotaxime.
In every case of meningococcal disease, the
potential for shock should be considered and
treated as necessary.  The patient should be placed
on respiratory isolation to minimize nosocomial
spread.
Chemoprophylaxis of Carriers
Household contacts of patients with meningo-
coccal disease are 500- to 800-fold more likely to
contract the infection than the general population.
Military barracks, college dormitories, chronic-care
hospitals, and nursery schools also have high-risk
populations.  These people should receive prophy-
lactic therapy.  Hospital personnel and medical
staff are not recommended for prophylaxis unless
they have had intimate contact with a patient (eg,
mouth-to-mouth resuscitation).44
Initially, sulfadiazine was highly effective in
eradicating the carrier state.  However, the bacteria
became resistant during the mid-1960s, and it is no
longer used unless the meningococcus is known to
be sensitive.  The current choice for chemopro-
phylaxis in adults is rifampin, administered orally,
600 mg every 12 hours for four doses.  The patient
should be forewarned about red urine.  Rifampin-
resistant meningococci also occur.44  Minocycline
can also be used for prophylaxis but this drug has a
high incidence of vertigo and staining of tooth
enamel in young children.  Recently, a single dose
of ceftriaxone (250 mg, administered intramuscu-
larly) was reported as effective in eradicating pha-
ryngeal carriage of group A N meningitidis.55  This
could be particularly helpful if other serogroups are
sensitive.  It would also be especially useful in
pregnant women.  Ciprofloxacin (250 mg every 12 h
for 2 d) has also been effective.56
Vaccines
A quadrivalent vaccine that is effective against
serotypes A, C, Y, and W-135 is licensed for use in
the United States.  It is recommended for high-risk
patients with terminal complement defects and func-
tional or anatomical asplenia.  It is also recom-
mended for travelers to high-risk areas, such as the
meningitis belt in Africa.46
There is no effective vaccine for group B menin-
gococcus, the predominant serotype in the United
States.  Group C is a poor immunogen for children
under the age of 2 years—the age group usually
affected by this serotype.44
Recruits into the U.S. Army are routinely given
the quadrivalent vaccine.

Bacterial Skin Diseases
309
LYME DISEASE
Lyme disease (Lyme borelliosis) is a multisystem
infection caused by the spirochete Borrelia
burgdorferi, which is transmitted by ticks of the
genus Ixodes.  The characteristic skin lesion and
earliest manifestation of this disease is erythema
chronicum migrans (ECM, also known as erythema
migrans).  This may be followed by localized involve-
ment of the nervous system, heart, or joints.57  Some
patients recover spontaneously without treatment,58
but others will have disabling arthritis, neurological
impairment, or cardiac conduction abnormalities.
Lyme disease is not only the most commonly
reported tick-borne disease in the United States,58
according to T. E. Woodward, former president of
the Armed Forces Epidemiology Board, it is also
potentially of massive importance to both the mili-
tary and the public in many areas of the continental
United States.  Many epidemiologists believe that,
were it not for the advent of [acquired immunode-
ficiency syndrome], Lyme disease would now be
the nation’s primary infectious disease problem.
Incidence of the disease is steadily rising in the
United States, more commonly among males, and
with widespread distribution.59(p269)
In Lyme, Connecticut, in 1975, a cluster of pa-
tients with presumed juvenile rheumatoid arthritis
prompted an investigation by Steere60 into a disor-
der now recognized as Lyme disease.57  The rural
setting of the case cluster and the identification of
ECM as a feature of the disease suggested that it was
passed by an arthropod vector.  In 1982, Burgdorfer
et al61 reported the isolation of the causative spiro-
chete, subsequently named Borrelia burgdorferi, from
an Ixodes scapularis tick.  In retrospect, it is clear that
the borelliosis we now call Lyme disease had been
seen and treated earlier57:
• In Sweden in 1909, Afzelius62 described a
patient with migrating annular skin lesions
presumed to be caused by the tick Ixodes
reduvius.  He coined the term erythema
chronicum migrans.
• In 1948, Lennhoff63 described spirochetes in
lesions of ECM.  This received little attention.
• In 1951, Hollstrom64 reported successful
treatment of ECM with penicillin, and dur-
ing the 1950s, ECM was widely treated in
Europe with penicillin.
Epidemiology
In this country, Lyme disease is most prevalent
from April to October in the three geographical
areas where the tick vector is endemic: in the North-
east, from Maryland to Massachusetts; in the Mid-
west, in Wisconsin and Minnesota; and in the West,
in northern California and Oregon.  Lyme disease
was reported in 47 states during 1991.65  Thousands
of new cases are estimated to occur every summer
in Europe, especially in Germany, Austria, France,
Switzerland, and Sweden.  In Russia, Lyme disease
has been reported from the Baltic to the Pacific.  The
disease has also been found in Australia, China, and
Japan.57
Ticks, particularly the genus Ixodes, are the major
vectors for Borrelia burgdorferi.  In the United States,
Ixodes scapularis is the most common vector in the
East and Midwest and I pacificus in the West; in
Europe, the vector is I ricinus.58
The risk of contracting Lyme disease depends on
both the density of the tick population and their
degree of infection by Borrelia.  In the eastern United
States, as many as 60% of the Ixodes scapularis may
be parasitized with B burgdorferi; in the West, only
1% to 2% of I pacificus are parasitized.58
All stages (larva, nymph, adult) of the Ixodes tick
are capable of passing the disease, the nymphal
being the most common.  The nymph is so small that
it is difficult to recognize (beware the freckle that
moves!).  The bite is painless and often unnoticed.
The tick must remain attached for 1 to 3 days to pass
the disease.58
Many organisms may serve as a reservoir for B
burgdorferi, but the most common are the deer and
white footed mice.  Ixodes ticks feed on many spe-
cies of song birds.  Migration of birds infested with
these ticks may be one means through which new
endemic areas develop.  The illness of Lyme disease
is not known to occur in wild animals but is well
known to occur in domestic animals, including dogs,
horses, and cattle.66
Clinical Manifestations
Lyme disease has three major clinical stages: (1)
localized ECM, (2) disseminated infection, and (3)
persistent infection.  These stages are arbitrary, and
systemic progression from one stage to another is
frequently not seen.  In fact, a patient may present

Military Dermatology
310
with manifestations of two stages or may present in
the third stage without evidence of preceding find-
ings.  A revised classification also recognizes three
stages of disease but groups them differently: (1)
early infection, which encompasses stages 1 and 2;
and (2) late infection, encompassing stage 3, which
usually begins a year or more after the onset of the
disease.57
Early Infection: Stage 1 (Localized Erythema
Chronicum Migrans)
Stage 1 begins 3 to 30 days after the tick bite,
which only about one third of patients recall.  This
stage is characterized by nonspecific constitutional
symptoms: fever, chills, malaise, fatigue, arthralgias,
and headache.  The most prominent manifestation
is ECM, which is present in 60% to 83% of adults,67
but in fewer than 25% of children.58  ECM typically
begins at the site of the tick bite as an erythematous
papule that enlarges to an annular configuration
(Figure 13-13).  The edge may be raised and indu-
OK to put on the Web
Fig. 13-13. This early lesion of erythema chronicum
migrans developed 2 weeks after a tick bite to the patient’s
leg. The site of the tick’s attachment is clearly seen in the
center of the peripheral erythema.
OK to put on the Web
Fig. 13-14. As the annular erythematous border of the
eruption of erythema chronicum migrans advances away
from the central bite site, very large lesions may develop.
rated or flat.  The central portion partially clears,
often leaving an erythematous central punctum,
but may remain red and indurated or, rarely, be-
come necrotic.  These signs suggest a differential
diagnosis of brown recluse spider bite, cellulitis, or
tularemia (Figure 13-14).67
The lesion is frequently found where ticks char-
acteristically feed: the axilla, popliteal fossa, thigh,
groin, buttocks, and underwear lines.  ECM is usu-
ally asymptomatic.  The average size of the lesion is
15 cm, but lesions up to 68 cm in diameter are
sometimes seen.  When left untreated, ECM fades in
weeks to months.  The average duration is 1 month.
With appropriate antibiotic treatment, ECM usu-
ally resolves within days.67
The histological findings of ECM are relatively
nonspecific.  Hence, the presence of B burgdorferi
must be shown on silver stain, labeled-antibody
staining, or culture for confirmation of the disorder.
Spirochetes are most commonly found in the der-
mis of the advancing edge of the lesions.67
Early Infection: Stage 2 (Disseminated Infection)
Within days to weeks of inoculation, the spiro-
chete spreads to many parts of the body.  One or
more secondary skin lesions may occur and have
been reported in 6% to 48% of cases.  These second-
ary lesions tend to be smaller than the originals and
to migrate less.  However, multiple lesions may
become confluent and produce polycyclic or geo-
graphical patterns.  If untreated they tend to disap-
pear within a month but can persist for more than a
year.  In patients who are receiving appropriate

Bacterial Skin Diseases
311
therapy, the lesions usually resolve in a few days.  The
differential diagnosis includes erythema multiforme,
erythema annulare centrifugum, secondary syphilis,
erythema marginatum, and drug eruption.67
In Europe, approximately 1% of cases develop a
borrelia lymphocytoma, a form of B-cell pseudo-
lymphoma, also known as Spiegler-Fendt lymphoid
hyperplasia.  (The borrelia organism has been found
on silver stain and also on tissue culture.)  This
lesion (described as a firm, red, red-brown, or red-
purple nodule or plaque) has been known to occur
at the time of ECM or as late as 10 months after the
tick bite.  In children, the lesion tends to develop on
the ear’s pinna.  In adults, it is found on the nipple
or areola.  This lesion has not been described in the
United States.67
Musculoskeletal Manifestations.  Disseminated
infection is associated with characteristic symp-
toms related to involvement of the musculoskeletal
system.  Musculoskeletal pain is generally migra-
tory, lasting only hours or days at a given location.
The patients often appear quite ill with debilitating
malaise and fatigue.  A mean of 6 months after the
onset of the disease (range: 2 wk–2 y), approxi-
mately 60% of patients in the United States begin to
have brief attacks of asymmetric oligoarthritis in
the large joints, especially the knee.57
Neurological Manifestations.  The earliest neu-
rological manifestation is seventh cranial nerve palsy
(Bell’s palsy).  This is seen in 5% of patients with
early untreated disease.  Gradual resolution over
several weeks is generally seen, even in untreated
patients.  In the United States, approximately 15%
of untreated patients develop a spectrum of neuro-
logical abnormalities, including lymphocytic men-
ingitis, meningoencephalitis, cranial nerve palsies,
peripheral neuritis, and radiculoneuritis.66
The most common manifestation of central ner-
vous system Lyme disease is meningitis, which is
characterized by fluctuating symptoms mimicking
those of aseptic meningitis.  Complaints include
severe headache (typically occurring in short at-
tacks lasting over hours), irritability, neck stiffness
without frank meningism, photophobia, and nau-
sea and vomiting.  Examination of the cerebrospinal
fluid shows a lymphocytic pleocytosis of a few to a
few hundred cells, a normal glucose level, and mild
protein elevation.  These findings are indistinguish-
able from those found in aseptic meningitis.66
Syndromes involving the peripheral nervous sys-
tem include peripheral neuritis; sensory radiculitis;
sensorimotor radiculoneuritis; and brachial, lum-
bar, or sacral plexitis.  Several neurological mani-
festations may occur simultaneously or in sequence.
The combination of radiculoneuritis and cerebrospi-
nal fluid pleocytosis, known as Bannwarth’s syn-
drome or tick-borne meningopolyneuritis, is par-
ticularly common in Europe and the countries of the
former Soviet Union.66
Myocardial Manifestations.  Fewer than 10% of
untreated patients develop Lyme carditis, which
appears, on average, 2 to 6 weeks after disease
onset.  Lyme carditis is generally seen in patients
with minimal or no symptoms associated with the
onset of the infection.  Varying degrees of atrioven-
tricular block occur, often changing from minute to
minute or hour to hour.  Even in untreated patients,
these conduction abnormalities are usually brief.
High-grade atrioventricular block frequently re-
quires the insertion of a temporary pacemaker.
Rarely, a permanent pacemaker may be required.66
Late Infection: Stage 3 (Persistent Infection)
Episodes of arthritis, which is the characteristic
sign of persistent infection, often become longer
during the second and third years of illness.  They
last months rather than weeks, and chronic arthritis
begins during this time.  Only one or a few of the
large joints are affected.  Usually it is the knee.57
Acrodermatitis chronica atrophicans is a unique
late complication of Lyme disease, which about
10% of patients in Europe develop.  However, it has
rarely been reported in the United States.  Acro-
dermatitis chronica atrophicans occurs 6 months to
8 years after the initial infection and is more com-
mon in elderly patients.  An initial, nonspecific,
often bilaterally symmetrical, inflammatory state
usually occurs on acral sites.  Typically, this is an
erythematous or violaceous discoloration in doughy
or swollen skin with plaques or nodules.  The le-
sions may wax and wane over weeks to years before
atrophy occurs.  In the atrophic stage, the skin
resembles cigarette paper, with prominent blood
vessels.  There may be hypopigmentation or hyper-
pigmentation with scaling.  The lesion may be asso-
ciated with pain, pruritus, or paresthesias.  Re-
gional lymphadenopathy may be present.  B
burgdorferi may be demonstrated by special stains
in these lesions.  Early acrodermatitis chronica
atrophicans does not resolve spontaneously but
may respond to antibiotic therapy.  Later lesions
may not resolve even with antibiotics, but their
progression can usually be halted.67
Other skin conditions rarely reported to be asso-
ciated with Borrelia infection include benign lym-
phocytic infiltrate, morphea, lichen sclerosus et
atrophicus, atrophoderma of Pasini and Pierini,

Military Dermatology
312
TABLE 13-1
RECOMMENDATIONS FOR TREATMENT OF ADULTS WITH LYME DISEASE
Disease Stage
Recommended Treatment
Early infection, Stage 1
Doxycycline 100 mg PO b.i.d. for 10–21 d*
Amoxicillin 500 mg PO t.i.d. for 10–21 d
Tetracycline 250–500 mg PO q.i.d. for 10–21 d*
Cefuroxime axetil 500 mg PO b.i.d. for 20 d
Phenoxymethyl penicillin 250–500 mg PO q.i.d. for 10–21 d
Erythromycin 250 mg PO q.i.d. for 14–21 d
Neurological manifestations
Bell’s Palsy or mild symptoms
Treat as above, but for at least 3 wk
Other neuoropathies, meningitis, encephalitis
Ceftriaxone 2 g, IV, single daily dose for 14–21 d
Penicillin G, 20 million U/d, IV, in divided doses for 14–21 d
Lyme carditis
Mild disease (1st-degree heart block)
Doxycycline 100 mg PO b.i.d. for 14-21 d*
Amoxicillin 500 mg PO t.i.d. for 14–21 d
More serious disease
Ceftriaxone 2 g IV single, daily dose for 14–21 d
Penicillin G, 20 million U/d, IV, in divided doses for 14–21 d
Lyme arthritis
Doxycycline 100 mg PO b.i.d. for 30 d*
Amoxicillin and probenecid, 500 mg of each PO q.i.d. for 30 d
Penicillin G, 20 million U/d, IV, in divided doses for 14–21 d
Ceftriaxone 2 g, IV, single daily dose for 14–21 d
*Not recommended for use in pregnant women and children ≤ 8 years of age
IV: intravenous; PO: by mouth; b.i.d.: twice daily; t.i.d.: three times daily; q.i.d.: four times daily; U: units
Data sources: (1) Rahn DW, Malawista SE. Lyme disease: Recommendations for diagnosis and treatment. Ann Int Med. 1991;114:472–
481. (2) Rahn DW, Malawista SE. Lyme disease. West J Med. 1991;154:706–714. (3) Nadelman RB, Luger SW, Frank E, et al. Comparison
of cefuroxime axetil and doxycycline in the treatment of early Lyme disease. Ann Int Med. 1992;117:273–280. (4) Abele DC, Anders
KH. The many faces and phases of borreliosis: Lyme disease. J Am Acad Dermatol. 1990;23:167–186; 401–410. (5) Rahn DW. Lyme
disease: Clinical manifestations, diagnosis, and treatment. Semin Arthritis Rheum. 1991;20:201–218.
eosinophilic fasciitis, and progressive facial
hemiatrophy.  Only a minority of these lesions are
believed to be caused by Lyme disease.67
In this third stage, the following neurological
conditions have occurred: chronic encephal-
omyelitis, spastic paraparesis, ataxic gait, subtle
mental disorders, chronic axonal polyradiculopathy,
and dementia.57
Diagnosis
The diagnosis of Lyme disease is usually made
by the observation of a typical ECM lesion and the
history of its expanding character.  In an endemic
area, this is sufficient to treat the patient for Lyme
disease.  The history of a tick bite is helpful but
present in only about one third of cases.  More than
one half the patients have other acute symptoms,
especially fatigue, headache, fever, myalgias,
arthralgias, and mildly stiff neck.  Serologic tests
are often negative in early disease.  Perhaps the best
diagnostic test is a biopsy of the expanding edge of
the lesion with a modified Steiner stain for organ-
isms, but this is only positive in approximately half
the cases.68  Special cultures have made possible an
isolation of 86% from 4-mm punch biopsies of the
expanding edge of the lesions of erythema migrans.69
With chronic manifestations of Lyme disease, a
serology test is much more likely to be helpful.  These
tests are not standardized and there may be signifi-
cant variation between laboratories.  Additionally,
false positives from other conditions, such as syphilis,
confuse the picture.70  A significant percentage of
patients in endemic areas may have positive sero-
logic results with no evidence of Lyme disease.65
Treatment
Current recommended therapy71,72 for early Lyme
disease consists of

Bacterial Skin Diseases
313
1.
doxycycline, 100 mg, administered orally
twice daily for 10 to 21 days, or
2.
amoxicillin, 500 mg, administered orally
thrice daily for 10 to 21 days (this is particu-
larly useful when the patient is pregnant).
The duration of therapy depends on the rapidity of
the clinical response.72  Earlier regimens included
tetracycline, 250 to 500 mg, administered orally
four times daily for 10 to 21 days.  Doxycycline is
given only twice daily, is better absorbed and toler-
ated, and penetrates into the cerebrospinal fluid
better than tetracycline.  The major drawback with
doxycycline is that it causes photosensitivity in
many patients.  It should also not be used in preg-
nant or lactating women or young children.
Phenoxymethylpenicillin, 250 to 500 mg, adminis-
tered orally four times daily for 10 to 21 days, has
largely been supplanted by amoxicillin.71
For pregnant patients who are allergic to penicil-
lin, and others who are allergic to or intolerant of
penicillins and tetracyclines, erythromycin remains
a good alternative at a dose of 250 mg administered
orally four times daily for 10 to 21 days.  Erythromy-
cin is less effective than doxycycline or amoxicillin.
Cefuroxime axetil, 500 mg administered orally twice
daily for 20 days, has been reported73 to be effective
in the treatment of early Lyme disease.  Up to 15%
of patients with early Lyme disease experience a
Jarisch-Herxheimer reaction after the first or sec-
ond dose of antibiotic therapy, particularly when
penicillin or tetracycline is used.58
Late skin manifestations should be treated for 30
days.  Other systemic late manifestations often re-
quire intravenous penicillin G or ceftriaxone.
Ceftriaxone is particularly useful because it can be
administered parenterally once a day.66,71  The dose
and duration of medications used for therapy are
continually being refined.  Lyme disease is a diffi-
cult one in which to define a cure from therapy, but
Table 13-1 contains information that medical offic-
ers may find helpful.
SUMMARY
Cutaneous bacterial infections have had a major
impact on wars.  Pyodermas (eg, furuncles, ab-
scesses, impetigo, ecthyma), frequently caused by
Staphylococcus aureus or Streptococcus pyogenes, are
especially common in soldiers—probably due to
poor hygiene in the field and the predisposition to
superficial injuries to the skin.  Pyodermas may be
difficult to treat in deployed soldiers because local
skin care and strict antistaphylococcal antibiotic
administration can not be assured.
More lethal bacterial infections with cutaneous
manifestations (eg, plague, tularemia, diphtheria,
meningococcal infections) are fortunately much less
common than are the pyodermas.  Plague—the great
scourge of the Middle Ages—is endemic in certain
parts of the world today.  (However, plague is a
greater threat in its role as a biowarfare weapon.)
Meningococcal meningitis was a curse of training
bases in the past and still remains a threat today.
Meningococcal disease is one of the few that can kill
a healthy young adult in a matter of hours to a few
days.  Medical officers should view with great seri-
ousness a petechial rash in a recruit who also has a
spiking fever, chills, and myalgia and arthralgias.
Although penicillin remains the antibiotic of choice,
the recent report of penicillin-resistant Neisseria
meningitidis is worrisome.
Lyme disease, which is caused by a spirochete
transmitted by a tick and is endemic to many parts
of the continental United States, is becoming a pub-
lic health problem of increasing importance.  The
occurrence of erythema chronicum migrans in a
patient who goes on to develop protean symptoms
involving the central nervous system, heart, and
joints is highly suggestive of Lyme disease.  In
endemic areas, the presence of typical erythema
chronicum migrans is sufficient to justify treatment
with doxycycline or amoxicillin.
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Infectious Diseases. 22nd ed. Elk Grove, Ill: American Academy of Pediatrics. 1991: 191–195.
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Agents Chemother. 1974;6:166–169.
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Berg D, Abson KG, Prose NS. The laboratory diagnosis of Lyme disease. Arch Dermatol. 1991;127:866–870.
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1991;114:472–481.
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early Lyme disease. Ann Int Med. 1992;117:273–280.

Leprosy
319
Chapter 14
LEPROSY
JAMES W. STEGER, M.D.* AND TERRY L. BARRETT, M.D.†
INTRODUCTION
HISTORY
Leprosy in Antiquity
Leprosy in Medieval and Renaissance Europe
Modern Advances in the Study of Leprosy
Leprosy in the U.S. Military
EPIDEMIOLOGY
MICROBIOLOGY
Natural Reservoirs and Laboratory Transmission
The Cell Wall
Molecular Biology and Genetics
IMMUNOLOGY
Humoral Immunity
Cell-Mediated Immunity
The Lepromin Test
LABORATORY DIAGNOSIS
The Slit-Skin Examination Technique
Bacterial Index
Morphologic Index
Cutaneous Nerve Biopsy
Serologic Assays
CLINICAL AND HISTOLOGICAL DIAGNOSTIC CRITERIA
TREATMENT
Paucibacillary Leprosy
Multibacillary Leprosy
The Most Potent Antileprosy Drugs
Drug Resistance
Microbial Persistence
Promising New Drugs
COMPLICATIONS: THE REACTIONAL STATES
Reversal Reaction
Erythema Nodosum Leprosum
Downgrading Reaction
Lucio’s Phenomenon
VACCINATION
LEPROSY AND ACQUIRED IMMUNODEFICIENCY SYNDROME
SUMMARY
*Captain, Medical Corps, U.S. Navy; Head, Dermatology Clinic, Naval Hospital, San Diego, California 92134-5000
†Captain, Medical Corps, U.S. Navy; Pathology and Dermatopathology Consultant, Naval Hospital, San Diego, California 92134-5000

Military Dermatology
320
INTRODUCTION
Leprosy (also called Hansen’s disease) is an in-
fectious disease caused by Mycobacterium leprae that
affects principally the skin, the peripheral nervous
system, and certain other organs.  Depending on
their immune status, patients with leprosy may
present with a wide range of cutaneous and neu-
rological signs and symptoms.  These signs and
symptoms have been grouped together to delineate
leprosy into a spectrum of clinical forms or stages
whose complications and therapies differ from one
another.  Thus, it is important at the outset to be
aware of these clinical forms.
The simplest classification scheme is based on
the relative immune status of the host.  The form
found in hosts with the highest immunity is known
as tuberculoid leprosy; with the lowest immunity,
lepromatous leprosy; and with intermediate immu-
nity, borderline leprosy.  Unfortunately, there are
unstable transition forms between these groupings
and very stable polar forms at the high and low ends
of the immune state.  Consequently, leprosy is now
subdivided into seven stages of disease, arranged
from lowest to highest immune status of the host:
• lepromatous lepromatous polar type (LLp),
• lepromatous lepromatous subpolar type
(LLs),
• borderline lepromatous type (BL),
• borderline borderline type (BB),
• borderline tuberculoid type (BT),
• tuberculoid tuberculoid subpolar type (TTs),
and
• tuberculoid tuberculoid polar type (TTp).
The polar forms never change to any other form,
whereas all the remaining forms can change from
one form to the next.  These transitional forms arise
through fluctuations in the host’s immune system.
Transitions from a higher to a lower immune status
are reactional states known as downgrading reac-
tions, the converse as reversal reactions.  Both types
of reactional states complicate therapy.  An infected
patient whose clinical presentation (usually a
hypopigmented patch) is not diagnostic is said to
have indeterminate leprosy.  In time, one of four such
patients will develop lesions characteristic of one of
the other forms of leprosy; the other three patients
will clear spontaneously.  Where no skin lesions are
present but nerve damage has occurred, the disease
is designated primary neuritic leprosy.
Although it was epidemic during the Middle
Ages, today leprosy is acquired primarily by sus-
ceptible individuals and then only through pro-
longed contact (months to years) with infected indi-
viduals.  In general, oriental and black people tend
to be much more susceptible to the disease than
white people.
Individuals infected with the lepromatous forms
of the disease, whose immune status is low and who
harbor enormous bacterial loads, particularly in
their nasal mucosa, are the most dangerous sources
of infection to susceptible troops.  Therefore, mili-
tary interest centers chiefly on the chance encounter
with such patients in those countries where the
prevalence of lepromatous leprosy is high, and on
those troops from susceptible racial backgrounds.
Because even mention of the word leprosy may
elicit irrational and hysterical responses based on
fear and ignorance, it behooves unit commanders
and medical personnel to be well informed on the
low infectiousness of the disease and to educate
their troops accordingly.
Euphrates, a disease was known that resembles
what we call leprosy, and was recognized as being
related to human association.1  On the other hand, it
seems clear that the disease called leprosy in the
Bible could not have been the disease we call lep-
rosy today.
Unless otherwise specified, the following gen-
eral historical review of leprosy is translated from
the German and adapted for this chapter (by JWS)
from Klingmüeller’s comprehensive history of lep-
Perhaps because leprosy is of ancient origin and
was feared and loathed, historical records abound
that describe diseases that (a) are strikingly similar
to the disease we know as leprosy, albeit by differ-
ent names, and (b) diseases that may have been
called leprosy then but clearly are not the disease
we know today.  The following brief account at-
tempts to tease apart these sometimes intertwined
historical trails.  For example, from the time of
Hammurabi (1958–1916 BC), the King of Babel on the
HISTORY

Leprosy
321
rosy,1 which was published in 1930 and is difficult
to obtain in the United States.
The review of leprosy in military history prior to
the Vietnam conflict has been abridged and adapted
from the official history of the U.S. Army Medical
Department in World War II.2  This unique source
documents the military significance of and experi-
ence with leprosy through World War II.
Leprosy in Antiquity
Egypt
Egypt is generally agreed to be the land where the
earliest history of leprosy can be found.  In the Berlin
Papyrus from the time of Rhamses II (1333 BC) is a letter
concerning the treatment of leprosy, which concerns the
time of Pharaoh Sapti 5th who, according to Brugsch,
lived about 4266 BC.  The German dermatologist, Iwan
Bloch, a student of Unna, has determined that the charac-
ter “aat” in the Ebers Papyrus was a designation for
leprosy—on account of hyperaesthesia, hair loss, and
sudden collapse of the nose.  (However, his findings were
contradicted by Richter.)  Around 1700 BC, the Hyskos, a
seminomadic tribe out of Asia Minor, invaded Egypt,
resulting in a mixing of Egyptians and Asians.  This may
be important as it is believed that leprosy arose in Asia.1
The Exodus of the Jews from Egypt occurred around
1440 BC under Amenhotep II, or in the 16th century under
Thothmes IV (according to Conder).  At the time of the
Exodus, according to the Egyptian historian Manetho
(circa 300 BC), about 80,000 Jews were affected with lep-
rosy.  However, they lived in Goshen on the east side of
the Nile, and did not mix with the Egyptians to any great
extent—and later departed for Canaan.  In the 6th to 5th
centuries BC, the Persians ruled Egypt, resulting in a great
mixing of populations.  Around 250 BC, the Septuigent, a
Greek translation of the Hebrew Bible, was started by
Hebrew scholars.  They translated the Hebrew word
Zaraath as Lepra, which, according to the Greek physi-
cian Hippocrates, was the name given to a scaly skin
condition.  Hopes that the skulls and bones of Egyptian
mummies might reveal earlier evidence of leprosy have
not been fulfilled; the earliest pathological changes sug-
gestive of leprosy date from the 2nd century BC.1
In the Bible
t[‘r”Ÿx;, pronounced “tzah-rah-AHT,” and usually
transliterated as zaraath, is the Hebrew word found in the
Tanakh (the Hebrew Bible, ie, Old Testament) that has
traditionally been translated as “leprosy” in many edi-
tions of the Bible.  In the Torah, as described in Leviticus,
the Third Book of Moses, t[‘r”Ÿx; is (a) diagnosed by the
priests and (b) associated with periods of quarantine,
both suggesting that its presence is due to the wrath of
God.  This may be the origin of the irrational horror of the
disease and the ostracism of afflicted individuals.
The clinical characteristics of t[‘r”Ÿx; as revealed in the
Scriptures of Leviticus 13 include the triad of (1) a white
or shiny patch in the skin, (2) depression of the skin [also
translated as deeper than the skin—JWS], and (3) whitening
of the hair.  However, the account seems not to have
mentioned hyperpigmentation, alteration in cutaneous
sensation, facial disfigurement, or loss of eyebrows; and
no blindness, muscular palsies, or hideous mutilations.
Lastly, and most interestingly: if the condition in-
volves the entire cutaneous surface, the individual is to
be pronounced “clean” (ie, not infectious), and no longer
to be excluded from the community:
If t[‘r”Ÿx; breaks out all over his skin and, so far as the priest
can see, it covers all the skin of the infected person from head
to foot, the priest is to examine him, and if the t[‘r”Ÿx; has
covered his whole body, he shall pronounce that person
clean.3  [Hebrew word t[‘r”Ÿx; not translated—JWS]
Obviously, then, t[‘r”Ÿx; and leprosy cannot be equated.
No leper with disease from head to toe would ever be
clean according to Jewish law.
Interestingly, in the New Testament when Jesus en-
countered the man full of “leprosy” in the Gospel Ac-
cording to Luke, Chapter 5, and cleansed him of his
leprosy, Jesus told him to go and show himself to the
priest and make an offering for his cleansing, just as
Moses had commanded regarding t[‘r”Ÿx;.  [Similarly, for
the 10 lepers in the Gospel According to Luke, Chapter 17—
JWS]  Consequently, it is obvious that the leprosy of the
Bible is something quite different from Hansen’s disease.
In fact, there is no known dermatologic disease that
incorporates all its features.  Modern interpreters con-
sider the term to represent a variety of infections or skin
inflammations.  In Biblical context, it appears to be a sign
of God’s displeasure.4
Persia
Concerning Persia in the 6th century BC, Herodotus
(484?–425? BC) writes in The History, Book 1, 138:
If a citizen has “leprae” or a white rash, he should not go
into the city or into a group of people, but becomes a
stranger, and is to be driven out of the land.1(p6)
It has not been shown that the conquests of Darius I
(521–486 BC) and Xerxes I (486–465 BC) spread leprosy to
the western parts of Asia minor, the Grecian Islands, or
Greece proper, even though Xerxes’ troops and logistic
supports numbered over 1 million individuals.1
Greece
The contact of the Greeks with the eastern populaces
through the Persian wars, and especially through the far-
reaching (to India) campaigns of Alexander the Great
(336–323 BC) and the subsequent campaigns of Diadochen
(323–301 BC), surely have contributed to the spread of
leprosy.  The Greek writer Ktesias from Persica described
in the 5th century BC that leprosy had “ruled” in Persia.1

Military Dermatology
322
The Phoenicians operated as agents between Asia and
Europe in the spread of leprosy.  In the 7th through the
6th centuries BC, they carried their trade from Asia to the
French and English coasts.
In Greece up to the time of Hippocrates (460–377 BC),
leprosy was essentially unknown.  The term “leprae” was
used to describe scaly rashes more on the order of psoria-
sis or eczema.  It appears that Aristotle (384–322 BC),
under the name Satyriasis, possibly described true lep-
rosy (de generat. animal IV, 3).1  The earliest description of
a disease that is unmistakably leprosy was by Aretaeus,
in Greece, about AD 150.  He called the disease
elephantiasis.5  Plutarch (AD 46?–120?) (Sympos VIII, Qu
IX) quoted the Greek physician Philon as stating that
none of the ancient Greek physicians had given any
information about elephantiasis.  In Persian references
and through Persian military campaigns, leprosy could
have been transmitted from the peoples of Persia, Syria,
or Phoenicia to Greece.1
The oldest Alexandrian physician (3rd century), Galen,
brings us a detailed description of leprosy and notes the
following symptoms (Galen, introductio cap. XIII)1:
• the superficial changes in the skin from inflam-
mation and ulcers/abscess/boils as leprosy,
• the thickening of the joints and other parts of the
body as elephantiasis,
• the changes on the face as “leontiasis,”
• the loss of hair as ophiasis and alopecia, and
• mutilations.
The Roman Empire
It was during the time of Asklepiades, a contemporary
of Pompey (106–48 BC), according to Plutarch (AD 46?–
120?), (Sympos. VIII, 9), that leprosy first made its appear-
ance in Italy.  However, it appeared only rarely in the 1st
century BC in Rome.  But it was at this time that the
nomenclature became clear: what one called lepra (Greek)
in the Hippocratic sense was a scaly skin disease, and
what one called elephantiasis (Greek) was true leprosy in
today’s sense.  In 95 BC Lucretius wrote of an “elephant
disease” (elephas morbus) that raged on the banks of the
Nile.  The notion that this was leprosy is rendered more
probable by a passage in Celsus concerning “elephan-
tiasis.”  Around the time of Christ, characteristic descrip-
tions of leprosy are found.  Aulus Cornelius Celsus, a
contemporary of Tiberius (AD 14–37) wrote:
Totally unknown in Italy, but very frequent in a few other
lands is the disease which the Greeks call elephantiasis.  It
is heard to be chronic.  The whole body is so afflicted with
it, that even the bones are afflicted.  The surface of the
body shows many spots and ulcers/abscesses which are
closest to red in color, but progressively assume a black
color.  The skin is thick in many places, in other areas it is
thin, in a few hard, in a few soft, and somewhat rough
from scaling, thereby the body appearing emaciated,
while, on the contrary, the face, the lower extremities and
the feet are swollen.  Where the disease has been present
for a long time, there is a disappearance of the fingers of
the hands and the toes of the feet in the swelling, and a
slight fever occurs all of which causes great sorrow.1(p8)
At a later time, Cajus Plinius Secundus (AD 23–39) in
Natural History XXVI, 5 and XX, 14 writes: “We have
already said that the elephantiasis had not arrived in
Italy before the time of Pompey the Great.”1(p8)  Caelius
Aurelianus (morb. chron IV, cap 1), who lived in Rome,
was a founder of the method school, a contemporary of
Pliny the Elder, and the first to extensively deal with the
treatment of lepra.  Philumenus (circa AD 150) extensively
described the treatment of elephantiasis: baths of albula
and nepete; mineral springs in Macedonia, Thrace, Crete,
and Anchialus; and steam baths followed by cold sulfur
application or alum baths, all of which shorten the heal-
ing, “if the skin is as repulsive as that of a snake!”1(p8)
In the 2nd century the campaigns of the Roman em-
perors, especially towards Asia (eg, Trajan against the
Parthians in AD 114–116, his campaign to the Tigris River
and the Persian Gulf) resulted in the greater possibility of
a spread of leprosy to Italy and Europe.  And so it appears
that in this time, courtesy of the Roman legions’ travel-
ing, leprosy reached Spain, France, Germany, and espe-
cially Lombardy, and continued to spread throughout
the Roman Empire.1
India
A larger outbreak of leprosy appeared to have oc-
curred in India.  In the 14th and 15th centuries AD, the Rig
Veda sanhita used the term kushtah for a disease that was
undoubtedly leprosy, a term that is still used today in India
for the disease.  In the interpretations of the text, there is the
suggestion of references back to the 7th century AD.  In the
4th century AD in the canonical texts, similar writings are
found.  In the Ayurveda (2000–500 BC), various treat-
ments—including chaulmoogra oil—were suggested for
the treatment of leprouslike conditions.  More recent
investigations have found that kushtah was first described
about 600 BC in the Susruth Samhita.  Treatment at that time
was also undertaken with chaulmoogra oil, a folk remedy
that has had continued use up to the present day.5
China
Leprosy has definitely been present in China for at least
2,000 years.  The first reported incidence of leprosy in
China was 1100 BC, and 200 to 300 years before Confucius
(5th century BC), leprosy was thought to be a punishment
for sins.  In the last book of medical science of Su-wen,
written toward the end of the Chon dynasty (1130–250
BC), the disease lei-fon is described as having (1) loss of
sensation, (2) destruction of the nasal structures, and (3)
discoloration, ulcers, or abscesses of the skin.6
Recently, an ancient book from the Ch’in dynasty
(221–206 BC), the Bamboo Book, has been excavated from
the tomb of magistrate Hsi in Yun Meng, Hupeh.  In it,
leprosy is well described:

Leprosy
323
Cha went to see Bing and said to Bing, “I think you have
Leprosy (Li).”  Bing replied, “At age three I was sick, my
eyebrows were swollen and nobody knew what the sick-
ness was.  I was directed to see a doctor, Ting.  The doctor
said, you don’t have eyebrows because they are rootless.
Your nostril is destroyed; you cannot sneeze on irritation;
your legs are halt because one of them burst, and your
hands have no hair.”  He asked Bing to shout and the
voice was hoarse.  That is leprosy.6(p291)
This historically significant document, having been exca-
vated and dated, represents original material rather than
a redacted version from subsequent generations.6
Chang Chung-ching (AD 150–219), often referred to as
the Hippocrates of China, wrote in his classic book, Shang
Han Lun (Essay on Typhoid) that a person having leprosy
has very little hair and eyebrows left, and his body is full
of sores that have a fishy and stinking smell.6
In Chou-hau-hong, during the Chin Dynasty (AD 265–
419), a disease with the name of lai-ping, whose manifes-
tations included a loss of sensation and formication was
described by Kwo-Hon (AD 281–361).1  He described a
second man whose leprosy was cured with pine cones.  In
another work, Kwo-Hon describes a military official named
Tsui Yen who was suddenly afflicted with leprosy:
His eyes grew dim, he could not distinguish either objects
or men.  The eyebrows and hair fell off, the nasal bridge
dropped and the skin was covered with sores.6(p294)
The man was later cured with saponin and rhubarb
solution.  Pine cones and saponin are still in the Chinese
pharmacopoeia for leprosy and ulcers, respectively.6
Later in China, Pin-yüan-hou-lun (AD 589–617), de-
tailed the signs of leprosy so clearly that no confusion
with any other disease is possible: anesthesia, paresthesia,
pains in the joints, insensibility to needle stick, anhidro-
sis, loss of fingers, cutaneous nodules, loss of the eye-
brows, and roughness of the voice.1
Chaulmoogra oil, obtained from the seed of a coconut-
shaped fruit of the Hydnocarpus tree, native to Cambo-
dia, was probably imported into China in the Southern
Sung period (1127–1278).  Its value in the treatment of
leprosy was well known, but required careful monitor-
ing for side effects since it was poisonous to the blood
and the eyes.  One herbalist gives directions for the
preparation of the oil as follows:
Take three catties of the seeds, discard those that have
turned yellow, remove the husks and grind into a fine
powder.  Pack in earthenware jar and seal up tightly.  Put
the jar into a pot of boiling water and seal the pot so that
no steam can escape.  Boil until the oil assumes a black
and tar-like appearance.  It is administered in the follow-
ing way:
Chaulmoogra oil
1 ounce
Saphoro flavescens
3 ounces
Mix into a paste with wine and make into pills the size of
a stercula seed.  Sig: Take 50 pills with hot wine before
meals.6(p301)
Japan
Written about the year AD 702 in a place called Reino-
gige, in the Commentary of Taiho-rei, the second-oldest
Japanese law book, the following comments are found
about leprosy:
There is loss of the eyebrows, destruction of the nasal
structures, hoarseness, mutilation of the joints; one must
not share a bed with such a diseased person, because the
disease can be communicated to the next person.1(p 4)
Leprosy was apparently endemic in Japan for 1,000
years.  In AD 1554, the Portuguese Louis Almeida estab-
lished a hospital in Funai, Japan, for syphilis and leprosy.
The oldest leprosy colony, however, was apparently es-
tablished in Nara, near Kyoto, perhaps going back to the
time of Emperor Gwyo (AD 718–740), who, according to
legend, washed 1,000 lepers with his royal hands, for
chastening.  The famous Chinese monk Chien Chen (688–
763) became a medical missionary to Japan, and while in
Nara, he became medical consultant to the Empress
Komyo, whose own tragic life led her to take a major
interest in the care of patients with leprosy.  Chien Chen
spent 10 years in Japan and wrote many medical books.
He is worshiped as Kanjin, the ancestor of medicine.6  In
740, the Empress Komyo herself provided for the nursing
of leprosy patients at the time of the blossoming of
Buddhism in Japan, by increasing the hospitals for lep-
ers, which were founded by Prince Shotokautaifa (born
621).  It was at this time that the Chinese medical book,
Byogenkoronsenkin-ho, was carried to Japan, in which lep-
rosy with its characteristic signs was described, which
was thought to be due to unhealthy air and an insect that
penetrated human flesh.  That lepers may go blind was
not mentioned.  In 833, in Reisikai, a commentary on the
law mentioned that leprosy was transmitted to men who
were in the vicinity of the afflicted.  This insight was
apparently lost when the Buddhist priests taught that
leprosy was a punishment for sins committed in a previ-
ous life.  The lepers then suffered pitifully as beggars
near the temples.1
Leprosy in Medieval and Renaissance Europe
Because of the increase in the number of cases and the
horror with which leprosy was regarded during the
Middle Ages, it was not a diagnosis to be taken lightly.
Nonetheless, it was not only physicians but also laymen
who made the diagnosis.  In general, diagnosis was
conservative, tending to recognize only the most se-
verely affected individuals.
As early as 757, Frankish law permitted divorce be-
cause of leprosy.  In 1179, the Lateran Council decreed
that lepers could not share church, cemetery, or even
social life with the healthy.  By 1220, it was a civil crime
for a leper to live with a nonafflicted individual.  The
afflicted were officially cut off from the rest of Medieval
society.  In some parts of Europe they were considered

Military Dermatology
324
legally dead and the leper’s heirs could inherit his prop-
erty while he yet lived.7
Because leprosy had spread during the Crusades, the
Order of Sacred Lazarus was founded in 1048 in Pales-
tine, under Pope Damasius II.  The head of the order was
frequently afflicted with leprosy himself.  By the 13th
century, many branches had been established through-
out the whole of Europe.  Their monasteries were asy-
lums for lepers, where they could remain until they died.
Some 19,000 leprosaria were present in Europe by this
time—a testimony to the rampant spread of leprosy dur-
ing the Middle Ages.1
Theodoric of Cervia, who was both a bishop and a
surgeon (1205–1298), drawing on the earlier medical
writings of the Arabic physician Avicenna, described
two types of leprosy: one that was self-limited and prob-
ably corresponds to tuberculoid leprosy; the other, to
lepromatous leprosy.  His description of the latter is
unmistakable:
the face becomes puffy, the hairs of the eyebrows and
eyelids thin out,... nodules are felt in the skin,... the voice
wavers, tending to lower,... patients are pricked in the
ankle bone and are unaware, they feel little, similarly on
the leg.5(p301)
Whereas early in the Medieval period leprosy was less
precisely recognized and was equated with heresy, as the
diagnosis became more widely and reliably recognized,
the social stigmata changed to that reflecting worldliness
of the part of the victim: in particular, pride, avarice,
gluttony, sexual promiscuity, and neglect of spiritual
matters.  This change in attitude is reflected in the litera-
ture of the period, for example, Dante’s Inferno and
Hartmann von Aue’s famous middle-high–German poem
“Der Arme Heinrich” (The Lamentable Henry).7
With time, there was some easing of the social situa-
tion for the patient during the Middle Ages.  John of
Gaddesden in the 14th century counseled that no man be
judged a “leper” until his face had been destroyed by the
disease.  This advice was generally followed, since the
diagnosis brought severe legal and religious sanctions.
Indeed, seen as the outward figure of an unclean soul,
leprosy evoked a special church ceremony in which the
“leper” was enjoined to be “dead unto the world, but
alive unto Christ.”8(p347)  Later, the Church decreed that
leprosy was not grounds for divorce or dissolution of
marriage, and the remarriage could not take place until
the death of the infected person.8
However, within another century leprosy was clearly
declining in England, while the population was greatly
increasing.  Only half of the available hospital spaces
were still being used and many of the leprosaria began to
be converted to other uses.  Indeed, by the time of the
Black Death (1347–1350), which killed one third of the
population of Europe, many of the leprosaria were empty
on the continent as well.  In Scandinavia, where the popu-
lation density was much less, leprosy persisted longer.8
Any doubts that the disease in the Middle Ages was
leprosy have been dispelled by the paleopathologic stud-
ies of Møller-Christensen: he discovered, in Naestved,
Denmark, the burial ground of a “lazar” hospital that
existed between the years 1250 and 1550.  He was able to
demonstrate classical changes of lepromatous leprosy in
many of the skulls and bones of 202 skeletons that were
excavated at this Medieval leprosarium.5  Characteristic
was the destruction of the alveolar process of the maxilla,
the loss of central incisors and canine teeth, erosion of the
hard palate, and loss of the nasal bone.8  Similar changes
have been noted in skeletons from England and from
Aachen, Germany.7
By the time of Fracastorius (1478–1553) during the
Renaissance, leprosy had waned considerably.  How-
ever, the rise of syphilis following the discovery of the
New World led to the belief in the 16th century that
leprosy and syphilis (“the French sickness”) were the
same disease.  Using all the pertinent classical texts,
original manuscripts, and the medical works of Pliny,
Galen, and Avicenna, Fracastorius critically examined
the language and descriptions of leprosy.  He noted that
the disease known as leprosy was described by the Greeks
under the term “elephantiasis,” and that the term “lepra”
corresponded to milder, no-longer-recognizable condi-
tions.  He additionally distinguished the cutaneous nod-
ules of leprosy from syphilis, and emphasized the slow
progression of leprosy in contrast to syphilis.  Whereas
syphilis was considered a venereal disease, leprosy was
recognized by Fracastorius to be contagious, transmitted
by contact with lesions, by fomites, and by the breath of
patients.9
Leprosy was first introduced in North America in the
middle of the 16th century by immigrants from Europe.
Later, slaves from Africa imported leprosy to America
and Brazil.10
Modern Advances in the Study of Leprosy
One of the greatest strides in the knowledge of leprosy
came in 1874, when G. Armave Hansen first described the
microorganisms present in nodular leprosy.  In 1884, he
defined the morphologic characteristics of M leprae using
a methyl violet staining method, describing rodlike or-
ganisms, chains of coccoid forms, and the clumping of
organisms that is now called globi.  Paul Gerson Unna
later confirmed this peculiar clumping.11
As early as 1884, Patrick Manson described a method
of diagnosing leprosy.  His suggestion was to squeeze the
nodule and then pierce it.  Exudate obtained was spread
on cover slips or slides.  It was dried, stained, and then
examined microscopically for organisms.  But the major
breakthrough for microscopical examination was made by
Wade in 1913, when he introduced the skin-slit procedure.
The enigmatic granularity of bacilli frequently seen
with acid-fast staining was finally explained by Rees and
Valentine in 1962, when they demonstrated by electron
micrographs that the irregular acid-fast staining corre-
sponded with degenerative changes in M leprae.11
The first major therapeutic breakthrough in leprosy
came in the 1940s, when sulfones were shown to be

Leprosy
325
effective against the leprosy bacillus.  In 1941, Dr. Guy
Faget of Carville, Louisiana, began to use promin, and by
1943 began to report its beneficial effects.12
The first successful cultivation of M leprae occurred in
1960, when Dr. Charles Shepard of the Centers for Dis-
ease Control in Atlanta, Georgia, reported its propaga-
tion in the footpad of the mouse.  Dr. Waldemar
Kirchheimer of Carville, and Dr. Eleanor Storrs of the
Gulf South Research Institute in New Iberia, Louisiana,
demonstrated an animal model of leprosy in the nine-
banded armadillo in 1968.  These two advances have had
a major impact in the basic understanding of leprosy and
have led to a wide range of scientific studies on the nature
of and the treatment of the disease.10
Leprosy in the U.S. Military
The importance of leprosy as a military problem is
limited by certain of its epidemiological characteristics.
The most pertinent of these are (a) geographical distribu-
tion, (b) low prevalence rates even in areas in which the
disease is considered to be highly endemic, and (c) rela-
tively low attack rates in adult life.2
For practical purposes, leprosy may be considered a
disease of the tropics and subtropics.  Every country with
high prevalence rates is situated within the tropics, and
such tropical countries are inhabited mainly by back-
ward people living in overcrowded huts under condi-
tions favorable to the spread of the disease.
Every country with a very high leprosy rate (ie, 3 or
more cases per 1,000 population) is situated in the trop-
ics.  In practically all, the climate is hot and damp.  The
tropical belts of Africa and India are considered to have
the highest prevalence rates in the world.13
In contrast, prevalence rates are low (< 1 per 1,000
population) in most temperate regions of the world, and
are virtually nonexistent in cold climates.13  The attack
rate is very low in adults.  Acquisition of the disease
normally requires prolonged respiratory contact with a
person with untreated lepromatous leprosy.  Nonethe-
less, more than 99% of the exposed population will fail to
develop the disease.14  For the remaining 1% who do, the
incubation period averages 2 to 5 years.10
Leprosy in the U.S. Army Before World War II
There are no records of leprosy occurring in the U.S.
Army before the Spanish-American War.  During the
War of 1812, troops were engaged in New Orleans in the
vicinity of an old endemic focus, but the number of men
involved was small and the duration of the conflict short.2
The earliest records of leprosy in the armed services of
the United States relate to cases among soldiers who
served in the Spanish-American War, the Boxer Rebel-
lion, or the Philippine Insurrection.  Actually, the cases
did not occur during the hostilities; they were reported at
intervals over several subsequent decades, and the onset
dates are not known with exactness.  One or perhaps two
of the cases may have originated as early as 1901.  From
1921 to 1940, 32 veterans were admitted to the U.S.
Marine Hospital (also called the National Leprosarium)
at Carville, Louisiana.  Of these, 28 had served in the
army, three in the navy, and one in the marines.  Thirty
patients had had military service outside the United
States in places known to be focuses of leprosy; 25 of the
30 had served in the Philippines.  There is no record of
foreign service for two of the patients; one was born in
Louisiana and the other in Texas.  Five were born outside
the continental United States; 19 were born in parts of the
United States where the disease rarely occurs.  For 18 of
the latter, the periods of service in endemic areas ranged
from 9 months to 32 years.  A large portion of the Spanish-
American War veterans who had been admitted to the
National Leprosarium were born in nonendemic areas;
the average age on admission of the entire group of
Spanish-American War veterans was 52.  The dates at
which the first signs of the disease are stated to have
appeared ranged from 1901 to 1938, but, of 27 patients for
whom dates are given, all except 4 are stated to have
observed their first symptoms after 1910.  A number of
veterans who developed the disease had remained in the
Philippines in military or civilian capacity for some years
following termination of the Philippine Insurrection.2
From 1921 to 1940, 51 World War I veterans were
admitted to the National Leprosarium.  Of this popula-
tion, 41 had served in the army, one in the Students
Training Corps, eight in the navy, and one in the marines.
Records show that 33 had no service outside the conti-
nental United States, 12 had served in France, two in
Mexico, and one each in Hawaii, Panama, the Philip-
pines, and Puerto Rico.  Of the group of 51, 18 had been
born outside the continental United States, and, of the
remaining 33, 15 had been born in Louisiana, 10 in Texas,
5 in Florida, 2 in Mississippi, and 1 in Georgia.  None had
been born in the northern States.  Age on admission to the
National Leprosarium averaged 33.2 years (range: 22 to
43 y).  In 35 patients (68.6%), the first signs of the disease
were noticed during the years 1917 through 1923.2
Preventive Measures During World War II
Because [a] knowledge was lacking about the mode of
spread of the disease and [b] there were no effective
vaccines or chemical prophylactics, there was not much
that the U.S. Army’s Preventive Medicine Service, Office
of The Surgeon General, could do to protect troops and
other military personnel against leprosy.  Protection de-
pended almost entirely on recognition of the disease
when it occurred and avoidance of contact.  At the same
time, measures were invoked to counteract the fears, the
military and public alarm, and the dangers of irrational
behavior (eg, violence, hostility) that were aroused by
age-old superstitions about the disease.  The Preventive
Medicine Service recognized that leprosy, because of its
long latency and low incidence of adult infection, could
not be a disease of military significance insofar as loss of
manpower during World War II was concerned.  It also
recognized that the area of exposure was vastly extended

Military Dermatology
326
and that the number of possible contacts was increased
when thousands of U.S. soldiers were deployed among
populations where incidence of leprosy was high, par-
ticularly in the Pacific regions.  The late consequences of
acquisition of leprosy during the war by soldiers exposed
in the course of their service were also matters of grave
concern.  A balanced program was adopted that was
designed to stimulate awareness of the disease and at the
same time to support reasonable precautionary measures.2
The prevention of contact of military personnel with
leprous persons within the service had been a long-
standing practice, as specified by army regulations.  Lep-
rosy was a fixed basis for rejection of men coming up for
induction through enlistment or draft.  Despite provi-
sions for rejection on account of leprosy, the records, exam-
ined later, showed that 15 men infected with leprosy before
1941 were inducted into the army during World War II.
Of these, five were men who had been discharged from
the National Leprosarium as “arrested cases.”  The other
10 men were from various parts of the United States and
Hawaii and, at various periods after induction, were
discovered to have leprosy.  The other 10 men were from
various parts of the United States and Hawaii and, at
various periods after induction, were discovered to have
leprosy.  No secondary cases among military personnel
are known to have arisen from these sources.2
Significant advances were made in the therapy of
leprosy during World War II.  For many years, the stan-
dard treatment had been administration of chaulmoogra
oil or its esters, and, although there was controversy as to
the results, there was nothing better at hand.  In 1940,
sulfanilamide was given to a group of patients at the
National Leprosarium.  However, “although secondary
infections were cleared up, little or no improvement was
noted in leprous lesions.”2(p34)
Promin, one of the sulfone drugs (which differ from
the sulfonamides in having two phenyl groups instead of
one, and which have in common the diaminodi-
phenylsulfone radical), was released in soluble form for
clinical study in 1938.  In March 1941, the first group of
leprosy patients at the National Leprosarium was placed
on promin.2
At first [the drug] was given orally, and toxic symptoms
were so severe that it had to be discontinued.  Shortly
afterward, a preparation for intravenous use was ob-
tained and found to be well tolerated.  Clinical improve-
ment observed was slow but definite; as a rule, it did not
become manifest until after 6 months of treatment.  Le-
sions of the mucous membranes of the upper respiratory
tract responded well, resulting in restoration of the voice
and disappearance of nasal obstruction.  Emergency tra-
cheotomies were much less frequently required.  Nod-
ules in the skin slowly flattened.  Areas of infiltration
gradually subsided.  Leprous ulcers of the extremities
gradually healed.  Occasionally, regrowth of hair oc-
curred in the eyebrows, beard, and on the arms and legs.
There was little evidence of improvement in eye lesions.
Skin and nasal smears remained positive in nearly all
patients even after a year of treatment, but there was
definite evidence of reduction after 2 years of treatment.
Slow and gradual disappearance of bacilli was confirmed.
Promin appeared to act by eliminating bacillary infection
from the blood vessels and bloodstream, thereby pre-
venting formation of new lesions and permitting natural
resolution of lesions to take place.2(p34)
Promin was in part replaced in 1943 by disodium
formaldehyde sulfoxylate diaminodiphenylsulfone, first
prepared under the name of Diasone.  It was given orally
in doses as large as about 1 g daily.  Other sulfones soon
came into use, but the results with all of them were more
or less equivalent to those obtained with Diasone.  It is
considered by many that beneficial effects of the sulfones
on leprosy are attributable to diaminodiphenylsulfone
(DADS).2
Records have been found of 69 cases of leprosy in
individuals who served in the armed forces during World
War II.  In 15 of the 60 leprosy patients from the army,
there is evidence that the disease had been present before
enlistment or induction, and 5 of the 15 had been treated
previously at the National Leprosarium.  Of the other 45
patients, 7 had definite histories of exposure to leprosy in
the family.  The records of the remaining 38 patients were
carefully examined in the search for the probable loci of ex-
posure.  All but six had been born in the areas in which the
disease is endemic [eg, the Gulf coasts of Louisiana and
Texas—JWS].  While this does not preclude the possibility of
exposure during military service, it would seem more prob-
able that the infection occurred at an earlier date.  This is
supported by the fact that the average age of these patients
at time of stated onset was 27.2 years and also by the fact that
there was no significant difference in average age at time of
onset between those who had served in theaters in which
the disease was endemic and those who had not.2
Leprosy During the Vietnam Conflict
The only statistics on leprosy reported out of the
Vietnam conflict dealt with indigenous Vietnamese pa-
tients seen at the 95th Evacuation Hospital Da Nang, I
Corps, from July to October 1970.  Fourteen cases, consti-
tuting 13% of the total (114) population presenting with
skin diseases, were seen.15(p41)
EPIDEMIOLOGY
The World Health Organization (WHO) currently
estimates the prevalence of leprosy at 10 to 12 million
cases, based on some 3.7 million registered cases, with
576,361 new cases detected in 1990 (Figure 14-1).13,16
The portal of entry for leprosy bacillus most
probably is the respiratory tract, although there is
evidence for transmission of leprosy through intact
skin and via penetrating wounds such as thorns and

Leprosy
327
Fig. 14-1. The world distribution of registered leprosy cases as of 1990. Data source: Noordeen SK. Leprosy control
through multidrug therapy (MDT). Bull WHO. 1991;69:264.
arthropod bites.14  It is widely accepted that the nose
is the major portal of exit for bacilli.  Multibacillary
patients can shed several millions of bacilli per
day in their nasal secretions.16  Patients with un-
treated lepromatous leprosy have great numbers of
bacilli in their nasal secretions.  However, patients
with borderline and tuberculoid disease have
few to none.  Chemotherapy rapidly renders the
nasal discharge bacteriologically negative.  Longi-
tudinal studies have repeatedly confirmed that
multibacillary patients constitute the major source of
infection.
The decline in leprosy documented in some coun-
tries at a time of improvement in living conditions,
but before the advent of modern control measures,
suggests that mitigation of overcrowding and
poverty, as well as improvements in nutrition and
hygiene, have beneficial effects in preventing the
disease.16
While humans are considered to be the major
host for the leprosy bacillus, natural infections of
wild armadillos occur in Texas and Louisiana, and
natural infections of chimpanzees and mangabey
monkeys occur in the wild.16  Anecdotal reports
suggest that transmission of M leprae between ar-
madillos and humans is possible.
Children, particularly infants and young chil-
dren, seem to be much more susceptible to leprosy
than adults in a given population.  Where children
are at risk because of leprosy in the family, up to
60% will develop disease after a 2- to 7-year incuba-
tion period.  Thus, peak ages of incidence are ages 5
through 9 years.17  In contrast, the incidence of
conjugal leprosy in spouses is only about 5%.5  Trans-
placental transmission has rarely been docu-
mented.17  However, one series18 of 91 children less
than the age of 1 year in whom leprosy was diag-
nosed has been reported.  In children, paucibacillary
forms of leprosy tend to predominate, with most
children expressing indeterminate and tuberculoid
lesions.17  However, in a recent series of 132 children
from a nonendemic area of northern India, 59% had
Fig 14-1 is not shown because the copyright permission granted to the Borden Institute, TMM, does not
allow the Borden Institute to grant permission to other users and/or does not include usage in elec-
tronic media. The current user must apply to the publisher named in the figure legend  for permission
to use this illustration in any type of publication media.

Military Dermatology
328
borderline tuberculoid (BT) disease and 20.4% had
borderline lepromatous (BL) disease.  Only 3.8%
had indeterminate leprosy.19  Also noteworthy is
the high frequency of nerve involvement in chil-
dren (seen in two thirds of all cases) and the low
frequency of reactional states.19  Nonetheless, most
people effectively resist infection even in highly
endemic areas.  It is now believed that only 0.5% of
those infected with the leprosy bacillus actually
develop an overt clinical case.14
The clinical profile of leprosy has changed con-
siderably since the mid-1970s.  Advanced leproma-
tous leprosy with leonine facies, ulcerating nodular
lesions, and progressive ulcerative erythema
nodosum leprosum leading to amyloidosis,
nephrotic syndrome, and death are less frequently
observed.  Such improvements are attributable to
efficient leprosy control programs and improve-
ments in chemotherapy.16
Pregnant women with incubating leprosy may
develop overt signs of disease; most women worsen
during pregnancy.  Reversal reactions occur during
puerperium, downgrading reactions during the
third trimester.  Erythema nodosum leprosum
reactions are most likely in the third trimester and
following parturition.  Infants born of lepro-
matous mothers tend to be small for their gesta-
tional age.5
MICROBIOLOGY
As seen in slit-skin smears, M leprae is a straight
or slightly curved, rod-shaped organism with par-
allel sides and rounded ends.  It measures 1 to 8 µm
in length and 0.3 µm in diameter.  M leprae is Gram-
positive with the additional property of resisting
decoloration of carbol-fuchsin with acid alcohol.  It
is primarily an intracellular organism commonly
seen in clumps (globi), which may contain hundreds
of bacilli.  In clumps, they occur in parallel array
and resemble bundles of cigars.
M leprae grows best at 27°C to 30°C (ie, in the
cooler parts of the body).  It divides every 12 to 15
days.  The organism may be a natural soil
saprophyte.
Natural Reservoirs and Laboratory Transmission
Investigations into the basic biology, metabo-
lism, and chemical structure of M leprae have been
hindered by the inability to date to culture the
organism in vitro.  Additionally, it seems to multi-
ply and produce disease in only a very limited
number of animal species.  The nine-banded arma-
dillo is currently the only source of the large amounts
of leprosy bacillus needed for research purposes
and vaccine production.  Inoculation into the
footpads of immunologically normal mice remains
the basic tool for assessing drug activity and resis-
tance of M leprae.  The use of immunodeficient
rodents (ie, thymectomized, irradiated, bone
marrow–reconstituted mice, nude mice, and neona-
tally thymec-tomized rats) is the most sensitive
method available for monitoring the presence of
viable M leprae in patients undergoing chemo-
therapy.16
Experimental transmission of infection to three
different species of monkey has been achieved
within the last decade: lepromatous leprosy (LL) in
mangabey monkeys, borderline lepromatous lep-
rosy (BL) in African green monkeys, and borderline
lepromatous–lepromatous leprosy (BL-LL) in rhesus
monkeys.16
The Cell Wall
The cell walls of all mycobacteria exhibit a simi-
lar complex structure of lipid-rich macromolecular
structures.  However, M leprae appears to differ
from other mycobacteria in the composition of the
peptide units and in the multiplicity of peptidogly-
can layers that constitute the complete cell wall
structure (Figure 14-2).  The most notable of the cell
wall–associated glycolipid molecules of M leprae is
phenolic glycolipid I (PGL-1), which is species-
specific and immunogenic during infection.  Immu-
nochemical and electron micrographic studies indi-
cate that PGL-1 is associated with the outer surface
of M leprae and may represent the “capsule” of the
organism.  This could function as a virulence factor,
providing an important interface between parasite
and host, critical for maintenance of the parasitic
relationship.  PGL-1 can accumulate in armadillo
tissues in quantities equal to one half the total
weight of the leprosy bacilli present.  The “foam”
seen in heavily infected macrophages—a character-
istic of the lepromatous granuloma—is thought to
contain PGL-1.14
Molecular Biology and Genetics
The advent of monoclonal antibody techniques
and T-cell cloning methods has permitted the iden-

Leprosy
329
Fig. 14-2. Mycobacterium leprae has a complex cell wall composed of many layers.  The outer layer contains the phenolic
glycolipid PGL-1, which may be an important virulence factor. Adapted with permission from Gaylord H, Brennan PJ.
Leprosy and the leprosy bacillus: Recent developments in characterization of antigens and immunology of the disease.
Annu Rev Microbiol. 1987;41:645–675.
tification of a number of epitopes (as opposed to
entire protein molecules) unique to Mleprae.  The
entire genome of M leprae has been cloned and
expressed in E coli; this development has opened a
wide avenue for future research, despite the ab-
sence of in vitro culture techniques.16
IMMUNOLOGY
Humoral Immunity
Because of the intracellular, sequestered location
of M leprae, it is doubtful that humoral immunity
plays a significant role in resistance to the organ-
ism.  However, humoral immunity is the source of
the antigen–antibody complexes in the pathogen-
esis of erythema nodosum leprosum reactions.
Lepromatous leprosy (LL) is generally associated
with hypergammaglobulinemia and a high circu-
Fig 14-2 is not shown because the copyright permission granted to the Borden Institute, TMM, does
not allow the Borden Institute to grant permission to other users and/or does not include usage in
electronic media. The current user must apply to the publisher named in the figure legend  for
permission to use this illustration in any type of publication media.

Military Dermatology
330
lating B lymphocyte count.  Patients with border-
line leprosy (BB) tend to have intermediate levels,
and patients with tuberculoid leprosy (TT) have
normal levels of B lymphocytes.  There tends to be
an inverse correlation between a patient’s anti–M
leprae antibody titer and the potency of the patient’s
cell-mediated immune response to the bacillus.14
PGL-1 was the first antigen specific to M leprae to
be identified and to have its antigenic moiety chemi-
cally synthesized.  Antibodies to PGL-1, primarily
of the immunoglobulin (Ig) M subclass, have been
detected in the sera of most multibacillary patients
with leprosy, in titers proportional to the bacillary
load.  In some limited studies, high antibody titers
have also been reported in some household contacts
of multibacillary patients, as well as in other habi-
tants of endemic areas, confirming that infection is
more frequent than overt disease.  However, false-
negative results in patients with tuberculoid lep-
rosy (TT) and their contacts limits the use of anti-
body titers for epidemiological purposes or for
detection of subclinical infection.16
Cell-Mediated Immunity
Experiments involving inoculations of M leprae
into athymic (nu/nu) mice and rats have shown the
importance of cell-mediated immunity in host re-
sistance to leprosy.14  The maximum number of T
lymphocytes tends to be present in tuberculoid
lesions, with a gradual decline across the spectrum
such that very few are present in disseminated
multibacillary lepromatous leprosy.20
At the lymphocyte level, the presence of T helper
cells specific for antigens of the leprosy bacillus is a
key characteristic of the tuberculoid end of the
clinical spectrum of leprosy.  T helper cells have
been found to be as high as 95% of the lymphocytes
in tuberculoid granulomas, whereas in lepromatous
lesions T cytotoxic/suppressor cells can constitute
up to 85% of the population.20  More importantly, in
tuberculoid lesions the cells are arranged in a dis-
tinct architecture within the lesion: T4 cells in the
centers of the epithelioid granulomas and T8 sup-
pressor cells in the margins.14  T4 cell counts are
often depressed and T8 cell counts increased in the
peripheral bloodstream of many patients with
lepromatous leprosy in proportion to their bacillary
load.20  These abnormal T cell counts slowly normal-
ize with adequate chemotherapy.20
Additionally, in lepromatous disease, the mac-
rophage fails to kill or inhibit M leprae and is unable
to produce interleukin-1 (IL-1), the cytokine that
can amplify the production of IL-2 by T cells.  Mac-
ro-phages, activated by lymphokines (especially
gamma interferon [IFN-g], which is released from
sensitized helper T cells responding specifically to
antigen), may play a major role in resistance to a
wide variety of obligate and facultative intracellu-
lar pathogens.  In an experimental model of leprosy
of the lepromatous lepromatous (LL) type, it has
recently been demonstrated that M leprae–engorged
macrophages from the footpad lesions of infected
nude mice (nu/nu) are refractory to IFN-g in vitro.
Of interest, lipoarabinomannan (LAM), a carbohy-
drate-rich component of the M leprae cell wall, not
only blocks the proliferation of T cells, but also
induces a refractory response to IFN-g in human
monocyte-derived macrophages.  Thus, newly ar-
riving macrophages may rapidly encounter local
bacterial-wall products that effectively restrict their
normal responsiveness and function.14  Hence, they
may then fail to produce IL-1, leading to nonreactive,
nonproliferative T cells in that microenvironment.
The Lepromin Test
The lepromin test is an indicator of the ability of
the host to mount a cell-mediated immune response
to M leprae.  Lepromin is a heat-killed suspension of
M leprae originally obtained from homogenized
human tissue sources, but now prepared from ar-
madillo tissue.  WHO’s Expert Committee on Lep-
rosy has recommended standardizing the concen-
tration at 40 million bacilli per milliliter.14  The test
itself is of no diagnostic value, but does establish
the immune status of the individual and is thus of
prognostic value.  A positive reaction is typically
biphasic:
• The early (24–48 h) Fernandez reaction is a
delayed hypersensitivity reaction (probably
to soluble protein antigens) and occurs in
patients with tuberculoid leprosy, their con-
tacts, and healthy individuals who are sensi-
tized either to M leprae or to cross-reacting
antigens from other mycobacteria.
• The late Mitsuda reaction, measured at 21
days, reflects the induction of acquired cell-
mediated immunity, which is manifested by
formation of an organized epithelioid cell
granuloma.  WHO has instituted the follow-
ing system for grading the Mitsuda reac-
tion20:
0
No reaction (induration)
+
Induration or papules less than 3 mm

Leprosy
331
1+
Induration or papules 4 to 6 mm
2+
Papule 7 to 10 mm
3+
Nodule larger than 10 mm, or of any
size that ulcerates
Positive reactions are seen in the vast majority of
contacts and unexposed individuals, as well as in
patients with tuberculoid leprosy.  Weakly positive
reactions aid classification of borderline disease.
Negative reactions are seen in lepromatous leprosy,
despite years of chemotherapy.
LABORATORY DIAGNOSIS
The Slit-Skin Examination Technique
Bacteriological examination is very important
and highly relevant to leprosy control.  The slit-skin
technique (in simple terms, a slit-scrape-smear
method) is the WHO-preferred method for the de-
tection of bacteria in patients suspected of harbor-
ing the leprosy bacillus11:
• Thoroughly clean the selected portion of
skin to remove saprophytic acid-fast bacilli.
• Pinch the skin to remove blood and decrease
hemorrhage.
• Using a sterile surgical blade, make a cut 5-
mm long by 2-mm deep.
• Wipe away any oozing blood.
• Holding the blade at right angles to the slit,
scrape the bottom and sides of the slit with
the point of the blade to obtain sufficient
material for a smear.
• Transfer the material to a clean, labeled,
glass slide.
• Use pressure hemostasis to stop bleeding at
the slit site.
It is essential that the Centers for Disease Control
and Prevention’s guidelines21 for preventing the
transmission of AIDS and hepatitis B infection
be followed during the process of taking skin
smears.
Site Selection
In lepromatous leprosy, the skin and the mucous
membranes of the nose and oral cavity are diffusely
infiltrated with bacteria—even in areas that appear
normal.  In tuberculoid leprosy, organisms are
sparse.  In borderline leprosy, only the border-
line lepromatous (BL) group may show bacilli
in uninvolved sites.  Thus, in lepromatous leprosy,
it is a question of selecting a site with the
highest density of bacteria, whereas in tuberculoid
and borderline groups, one has to select from le-
sions only.  The ear has traditionally been regarded
as the site of heaviest involvement.  The chin, but-
tocks, and fingers are also sites of high bacillary
counts.  Recently, it has been noted that in long-
treated cases, the bacilli are probably cleared from
the fingers last.11
In general, smears should be taken from a mini-
mum of three sites, including one ear lobe and two
representative active skin lesions.  In cases of
paucibacillary patients with one lesion, two smears
should be taken from the active border, diametri-
cally opposite each other.16  Sites previously shown
to be positive in specific patients are recommended
as sites for follow-up examination.
Acid-Fast Preparations
The Ziehl-Neelsen acid-fast staining of slit-skin
smears is the global standard, being inexpensive
and requiring minimal facilities.  Smears should be
dried for 15 to 30 minutes and fixed.  Fixation can be
done by passing slides carefully through a flame.
However, it is preferable to fix the smears in 40%
formaldehyde for 15 minutes.  Slides are then stained
by the Ziehl-Neelsen method, a complex, regres-
sive, staining method comprising three essential
steps22:
1.
Over-staining with basic fuchsin.  This
is achieved by using carbol-fuchsin con-
taining phenol and applying heat, or
keeping the staining solution on the slide
for a period of time.  Under field conditions
the cold staining method is easier.  The
basic fuchsin is left on the slide for 30
minutes.
2.
Decoloration (this is a regressive step) with
either acidified alcohol or acid in water.  All
material except mycobacteria (in this case,
M leprae or M tuberculosis) lose the red fuch-
sin stain.  At this moment, leprosy bacilli in
the preparation are stained red on a color-
less background.
3.
Counter-staining of the background with
methylene blue.

Military Dermatology
332
Bacterial Index
In the past in developing countries, the bacterial
examination had largely been neglected.  This prac-
tice was somewhat acceptable as long as therapy
was based on one and only one drug, which was
administered to patients no matter what form of the
disease they had.  However, now the differentiation
of paucibacillary leprosy from multibacillary lep-
rosy takes on added importance, as the two forms
use different therapeutic regimens.  The Ridley
Logarithmic Scale,23 proposed in 1958 as a bacterial
index, has gained wide acceptance; WHO has rec-
ommended its uniform adoption worldwide to fa-
cilitate comparison of results.16  Ridley’s Logarith-
mic Scale is as follows:
6+ Many clumps of bacilli in an average field
(> 1,000)
5+ 100–1,000 bacilli in an average field
4+ 10–100 bacilli in an average field
3+ 1–10 bacilli in an average field
2+ 1–10 bacilli in 10 fields
1+ 1–10 bacilli in 100 fields
0
No bacilli seen
Before a case is deemed negative, 200 fields are
generally scanned.  Otherwise, the bacterial index
of the patient is averaged from all the bacterial
indices of the individual sites.
The line between paucibacillary and multibacil-
lary cases is a bacterial index of 2 or more at any site.
Because of drug resistance and the need for
multidrug therapy, the microscopical examination
of smears for acid-fast bacilli is quite essential to
detect relapse.  Reading and interpretation of the
bacterial index can be schematized as follows22:
• In patients with new, untreated leprosy:
0
No leprosy or paucibacillary leprosy
1
Bacteriologically proven paucibacillary
leprosy
>2
Multibacillary leprosy
• In patients with old, previously treated  leprosy:
0
No leprosy, or treated paucibacillary or
multibacillary leprosy
1
Treated multibacillary leprosy
>2
Multibacillary leprosy, keeping in mind
that adequate treatment diminishes the
bacterial index by approximately 1 unit
per year
Thus, these results should be interpreted taking
into consideration the kind and duration of previ-
ous treatment.  Notably, a significant increase of the
bacterial index is the result of either irregular drug
intake or development of drug resistance.
There is a widespread impression that multidrug
therapy will hasten the attainment of smear nega-
tivity, but this is not substantiated by the available
evidence.  The rate of clearance of bacilli under
multidrug therapy is approximately 0.6 to 1 Ridley
Logarithmic Scale units per year.  It must be appre-
ciated that the bacterial index is a late marker for the
antibacterial action of drugs in leprosy, even though
it is of prime importance for the diagnosis of re-
lapsed cases.  Clinical improvement is accelerated
by multidrug therapy and precedes the fall in the
bacterial index.16
Bacilli in smears are seen only when the bacillary
load is more than 104 organisms per gram of tissue.
Negative results from a slit-skin examination do not
exclude leprosy: organisms can be seen in biopsied
specimens of skin, peripheral nerves, lymph nodes,
and testes despite cutaneous negativity.11
The greatest importance of positive slit-skin ex-
aminations is probably in the diagnosis of indeter-
minate leprosy.
For treatment purposes, WHO has recently rede-
fined multibacillary and paucibacillary disease.
Paucibacillary disease is smear-negative, and
multibacillary smear-positive.16
Both for patients currently under treatment and
for patients previously treated, WHO has laid down
certain guidelines for assessment.  Both past and
present bacterial indices should be considered.
Patients are classified as paucibacillary or
multibacillary on the basis of the highest bacterial
index at any time during treatment.
The bacterial index is a direct measure of the
bacillary load of an individual, and therefore of the
seriousness and infectiousness of the patient’s con-
dition.  Clearly, patients with a high bacterial index
(ie, those with lepromatous leprosy) are more infec-
tious.  Prolonged skin-to-skin contact with such
patients is a known mode of transmission of lep-
rosy.  Bacilli may also be continuously shed from
nasal discharge into the environment.  Thus, a high
bacterial index from the nose may have great epide-
miological significance.  Maximum load is harbored
in patients having a bacterial index of more than 3;
a priority treatment for these patients is therefore
logical.  Bacterial load decides the severity and
infectivity of the case.
A patient should be regarded noninfective if he
or she has a bacterial index of 0, determined from
multiple slit-skin smears repeated over 3 consecu-
tive months.11

Leprosy
333
Morphologic Index
Traditionally, the morphologic index was thought
to give an indication of the proportion of viable
bacilli in the patient.  This viability was based pre-
viously on the percentage of bacteria with solid
staining, as opposed to fragmented or granular
staining.  More sophisticated techniques such as
electron microscopy, mouse-footpad inoculation,
thymidine uptake studies, and so forth, have shown
poor correlation between the morphologic index
and true viability.11  Additionally, there are prob-
lems with reproducibility and standardization, espe-
cially under field conditions.  Therefore, WHO does
not recommend its use in routine control programs.16
Cutaneous Nerve Biopsy
A cutaneous nerve biopsy is frequently required
to establish the diagnosis of primary neuritic lep-
rosy (discussed later in this chapter).  Patients with
this form of leprosy have no cutaneous lesions other
than localized anesthesia.  Because standard skin
biopsies and smears for acid-fast bacilli are usually
nondiagnostic, cutaneous nerve biopsy may be the
only method by which the condition can be diag-
nosed with certainty.  The procedure for perform-
ing cutaneous nerve biopsy is as follows24:
1.
Find a palpable nerve in the area of anesthe-
sia and mark the skin overlying it with
gentian violet.
2.
Give local anesthesia.
3.
Make a transverse incision 1 cm in length
over the nerve.
4.
Tease through the subcutaneous tissue gen-
tly with an artery forceps until the nerve is
identified.
5.
Remove a 1-cm piece of nerve with a scalpel.
6.
Suture skin closed.
7.
Process the specimen for routine histopath-
ology and for acid-fast bacilli.
Serologic Assays
Cases of subclinical infection can now be
detected by serologic means including fluores-
cent leprosy absorption, radioimmunoassay for
antibodies to cell-wall antigen, and enzyme-
linked immunosorbent assay (ELISA) to detect an-
tibodies against the phenolic glycolipid derived
from the M leprae cell wall.10  However, because
only 0.5% of those infected with the leprosy bacillus
are believed to actually develop overt clinical
leprosy, it is difficult to interpret the meaning
of a positive test, other than for epidemiological
investigations.14
CLINICAL AND HISTOLOGICAL DIAGNOSTIC CRITERIA
Clinically, leprosy demonstrates a wide spec-
trum of dermatologic lesions.25,26  Untreated pa-
tients may present with any combination of the
following:
• a single, nondescript, hypopigmented
macule;
• single or multiple, asymmetric, dry, scaly,
or inflammatory plaques;
• symmetrical, widely disseminated, erythem-
atous papules and nodules associated with
coarse thickening and nodularity of the face
(leonine facies);
• lagophthalmos (Figure 14-3);
• blindness;
• severe peripheral neurological disease;
• deformities of the nose and extremities; or
• diffuse infiltration and edema of the skin.
Secondary cutaneous infections, osteomyelitis, neu-
rotropic ulcerations, and significant renal disease
(amyloidosis or glomerulonephritis) may occur in
severely affected and untreated patients.  Addition-
ally, psychiatric abnormalities are not uncommon
among patients with leprosy.  A study of 81 patients
conducted over a 4.5-year period at the Hansen’s
Disease Center in Carville, Louisiana, showed that
more than 80% of the patients had a psychiatric
disorder: 37 (46%) had a major affective disorder; 9
(11%) had an organic mental disorder; 9 (11%) had
schizophrenia; and 9 (11%) had substance abuse.27
The large number of patients with affective disor-
der and substance abuse may well be due to the
emotional effect of the diagnosis on patients and
their families in our society.
Histologically, established leprosy demonstrates
a continuous spectrum of disease from a localized,
self-healing, granulomatous disease with very few
organisms to a widespread, progressive, anergic
disease with massive numbers of bacilli.28  M leprae
tend to invade neuronal structures in the cooler areas
of the body.  Initially, only minor nerve infiltration
may be demonstrated histologically.  However, great
variation is present from patient to patient.

Military Dermatology
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TABLE 14-1
MODIFIED RIDLEY-JOPLING CLASSIFICATION FOR LEPROSY
Fig. 14-3. This patient has advanced lepromatous leprosy
with significant cutaneous and ocular disease. Note the
severe lagophthalmos, which has led to an exposure
keratitis, and the severe deformity of the fingers, which
is a consequence of chronic trauma and secondary infection
following anesthetic changes in the distal extremities.
To classify patients within this tremendous clini-
cal and histological spectrum, several classification
schemes have been proposed.  The most popular,
and the one endorsed by WHO, is the Ridley and
Jopling Classification, with minor modifications
(Table 14-1 and Figure 14-4).  Histological classifi-
cations, by contrast, are much more expensive (and
are thus impractical for use in third-world coun-
tries and in field situations) and they do not help
further categorize patients except for those in the
reactional states (which are discussed later in this
chapter).28  Exhibits 14-1 through 14-7 and Figures
14-5 through 14-12 are designed to aid in the diag-
nosis of leprosy in its various manifestations.
The polar forms—lepromatous leprosy (LLp) and
tuberculoid leprosy (TTp)—tend to be stable clini-
cally, whereas the borderline forms—borderline
lepromatous (BL), borderline leprosy (BB), and bor-
derline tuberculoid (BT)—tend to be unstable.  The
Characteristics of Lesions
Stage of Disease
Number
Size
Surface
Sensation*
Hair Growth
Polar lepromatous
Very many
Small
Shiny
Not affected
Not affected
(LLp)
Subpolar lepromatous
Very many
Small
Shiny
Not affected
Not affected
(LLs)
Borderline lepromatous
Many
Variable
Slightly shiny
Slightly diminished
Slightly diminished
(BL)
Borderline borderline
Several
Variable
Dry
Slightly to moderately
Moderately diminished
(BB)
diminished
Borderline tuberculoid
Few or 1
Variable
Dry
Moderately to
Moderately diminished
(BT)
markedly diminished
Subpolar tuberculoid
Usually 1
Variable
Very dry
Absent
Absent
(TTs)
Polar tuberculoid
Usually 1
Variable
Very dry
Absent
Absent
(TTp)
*Does not pertain to lesions on the face
†AFB: Acid-fast bacilli

Leprosy
335
75%
25%
Borderline 
Tuberculoid 
Leprosy = BT
Polar 
Tuberculoid 
Leprosy = TTp
Borderline 
Lepromatous 
Leprosy = BL
Borderline 
Borderline 
Leprosy = BB
Polar 
Lepromatous 
Leprosy = LLp
Lucio's Diffuse 
Lepromatous 
Leprosy = LLp
Indeterminate 
Leprosy = IL
Subclinical 
Infection 0.5%
Exposure to 
Leprosy 
Bacillus
Spontaneous 
Healing > 99%
Fig. 14-4. The pathogenesis of leprosy. Exposure usually
results in spontaneous healing. Subclinical infection
progresses to indeterminate leprosy, which spontane-
ously remits in 75% of patients; however, in 25% of
patients, the disease progresses to one of the more seri-
ous forms of leprosy.
AFB Found
Bacterial Index
Contain AFB†
in Nasal Secretions
(Ridley)
Lepromin Test
Comment
Very many (plus globi)
Very many (plus globi)
5–6
Negative
Polar lepromatous leprosy
Very many (plus globi)
Very many (plus globi)
5–6
Negative
Downgraded to LL from BL due
to lack of therapy
Many
Usually nil
4–5
Negative
Unstable immunity
Moderate
Nil
3–4
Negative
Unstable immunity
Nil or scanty
Nil
0–2
Weakly positive
Unstable immunity
(+ or ++)
Nil
Nil
0–1
Strongly positive
Upgraded to TT from BT
(+++)
due to treatment or nutrition
Nil
Nil
0–1
Strongly positive
Polar tuberculoid leprosy
(+++)

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EXHIBIT 14-1
THE DIAGNOSIS OF LEPROMATOUS LEPROSY
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Fig. 14-5. Lepromatous leprosy. This elderly man has
innumerable erythematous infiltrated papules and
plaques on his back. Notice the sparing of the spinal
and immediate paraspinal areas. These zones are
warmer and are consequently less hospitable to the
growth and survival of Mycobacterium leprae.
Fig. 14-6. Lepromatous leprosy. This teenaged Peru-
vian girl has a more nodular form of lepromatous
leprosy (compared with the patient shown in Fig. 14-
5). Note the symmetry of the lesions and the diffuse
infiltration of her nose.
Clinical Features
• The number of lesions is characteristically numerous to uncountable.  They are bilaterally symmetric,
widely distributed, hypopigmented (ie, dark-skinned) or erythematous, and may take any of these forms:
macules, plaques, papules, and nodules (Figures 14-5 and 14-6).
• The margins of macules are hazy (ie, they merge imperceptibly into the surrounding skin).
• The lesions are smooth and shiny.
• The ears may be infiltrated (Figure 14-7.)
• The face may become exceedingly infiltrated with nodules, creating the leonine facies.
• The axillae, groin, perineum, and hairy scalp are almost invariably spared of lesions.
• Chronic edema of the lower extremities is common.
• Eyebrows are frequently lost, although body hair and scalp hair are generally retained.
• Lagophthalmos and corneal anesthesia leading to exposure keratitis are common with advanced disease.
• Sweating is often normal.
• Multiple nerve thickenings occur only in the late states of the disease:  great auricular nerves in the neck,
supraclavicular nerves, ulnar nerves (olecranon fossae), radial and medial nerves at the wrist, lateral
popliteal nerves, sural nerves, and posterior tibial nerves.

Leprosy
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Fig. 14-7. Lepromatous leprosy. This elderly Peru-
vian man shows characteristic infiltration of the ears
and ear lobes. Note the multiple nodules and papules
on his face, many of which appear to be subcutaneous.
Fig. 14-8. Histology of lepromatous leprosy, low
power. Foamy histiocytes loaded with Mycobacterium
leprae bacilli are found diffusely infiltrating the der-
mis. Note the typical grenz zone beneath the epider-
mis and adjacent to the hair follicle.
Exhibit 14-1 (continued)
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Fig. 14-9. Histology of lepromatous leprosy, oil
emersion, Fite stain. Large numbers of acid-fast or-
ganisms are seen singly as well as in clusters (globi).
Clinical Features (continued)
• Nasal stuffiness, crusting, and discharge are characteristic.  Discharge is striking for the large number of
acid-fast bacilli.
• There may be systemic infiltration of liver, spleen, bone marrow, kidneys, and testes.
Histological Features
• The numerous, foamy macrophages in the dermis around blood vessels, nerves, and adnexa are character-
istic.  The entire dermis may not be involved (Figure 14-8).
• A well-preserved grenz zone is typical.
• The nerves are preserved and have an “onion peel” appearance.
• Acid-fast bacilli are numerous and are found in packets (ie, globi) within the macrophages (Figure 14-9).
Older lesions show vacuolated cytoplasm within the macrophages due to lipid accumulation (ie, the lepra
cells of Virchow).
• Bacterial Index (Ridley) = 5–6

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EXHIBIT 14-2
THE DIAGNOSIS OF TUBERCULOID TUBERCULOID LEPROSY
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Fig.14-11. Tuberculoid leprosy, low power. Elongated,
noncaseating granulomata coursing along the periph-
eral nerve twigs are characteristic.
Fig. 14-10. Tuberculoid leprosy. A young Filipino
man presented with this single, anesthetic, peripher-
ally infiltrated plaque on his ankle. Note the central
clearing and postinflammatory hypopigmentation.
Clinical Features
• One or a few hypopigmented or erythematous macules and plaques may be seen.
• The plaques are well defined, dry, scaly, and indurated (particularly at the periphery), and somewhat
saucer shaped.  The lesions may show central clearing or postinflammatory hyperpigmentation
(Figure 14-10).
• Due to significant nerve involvement, impairment or complete loss of sweating and of sensation are
common within the lesions.
• Alopecia may be partial or complete within the lesions.
• Thickening or tenderness or both in the nerves feeding or supplying the patch may be appreciated.
Histological Features
• Compact, often elongated, epithelioid granulomas surrounded by lymphocytes tend to be  located just
beneath the epidermis, and extend to the middermis or deep dermis (Figure 14-11).
• Infiltration and complete destruction of small cutaneous nerves is a constant feature (nerves may be
unidentifiable).  Histiocytes may be seen within the small nerves.
• The acid-fast bacilli are difficult to demonstrate by special stains, but can be seen with electron microscopy.
• Bacterial Index (Ridley) = 0–1

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EXHIBIT 14-4
THE DIAGNOSIS OF BORDERLINE LEPROMATOUS LEPROSY
Clinical Features
• Lesions show morphology of both tuberculoid and lepromatous leprosy.  However, the lesions resembling
lepromatous morphology are much more numerous than those resembling tuberculoid.
• The lesions are bilateral and tend to be symmetrical.
• The lesions are numerous and may be uncountable.
• Nerves may show thickening or tenderness or both.
Histological Features
• The presence of granulomata consist of histiocytes, lymphocytes, and macrophages containing acid-fast
bacilli.  The granulomata are diffuse and located in the mid- and lower dermis.
• The structure of the nerves is maintained, although they are infiltrated by histiocytes.  Their classic “onion-
peel” appearance is the hallmark of the diagnosis.
• Acid-fast bacilli are easily identifiable.
• Bacterial Index (Ridley) = 4–5
EXHIBIT 14-3
THE DIAGNOSIS OF BORDERLINE BORDERLINE LEPROSY
Clinical Features
• The lesions of borderline leprosy show morphology combining features of both tuberculoid and lepromatous
leprosy.
• The number of lesions resembling tuberculoid morphology is almost equal to those resembling lepromatous
leprosy.
• Lesions are bilateral but asymmetrical.
• Lesions are numerous but countable.
• Nerves may be thickened or tender or both.
Histological Features
• The granuloma is marked by the presence of epithelioid cells, absence of giant cells, and scanty lympho-
cytes scattered all over the lesion.
• A subepidermal zone relatively free of lesions is formed.
• The structure of the nerves is generally maintained, although they have been infiltrated by epithelioid
cells.
• The acid-fast bacilli are easily demonstrable.
• Bacterial Index (Ridley) = 3–4

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EXHIBIT 14-5
THE DIAGNOSIS OF BORDERLINE TUBERCULOID LEPROSY
EXHIBIT 14-6
THE DIAGNOSIS OF INDETERMINATE LEPROSY
Clinical Features
Borderline tuberculoid leprosy may appear similar to tuberculoid tuberculoid leprosy, with the following
exceptions:
• Satellite lesions are present.
• Lesions number fewer than 10.
Histological Features
• The well-developed granulomata are formed by epithelioid cells and plentiful lymphocytes.  Giant cells
are either absent or occasional.  The granulomata are elongated due to their presence along the nerves.
• Dermal nerves are swollen with infiltrate, but are recognizable in the earlier stages.  Later the nerves may
be destroyed by the granulomatous reaction.  Another common pattern is an intense epithelioid cell
granulomatous infiltrate encroaching on the basal epithelium.
• Bacterial Index (Ridley) = 0–2
Clinical Features
• The number of lesions is usually one or a few.
• The lesions are hypopigmented, irregularly shaped macules in patients with dark skin, and may be
erythematous in patients with lighter skin.
• The lesion margins are vague and ill-defined.
• Their surface is smooth and no infiltration is present.
• Sensations are equivocal.
• Nerves may or may not be thickened.
Histological Features
• There is a lymphocytic and histiocytic infiltrate around the adnexa, blood vessels, and nerve twigs of the
upper dermis.  The diagnosis requires clinical suspicion and is confirmed by the finding of acid-fast bacilli
within the nerves.
• Bacterial Index (Ridley) = –⁄+

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341
EXHIBIT 14-7
THE DIAGNOSIS OF PRIMARY NEURITIC LEPROSY
Fig. 14-12. This patient has advanced neuritic leprosy.
Note the interosseus muscle wasting in the hand
caused by infiltration and destruction of the periph-
eral motor nerves.
Clinical Features
• There are no skin lesions—either present or past.
• Nerves are thickened or tender or both.
• The involvement of the nerves is asymmetrical.
• Sensations are lost in this order: temperature, touch, pain.
• Tendon reflexes normal or exaggerated.
• The muscles supplied by affected nerves atrophy (Figure 14-12).  In the late stages, contractures and
deformities may be present.
Histological Features
• A histological diagnosis of indeterminate leprosy is made when the nerve shows lymphocytic infiltration.
• A diagnosis of tuberculoid tuberculoid leprosy is made when the infiltrate contains epithelioid cells (with
or without giant cells) and lymphocytes.
• A diagnosis of borderline borderline leprosy is made when some foam cells are present in addition to the
above.
• A diagnosis of lepromatous leprosy is made when macrophages are filled with acid-fast bacilli and a round
cell infiltrate.
• A diagnosis of lepromatous neuritis is made when a mononuclear infiltrate is present, with fibrosis and
hyalinization.
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Military Dermatology
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lepromatous leprosy group has been subdivided
into polar lepromatous (LLp) and a subpolar
lepromatous (LLs) forms.  The subpolar lepromatous
classification is used to differentiate those patients
who were previously in an unstable borderline
group and who “downgraded” into lepromatous
disease through lack of treatment and waning im-
munity.  The main reason for the subdivision is that
the patients in the subpolar lepromatous leprosy
group are capable of regaining their lost cell-medi-
ated immunity during an “upgrading” (ie, reversal)
reaction.  Thus, although their conditions resemble
polar lepromatous leprosy clinically, these patients
are immunologically unstable, and, with chemo-
therapy, may become bacteriologically negative
much sooner than with the polar lepromatous lep-
rosy form.  Similarly, the tuberculoid leprosy (TT)
form of the disease has been divided into polar and
subpolar (TTp and TTs), the subpolar form desig-
nating those patients who have developed tubercu-
loid leprosy on a secondary basis, an upgrading
from their previous borderline form.5
Patients with lepromatous leprosy present with a
large number of symmetrically distributed, cutane-
ous lesions, which may include macules, papules,
infiltrated plaques, nodules (known as lepromas),
or edematous, diffusely infiltrated skin.  Lesions
may vary from a few millimeters in size to several
centimeters, be skin-colored, erythematous, or
hypopigmented, and tend to localize in the cooler
areas of the body.  Infiltration of the earlobes is
characteristic.  Loss of hair may occur from the
scalp, eyebrows, and eyelashes.  The latter two are
particularly characteristic.  Nodular infiltration of
the face, particularly around the orbits, may result
in the grotesque leonine facies.  Histological exami-
nation of lesions reveals granulomas composed of
numerous foam cells stuffed with acid-fast bacilli.
In contrast, patients with tuberculoid leprosy
typically present with one or a few asymmetric,
erythematous or hypopigmented plaques, from a
few centimeters to several decimeters in diameter.
These tend to be thicker at the periphery than in the
center, forming a platelike topography.  Complete
central clearing may occur.  Dyspigmentation is
common, particularly in people with darker skin
color.  Significant nerve involvement with anesthe-
sia is the rule in this form, often corresponding to
the nerve supplying the area of involved skin.  His-
tologically, acid-fast bacilli are absent to very rare.
The dermis may contain a few to numerous epithe-
lioid granulomas with mantles of lymphocytes.
Infiltration and destruction of small cutaneous
nerves is a prominent feature.
The clinical features of borderline leprosy are
intermediate between lepromatous and tubercu-
loid.  Lesions resembling those in lepromatous lep-
rosy appear approximately equal in number to those
resembling tuberculoid leprosy.  Lesions are nu-
merous but countable, bilateral, but not symmetric.
Pathologically, nerves are infiltrated but not de-
stroyed, and acid-fast bacilli are easily seen.
Borderline lepromatous leprosy is characterized
by lesions resembling those found in both
lepromatous and tuberculoid leprosy, but with the
lepromatous lesions predominating.  Similarly, bor-
derline tuberculoid leprosy consists primarily of up
to 10 asymmetric tuberculoid plaques surrounded
by satellite nodules, resembling those seen in
lepromatous leprosy.  Both represent intermediate
transitional forms—both clinically and histologi-
cally—between borderline and lepromatous or tu-
berculoid leprosy, respectively.
Indeterminate leprosy is recognized as a definite
clinical entity, but there is no unanimity of opinion
regarding its frequency, significance, and progno-
sis.  Patients present with a single macule or a few
asymmetrical macules, with alterations in color but
with no change in the surface texture or consistency
of the skin.  The peripheral nerves are usually nor-
mal.  Slit-skin smears are usually negative.  To
confirm the diagnosis, sensory impairment or his-
tological evidence of acid-fast bacilli or infiltrate
must be present selectively in a nerve bundle in the
dermis.  Thermal sensibility may be lost earlier than
tactile sensibility.16  Indeterminate leprosy has a
variable course: in approximately 75% of patients,
the disease remits spontaneously; the remainder
progress to one of the established forms of the
disease.14
Primary neuritic leprosy is increasingly being
recognized as a clinical form of presentation.  Most
will be of the paucibacillary type.  A lepromin test,
the number of nerves affected, and nerve biopsy
may all give some indication of the correct classifi-
cation, but further research is needed to provide
reliable clinical indicators for correct classification
of patients with primary neuritic leprosy within the
Ridley-Jopling system.16
Skin biopsies from anesthetic areas may fail to
show histological changes suggestive of leprosy.
Cutaneous nerve biopsy (a simple office procedure
discussed above) can be performed for both histo-
pathological examination and for acid-fast bacilli
staining.  This technique yields surprisingly good
results.24

Leprosy
343
TREATMENT
The treatment of leprosy varies considerably
depending on the number of bacilli present and
whether reactional states are present.  WHO has
recommended standard treatments for each type of
leprosy (Figure 14-13).
Paucibacillary Leprosy
The 1988 WHO recommendations for the standard
treatment of paucibacillary leprosy are as follows16:
• Rifampin 600 mg (450 mg for patients who
weigh < 35 kg), once per month for 6 months
(10 mg/kg in children17).
• Dapsone 100 mg daily for 6 months (1–2
mg/kg in children17).
The administration of rifampin should be fully su-
pervised; on the other hand, dapsone may be given
unsupervised.  Relapses, which need to be distin-
guished clinically from delayed reversal reactions
by slit-skin smear or biopsy, should be retreated
with a 6-month course of the multidrug regimen
outlined below.
Multibacillary Leprosy
The 1988 WHO recommendations for the stan-
dard treatment of multibacillary leprosy are as fol-
lows16:
• Rifampin 600 mg once per month, super-
vised (10 mg/kg in children17).
• Dapsone 100 mg daily, self-administered (1–
2 mg/kg in children17).
• Clofazimine 300 mg once per month, super-
vised, and 50 mg daily, self-administered
(1–2 mg/kg in children for both the monthly
and daily doses17).
This treatment should be continued for at least
2 years, and, wherever possible, up to smear
negativity.  In multibacillary leprosy, rifampin
should never be used alone or in combination
with dapsone without a third bactericidal drug
because of the high prevalence of dapsone resis-
tance and the high risk of the development of
rifampin resistance.
The addition of monthly supervised doses
of ethionamide or prothionamide to this regimen
is not recommended by WHO, as the triple-
drug therapy is deemed adequate.  Where
clofazimine pigmentation has been objection-
able, clofazimine has been replaced by daily
thioamide (either ethionamide or prothiona-
mide).  However, this substitution is not recom-
mended by WHO unless absolutely necessary,
because it is now clear that the recommended
daily dose of 50 mg is well accepted by patients
and has a marked influence on the frequency and
severity of reactional states.16  Ethionamide and
prothionamide can have serious hepatotoxic side
effects, particularly when administered with
rifampin.  Both have poor gastrointestinal tolerance
as well.
The Most Potent Antileprosy Drugs
Rifampin
Rifampin is by far the most potent drug against
M leprae.  A single dose of 20 mg/kg was shown (by
the proportional bactericidal test method) to kill
about 99% of the viable leprosy bacilli in the mouse
footpad, while single, 600-mg doses of the drug
given to previously untreated multibacillary pa-
tients rendered the bacilli harvested from biopsies
taken 4 days later noninfectious for mice, suggest-
ing that such a dose had killed at least 99% of the
viable M leprae.29  Rifampin induces the metabolism
of dapsone, but in the usual clinical setting this is of
little importance.30
Dapsone
Dapsone is a sulfonamide analog of p-aminoben-
zoic acid (PABA) that inhibits M leprae’s de novo
synthesis of folic acid.  The drug is essentially bac-
teriostatic.  It is metabolized in the liver and ex-
creted, as metabolites, in the urine.  It is well ab-
sorbed in the gastrointestinal tract and well
tolerated.  Dapsone’s mean half-life is 28 hours in
human plasma.  The predominant side effect is
hemolytic anemia (especially with glucose-6-phos-
phate dehydrogenase deficiency).  Another side
effect, the dapsone syndrome, is a rare clinical syn-
drome that usually develops within 6 weeks of the
start of therapy and consists of exfoliative dermati-
tis, hepatosplenomegaly, fever, generalized
lymphadenopathy, and hepatitis.  Agranulocytosis
is occasionally seen.30

Military Dermatology
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600 mg in adults
(450 mg < 35 kg)
10 mg/kg in
children
Rifampin
supervised,
1 dose/mo • 6
Paucibacillary
Disease
100 mg in adults
1–2 mg/kg in
children
Plus Dapsone,
unsupervised OK,
daily for 6 mo
600 mg in adults
10 mg/kg in
children
Rifampin,
supervised,
1 dose/mo for
≥ 24 mo
100 mg in adults
1–2 mg/kg in
children
Plus Dapsone,
unsupervised OK,
daily for ≥ 24 mo
Multibacillary
Disease
Plus
unsupervised,
50 mg daily for
≥ 24 mo
Supervised,
300 mg in adults,
1 dose/mo for
≥ 24 mo
Children,
1–2 mg/kg for
both monthly and
daily doses
Plus Clofazimine
Fig. 14-13. World Health Organization guidelines for the treatment of uncomplicated leprosy. Data source: WHO
Expert Committee on Leprosy. World Health Organization Technical Report Series 768. 6th report. Geneva, Switzerland:
World Health Organization; 1988.
Treatment
Of
Leprosy

Leprosy
345
Clofazimine
Clofazimine is the third-most-potent antileprous
drug, and has both antibacterial and anti-inflam-
matory effects.  Its mechanism of action is not known.
The drug has a complex pattern of distribution in
the body, with high concentrations found in the
reticuloendothelial system, the subcutaneous fat,
and in the distal small bowel at the site of absorp-
tion.  The half-life for elimination is estimated to be
3 months.  The most dramatic side effect is dose-
related skin pigmentation caused by drug accumu-
lation (Figure 14-14).  Gastrointestinal toxicity is
caused by deposition of drug crystals in the distal
small bowel and draining mesenteric lymph
nodes.30
Ethionamide and Prothionamide
Ethionamide and prothionamide are essentially
identical in their effects and toxicities.  Ethionamide
is bactericidal in the mouse footpad system and has
been used in leprosy treatment for more than 20
years.  It is metabolized in the liver and excreted in
the urine, with a mean half-life of 3 hours.  A dose
of 250 to 500 mg/d is used in adults.  These drugs
are hepatotoxic, but when used alone rarely present
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a problem.  When combined with rifampin, another
hepatotoxic drug, the toxicities are additive.  Be-
cause bacterial resistance may develop within a
few years of treatment, combination therapy is
mandatory.26
Thalidomide
Thalidomide, a sedative-hypnotic widely used
between 1957 and 1961, caused severe and charac-
teristic fetal malformations (phocomelia) when
taken by pregnant women between days 35 and 50
after the last normal menstrual period.  In 1965, it
was shown to be very effective in cases of erythema
nodosum leprosum reactions and is now the drug
of choice in men and nonfertile women.  Thalido-
mide appears to inhibit de novo synthesis of IgM
antibodies and to inhibit neutrophil chemotaxis.  It
has no antibacterial effect whatsoever.  It is metabo-
lized in the blood and excreted in the urine.  Its half-
life is 3.5 hours.  Other than embryopathy, the only
other significant side effect is a peripheral
neuropathy.30  Minor side effects, which are often
transient, include dry mouth, rash, and constipa-
tion.  Thalidomide is now supplied only through
national governments that will indemnify the manu-
facturer (Chemie Grunenthal GmbH, Postfach 129,
Zweifallerstrasse 24, 5190 Stolberg/Reinland, Fed-
eral Republic of Germany) against litigation31 and is
indicated only for Type 2 reactions (ie, erythema
nodosum leprosum).32
Drug Resistance
Extensive evidence shows that the emergence of
secondary resistance of M leprae to dapsone is a
worldwide phenomenon, occurring in as many as
40% of treated multibacillary patients in some ar-
eas.  They are resistant to high or intermediate
levels of the drug.  During the 1980s, primary
dapsone resistance was found in up to 70% of newly
detected, previously untreated patients.  Most pri-
mary resistant strains of M leprae have been shown
to be resistant to low or intermediate levels of
dapsone.16
From data collected during the 1980s, it has be-
come clear that when rifampin is used alone, sec-
ondary resistance develops easily and rapidly in
multibacillary patients with leprosy.  No primary
resistance is known at present.
Clofazimine resistance is unknown or uncon-
firmed.
Secondary resistance to ethionamide has been
demonstrated in patients treated with ethionamide
Fig. 14-14. This patient with advanced lepromatous lep-
rosy demonstrates significant dyspigmentation second-
ary to clofazimine accumulation within the lesions. Note
the mild leonine facies, ear and nose deformities, and
symmetry of the facial lesions.

Military Dermatology
346
alone.  Resistant strains of M leprae have also shown
cross-resistance to prothionamide, thiacetazone, and
thiambutosine.
Microbial Persistence
Viable, fully drug-susceptible M leprae that are
able to survive for many years in patients with
lepromatous leprosy, despite the presence of bacte-
ricidal concentration of an antileprosy drug, are
termed persisters.  They have been detected in about
10% of all biopsy specimens from patients with
lepromatous leprosy who are receiving multidrug
regimens containing rifampin—irrespective of the
regimen or duration of treatment.  It therefore seems
likely that none of the existing drugs, used alone or
in combination, greatly affects the occurrence of
persisters.33
No clear relationship has yet been established
between the existence of persisting organisms and
the occurrence of relapses, and accumulating evi-
dence from clinical trials is beginning to suggest
that persisters may not pose a serious threat of
relapse in patients who complete multidrug therapy,
at least as far as early relapses are concerned.  The
rate of relapses following multidrug therapy in
paucibacillary cases is about 1%, for multibacillary
cases about 0.2%.33
Promising New Drugs
The quinolones pefloxacin and ofloxacin act by
inhibiting DNA synthesis during bacterial replica-
tion, probably by interfering with DNA gyrase
(topoisomerase) activity.  Several rifampin deriva-
tives, ansamycins, have shown antilepromatous
activity up to 7-fold greater than rifampin.  Like
rifampin, however, they are very expensive.34
Minocycline has been shown to be much more
bactericidal for M leprae than any other drug except
rifampin.  Its high lipid solubility may allow it to
penetrate the outer capsule and cell wall.  It appar-
ently has additive effects when used in combination
with dapsone and rifampin.34
Streptomycin is bactericidal and is synergistic
with rifampin, even when given once per month.
Deoxyfructo-5-hydroxytryptamine (DF5-HT) has
shown an ability to clear bacilli faster than dapsone,
perhaps due to an immunostimulating effect.34
Investigational work is being done on clofazimine
derivatives, including long-acting dapsone injections,
macrolides, and pyrazinamide, among others.34
Were it not for its various reactional states, which
represent alterations in host immunity, leprosy
would be considered a rather straightforward bac-
terial disease with a “cookbook” approach to
therapy.  Fortunately, however, the reactional states
that are the source of so much difficulty—for
healthcare providers as well as for patients—have
also stimulated significant research into leprosy
and the immune system.  Currently, there are four
well-recognized reactional states: (1) reversal reac-
tion, also called Type 1; (2) erythema nodosum
leprosum, also called Type 2; (3) downgrading reac-
tion; and (4) Lucio’s phenomenon (Figure 14-15).
All reaction states are uncommon in children with
leprosy.  In a series of 132 cases of leprosy in chil-
dren from northern India, 4 patients (3%) had rever-
sal reactions, 2 (1.5%) had downgrading reactions,
and only 1 (0.7%) had a Type 2, or erythema nodosum
leprosum, reaction.19
Reversal Reaction
Reversal reactions, also called Type 1 reactions,
occur in patients with unstable borderline disease
in the Ridley-Jopling classification scheme (ie, BT,
BB, BL), who experience a rapid increase in specific
cell-mediated immunity often brought on by either
treatment or improved nutrition.  This reaction is
called a reversal because patients with borderline
disease typically worsen slowly in the opposite
direction (ie, toward the lepromatous end of the
spectrum), but in this reaction, the patients are
improving slightly (ie, the downward spiral of the
natural course of the disease is reversing).
The reversal reaction is a Type IV hypersensitiv-
ity reaction, in which the host has an increased
immune response against the antigens of M leprae.
Thus, in terms of the killing and clearing of bacteria,
this reaction is beneficial.  However, the inflamma-
tion, particularly in nerve tissue, may be devastat-
ing.  It is important to warn patients with borderline
disease ahead of time about reversal reactions; oth-
erwise, when the inflammation occurs, the patient
may think the therapy is not working, lose confi-
dence in the physician, and risk permanent disabil-
ity from neglect.32
Most commonly, reversal reactions occur during
the first 6 months of treatment, particularly in pa-
COMPLICATIONS: THE REACTIONAL STATES

Leprosy
347
Polar
Tuberculoid
Leprosy = TTp
Subpolar
Tuberculoid
Leprosy = TTs
Borderline
Tuberculoid
Leprosy = BT
Borderline
Borderline
Leprosy = BB
Borderline
Lepromatous
Leprosy = BL
Subpolar
Lepromatous
Leprosy = LLs
Indeterminate
Leprosy = IL
Polar
 Lepromatous
Leprosy = LLp
Lucio’s Diffuse
Lepromatous
Leprosy = LLp
Erythema
Nodosum
Leprosum (rare)
Erythema
Nodosum
Leprosum
Lucio’s
Phenomenon
Erythema
Nodosum
Leprosum
Reversal
Downgrading
Fig. 14-15. The possible reactional states in leprosy: reversal reaction, also called Type 1 (red); erythema nodosum
leprosum, also called Type 2 (blue); downgrading reaction (green); and Lucio’s phenomenon (yellow). Note that
erythema nodosum leprosum can occur via three pathways.

Military Dermatology
348
tients with borderline borderline (BB) and border-
line tuberculoid (BT) leprosy.  The normal progres-
sion in clinical classification in reversal reactions is
LLs —> BL —> BB —> BT —> TTs
The cardinal signs of a reversal reaction are the
rapid development of erythema, warmth, and swell-
ing in one or several preexisting clinical lesions
(Figure 14-16).  Nerve involvement, seen clinically
as pain, swelling, and motor or sensory distur-
bances, is common and can constitute a medical
emergency.  Delay of treatment for even 2 days may
result in severe adverse effects (eg, paralysis of the
ulnar nerve, causing claw hand; of the lateral
popliteal nerve, causing foot drop; and of the facial
nerve, causing facial palsy).  In the field or clinic, the
following simple test of nerve function32 can rap-
idly be carried out by checking
OK to put on the Web
• the eyes for complete closure and normal
blinking;
• the hand for loss of sensation, using nylon
bristles or a ballpoint pen, and for loss of
strength by abduction of the fifth finger and
opposition of the thumb against firm pres-
sure; and
• the foot for loss of sensation as above, and
for loss of strength by dorsiflexion of the
foot against firm pressure.
Systemic symptoms such as fever or malaise are
unusual.  Associated findings may include edema
of the hands, feet, and face in any combination.
Rarely, new lesions with tuberculoid characteris-
tics may develop and cause confusion with a down-
grading reaction.  However, histology and lepromin
testing are confirmatory.5
Histological Findings
Histological findings show a shift of classifica-
tion toward the tuberculoid end of the spectrum.
Edema is present; the bacilli are reduced; and in-
creased numbers of defensive cells such as lympho-
cytes, epithelioid cells, and giant cells are seen.
Treatment
Systemic corticosteroids are very effective in re-
ducing the edema and inflammation in reversal
reactions and, thus, are most helpful in preventing
nerve damage (Figure 14-17).  Initial doses of
prednisone, 40 to 80 mg/d for 5 to 7 days, may
alleviate neuritis and edema.  Tapering must be
done slowly: the dose must not be reduced by
more than 5 mg once or twice per week.  Treatment
with prednisone for 3 to 6 months is necessary in
most cases and is definitely associated with de-
creased frequency and severity of disabilities and
deformities as compared to shorter courses of
prednisone.35
Thalidomide is not useful in the treatment of
reversal reactions.  Clofazimine’s usefulness has
not been clearly demonstrated for acute reversal
reactions, in contrast to its usefulness in erythema
nodosum leprosum, but clofazimine does play
a role in chronic reversal reactions, where it may
be steroid sparing.  When used, clofazimine is
begun at 100 mg three times daily for 6 weeks; then,
if steroid sparing, reducing the dose to twice daily
for several months, then daily for a few more
months.35
Fig. 14-16. Type 1 reversal reaction. This Filipino woman
developed a rapid increase in erythema, warmth, and
swelling in her preexisting lesions of borderline
lepromatous leprosy.

Leprosy
349
Fig. 14-17. Treatment algorithm for reactional states in leprosy.
Type 1:
Reversal
Reaction
Thalidomide
not useful
Mild reactions
Analgesics (ie,
aspirin)
Chloroquin,
Antimonials
(Stibophen)
With neuritis
Without neuritis
Acute reactions
Prednisone
40–80 mg/d
tapering slowly
over months
Prednisone
40–80 mg/d,
quick taper
possible
Type 2:
Erythema
Nodosum
Leprosum
Treatment of
Reactional
States
Drug of choice
in relapses and
chronic cases
Thalidomide
100 mg qid,
taper over
few weeks
Chronic
reactions and
relapses
Clofazimine 100
mg tid 4–6 wk,
bid for months
Slow onset, may
be used in
pregnancy
Contraindicated
in pregnant
females
Prednisone
May be used in
pregnancy
Downgrading
Reactions
Treat for
multibacillary
disease
Prednisone
Dapsone
plus
Rifampin
Lucio’s
Phenomenon
Prednisone
40–80 mg/d
with taper over
3–6 mo
Clofazimine may
be steroid-
sparing in
chronic reactions

Military Dermatology
350
Erythema Nodosum Leprosum
Erythema nodosum leprosum, also called the
Type 2 reaction, is named for its most prominent
clinical finding: an eruption of tender, red nodules.
It is an immune complex disease, a Type III hyper-
sensitivity reaction, and occurs almost exclusively
in patients with lepromatous leprosy (LLp and LLs),
and only occasionally in patients with borderline
leprosy (BL).  Antigens of M leprae and antibodies
form immune complexes with complement, which
precipitate in the tissues of the skin, blood vessel
walls, nerves, and other organs; these precipitates
attract neutrophils, which further damage the tis-
sues.  Predisposing factors include infections (eg,
malaria, filaria, bacterial infections), trauma, sur-
gery, physical or psychological stress, immuniza-
tions or vaccinations, pregnancy, parturition, in-
gestion of potassium iodide, and antileprous therapy
(ie, dapsone, thiacetazone, rifampin).5
Clinically, the preexisting lesions of leprosy re-
main unchanged.  However, new crops of brightly
erythematous, painful nodules may come and go.
Fever and malaise are common.  The reaction tends
to occur late in treatment, unlike reversal reactions,
and often at a time when the skin lesions are quies-
cent and most of the bacteria are granular on the
morphologic index.  The skin lesions alone are also
known as erythema nodosum leprosum.  The le-
sions tend to be small, variably sized, slightly raised,
tender nodules and plaques, which are brightly
erythematous, warm, and blanchable.  In contrast to
classic erythema nodosum, the lesions of erythema
nodosum leprosum last only 2 to 3 days, often
resolving with hyperpigmented residua.  They can
be very numerous and widely disseminated.  The
scalp and the intertriginous areas tend to be spared.
The lesions leave a blue stain when they regress.
Associated features of Type 2 reactions include
nerve pain, periosteal pain (especially in the tibia),
myalgias or myositis or both, arthralgias or arthritis
or both, rhinitis, epistaxis, acute iritis, dactylitis,
lymphadenitis (especially the femoral chain), acute
epididymo-orchitis, and proteinuria.  Although
nerve involvement occurs both in reversal and Type
2 reactions, it progresses much more slowly in the
latter.  If left untreated, however, it may still pro-
duce severe and extensive nerve damage.  Edema of
the hands and feet can be one of the major present-
ing features of erythema nodosum leprosum.  If
edema is present for more than a few days, stiffness
and deformityof the fingers may result, hence
treatment is imperative.  Overall, erythema nodosum
leprosum tends to be a chronic, smoldering process
that often lasts for years.
In the laboratory, circulating immune complexes
can be detected.  Additionally, tests for antinuclear
antibody and rheumatoid factor may be positive.
Histological Findings
Existing leprosy lesions show some edema.
Erythema nodosum leprosum lesions show a
leukocytoclastic vasculitis of both veins and arteri-
oles; polymorphonuclear lymphocyte infiltrate; and
scanty, fragmented bacilli.
Treatment
Mild cases of erythema nodosum leprosum may
hardly be noticed and often respond to minor symp-
tomatic care with analgesics such as aspirin.
Chloroquin and antimonials such as stibophen have
also been used for mild cases, but are not indicated
for neuritis or chronic reactions.  Stibophen is given
as a 5-mL intramuscular injection on alternate days
for 3 doses.  A second course may be given after a 2-
week interval.32
Treatment for more extensive or severe Type 2
reactions requires systemic corticosteroids or thali-
domide.35  Acutely, prednisone in doses of 40 to 80
mg/d is begun.  In the absence of neuritis, the
dosage may be tapered moderately quickly once
symptoms have been suppressed.  Relapse is com-
mon and the dosage needs to be individualized.
Where neuritis is present (or if nerve function has
been lost within the preceding 6 mo), daily cortico-
steroids may be necessary for months.  If the daily
dose remains above 30 mg of prednisone, then
switching to alternate-day steroids may be helpful.
However, if nerve pain returns on the “off” day,
then the physician must assume that nerve damage
is occurring and reinstitute daily steroids.  For acute,
painful, hand edema, splinting of the hands in a
position of function for a few days, as well as ad-
ministering prednisone, are indicated.  Subse-
quently, physical therapy may be started to prevent
stiffness and loss of function.  Thalidomide has
rapid onset of action, often bringing relief within 24
hours.  It is steroid sparing.  Consequently, it is a
drug worthy of serious consideration in severe
erythema nodosum leprosum.31
For more chronic cases or for relapses, thalido-
mide is the drug of first choice (except in fertile
women, due to its teratogenicity).  The initial dose
is 100 mg four times daily, which can be tapered

Leprosy
351
within a week to 100 to 200 mg/d.  Further tapering
to 50 to 100 mg/d may be possible.  This dosage may
need to be continued for 1 to 2 months, then discon-
tinued.  If erythema nodosum leprosum recurs,
treat again with thalidomide.35
Alternatively, clofazimine can be beneficial, not
only in suppressing the reaction, but also in its
antibacterial and steroid-sparing effects.  Unfortu-
nately, its onset of action is delayed for 4 to 6 weeks.
Clofazimine is given 100 mg three times daily
for 4 to 6 weeks, then tapered to twice daily for
several more months.  Gastrointestinal intol-
erance may force a reduction in dose to 100 mg/d.
The other major side effect of clofazimine is skin
darkening.35
Some patients may require a combination of all
three medications.  In select circumstances such as
in the case of nerve entrapment, surgical decom-
pression may be indicated.35
In pregnancy, clofazimine and steroids may be
used, as well as dapsone.  However, thalidomide is
absolutely contraindicated.  Rifampin has also
been associated with fetal anomalies (in animals only)35;
hence its use should be avoided in pregnant women.
Downgrading Reaction
Untreated patients are sometimes seen with a
reaction that clinically appears similar to a reversal
reaction, but who are, in fact, undergoing a down-
ward shift in their immunity toward the lepromatous
end of the spectrum.  They are described as having
a downgrading reaction.  However, the diagnosis is
difficult to make unless the patient is followed for a
long period of time.
There is a shift in the Ridley and Jopling Classi-
fication system toward the lepromatous end of the
spectrum, with an increase in bacilli and macro-
phages, and a decrease in lymphocytes, epithelioid,
and giant cells.
The treatment for downgrading reactions is the
same as that for multibacillary disease.  Where
drug-resistant organisms are suspected, additional
measures (eg, the administration of additional and
more toxic antibiotics) may be necessary.
Lucio’s Phenomenon
The fourth state, Lucio’s phenomenon, is a rare
type of acute, reactional leprosy.  This state occurs
only in patients with Lucio’s leprosy, the rare, dif-
fuse, nonnodular form of lepromatous leprosy that
is seen in Mexico and Central America.  Lucio’s
phenomenon is unique in that it occurs only in
untreated patients.  The reaction is characterized by
crops of painful, tender, red macules that become
purpuric, then necrotic, and finally ulcerative.  The
lesions eventually heal with atrophic, stellate scars.
Patients are usually afebrile.  The extremities are
involved predominantly.
The lesions are essentially due to a necrotizing
vasculitis that is caused by circulating immune com-
plexes including mixed cryoglobulins.36  Appar-
ently, patients with Lucio’s phenomenon have a
deficient cell-mediated defense mechanism that
permits unhindered multiplication of bacilli and
production of circulating bacterial antigen.  Pro-
duction of antibodies by an active humoral immune
system then results in vasculitis, infarction, and
skin necrosis.
Histological findings include ischemic epider-
mal necrosis; necrotizing vasculitis of small blood
vessels in the upper dermis; severe, focal, endothe-
lial proliferation of middermal vessels; and large
numbers of bacilli in the endothelial cells.5
Treatment with corticosteroids or dapsone com-
bined with rifampin is beneficial.  Thalidomide is of
no value.5  Many of these patients will develop the
Type 2 reaction, erythema nodosum leprosum, once
definitive antilepromatous therapy is begun.
VACCINATION
Information on the value of Bacille bilié de
Calmette-Guérin (BCG) vaccination against leprosy
is available from five large field studies conducted
by WHO16: the protective effect of BCG was gener-
ally high (80%) in Uganda, moderate (45%–55%) in
Malawi and Papua New Guinea, and low (20%–
30%) in Burma and India.  In all these studies, the
observed protective effect of BCG was primarily
against paucibacillary leprosy.  Currently, studies
are underway to assess the use of vaccines of killed
M leprae combined with BCG versus BCG alone in
120,000 subjects in Malawi.16
The goal is to produce a genetically engineered,
safe, potent leprosy vaccine consisting of highly
immunogenic BCG that contains the appropriate
genes of M leprae.  This approach may allow those
antigens associated with a protective immune re-
sponse to be expressed.14

Military Dermatology
352
LEPROSY AND ACQUIRED IMMUNODEFICIENCY SYNDROME
6 (33%) also had antibodies to human immunodefi-
ciency virus (HIV), as detected by the Wellcozyme
VK51 (ELISA) test.  Positive results were confirmed
on a second date and then reconfirmed using other
serologic testing.  Because the serologic prevalence
of infection with HIV was significantly higher than
that found in blood donors and surgical patients,
and because the patients with leprosy tended to
have more serious symptoms such as paralysis or
neuritis, rather than a skin lesion, this study sug-
gests that AIDS may predispose to leprosy.  For
comparison, 50% of the confirmed cases of tubercu-
losis showed evidence of HIV infection.
Because leprosy is associated with a defect in
cell-mediated immunity, and because tuberculosis
is now seen as a presenting sign of acquired
immunodeficiency syndrome (AIDS), will leprosy
also be seen as a presenting sign of AIDS,
especially because AIDS suppresses cell-mediated
immunity?
The only data on this question have been re-
ported from rural Zambia.  This study37 included all
patients with tuberculosis and leprosy at the
Chikankata Salvation Army Hospital who were seen
from October to December 1987.  Of 27 patients with
leprosy, 18 had new cases.  Of those 18 new patients,
SUMMARY
Leprosy is an infectious disease caused by the
bacterium Mycobacterium leprae.  The major source
of infection is patients already infected with the
most severe form of the disease, lepromatous lep-
rosy, who shed millions of organisms per day in
their nasal secretions.  Acquisition of the disease
requires prolonged contact with patients with
lepromatous leprosy, and fewer than 1% of exposed
individuals will ever develop the disease.  Of those
who do, 75% will heal spontaneously.  Thus, only
about 0.25% of exposed individuals ever develop
clinical disease, and then many months or years
after exposure.
The disease can take a wide variety of forms,
depending on the immune status of the patient.
Initially, no lesions or nondiagnostic hypopig-
mented macules are seen.  This stage is known as
indeterminate leprosy.  Over time, 25% of these
patients will progress to a more serious form of the
disease.  Those with poor immunity tend to develop
the widely disseminated, symmetric, infiltrated
papules and plaques of lepromatous leprosy, the
skin lesions of which teem with acid-fast organ-
isms.  The involvement of the internal organs may
be substantial in such patients.  Patients with good
immunity tend to develop one or a few asymmetric,
indurated plaques, with a tendency for central clear-
ing associated with significant nerve involvement.
Other patients with moderate immunity develop an
intermediate form—between lepromatous and tu-
berculoid leprosy—known as borderline leprosy.
Patients whose disease leans more toward lepro-
matous leprosy than tuberculoid are said to have
borderline lepromatous leprosy; whereas those
whose disease leans more toward the tuberculoid
side are said to have borderline tuberculoid leprosy.
Diagnosis is made on the basis of clinical find-
ings including characteristic skin lesions, nerve in-
volvement with anesthesia or nerve enlargement,
and demonstration of acid-fast organisms in biop-
sies, nasal secretions, or from slit-skin prepara-
tions.
Currently, for treatment purposes, paucibacillary
disease is defined as being smear negative, whereas
multibacillary disease is defined as being smear
positive.  WHO treatment guidelines for both
paucibacillary and multibacillary disease should
be followed exactly and continued for a minimum
of 2 years and until the smear is negative.  Deviating
from the guidelines may lead to antibiotic-resistant
organisms.
Reactional states are frequent in leprosy.  They
constitute fluctuations in the patient’s immune sta-
tus that may be deleterious to the patient’s health
and lead to life- and limb-threatening complica-
tions.  There are four reactional states.  Type 1
reactions, also called reversal reactions, occur early
in treatment in patients with unstable borderline
disease of the borderline tuberculoid (BT), border-
line borderline (BB), or borderline lepromatous (BL)
types.  Here, because of improving immunity, in-
flammatory reactions develop in preexisting le-
sions and may result in nerve paralysis.  Reversal
reactions constitute a medical emergency.  Pred-
nisone continues to be the initial drug of choice.
The Type 2 reaction, also called erythema nodosum
leprosum, is a Type III immune-complex hypersen-
sitivity reaction that occurs primarily in long-stand-

Leprosy
353
ing lepromatous leprosy of the lepromatous
lepromatous polar or subpolar (LLp or LLs) forms,
or, rarely, in borderline lepromatous (BL) disease.
Systemic symptoms (eg, fever and malaise, neuritis,
myalgias and arthralgias) accompany the bright-
red crops of new, painful skin nodules.  The third
reactional state is called downgrading, in which the
patient slips toward the lepromatous end of the
spectrum.  Downgrading reactions are difficult to
diagnose, appear similar to reversal reactions, and
are treated for ongoing or drug-resistant multi-
bacillary disease.  The fourth reactional state, Lucio’s
phenomenon, occurs only in patients who have the
diffuse lepromatous leprosy known as Lucio’s lep-
rosy.  The reaction, a necrotizing cutaneous
vasculitis, occurs only in untreated patients.
Medical officers need to understand that leprosy
does not constitute a health threat to most troops.
Prolonged, intimate contact with untreated indi-
viduals with lepromatous leprosy is necessary to
transmit the disease, and more than 99% of all
exposed individuals will resist infection. Such con-
ditions are present in underdeveloped areas of the
world, and may certainly be exacerbated by condi-
tions of war (eg, famine, confinement, internment
in concentration camps).  Despite these well-estab-
lished medical facts, the popular concept of lep-
rosy—a horrible, disfiguring, infectious disease sent
as a punishment from God—continues to terrify the
uninformed.
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Sansarricq H. Technical problems related to multidrug therapy in leprosy control. Acta Leprol. 1989;7:59–62.
33.
Baker RJ. The need for new drugs in the treatment and control of leprosy. Int J Lep. 1990;58:78–97.
34.
Wheate HW. Management of leprosy. Br Med Bull. 1988;44:791–800.
35.
Yoder LJ. Management of reactions in Hansen’s disease. The Star. 1987;47:1–7.
36.
Quismorio FP, Rea T, Chandor S, Levan N, Friou GJ. Lucio’s phenomenon: An immune complex deposition
syndrome in lepromatous leprosy. Clin Immunol Immunopathol. 1978;9:184–193.
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Meeran K. Prevalence of HIV infection among patients with leprosy and tuberculosis in rural Zambia. Br Med
J. 1989;298(6670):364–365.

Cutaneous Tuberculosis
355
CUTANEOUS TUBERCULOSIS
Chapter 15
JAMES W. STEGER, M.D.* AND TERRY L. BARRETT, M.D.†
INTRODUCTION
HISTORY
Tuberculosis in Antiquity
Observations During the 4th Through 19th Centuries
The Contributions of Robert Koch
Tuberculosis in the Military
EPIDEMIOLOGY
BACTERIOLOGY
HISTOPATHOLOGY
CLASSIFICATION
Primary Inoculation Tuberculosis
Tuberculosis Verrucosa Cutis
Miliary Tuberculosis of the Skin
Scrofuloderma
Tuberculosis Cutis Orificialis
Lupus Vulgaris
Other Rare Forms of Cutaneous Tuberculosis
DIAGNOSIS
TREATMENT
PREVENTION
TUBERCULOSIS AND ACQUIRED IMMUNODEFICIENCY SYNDROME
TUBERCULOSIS CONTROL IN REFUGEE SETTLEMENTS
THE TUBERCULIDS
Erythema Induratum
Papulonecrotic Tuberculid
Lichen Scrofulosorum
SUMMARY
*Captain, Medical Corps, U.S. Navy; Head, Dermatology Clinic, Naval Hospital, San Diego, California 92134-5000
†Captain, Medical Corps, U.S. Navy; Pathology and Dermatopathology Consultant, Naval Hospital, San Diego, California 92134-5000

Military Dermatology
356
INTRODUCTION
Just as systemic tuberculosis can be protean and
diverse in its clinical manifestations, so tuberculo-
sis of the skin is also highly variable in its clinical
appearance, significance, and prognosis.  Five fac-
tors that are important for the clinical presentation
of cutaneous tuberculosis are (1) the pathogenicity
of the organism, (2) its antibiotic resistance profile,
(3) the portal of infection, (4) the immune status of
the host, particularly the presence or absence of
acquired immunodeficiency syndrome (AIDS) sec-
ondary to infection with human immunodeficiency
virus (HIV), and (5) various local factors in the skin
(eg, relative vascularity, trauma, lymphatic drain-
age, and proximity to lymph nodes).
The incidence of tuberculosis in the United States
has been increasing since 1984 owing to the follow-
ing factors:
• immigration of previously infected people
from developing countries,1
• increasing homelessness and malnutrition,2
• worsening urban economic and social envi-
ronments,3
• increased drug resistance,4
• the relaxation, reduction, or elimination of
tuberculosis-control programs over the past
two decades,3
• physicians who have not treated their pa-
tients in accordance with recommended
treatment guidelines,5
• the increasing prevalence of AIDS.6
At present, the incidence of tuberculosis in the
United States is approximately 10.5/100,000/y,7
(up 15% since 1990), the largest group being 25 to
44 years of age—a group likely to have children
in their households who are at risk of becoming
infected.8
The worldwide incidence of tuberculosis in 1990
was estimated by the World Health Organization
(WHO) to be 7.5 million cases, with the greatest
number occurring in Southeast Asia and the west-
ern Pacific regions with 4.9 million cases, followed
by India with 2.1 million, then China with 1.3 mil-
lion, and Indonesia with 0.4 million.9  This inci-
dence is anticipated to climb by 58% to 11.9 million
cases per year by the year 2005.9  The rate of inci-
dence of tuberculosis in the developing countries of
the world is much greater: approximately 500/
100,000/y.10  These same factors that have led to the
increases in the United States are operative world-
wide.  Of especially great alarm has been the pro-
gressive increase in numbers of strains of tubercu-
losis that are resistant to multiple antibiotics11,12 as
well as the rampant spread of such strains in AIDS-
infected patients.6,12,13
Since 1984, the incidence of extrapulmonary tu-
berculosis has increased at an even faster rate than
that of pulmonary tuberculosis14,15 and is consid-
ered a diagnostic criterion in the case definition for
AIDS.16  Because immunocompromised individuals
are at increased risk for extrapulmonary tuberculo-
sis, dermatologists are renewing their historic role
in the diagnosis of cutaneous lesions of tuberculosis.
From the military standpoint, the risk of tubercu-
losis exposure virtually worldwide has increased
dramatically since the end of the Vietnam conflict.
The continued rise toward a worldwide pandemic
of tuberculosis, AIDS-associated tuberculosis, and
drug-resistant tuberculosis portends a perilous fu-
ture for troops who deploy to any underdeveloped
country.  Vigorous surveillance for tuberculosis,
coupled with comprehensive drug treatment and
aggressive public health programs will be essential
to ensure that our military forces do not fall victim
to this age-old malady.
Unless otherwise noted, the general history of
the study of tuberculosis up to the time of Robert
Koch is quoted from Baldwin’s “Tuberculosis: His-
tory and Etiology,” a chapter in Osler, McCrac, and
Funk’s Modern Medicine: Its Theory and Practice, origi-
nally published in 1925.17  The discussion of the
contributions of Robert Koch is quoted from
Neisser’s “Chronic Infectious Diseases of the Skin,”
a chapter in Ziemssen’s Handbook of Diseases of the
Skin, originally published in German in 1885.18
Material relating to tuberculosis in the military
in this chapter is quoted from Long’s “Tuberculosis
in the Army,” published in 1963,19 and Guiton and
Barrett’s “Tuberculosis,” published in 1982,20 both
of which are chapters in official histories published
by the U.S. Army Medical Department.  The infor-
HISTORY

Cutaneous Tuberculosis
357
mation contained in these sources is essentially
unavailable elsewhere.
Tuberculosis In Antiquity
Pulmonary tuberculosis (also called consumption and
phthisis) has existed from very remote times.  It tran-
scends all other maladies in the total number of its vic-
tims and the cost to society in civilized countries.  Tuber-
culosis was a disease familiar to the most ancient
civilizations, judging from the inscriptions on Babylonian
tablets, which represent the earliest human records.17
Pathological evidence of tuberculosis of the spine has
been found in Neolithic burial sites in Heidelberg, Ger-
many.  Bone lesions have also been recognized in the
mummified body of a priest of Ammon, exhumed from a
tomb of the 21st Egyptian Dynasty, 1000 BC.21
Hippocrates (460–376 BC) first gave an intelligent de-
scription of phthisis, although empyema and phyma (ab-
scess of the lung), were included.  Otherwise, his por-
trayal of the symptoms of consumption was unsurpassed
for many centuries.  The Hippocratic school believed in
the curability of phthisis in all stages and the benefits of
a change of residence.  Contagion was mentioned by
Isocrates.  Aristotle, a contemporary of Hippocrates,
notes that it was a general belief among the Greeks of his
day that phthisis was contagious.  Celsus (30 BC) wrote of
the disease in three forms: atrophy, cachexia, and ulcer-
ation.  Aretaeus (AD 50) gave a very clear description of
the disease and differentiated it from empyema.  He
believed in the efficacy of sea voyages and country air.
Pliny lauded pine forests for their healing powers.17(p267)
Galen (AD 131–201) considered the disease an ulcer-
ation that should be treated by measures designed to dry
the secretion.  He therefore sent patients to the high land
of Phrygia.  In other details, the conceptions of the dis-
ease held by Galen were like those of Hippocrates; nor
was any further light shed on the nature of consumption
for 1,400 years, when anatomical study began.17(p267)
Observations During the 4th Through 19th
Centuries
[A clue to the prevalence of tuberculosis in different periods
of European history is found in the accounts of the ceremony of
the “touch” performed by French and English monarchs to
cure the swollen glands that occurred in the necks of those
suffering from scrofula.  Ever since Clovis in the 5th century,
the kings of France were believed to receive from God this
healing power at the time of their anointment.  Edward the
Confessor had also claimed it for the English kings in the 11th
century.  The first act of Henry of Navarre, when he entered
Paris as Henry IV in 1594, was to touch 600 scrofulous
persons.  The 17th century seemed to be the heyday for touch-
ing, as well as for deaths from pulmonary consumption.  In
England, the largest number of persons applying to be touched
was recorded in 1684, when many of them were trampled to
death in attempting to reach the hand of the king.21—JWS]
Sylvius (1614–1672) was the first to indicate the con-
nection between tuberculous nodules and phthisis.  He
regarded these nodules as enlarged lymph glands in the
lung, analogous to scrofula, and on the scrofulous consti-
tution depended the inheritance of phthisis.  He gave a
careful description of the symptoms and believed in
contagion.  Morton, (1689) whose celebrated book [on
phthisis] was widely known among English physicians,
brought the tubercle prominently to attention as the true
cause of phthisis.  He also believed in the hereditary
predisposition to and contagious nature of tuberculosis.
Morgagni (1682–1771) was uncertain that tubercles and
glands were identical, and thought that phthisis could
originate from other things; he regarded it as extremely
infectious, and refrained from doing autopsies on
consumptives.17(pp267–268)
The teachings of Benjamin Rush exerted a powerful
influence on American medicine in Revolutionary times.
In his Thoughts upon the Causes and Cure of Pulmonary
Consumption (1783), he regarded tuberculosis as a disease
of debility and considered tubercles to be the result of
hypersecretion from the bronchial vessels.  He believed
in contagion at first, but doubted it later in his life.  Stark
described the miliary tubercles, and near the end of the
18th century, Reid (1785) and Baillie (1794) completed
the description.  Most noteworthy is the work of Gaspard
Laurent Bayle (1810), who is justly named as the founder
of correct teaching about tuberculosis.  He studied mil-
iary tubercles in all stages, and laid great stress on their
varying degrees of opacity.17(p268)
Réné Laennec (1819), whose work soon followed
Bayle’s, summarized and simplified the knowledge thus
far gained.  He recognized the unity of all phthisis as
tuberculosis, and scrofula as tuberculosis of lymph glands;
his ideas in general as to causation and infection were
distinctly modern, and his descriptions of the tubercle and
its transformation toward ulceration are unsurpassed.3(p268)
During this period, America was represented but mea-
gerly until 1834, when Samuel Morton, of Philadelphia,
published the first pathological studies on consumption.
He was a student of Laennec, and his conclusions as to
the nature of tubercles were fairly accurate; they were
ascribed to altered secretion and not to inflammation.
Samuel Morton’s work on Pulmonary Consumption found
much favor in America, and included excellent therapeu-
tic advice as to open-air life and exercise.17(p268)
English, American, and German physicians accepted
the probability of infection under special conditions, but
the strongest opinions were held by the Latin races [Medi-
terranean peoples—JWS], among whom the disease was
said to be more virulent.  The influence of Valsalva and
Morgagni was certainly most potent in causing fear in
Italy.  The first recorded inoculations were by Kortum
(1789), which, like some of those of his successors, were
fortunately unsuccessful, since they were partly on hu-
mans including themselves.  The strife over the question
of the danger of inoculation of scrofula with vaccination
led to these first attempts.17(p268)
Virchow (1847–1850) classified scrofula and tubercu-
losis entirely apart, restricting the latter term to the
miliary form and considering it a form of lymphoma due

Military Dermatology
358
to an unknown diathesis; caseation was a nonspecific
process.  Hence, the idea of unity in tuberculous diseases
received a serious rebuff despite the important discovery
by Buhl (in 1857) that miliary tubercles were most often
associated with preexisting caseous foci, from which he
thought the specific poison originated.  The microscopi-
cal studies brought out valuable data, but withal much
confusion.17(p369)
Jean Antoine Villemin presented his important com-
munication, On the Cause and Nature of Tuberculosis and
the Inoculation of the Same from Man to Rabbit, in December
1865.  His conclusions were positive: (1) Tuberculosis is
a specific affection.  (2) It has its origin in an inoculable
agent.  (3) The inoculation from man to rabbits is very
successful.  (4) Tuberculosis pertains, therefore, to the
virulent diseases, and should be classed with variola,
scarlatina, syphilis, or, better still, with glanders.  Villemin
covered a wide field in his inoculations, employing frag-
ments of lung tubercle, sputum, blood, scrofulous gland,
and perlsucht or bovine tubercle, with positive results in
nearly all cases.  His conclusions excited widespread
discussion and experimentation.  A new era in microbiol-
ogy was founded about the same time by [Louis]
Pasteur.17(p269)
The contest over the specificity of the giant cell, the
importance of which was emphasized by Langhans (1868),
was settled in the negative.  Tubercles were studied in all
the tissues hitherto unassociated with the conception of
tuberculosis, as fungous joints, carious bones, and lupus,
by Koster (1873) and Friedländer (1873).  The develop-
ment and spread of miliary tubercles were traced to
venous infection by Weigert (1879–1892).  The pathway
of infection was already inferred by the many feeding
and inhalation experiments, so that, with the rapidly
developing investigation of bacteria caused by Pasteur’s
discoveries, search was being made for a specific living
organism.  E. Klebs (1877) was the first to observe actual
transference of the virus by artificial culture on egg albumin
through several generations before inoculation, but he
did not recognize the bacillus; instead, he found a motile
organism, Monas tuberculosum, which he presumed to be
the contagium vivum.  Aufrecht (1881) and Baumgarten
(1882), working independent of Koch, described bacilli in
the center of the tubercles, which, owing to lack of culture
and staining methods, were not positively identified as
the infective agents.  The actual achievement was due to
[the German physician] Robert Koch, whose demonstra-
tion [in 1882] of the causative relation of the tubercle
bacillus to tuberculosis22 was so complete that but little of
importance has been added since.17(p269)
The Contributions of Robert Koch
[Because Koch’s contributions were so brilliant and of such
great importance, albeit published in German, the following
historical review of his work is reproduced verbatim from the
account of his work written in 1885 by Professor Albert L. S.
Neisser (1855–1916), the dermatologist from Breslau, Ger-
many, now Poland.—JWS]
At the present time, tuberculosis, and with it
scrofulosis, is the best-known chronic infectious disease
of man, and the only one demonstrated with certainty.18(p275)
Villemin was the first to class tuberculosis as an
inoculable infectious disease, but his doctrine failed to
secure universal recognition.  Further inoculation ex-
periments were made by different savants in the most
variable manner.  The experimenters introduced the
material into the animals from all possible points, so that
the following result was rendered certain.  If tuberculous
material be transferred to an (appropriate) organism,
there is developed in it, in a typical manner, a tuberculo-
sis which sometimes remains more local, at other times
spreads through the body generally.  Only specific tuber-
culous material is capable of communicating this disease.
Nontuberculous matters, or those deprived of their infec-
tious quality, never produce tuberculosis.  It was shown
at the same time that the “predisposition” of some classes
of animals was variable as regards the receptivity for the
disease.18(p275)
Klebs described a form of micrococcus as peculiar to
tuberculosis and cultivated it.  In the same way, Schüller
has reported experiments in cultivation and inoculations
with its result.  A landmark has been furnished also by
the interesting experiments made by Deutschmann, who
by leaving at rest inoculable tuberculous pus, separated
it into a light wine-yellow serum inactive in inoculation,
and a thick, tenacious sediment which produced tu-
bercle.  Recently, Damsch, in Ebstein’s clinic, has been
able to demonstrate tuberculosis of the urinary passages
in the living, by successful inoculations into the anterior
chamber of the eye of rabbits.  Aufrecht alone has de-
scribed microscopically specific bacteria in the tissues,
without having been able to gain general recognitions of
his results.18(p275)
But the credit of having finally elucidated the nature
of tuberculosis belongs to Robert Koch, who furnished
the incontrovertible proof that a specific bacillus is the
cause of tuberculosis and of scrofulosis.18(p275)
The proof consisted, first, in the demonstration of a
parasitic microorganism in tuberculous neoplasms.  For
this a new staining process had to be invented since
alkaline solutions alone were appropriate.  The method
originally devised by Koch was very soon modified by
Ehrlich, who found the alkalinizing factor in aniline oil
(or, according to Ziehl, in carbolic acid).  His procedure
is as follows: the sections are warmed, then stained in a
mixture of a concentrated alcoholic-fuchsin or gentian-
violet solution and an aqueous solution of anilin oil
(carbolic acid solution) for several hours, or for a short
time if heated.  The sections are then freed from excess
color by alcohol or water washing, then immersed in a
solution of one part of officinal sulphuric (or nitric) acid
with two or three parts of distilled water.  The deep blue
(or red) color gives place at once to a faint yellow, the
stain being bleached in all parts of the tissue.  The bacilli,
however, retain the color and may now be recognized
under comparatively low power.  It is better to further
stain the background with anilin brown or methylene

Cutaneous Tuberculosis
359
blue, because then the blue (or red) bacilli can be more
easily distinguished.  The preparations, after having been
dehydrated in alcohol, are rendered transparent in oil of
cloves and preserved in Canada balsam.  The prepara-
tions are not always permanent, the color of the bacilli
gradually fading, probably because the acid is not thor-
oughly washed out.  The gentian preparations are cer-
tainly more constant in their color than the fuchsin prepa-
rations.  The color keeps best when the specimens (dry
preparations) are not enclosed in Canada balsam, but are
directly examined in oil of cedar (with homogeneous
immersion).18(pp275–276)
The bacteria rendered visible by this method have a
rod shape, hence are bacilli.  Their length corresponds
about to one-fourth to one-half the diameter of a red
blood corpuscle.  Their breadth differs according to the
method employed; Koch’s original methylene blue re-
sults in exceedingly slender bacilli, while Ehrlich’s and
Baumgarten’s method additionally colors the sheath en-
closing the bacillus.  Characteristic of the tubercle bacilli,
in Koch’s older method, is their rejection of the anilin
brown staining after they have already taken the methyl-
ene blue.  In Ehrlich’s method, the tubercle bacilli retain
the tint present in the anilin oil and are not decolored by
acid or subsequent methylene blue staining.18(p276)
Bacilli are aggregated in great numbers wherever the
tuberculous process is of recent inception and in rapid
progress—forming closely packed groups often arranged
in intracellular bundles.  There are also numerous free
bacilli, especially at the border of large cheesy patches
where they are present in large free swarms.  After the
pinnacle of the tubercular eruption has been passed, the
bacilli become sparser and can be seen only as isolated,
often faintly colored, probably dying or dead formations.
If giant cells are present, the bacilli are most numerous
within them.  Here, too, those with bacilli are the more
recent, those without them the older cells in which the
bacilli originally present have died or have passed into a
subsequent dormant state.  Besides the ordinary bacillus
forms, we find others with two to four oval spores which
are placed at regular intervals along the bacillus [produc-
ing the pathognomonic “beaded” appearance of this distinctive
mycobacterium—JWS].18(p276)
Subsequent examinations, wherever made, confirmed
the correctness of Koch’s statement as to the constant
presence and the diagnostic value of these bacilli in
tuberculous infections.
But even this did not satisfy Koch himself.  He said:
It does not follow, however, from this coincidence of
tuberculous affliction with bacilli that both phenomena
stand in causal relation to each other, though no slight
degree of probability for this assumption is furnished by
the fact that the bacilli are found chiefly wherever the
tuberculous process is in its inception or progress, disap-
pearing where the disease comes to a standstill.4(p276)
. . . .
In order to prove that tuberculosis is a parasitic disease
caused by the immigration of the bacilli and is originally
due to their growth and increase, the bacilli must be
isolated from the body and cultivated in pure fluids until
they are freed from any possibly still adhering morbid
product derived from the animal organism, and finally,
by the introduction of the isolated bacilli into animals, the
same morbid picture of tuberculosis must be produced
which experience has shown us to result from inoculation
with tuberculous matters of natural origin.18(p276–277)
This task Koch has performed in a brilliant and abso-
lutely irrefutable manner.
The cultivations were made in sterilized, coagulated
blood serum.  They were distinguished by an exceed-
ingly slow growth which proceeds only at a temperature
of 37° to 38°C; they form minute compact scales which
can be easily detached in toto and by appropriate exami-
nation are shown to consist only of the well known,
extremely delicate bacilli.  The cultivations yielded cor-
responding results, whether the matter was derived from
animal or human tuberculosis; they were continued for
months outside of the animal body, by successive trans-
fer from serum to serum.18(p277)
But in every case inoculations of healthy animals with
the cultivation yielded a positive and constantly uniform
result—a typical inoculation tuberculosis of the
animal.18(p277)
In guinea pigs, the inguinal glands swelled after 2
weeks.  The inoculation sites on the abdomen changed
into an ulcer, and the animals emaciated.  After 32 to 35
days the animals were killed.  They all exhibited intense
tuberculosis of the spleen, liver, and lungs; the inguinal
glands were greatly swollen and cheesy, the bronchial
glands were only slightly swollen.18(p277)
In the same way rabbits, rats, cats, dogs, etc., were
successfully inoculated.  The experiments with rats and
dogs are especially interesting because these animals
have otherwise shown themselves uncommonly resis-
tant toward inoculations of tuberculosis.18(p277)
The result of the experiments is independent of the
point of inoculation: subcutaneous connective tissue,
anterior chamber of the eye, abdominal cavity, direct
introduction into the blood current, etc.  It is necessary,
owing to their exceeding slow growth, that the infectious
matters be brought to a spot where, protected from exter-
nal injury, the bacilli have the opportunity to increase
and penetrate into the tissues, otherwise the bacilli are
eliminated before they secure a habitat.18(p277)
Small shallow cutaneous incisions are no wounds appro-
priate to the invasion of bacteria.  Similar conditions will
be requisite to ensure the adherence of the bacilli which
have reached the lungs.  Probably, factors favorable to the
retention of the bacilli, such as stagnating secretions,
denudation of the mucosa of its protective epithelium,
etc., will be of assistance in effecting the infection.18(p277)
Furthermore, it appeared that the rapidity of the course
of inoculated tuberculosis, as well as its extent and spread
over the several organs, is dependent upon the larger or
smaller quantity of infectious matter introduced.  The

Military Dermatology
360
picture of acute miliary tuberculosis occurred only when
the body was at once overwhelmed, as it were, by a large
quantity of infectious organisms.  Otherwise, when but
few bacilli are inoculated, the processes are of slow
development or circumscribed locally (nodules on the
iris, opacity of the cornea, affections of the lymphatic
glands), which are very much later succeeded by general
infection, unless the disease terminates altogether with
the local process.18(p277))
[In 1882, only 2 years after the discovery of Mycobacterium
tuberculosis, Robert Koch found the tubercle bacillus in the
lesions of lupus vulgaris.  This revelation gave rise to the
concept of “localized tuberculosis of the skin.”  Sir Jonathan
Hutchinson accepted the bacillary origin of lupus, in contrast
to that of leprosy, and in a series of lectures in 1888, used the
term “apple jelly nodule” to describe their peculiar transpar-
ency.  Paul Gerson Unna later introduced the use of the
diascope, which is particularly useful in the diagnosis of lupus
vulgaris.23
In 1891, Koch recognized the reactivity of the skin to
inoculation of virulent or killed tubercle bacilli when the host
had had previous tuberculosis.  In 1906, the Viennese pediatri-
cian Clemens von Pirquet perceived that this reactivity to
killed or heated bacilli after the development of a primary
tuberculous complex was a tuberculosis specific allergy.24  In
1907, Charles Mantoux introduced the Mantoux skin test, the
standard method for determining previous exposure to tuber-
culosis.  Since that time, the tuberculin skin test has been one
of the most important methods of diagnosis of infection as well
as for determining the cellular immune status (anergic, nor-
mal, hyperergic) of the host.—JSW]
Tuberculosis in the Military
Tuberculosis has been a problem since antiquity and
for centuries was a principal cause of death in men of
military age.  Records of hospital admissions and medi-
cal discharges from military service for tuberculosis have
been maintained by the U.S. Army since the Civil War.
During that conflict, there were 13,499 tuberculosis ad-
missions and 5,286 deaths from the disease among white
soldiers.  The mean annual rate of discharge for tubercu-
losis was 8.6 per 1,000 in white troops and 3.1 per 1,000 in
black troops.  However, in neither the Civil War nor the
Spanish-American War was the disease frequent enough
to prompt any unusual comment in the analyses record-
ing the medical aspects of military operations.20(p214)
Tuberculosis in World War I
During World War I, men with tuberculosis were
detected and excluded from military service almost en-
tirely on the basis of the physical examination, as roent-
genology was in its infancy and screening skin testing
resources were not available.  There were 22,812 disabil-
ity separations because of tuberculosis during the war,
or 5.52 per 1,000 strength per annum.  The disease was
the leading cause of disability separation, accounting
for 11.1% of the total.  Further, the full magnitude of the
problem did not become evident until several years after
the war.  Goldberg (1941) calculated that the approxi-
mate expenditure by the Veterans Administration for
service-connected tuberculosis from the close of World
War I through 1940 was $1,186,000,000.  The number
of hospitalized tuberculosis beneficiaries peaked in 1922
at 44,591.20(p215)
Tuberculosis in World War II
At the beginning of World War II, the Office of The
Surgeon General recognized that drastic revision of the
physical standards in the existing Mobilization Regulations
was necessary because of technical developments in tu-
berculosis control.  In April 1939, a chest X-ray examina-
tion was required before applicants could be commis-
sioned.  As early as 1940, routine screening chest X-ray
examinations for all inductees were considered, but they
were not made a mandatory part of all physical examina-
tions at induction stations until 3 June 1941.  While
approximately 10 million men had chest X-ray examina-
tions, about 1 million were inducted without them.20(p215)
The average incidence rate of tuberculosis for World
War II from 7 December 1942 to 14 August 1945 was 1.2
per 1,000 per annum.  Tuberculosis accounted for 1.9% of
all discharges for disability from disease between 1942
and 1945, ranking 13th on the list.  Among Americans
who had been prisoners of war, the rates were higher.
Prisoners from the European theater had an incidence
five to seven times that of the U.S. Army in general.
Statistics on those returned from the Pacific area were
more difficult to obtain, but a special study of repatriated
prisoners at West Coast debarkation hospitals, directed
by The Surgeon General, showed that 2.7% of 3,742 indi-
viduals studied with chest X-ray examinations had evi-
dence of active pulmonary tuberculosis.20(p215)
Extrapulmonic forms of tuberculosis were rare.  A
total number of 140 cases of cutaneous tuberculosis were
reported by the U.S. Army between 1942 and 1945, or 0.01
case per 1,000 per year (ie, less than 1% of patients with
systemic tuberculosis).19(p369)
The semiannual report of the senior consultant in
tuberculosis in the European theater, dated 3 July 1945,
called attention to an excessive and steadily rising preva-
lence of all forms of tuberculosis in nurses for the 31⁄2
years of the war.  The mean rate for the 31⁄2 years was 3.8
times as high as the general tuberculosis admission rate
for troops in the theater.…[I]n analyzing the responsible
factors, [the report] called attention to the carelessness in
technique that develops in times of strain and stressed
the failure of medical officers to maintain proper mea-
sures, designed to prevent spread of the disease in
hospitals.19(pp342–343)
In the final weeks of the war in Germany, Allied
troops overran a large number of the notorious concen-
tration camps in which the German government impris-
oned political nonconformists, Jews, nationals of sur-
rounding states, and others who had offended the Nazi
Party.  These camps included Auschwitz, Buchenwald,

Cutaneous Tuberculosis
361
Nordhausen, Dachau, Belsen, and many others.  Thou-
sands of dead were found in the camps at the time of their
liberation, and many more thousands were sick and
dying.  Among the latter were hundreds of persons with
advanced tuberculosis, who constituted an immediate
problem for the evacuation hospitals of the advancing
armies.19(p349)
A vivid description of conditions at the Dachau con-
centration camp, and the extent of tuberculosis in hospi-
talized inmates of that camp, has been given by Piatt.25
He made a statistical analysis of 2,267 roentgenograms of
the chest of patients removed from the concentration
camp hospital and examined by X ray on admission to the
receiving and evacuation section of the 127th Evacuation
Hospital.  In only 45.3% of the films was no abnormality
discovered.  Tuberculosis, pneumonia, and heart disease
were the chief abnormalities.  Six hundred twenty-six
definite cases of tuberculosis, or 27.6% of the total num-
ber examined, were detected.  In more than half of these,
the disease was bilateral, and in four fifths of the cases,
the process was either moderately or far advanced.  In
addition to definite tuberculosis, there were 94 patients
(4.1% of the total) with pleural effusion, probably tuber-
culous in origin.  There were five cases of miliary
tuberculosis.19(p350)
Piatt, among others, expressed the view that the inci-
dence of tuberculosis in Europe would increase apprecia-
bly in the years to come as a result of the return of
numerous persons with undiagnosed active disease from
concentration camps to their homes.19(p350)
Tuberculosis in the Korean and Vietnam Conflicts
While specific incidence rates are not available for the
Korean conflict, tuberculosis continued to be a problem
for the U.S. Army, as reflected by the approximately 600
admissions per year to Fitzsimons General Hospital dur-
ing that period.20(p215)
Rightful concern was expressed about the exposure of
American troops in Vietnam to a population with a high
tuberculosis infection rate.  The conflict in Vietnam placed
an estimated 500,000 American military personnel annu-
ally in varying degrees of contact with a highly infected
population.  In 1968, a chest X-ray survey by Siegler, et al,
of Vietnamese civilians showed that 31.7% [of the popu-
lation] over the age of 15 had definite radiologic evidence
of active pulmonary tuberculosis.  Another study dem-
onstrated that nearly 100 percent of the adult population
was tuberculin skin test positive.20(p216)
Among U.S. troops, approximately 95% had had no
previous exposure to tuberculosis and were tuberculin-
negative on arrival in Vietnam.  Data from the 20th
Preventive Medicine Unit indicated that only 6.2% of 901
first-time personnel were tuberculin positive on entering
the country, whereas 13.7% of 190 personnel who had
served a previous tour in Vietnam were positive.  In the
first-tour group, breakdown by race showed that 3.2% of
whites, 7.4% of blacks, 9.1% of Orientals, and 15.6% of
Spanish-surnamed persons were tuberculin positive; a
similar racial distribution was noted in the group with
previous tours in Vietnam.20(p216)
The clinical course of tuberculosis was apparently no
different in U.S. servicemen in Vietnam than it was in
patients in the United States.  Extrapulmonary forms and
pleural effusion were uncommon.20(p218)
[Currently, from a military perspective, the incidence
of tuberculosis is highest in Africa, where estimates run
165 cases per 100,000 population.  In Asia, the estimated
incidence is 110 per 100,000.  Because the population in Asia
is much larger than Africa’s, however, the total number of
cases in Asia is thought to be 3.7 times greater.  In the western
Pacific, the highest rates occur in the Solomon Islands, the
Philippines, and South Korea, and the lowest in Australia,
New Zealand, and Japan.  Some third-world countries may
have incidences approaching 500 cases per 100,000 popula-
tion.8—JWS]
EPIDEMIOLOGY
An estimated 1.7 billion people are infected with
Mycobacterium tuberculosis: approximately one of
three living persons.26  In 1982, WHO estimated that
of the 10 million new cases of tuberculosis that
occur each year worldwide, 4 to 5 million are highly
infectious, smear-positive cases, and approximately
3 million cases prove fatal.27  In 1990, WHO esti-
mated an incidence of 7.5 million cases of tubercu-
losis and 2.5 million deaths.  HIV infection was
considered responsible for 116,000 deaths (4.2%).9
Case-fatality rates were estimated at 15% for those
receiving treatment and 55% for those receiving no
treatment.27  For the decade 1990 through 1999, 30
million deaths (12.3 million in Southeast Asia, 6
million in sub-Saharan Africa) are anticipated from
tuberculosis, with approximately 10% expected to
be associated with HIV.27
Although in most areas of the world the inci-
dence of tuberculosis is anticipated to decline or
remain stable, the incidence rates in Africa are an-
ticipated to rise by some additional 10 cases per
100,000 population per year through 2005, prima-
rily because of the HIV epidemic.9
In the United States, the large influx of immi-
grants from Southeast Asia and Haiti and the grow-
ing numbers of homeless—up to 50% of whom are
infected with tuberculosis26—have posed a new
threat to a previously well-administered tuberculo-
sis-control program.  More than 20% of the new
cases in the United States occur among the foreign-

Military Dermatology
362
born,28 virtually all of whom are from resource-poor
countries with high rates of tuberculosis.  For ex-
ample, in 1988, not only did Asians and Pacific
Islanders have the highest incidence of tuberculosis
in the United States, with 49.6/100,000 (compared
to 26.7/100,000 for blacks and 5.7/100,000 for
whites), but in addition, 93.6% of those affected
were foreign-born.29  Selected incarcerated popula-
tions are at even greater risk for developing tuber-
culosis.  For example, the incidence of tuberculosis
in New York state prisons between 1980 and 1990
was 134/100,000—almost 14-fold higher than the
national average.26
In the United States from 1963 through 1986, the
incidence of pulmonary tuberculosis declined at an
average annual rate of 5.0%; however, the incidence
of extrapulmonic tuberculosis declined only 0.9%
annually.  Immigrants from developing areas, par-
ticularly from Africa, India, tropical America, and
Southeast Asia, have been a major source of these
extrapulmonary forms.  In the United States in 1986,
only 17.5% of all cases of tuberculosis were
extrapulmonic, but of those, 71.2% of patients be-
longed to racial ethnic minorities or were foreign-
born.30  (Likewise, of patients with pulmonic tuber-
culosis, 63% belonged to racial ethnic minorities or
were foreign-born.30)
As might have been expected, some of the most
dreadful epidemics of tuberculosis have occurred
in populations who had had little or no previous
contact with the disease:
• Scrofula and pulmonary tuberculosis were
extremely rare among native Pacific Island-
ers before contact with European immi-
grants; however, within a few decades, tu-
berculosis was the cause of 40% of all deaths
in New Caledonia and Hawaii.
• The highest mortality rate on record (9,000/
100,000) occurred among the Indians of the
Qu’Appelle Valley Reservation in Western
Canada.
• Tuberculosis was both fulminant and ram-
pant in the Senegalese troops and Capetown
men who were brought to France during
World War I.  Large numbers of these sol-
diers succumbed to what was then called
“galloping consumption.”21
Cutaneous tuberculosis is also found worldwide
with higher frequency in the cooler latitudes.  How-
ever, fewer than 1% of all cases of tuberculosis are
expected to have cutaneous manifestations.19  None-
theless, with the sharp increases in AIDS, cutaneous
forms of tuberculosis such as miliary tuberculo-
sis,31,32 tuberculous abscesses,33 and scrofuloderma34
are beginning to be reported among AIDS patients.
Infection with M tuberculosis can occur from contact
with contaminated bodily fluids, secretions or dis-
charges, or through direct contact with diseased
skin.  Modes of transmission for infection include
(a) respiratory, (b) gastrointestinal (from unpas-
teurized milk from infected animals), (c) genitouri-
nary (through sexual intercourse), and (d) inocula-
tion through skin or mucous membranes (eg, the
conjunctiva).  Sources of infection include humans,
cattle, swine, dogs and cats, monkeys, and labora-
tory bacteriological cultures.  Exogenous iatrogenic
inoculation has occurred in laboratory workers.35
Social and economic conditions are important
factors in the incidence and prevalence of tubercu-
losis.  Extreme youth, old age, poverty, overcrowd-
ing, and inadequate hygiene and nutrition increase
the risk of infection, as does immunosuppres-
sion during the course of pregnancy, diabetes,
sarcoidosis, leukemia, and lymphoma.  Increased
genetic susceptibility is associated with HLA-BW15
antigen.  Treatment with cytostatic medications or
systemic glucocorticosteroids can also increase the
risk of acquisition or reactivation of pulmonary
tuberculosis.
Wars usually bring into sharp focus the inad-
equacy of hereditary resistance and immunity when
environmental stress, malnutrition, and hygienic
conditions become too formidable.  Tuberculosis
mortality increased suddenly and dramatically in
Paris during the siege by the Prussian Army in 1871.
Similarly, it increased everywhere in Europe within
a few months after two world wars began—even in
countries that did not take a direct part in the
conflict and where food was never scarce.21
Once tuberculosis is established in the host,
spread to the skin may occur by contiguous exten-
sion of underlying lymph nodes or osseous lesions,
from hematogenous or lymphatic dissemination, or
through secondary exogenous inoculation.
An epidemiological analysis published in 199036
reviewed 400 cases of tuberculosis with skin mani-
festations seen in hospitals in Poland over the past
25 years.  Of these, 268 (67%) had tuberculosis of the
skin and 132 (33%) had tuberculids (which are dis-
cussed later in this chapter).  The investigator noted
that the prevalence of skin tuberculosis was 5.8-fold
lower during the period 1983 through 1987 than it
had been during the period 1963 through 1967.  The
frequency of the different forms of tuberculosis
were as follows: lupus vulgaris (57.5%), scrofu-
loderma (35.4%), verrucous tuberculosis (4.5%), and

Cutaneous Tuberculosis
363
ulcerative tuberculosis (2.6%).  The male-to-female
ratio was 1:2.05.  Women were more likely to have
lupus vulgaris or scrofuloderma, while men more
frequently had verrucous or ulcerative tuberculo-
sis.  The young more frequently had scrofuloderma
and the elderly more frequently had lupus vulgaris.
In western Algeria, 45 cases of cutaneous tuber-
culosis were diagnosed from March 1981 through
December 1987.  Both sexes were equally repre-
sented.  The different forms of tuberculosis were
seen in the following frequency: lupus vulgaris
(28.8%), scrofuloderma (28.8%), specific adenitis
(13.3%), verrucous tuberculosis (13.3%), tubercu-
lous gumma (13.9%), and ulcerative tuberculosis
(2.2%).  The tuberculin skin test was positive in 86%
of the cases.37
The bacterium M tuberculosis measures 2.5 to 3.5
µm in length by 0.3 to 0.6 µm in width.  This slightly
curved, sporeless, motile, obligate aerobic, Gram-
positive bacterium is acid-, alkali-, and alcohol-fast.
It has a high lipid content and a slow growth rate.
Its peptidoglycan skeleton contains approximately
30 different antigenic substances, of which the most
important is the tuberculoprotein, the active com-
ponent of tuberculin, which is the agent used for
intradermal testing for delayed hypersensitivity.
Within the cell wall of M tuberculosis may lie all of
the elements associated with tuberculosis, includ-
ing the factors responsible for caseation and other
features of hypersensitization, the antigens respon-
sible for humoral immunity, the agents of toxicity,
and, indeed, the very antigens implicated in protec-
tive immunity.38
There are two types of M tuberculosis—human
and bovine—but apparently no clinical difference
between infections caused by either type.  Bacille
bilié de Calmette-Guérin (BCG) is an attenuated
strain of the bovine form that is used for vaccination
in many parts of the world.  In a prospective series
of 70 patients with cutaneous tuberculosis that was
published in 1989,39 researchers were able to culture
M tuberculosis (using a concentration procedure from
biopsy tissue homogenates inoculated on Lowen-
stein-Jensen medium) from 24 of 70 (34.03%) of
their patients overall: from 4 of 30 (13.3%) patients
with lupus vulgaris, 3 of 7 (42.85%) patients with
verrucous tuberculosis, and 17 of 33 (51.05%) pa-
tients with scrofuloderma.
Tubercle bacilli grow in 3 to 4 weeks when cul-
tured on Lowenstein-Jensen medium.  In contrast,
guinea pig inoculation requires 6 to 7 weeks for
confirmation.
BACTERIOLOGY
The histopathological inflammatory reactions to
M tuberculosis can be organized along an immuno-
pathological spectrum, as can be done with leprosy.
A sequence from nonnecrotic epithelioid cell granu-
lomas with no acid-fast bacilli (high-immune),
through necrotic epithelioid granulomas with some
acid-fast bacilli, to necrosis with abundant acid-fast
bacilli (low-immune) can be arranged.  Lupus
vulgaris typifies the high-immune pole; tuberculo-
sis cutis orificialis and acute miliary tuberculosis,
the low-immune pole.
A similar immunopathological spectrum has been
devised for cutaneous tuberculosis, extending from
lupus vulgaris toward scrofuloderma through tu-
berculosis verrucosa cutis.40
In the classic case, the hallmark of the histopatho-
logical diagnosis of cutaneous tuberculosis is the
presence of tuberculous or tuberculoid granulomata.
However, the diagnosis may be missed if one
searches solely for the classic tuberculoid gran-
ulomata.41  Seven additional patterns of inflamma-
tion have been described42:
• Classic tuberculoid granulomas, which con-
sist of typical granulomas with Langhans’-
type giant cells.  A peripheral cuff of inflam-
matory cells, predominantly lymphocytes,
surrounds the giant cells.  Caseation necro-
sis may or may not be present (Figure 15-1).
• Abscess formation, which consists of acute
or chronic (or a mixture of both) inflamma-
tory cells with variable degrees of necrosis.
The amount of fibrosis varies during the
healing phase.  Giant cells are present in
some cases only.
• Diffuse infiltration of histiocytes, in which
the infiltrate is composed primarily of his-
tiocytes; few other types of inflammatory
cells are present.  Only a few well-formed
granulomas are seen.  Necrosis is universal.
HISTOPATHOLOGY

Military Dermatology
364
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taneous tissue, or both, of central necrosis
surrounded by palisading histiocytes.  A
mild, chronic, inflammatory infiltrate may
be present, and giant cells are occasionally
seen.
Several points must be emphasized when con-
sidering these patterns of inflammation: (1) The
patterns do not correlate with either a specific my-
cobacterium or a specific clinical presentation.  In
fact, subsequent biopsies in the same patient may
show a different pattern.  (2) These patterns are not
pure but represent a spectrum of changes; the pat-
terns may be seen in any combination.  (3) Patients
with mycobacterial infections do not always present
with tuberculoid granulomas, nor does the pres-
ence of tuberculoid granulomas necessarily indi-
cate cutaneous tuberculosis.  Infections (eg, syphi-
lis) and noninfectious granulomas (eg, zirconium
granuloma) may give identical histological patterns.
The sections that follow give the clinical presen-
tations of diseases caused by M tuberculosis.  The
histological descriptions given are those most com-
monly encountered for each of the clinical entities;
however, the general patterns given above must be
kept in mind.
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• Panniculitis, which is unusual in that both
septae and lobules are involved.  The infil-
trate may be an acute inflammation, a chronic
inflammation, or both.  Abscess formation may
occur as well as necrosis.  Phlebitis can be
found rarely.  One reported case42 exhibited
acid-fast bacilli in the vascular endothelium.
• Nonspecific chronic inflammation, which
includes sheets or scattered clusters of
chronic inflammatory cells consisting pre-
dominantly of lymphocytes and histiocytes.
However, other cell types, including plasma
cells and eosinophils, can be seen.  Giant
cells are absent in this pattern.
• Sarcoidal granulomas, which are classically
described as “naked” granulomas, due to
the absence of peripheral inflammatory cuff-
ing of the granulomas by lymphocytes.  The
granulomas in this pattern consist primarily
of Langhans’-type giant cells with little or
no lymphocytic cuffing.  Necrosis is mini-
mal or absent.  Lamellar calcifications iden-
tical to Schaumann bodies are sometimes
present (Figure 15-2).
• Rheumatoid-like nodules, the hallmark of
which is the presence in the dermis or subcu-
Fig. 15-1. Classic tuberculoid granuloma, seen on low-
power magnification. Note foci of caseation necrosis and
Langhans’-type giant cells.
Fig. 15-2. Lupus vulgaris, seen on medium-power mag-
nification. In this sarcoidal-type granuloma, the periph-
eral rim of lymphocytes, which is typical of lupus vulgaris,
helps to differentiate it from sarcoidosis.
Numerous attempts have been made to classify
cutaneous tuberculosis based on clinical morphol-
ogy, etiology, the immune status of the host, and so
forth.  Morphologic classification is unsatisfactory
because similarly appearing skin lesions can have
multiple causes and can differ histologically.
 Classifications based on etiology or immune status
are not helpful clinically.  Confusion abounds
CLASSIFICATION

Cutaneous Tuberculosis
365
regarding chronic, reactivation, and reinfection
tuberculosis; however, the complexities of cutane-
ous tuberculosis can be classified and the
general pathogenesis described (Table 15-1 and
Figure 15-3).
Primary Inoculation Tuberculosis
Primary inoculation tuberculosis is also called
tuberculous chancre, cutaneous primary complex,
and tuberculosis primaria cutis.43  This infection
with the tubercle bacillus develops as a result of
inoculation of M tuberculosis into the skin or mucosa
of a nonimmune host.  (Immunity can be conferred
by previous infection or BCG immunization.)  An
initial negative reaction to purified protein deriva-
tive of tuberculin (PPD) reflects the host’s absent
immunity.
Epidemiology
Inoculation tuberculosis accounts for only 5%
of total primary tuberculosis; the majority of pa-
tients have (a) respiratory exposure with the subse-
quent formation of a Ghon complex or (b) gas-
trointestinal exposure.44  Because M tuberculosis
cannot penetrate intact human skin, some sort of
injury must be present for an infection to be estab-
lished.  Portals of entry often include such minor
injuries as abrasions, puncture wounds, hangnails,
and pyodermas.  Overall, children are most fre-
quently affected with primary inoculation tubercu-
losis, with the face and exposed extremities being
sites of predilection.  (The most famous example of
inoculation tuberculosis, the “prosector’s wart,”
albeit a secondary or reinfection tuberculosis, was
frequently acquired by pathologists in years past
from handling tuberculous lungs or other tissues
without protective gloves at the autopsy table.)
Tuberculous chancres have also followed b’rit milah
(ritual circumcision), cardiopulmonary resuscita-
tion, tattoos, inoculations and injections for immu-
nization or therapy, ear piercing, venipuncture,
misinoculation of laboratory animals, and sexual
intercourse.  Inoculation can also occur in the mu-
cous membranes of the oral cavity after tooth ex-
traction, in the tonsils from ingesting nonpasteurized
milk, or in the ocular conjunctiva during ocular
surgery.43,44  Recently, primary inoculation tubercu-
losis has been reported following a needlestick in-
jury from a patient with AIDS and undiagnosed
tuberculosis.45
TABLE 15-1
CLASSIFICATION OF CUTANEOUS TUBERCULOSIS
Stage
Source
Mode
Histology
Course
Disease
Immunity
Bacilli
Primary
Exogenous
Inoculation
Nonspecific
Localized
Chancre
Developing
+++
TB specific
Localized
Primary TB complex
Good
+?
TB specific
Localized
Lupus vulgaris
Moderate
++
TB specific
Progressive
TB fungosa serpiginosa
Poor
+++
TB specific
Generalized
Miliary TB
Poor
+++
Secondary
Exogenous
Reinoculation
TB specific
Localized
TB verrucosa cutis
Good
+/–
TB specific
Progressive
TB cutis orificialis
Poor
+++
Endogenous
Contiguous
TB specific
Localized
Lupus vulgaris
Moderate
++
TB specific
Localized
Scrofuloderma
Poor
+++
Autoinoculation TB specific
Localized
TB verrucosa cutis
Good
+/–
TB specific
Progressive
TB cutis orificialis
Poor
+++
Hematogenous
TB specific
Localized
Lupus vulgaris
Moderate
+++
TB specific
Localized
Gumma (subcutaneous
abscess)
Moderate
++
TB specific
Localized
Ulcerative TB
Moderate
++
TB specific
Progressive
TB fungosa serpiginosa
Poor
+++
TB specific
Progressive
TB cutis orificialis
Poor
+++
TB specific
Generalized
Miliary TB
Poor
+++
Tuberculid Endogenous
Hematogenous
Variable
Localized
Erythema induratum
Moderate-to-good –/+
Variable
Scattered crops Papulonecrotic tuberculid Moderate-to-good –/+
Variable
Generalized
Lichen scrofulosorum
Moderate-to-good –/+
+++: numerous bacilli:   ++: some bacilli;   +/–: bacilli rarely found;   –/+: unusual to find bacilli;   +?: variable, depending on time course

Military Dermatology
366
Erythema
Induration
Tubercle Bacilli
Scrofuloderma
Autoinoculation
Tuberculids
Papulonecrotic
Tuberculid
Lichen
Scrofulosorum
Host with good
immunity
PPD convertor
Complete
healing
Reinoculation
Verrucous TB
Contiguous
spread
Lupus Vulgaris
Lupus Vulgaris
Gumma
(subcutaneous
abscess)
Inoculation: skin,
lungs, GI tract,
lymph nodes
Host with
moderate
immunity
Hematogenous
dissemination
Ulcerative TB
Tuberculids
Erythema
Induratum
Papulonecrotic
Tuberculid
Lichen
Scrofulosorum
Contiguous
spread
Orificial TB
Host with poor
immunity
Hematogenous
dissemination
TB Fungosa
Serpiginosa
Orificial TB
Acute Miliary
TB
Fig. 15-3. General pathogenesis of cutaneous tuberculosis
Chancre, primary
TB complex

Cutaneous Tuberculosis
367
Clinical Features
After an incubation period of 3 to 4 weeks follow-
ing inoculation, a small inflammatory papule de-
velops, which quickly breaks down into an indo-
lent, firm, nontender, sharply delimited ulcer with
no tendency for spontaneous healing for several
weeks (Figures 15-4 and 15-5).  After 3 to 8 weeks,
tubercle bacilli reach the regional nodes, producing
a painless lymphadenitis.  This ulceroglandular
complex is the prototype of primary inoculation
tuberculosis, the skin analog to the primary pulmo-
nary Ghon complex.  The PPD usually becomes
positive following the development of lymph-
adenopathy, although early treatment may prevent
conversion.
Laboratory and Histological Features
Tuberculin testing is negative early in the course
of disease.  Conversion will usually occur at the
time that lymphadenopathy becomes apparent.
Fig. 15-4. A painless, well-circumscribed ulcer of pri-
mary inoculation tuberculosis is seen on the nose of a
child.
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Fig. 15-5. A well-circumscribed, indolent, nontender,
clean ulcer (1.5 x 3.0 cm) of primary inoculation tubercu-
losis is seen on the right lateral thigh of a child.
The earliest histological sign of primary inocula-
tion tuberculosis is that of an acute neutrophilic
reaction with areas of necrosis, ulceration, and the
presence of numerous tubercle bacilli.  After 3 to 6
weeks, immunity usually develops and the infil-
trate becomes granulomatous.  Epithelioid cells,
Langhans’-type giant cells, and a peripheral rim of
lymphocytes are present.  Caseation necrosis may
develop with a subsequent decrease in the number
of tubercle bacilli.  Changes in the lymph nodes are
similar.
Course and Prognosis
After 1 to 3 months, the primary lesion usually
heals with scarring.  Rarely, the condition may last
up to 1 year.  In patients with poor immunity and
large bacterial load, acute miliary tuberculosis can
develop, with a fatal course.  Usually, however,
satisfactory host immunity with a high degree of
tuberculin sensitivity result.  Nonetheless, latent
foci of infection can later reactivate locally or shed
organisms hematogenously to distant sites.  By these
mechanisms, lupus vulgaris or even tuberculosis
verrucosa cutis may develop as late sequelae of
primary inoculation tuberculosis.  Regional lymph
nodes may liquefy, producing scrofuloderma.  In as
many as 10% of patients, erythema nodosum may
develop as a nonspecific hypersensitivity reaction.
Differential Diagnosis
The differential diagnosis of primary inoculation
tuberculosis includes primary syphilis, tularemia,
cat-scratch disease, sporotrichosis, and other

Military Dermatology
368
ulceroglandular infectious diseases.  Dark-field
microscopy can confirm syphilis.  The clinical set-
ting and culture of lesional tissue are most useful
for distinguishing the other conditions.
Tuberculosis Verrucosa Cutis
Tuberculosis verrucosa cutis, a verrucous (ie,
wartlike) form of reinfection tuberculosis, is also
called warty tuberculosis, prosector’s wart, verruca
necrogenica, tuberculosis cutis verruca, postprimary
inoculation tuberculosis, and verrucous tuberculo-
sis.  The disease occurs when the skin of a previ-
ously infected or BCG-immunized (sensitized) host,
who possesses a moderate or high degree of immu-
nity, is subjected to exogenous reinfection with
tubercle bacilli.
Epidemiology
Reinoculation occurs at sites of minor abrasions
or wounds.  In the past, tuberculosis verrucosa cutis
was an important occupational hazard for physi-
cians, pathologists, medical students, laboratory
attendants, and so forth, who were infected by
tuberculous patients or by autopsy material.  Vet-
erinarians, farmers, and butchers are likewise sus-
ceptible to infection from tuberculous cattle.
Autoinoculation from tuberculous sputum rarely
occurs.
Clinical Features
The initial lesion of tuberculosis verrucosa cutis
is a painless, dusky red, firm papule or papulo-
pustule that expands peripherally and is surrounded
by an inflammatory halo that develops at the site of
inoculation.  It quickly develops a verrucous
keratotic surface.  By gradual, irregular, centrifugal
expansion and growth, along with spontaneous
central resolution, a polycyclic, serpiginous, or an-
nular plaque with a warty, advancing border and
central area of atrophy develops (Figure 15-6).  Ar-
eas of softening, especially in the center, may be
present.  Pus and keratinous material may be ex-
pressed from the fissures in the warty areas.  Le-
sions occur on areas exposed to trauma.  Hands and
fingers are most common sites in the West, but the
lower extremities are affected most frequently in
the East.  The classic lesion is solitary, but multiple
lesions also occur.  Lymphadenopathy is character-
istically absent.  Lymph node enlargement, when
present, may be the result of secondary infection.
The lesions rarely ulcerate, and spontaneous invo-
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Fig. 15-6. Tuberculosis verrucosa cutis on the dorsal
surface of the left hand, demonstrating a large, warty-
appearing plaque with central clearing
lution may occur over months to years.
Some of the documented unusual clinical presen-
tations of tuberculosis verrucosa cutis are perianal
ulcerations from gastrointestinal inoculation, scle-
rotic masses, fungating granulomas, disseminated
tuberculosis with cutaneous and pulmonary in-
volvement in an immunocompetent patient, and
multifocal guttate tuberculosis verrucosa cutis.43
Laboratory and Histological Features
Tuberculin testing usually shows a moderate-to-
marked positive reaction.
Hyperkeratosis, hypergranulosis, acanthosis, and
papillomatosis of the epidermis are present in tu-
berculosis verrucosa cutis.  Abscesses form at the
dermo–epidermal junction and in the superficial
dermis.  Variable numbers of tuberculoid granulo-
mas with a modest amount of caseous necrosis and
a few acid-fast bacilli are seen in the mid-dermis.
With time, marked fibrosis occurs.
Course and Prognosis
Lesions may evolve and last for years or even
decades.  Overall, the prognosis is good.
Differential Diagnosis
The differential diagnosis of tuberculosis
verrucosa cutis includes iododerma and bromo-
derma, chronic vegetative pyoderma, squamous
cell carcinoma, verrucous carcinoma, North Ameri-
can blastomycosis, chromoblastomycosis, verrucous

Cutaneous Tuberculosis
369
Course and Prognosis
The general prognosis of miliary tuberculosis of
the skin is poor: it is usually a harbinger of death
due to overwhelming infection.  However, with
aggressive therapy, a few survive.  In patients whose
internal manifestations do not prove fatal, sponta-
neous healing occurs with significant scarring as a
sequela.
Differential Diagnosis
The differential diagnosis includes Letterer-Siwe
syndrome, pityriasis lichenoides acute et vari-
oliformis, secondary syphilis, and drug reactions.
The Venereal Disease Research Laboratory test
(VDRL, with prozone check) and biopsy are defini-
tive.
Scrofuloderma
Scrofuloderma, a subacute form of tuberculosis
that occurs in patients who have already evolved
through a primary tuberculous complex, is also
called tuberculosis colliquativa cutis and tubercu-
lous gumma.  The disease usually originates as a
tuberculous process of the subcutaneous tissues
leading to the formation of cold abscesses and then
secondary breakdown of the overlying skin.  The
tuberculous foci are commonly in the lymph nodes,
bones and joints, and epididymis.
Epidemiology
In earlier times, scrofuloderma was common in
children—80% following an oral or tonsillar pri-
mary inoculation of bovine tuberculosis from
infected milk.24  The elderly are also susceptible,
particularly when their immune defenses are com-
promised.  True tuberculous lymphadenitis is
becoming less common in children and is more
often due to atypical mycobacteria: M avium, M
intracellulare, or M scrofulaceum.43  Scrofuloderma
occurs rarely from the introduction of exogenous
tubercle bacilli into the subcutis by trauma, or by
injections into individuals with previous latent or
manifest tuberculosis.
Clinical Features
Patients with the initial lesion present with a
firm, subcutaneous or deep cutaneous swelling or
nodule, which is freely movable initially but soon
firmly attaches to the skin and later ulcerates.  The
atypical mycobacterial infection, verrucous lupus
vulgaris, and tertiary syphilis.  Consequently, bi-
opsy, culture, and macroscopic and microscopical
examination for aggregated colonies of organisms
(ie, grains) in exudates, when present, help to dis-
tinguish among these entities.
Miliary Tuberculosis of the Skin
Miliary tuberculosis of the skin, a rare form of
acute or subacute cutaneous tuberculosis, is also
called tuberculosis cutis miliaris disseminata, tu-
berculosis cutis miliaris acuta generalisata, and dis-
seminated miliary tuberculosis of the skin.  This
disease occurs primarily in infants or children and
is caused by hematogenous dissemination of M
tuberculosis from an internal focus of disease, usu-
ally pulmonary or meningeal, often following in-
fections that reduce the host immune response (eg,
measles).  Tuberculin sensitivity is usually absent
and bacterial load very high.
In the United States during the period 1963
through 1986, of the 22,506 cases of tuberculosis
reported, 289 cases (0.01%) were of miliary tubercu-
losis.30  Several cases associated with AIDS have
been reported.31,32,46
Clinical Features
Disseminated lesions occur on all parts of the
body with predilection for trunk, thighs, buttocks,
and genitalia.  The mucous membranes of the mouth
can also be affected.  The primary lesions erupt as
discrete, pinhead-sized, bluish red–to–brownish red
macules or papules, often with a hint of purpura.
They may be capped with minute vesicles, which
soon burst and desiccate to form crusts.  The lesions
are often densely packed.  Other forms of lesions
may accompany the eruption, including macules,
large pustular lesions, ulcerations, subcutaneous
nodules, and purpuric lesions.  All of these lesions
are bacteria rich.
Laboratory and Histological Features
Tuberculin testing is almost always negative.
The characteristic features of miliary tuberculo-
sis of the skin are (a) focal areas of necrosis and
(b) abscess formation containing numerous
tubercle bacilli.  These may be surrounded by a
zone of macrophages.  Bacilli may also be found
intravascularly.  If and when immunity develops,
lymphocytic cuffing of the vessels and tubercles
can be seen.

Military Dermatology
370
ulcers tend to have bluish, undermined edges and
soft, granulating floors.  Watery, purulent, or caseous
discharge may exude from the sinuses.
Cervical lymph nodes are infected most com-
monly on the side of the neck where the primary
tuberculous complex was located (Figures 15-7 and
15-8).  In the neck, the tonsillar, submandibular,
preauricular, postauricular, occipital, and supra-
clavicular lymph nodes are usually implicated.  The
parasternal, axillary, inguinal (Figure 15-9), and
epitrochlear nodes are potential sites, as well.  In
adults who have scrofuloderma, multiple lesions
may form through hematogenous dissemination,
especially on the trunk and pubic and buttock re-
gions.  Patients with lesions on the buttocks present
with liquefying abscesses, fistulae, and purulent
drainage resembling hidradenitis suppurativa.24
Occasionally, discharging sinuses may occur over
areas normally devoid of nodes.  Over weeks to
months the nodes enlarge, turn livid red, suppu-
rate, then perforate with resultant ulceration and
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Fig. 15-7. Scrofuloderma of the left cervical lymph nodes
in a Central American adolescent male. Note the en-
larged lymph nodes immediately inferior to the man-
dible and the multiple, perforating sinus tracts.
OK to put on the Web
Fig. 15-8. Scrofuloderma of long-standing duration in the
neck. Note the boggy, edematous skin surrounding a
number of perforating sinus tracts.
fistula formation.  Over time, multiple fistulae form;
severe, cordlike scarring bridges the ulcerations.
Spontaneous healing does occur, but it takes years
before it is completed.  Cordlike keloidal scars and
localized recurrences are characteristic.
Laboratory and Histopathological Features
Tuberculin sensitivity is usually marked.  Mas-
sive ulcers and abscesses form in the center of the
lesion.  Tuberculoid structures with marked
caseation necrosis are present in the lower dermis
and at the periphery of the ulcerations or abscesses.
Epithelioid cells form the major component.  A
OK to put on the Web
Fig. 15-9. Scrofuloderma of the left inguinal lymph
nodes showing subcutaneous swelling and purulent
ulceration

Cutaneous Tuberculosis
371
large number of giant cells are present.  Acid-fast
bacilli are easily identified.  As the lesion ages,
caseation necrosis occurs and the number of organ-
isms decreases.  Occasionally, granuloma forma-
tion may not be apparent and the sections may only
show a nonspecific, chronic, inflammatory infiltrate.
Course and Prognosis
Scrofuloderma is usually associated with mani-
fest tuberculosis elsewhere in the body, usually in
the lungs and occasionally in the abdomen.  Lupus
vulgaris may occur at the site, in the vicinity, or in
the scar of scrofuloderma.  Malignant change in the
form of an epithelioma can occur, and the very
infrequent association of cutaneous tuberculosis
with systemic amyloidosis was reported in a case of
scrofuloderma.43
Differential Diagnosis
The differential diagnosis includes tertiary syphi-
lis, deep fungi (eg, sporotrichosis, actinomycosis,
severe acne conglobata, hidradenitis suppurativa),
and chronic granulomatous disease.  Biopsy and
culture are the definitive tests for the diagnosis.
Tuberculosis Cutis Orificialis
Tuberculosis cutis orificialis is also called orifi-
cial tuberculosis and tuberculosis ulcerosa cutis et
mucosae.  Orificial tuberculosis is the tuberculosis
of the mucous membranes and the skin of the ori-
fices, resulting from autoinoculation of the tubercle
bacilli in patients with advanced visceral tuberculo-
sis.  Its occurrence by lymphatic or hematogenous
extension is rare.
Epidemiology
Tuberculosis cutis orificialis affects men more
often than women and is most prevalent in middle-
aged or older individuals.  The underlying disease
is advanced pulmonary, intestinal, or genitouri-
nary tuberculosis.  At a traumatized site, bacilli that
are shed from these foci become inoculated into the
mucocutaneous areas of the orifices.
Clinical and Diagnostic Features
Ulcerative lesions of tuberculosis cutis orificialis
occur in the oral cavity and the perineal or perirectal
areas.  The tongue—particularly its tip and lateral
margins—is the site most commonly affected in the
mouth.  Other sites in the mouth are the soft and
hard palate, lips, and in a tooth socket after extrac-
tion.  In a patient with intestinal tuberculosis, the
area on and around the anus is involved; with
genitourinary tuberculosis, the vulva, glans, penis,
and urinary meatus are involved.  The lesion con-
sists of a small, yellowish or reddish nodule that
rapidly breaks down to form an exquisitely painful,
shallow ulcer with bluish, undermined edges.  The
surrounding mucosa is swollen and the ulcer is
covered by pseudomembranous material.  Ulcers
do not heal spontaneously and are signs of a poor
prognosis.43
Cutaneous hypersensitivity to tuberculin in these
patients is controversial; however, there is an abso-
lute consensus that such patients ultimately de-
velop anergy.
Histologically, in most cases, tuberculoid infil-
trates with pronounced necrosis are found deep in
the dermis.  Acid-fast bacilli are easy to demon-
strate.  Ulceration and edema are the rule.
Lupus Vulgaris
Lupus vulgaris, also called tuberculosis cutis
luposa, is a reinfection tuberculosis of the skin oc-
curring in previously sensitized individuals who
have a high degree of tuberculin sensitivity.  The
disease may have protean and dramatic clinical
presentations.  Hypersensitivity to tuberculin is
high, although immunity is low to moderate.
Epidemiology
Lupus vulgaris is not only the most frequent type
of cutaneous tuberculosis, it also has the greatest
potential for disfigurement.  Worldwide, approxi-
mately 50,000 new cases are diagnosed each year,
and women tend to be affected twice as commonly
as men.24  Patients are usually tuberculin positive.
As many as two thirds of patients with lupus
vulgaris are found to have visceral foci of tubercu-
losis.  Of these, 40% have tuberculous adenitis or
involvement of the mucous membranes, and 10% to
20% have pulmonary, bone, or joint tuberculosis.43
Pathogenesis
Lupus vulgaris is a cutaneous form of postpri-
mary tuberculosis.  Because it may develop in the
site of primary inoculation tuberculosis, in the scar
of scrofuloderma, or after BCG immunization (par-
ticularly after multiple BCG vaccinations), it is likely
that lupus vulgaris arises from a latent focus of

Military Dermatology
372
tuberculosis that is triggered into activity by later
trauma or injury.  Alternatively, the disease can
arise from the perforation of tuberculous abscesses
into the skin or from endogenous dermal inocula-
tion of tubercle bacilli (via lymphatic or hematog-
enous metastasis) from a reactivated focus in an
internal organ.
Clinical Features
In western countries, lupus vulgaris is most com-
mon on the face, especially the nose and cheeks,
followed by the ears, the extensor surfaces of the
extremities, the buttocks, and the breasts.  How-
ever, in India and many developing nations, the
lower extremities, especially the buttocks, are the
primary site of involvement.  It is exceedingly rare
for the mucous membranes to be involved.
The initial lesions are usually solitary.  Occasion-
ally, two or more foci can occur.  Rarely, in the case
of a preceding period of anergy, disseminated le-
sions may occur, resulting in lupus vulgaris
postexanthematicus.
Clinically, the earliest lesion appears as small,
brownish red papules of soft gelatinous consis-
tency, often resembling a small hemangioma.  On
diascopy, the characteristic translucent, apple jelly–
colored lupoid infiltrates may be demonstrable (Fig-
ure 15-10), although they are rarely seen in the
tropics because of the natural dark color of the skin
of the indigenous populations.  From these small
granulomas, the various forms of lupus vulgaris
develop over the course of years.
As the lesions enlarge, caseation necrosis pro-
Fig. 15-10. The lesions of lupus vulgaris on this patient’s
nose show the characteristic apple jelly–colored papules
on diascopy.
OK to put on the Web
OK to put on the Web
Fig. 15-11. (a) An extensive plaque of lupus vulgaris can
be seen on the patient’s thigh. (b) A closer view of same
patient shows an active border, relative central clearing,
and new papules in previously cleared areas.
b
a
OK to put on the Web
ceeds, resulting in softening of the lesions. Probing
with a blunt instrument at this stage may cause
lesions to perforate.  With time, the lesions become
more infiltrated, elevated, and brown.  They grow
by peripheral extension and are accompanied by

Cutaneous Tuberculosis
373
central atrophy or scarring (Figures 15-11 and 15-
12).  The reactivation of nodules within previously
atrophic or scarred areas (ie, fresh papules may
appear in old areas) is characteristic of the disease.
A few sentinel lupus nodules may be present at the
periphery on the normal skin.  Lesions are usually
asymptomatic.
Several clinical variants are seen:
• Lupus vulgaris exfoliativus is characterized
by plaques with a psoriatic scale.  Over time,
serpiginous or polycyclic configurations may
develop with central clearing and atrophy.
Large plaques will have both (a) active scaly
and (b) scarred and/or atrophic nonscaly
areas.47
• Lupus vulgaris verrucosus results from a
wartlike pseudoepitheliomatous hyperplasia
of the epidermis.
• Lupus vulgaris ulcerosus forms when mas-
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Fig. 15-12. Lupus vulgaris on the neck and back. Scarring
with severe hypopigmentation and an active, advancing
margin, especially over the left scapula, can be seen.
sive necrosis occurs within the tuberculous
granulomas.  This ulcerative variant may be
accompanied by deep destruction of under-
lying tissues and cartilage.
• Lupus vegetans (also called lupus papil-
lomatosus) is a vegetative form of lupus
vulgaris that often occurs in regions of ero-
sive or ulcerative disease.
• Lupus vulgaris postexanthematicus is a dis-
seminated papular or nodular form that usu-
ally arises during a period of anergy or wan-
ing immunity (eg, following measles).
• Lupus vulgaris of the mucous membranes is
a rare and special form of lupus vulgaris
arising in the mucous membranes by direct
extension of skin lupus to the buccal, nasal,
or conjunctival mucosa.  This form can be
highly destructive and disfiguring.
Laboratory Features
Bacilli in lupus vulgaris are few and sparse.  In-
oculated guinea pigs usually succumb to dissemi-
nated tuberculosis at the anticipated time when
inoculated with lesional tissue.  Tuberculin testing
is usually positive.  The recent use of polymerase
chain reaction (PCR) techniques to diagnose the
presence of M tuberculosis deoxyribonucleic acid
(DNA) in formalin-fixed, paraffin-embedded tissue
within approximately 2 days promises to greatly
facilitate the diagnosis of this and other forms of
cutaneous tuberculosis.48
Diagnosis of the internal focus of tuberculosis
may be aided by modern methods such as
sonography, computerized tomography, and mag-
netic resonance imaging.
Histological Features
The most prominent histological feature of lupus
vulgaris is the presence of granulomas, usually in
the upper dermis, composed of epithelioid cells,
Langhans’-type giant cells, mononuclear cells, and
a peripheral zone of lymphocytes.  Epithelioid cells
and lymphocytes predominate.  Caseation necrosis
is uncommon and minimal.  Bacilli are difficult to
find.  Secondary epidermal changes (eg, atrophy,
ulceration, acanthosis, or pseudoepitheliomatous
hyperplasia) may be present.  Occasionally, squa-
mous cell carcinoma may be present.  Foreign-body
granulomas may develop.  Occasionally, the necro-
sis and ulceration are accompanied by nonspecific
inflammatory infiltrates, which may mask the tu-
berculous character of the disease.

Military Dermatology
374
Course and Prognosis
Lupus vulgaris can be a very protean, destructive
disease.  In the absence of treatment, it may progress
slowly over years or even decades.  Because of its
relatively slow progression, the disease is usually
present for more than 5 years before a definitive
diagnosis is made.  Yet, the lesions remain essentially
noncontagious (although the underlying organ tuber-
culosis may be quite contagious).  Severe scarring and
disfigurement of cosmetic areas may occur (eg,
ectropion, distortion of the mouth, or destruction of
the nose).  Where scarring encompasses an entire
lower extremity, distal elephantiasis can develop.
The most critical areas where severe mutilation can
result tend to be the face, hands, and feet.
Patients with pulmonary tuberculosis in combi-
nation with lupus vulgaris have a 4- to 10-fold
higher mortality rate than patients with pulmonary
tuberculosis alone.49
Long-standing lupus vulgaris can be complicated
by the development of squamous cell carcinoma.
Other tumors are exceedingly rare during the course
of lupus vulgaris but can include basal cell carci-
noma, sarcoma, and Hodgkin’s disease.
Tuberculids such as lichen scrofulosorum and
papulonecrotic tuberculid can be seen in conjunc-
tion with lupus vulgaris.
Differential Diagnosis
Although the presence of apple jelly nodules
is characteristic of lupus vulgaris, it is not
pathognomonic.  Other diseases with similar lupoid
infiltrates that look like apple jelly nodules include
lupoid leishmaniasis, sarcoidosis, lupoid rosacea,
lupus erythematodes lupoide, pseudolymphoma
of the skin, chronic granulomatous disease, and
Spitz nevi.  The real identification of a lupoid infil-
trate as lupus vulgaris is done with a blunt probe,
which easily breaks through the overlying epider-
mis into the nodule due to the caseous necrosis
present in the lesions.  Biopsy with special stains
for organisms and culture are important diagnost-
ic procedures to differentiate these other lupoid
conditions.
Other Rare Forms of Cutaneous Tuberculosis
Tuberculous Gumma
Tuberculous gumma (also called metastatic tu-
berculous abscess) is a rare form of tuberculosis that
results from hematogenous spread from a primary
focus of infection during periods of bacillemia and
lowered resistance.50  The disease usually occurs in
malnourished children, and immunodeficient or
immunosuppressed patients.  The lesions are single
or multiple, cold, subcutaneous nodules, which liq-
uefy into nontender abscesses and perforate the
skin, forming ulcers and sinus tracts.  Tuberculin
sensitivity is modest.  Occasionally, the lesions
mimic the lymphatic spread of sporotrichosis.  With
the spread of HIV infection, atypical forms of many
infectious diseases are being seen, including tuber-
culosis.  Several cases of isolated subcutaneous ab-
scesses arising through hematogenous spread have
been reported, two of which follow.
Case 1.—A 58-year-old, immunocompetent male pre-
sented with a 9-month history of several disseminated
subcutaneous ulcerative nodules, fever, and weight loss
associated with pulmonary tuberculosis.  Large skin biop-
sies grew M tuberculosis in 6 to 8 days, whereas sputum
samples and smaller biopsies grew out in 4 weeks.  These
lesions seemed to represent a type of hematogenous dis-
semination intermediate between classic cold abscesses
(gumma) and acute miliary tuberculosis of the skin.51
Even in areas where tuberculosis is endemic, ulcer-
ative forms are extremely rare and are often misdi-
agnosed because the physician has a low index of
suspicion.
Case 2.—A 19-year-old Filipino male presented with
(a) a 2-month history of persistent, dry cough; general
malaise; and 7-kg weight loss, despite good appetite; and
(b) a 5-month history of an enlarging, painful, purulent
ulcer 4- x 8-cm in diameter, in the midlumbar area; and a
nonfluctuant, 4-cm swelling involving the sternum.  The
ulcer was well demarcated, with a violaceous, slightly
heaped-up border; an undermined edge; and a scant,
light brown, cheesy, purulent discharge.  Histological
examination showed early granuloma formations.  No
organisms were identified.  Roentgenograms of the chest
showed bilateral, upper-lobe, nodular densities without
definite hilar lymphadenopathy.  A solitary lytic lesion was
present in the sternum, consistent with osteomyelitis.
Culture from bronchial washings and from tissue biopsy
grew M tuberculosis in 2 and 6 weeks, respectively.  PPD
was strongly positive at 27-mm induration and 55-mm
erythema (such hypersensitivity is consistent with the
negative acid-fast stains since a higher degree of immu-
nity is presumed).  Triple drug therapy with isoniazid
(isonicotinic acid hydrazide [INH]), rifampin, and
ethambutol cleared the ulcer in 5 months.  Therapy was
continued for 1 year.52
Such ulcerated tuberculous gummas usually arise
in adolescents, and are found on the extremities;
occasionally on the trunk; and often in the presence
of silent, deep foci of tuberculosis.  These gummas

Cutaneous Tuberculosis
375
result from secondary breakdown of subcutaneous
cold abscesses.
Tuberculosis Fungosa Serpiginosa
Tuberculosis fungosa serpiginosa is a very rare,
chronic form of skin tuberculosis that occurs in
anergic, elderly individuals via endogenous or ex-
ogenous inoculation.  Patients with this disease
present with thick, papillomatous, vegetative,
noncornified plaques (commonly in the axilla or on
the backs of the hands) that resemble a chronic,
vegetative pyoderma.  The lesions are notable for
fissures and fistulae with serous or purulent exu-
date.  The lesions and exudates are bacillary rich.
Tuberculin sensitivity is absent.  With peripheral
extension and central healing, annular and
serpiginous lesions are formed.
Iatrogenic Immunization Tuberculosis
Tuberculosis infection—ranging from primary
inoculation complex to scrofuloderma, lupus
vulgaris, or acute miliary tuberculosis—can also
result from BCG immunization.50,53  Since the BCG
immunization organism is an attenuated M tubercu-
losis bovis, it can behave as a virulent opportunistic
pathogen where immunity is depressed or lacking.
With the worldwide increase in AIDS, the potential
for such iatrogenic disease is growing.
Tuberculous Mastitis
Patients with this rare form of tuberculosis in-
volving the breast present with a nontender, cold
abscess.  Diagnosis depends on microbiologic and
histological investigations.
DIAGNOSIS
Diagnosis of cutaneous tuberculosis certainly
requires (a) evidence of the tubercle bacilli either in
the smear or in tissue sections or (b) its recovery in
vitro (Exhibit 15-1).  Various workers have tried but
failed to demonstrate the bacilli in the histological
sections of the usual variants of cutaneous tubercu-
losis using the routine acid-fast staining.  Fluores-
cent staining with auramine or rhodamine is more
effective; the results in lupus vulgaris, however, are
still disappointing.  Thus, the absolute diagnosis
can be established only when the bacilli are iso-
lated.  Unfortunately, however, most investigators
report a low incidence of positive culture growths
in cutaneous tuberculosis.
The immunological diagnosis may be established
in pulmonary tuberculosis by the tuberculin test,
enzyme-linked immunosorbent assays for antibody
to PPD and to M tuberculosis antigen 6, and specific
tests using monoclonal-antibody and recombinant-
DNA techniques.  These latter two techniques might
be employed in the diagnosis of cutaneous tubercu-
losis in the future.
One group of investigators,39 utilizing the
Mantoux test (ie, an intradermal injection of 0.1 mL
of tuberculin [10 tuberculin units/0.1 mL]) in a
prospective study of 70 patients with cutaneous
tuberculosis (lupus vulgaris, verrucous tuberculo-
sis, and scrofuloderma only), noted that all patients
were moderately to highly reactive.
However, the most promising and exciting new
technique for the rapid diagnosis of tuberculosis is
the use of the PCR for the detection of M tuberculo-
sis–specific DNA fragments.  This amplification
technique yields millions of copies of tuberculosis-
specific target nucleotide sequences.  The particular
EXHIBIT 15-1
CRITERIA FOR THE DIAGNOSIS OF
CUTANEOUS TUBERCULOSIS
Absolute Criteria
Culture
Guinea pig inoculation
Positive polymerase chain reaction to Mycobac-
terium tuberculosis complex
Relative Criteria
Compatible history and skin examination
Active, visceral tuberculosis
Positive tuberculin-purified protein derivative
reaction
Positive enzyme-linked immunosorbent assay
for antibody to purified protein derivative of
tuberculin reaction or to M tuberculosis antigen 6
Compatible histopathology
Acid-fast bacilli in lesion
Fluorescent staining of M tuberculosis organisms
with auramine or rhodamine
Response to specific tuberculosis therapy

Military Dermatology
376
assay having the greatest promise, due to its high
sensitivity and specificity, is based on detection of a
putative insertion sequence IS6110.  This is usually
present in 6 to 15 copies in most strains of M tuber-
culosis.  Unlike other PCR-based assays, this method
does not require hybridization of the PCR product
to DNA probes, thus simplifying the test for routine
clinical use.  Other primer–probe sequences in use
include ribosomal RNA, the DNA sequence mtp40,
DNA encoding on a 38-kilodalton or 65-kilodalton
protein, and MPB64.26
Because PCR reactions can be performed on for-
malin-fixed, paraffin-embedded sections, they hold
great promise for the diagnosis of extrapulmonary
tuberculosis, especially of the cutaneous type.  Not
only has M tuberculosis–complex DNA been demon-
strated in paraffin-embedded sections taken from
proven cases of lupus vulgaris,54 scrofuloderma,55
and several other types of cutaneous tuberculosis,56
but such probes have also been used to diagnose
several tuberculid reactions as being truly tubercu-
lous in origin,57 allowing for a quicker diagnosis
and treatment of the underlying systemic tubercu-
losis.58  Turnaround time for the diagnosis takes
only a few days, in contrast to the weeks required
for culture and identification or inoculation.
TREATMENT
As in tuberculosis of other organs, chemotherapy
is the treatment of choice for cutaneous tuberculosis
(Table 15-2).  The only exception is the occasional
use of cryosurgery or electrocautery for destroying
small lupus nodules within scarred areas.43
Of great importance, especially in the Third
World, has been the development of short-course,
four-agent chemotherapy regimens for 6 months.59
Treatment of smear-positive or culture-positive
pulmonary or extrapulmonary tuberculosis is es-
sentially identical.  For the four-agent regimen, an
initial combination of isoniazid, rifampin, pyra-
zinamide, and either ethambutol or streptomycin is
given daily for 2 months.  Subsequently, a 4-month
course of isoniazid and rifampin is given.  How-
ever, due to the increasing number of patients with
single or multiple drug resistance, cure rates may
drop as much as 20% to 25% for each drug the
mutant bacilli are able to resist.10  Resistance rates in
New York City for one drug are as high as 33%, for
two drugs, 26%.  One study60 found resistance to
isoniazid to be 25%; rifampin, 20%; isoniazid-
rifampin, 16%; and isoniazid-rifampin-streptomy-
cin-ethambutol resistance, 13%.  The virulence of
this modern plague is accentuated in that the case-
fatality rate exceeds 50% for patients with multidrug-
resistant diseases, and approaches 90% for patients
with HIV infection.  The extent of the problem is
illustrated by conditions in Manila, where as many
as 80% of patients who present for treatment of
tuberculosis are resistant to at least one, if not to
several, drugs.10
Nosocomial outbreaks of multidrug-resistant
organisms have been devastating.  In a survey of
outbreaks in hospitals and prisons in New York and
Florida,61 96% of patients had underlying HIV infec-
tion.  The case-fatality rate was 72% to 89%, with death
occurring in 4 to 19 weeks following diagnosis, de-
spite aggressive multidrug therapy.  Six of eight hos-
pital staff who became infected with these resistant
organisms were also positive for HIV; four have died.
Factors leading to multidrug resistance include
monotherapy, erratic drug ingestion, omission of
one of more of the prescribed chemotherapeutic
agents, suboptimal dosage, poor drug absorption,
insufficient number of active chemotherapeutic
agents in a regimen, cavitary disease, and HIV
infection.60,61,62  In one study62 of HIV-infected indi-
viduals, the median survival time for those with
AIDS was 1.5 months versus 14.8 months for those
without AIDS.  Various social factors that contrib-
ute to these factors include homelessness, jobless-
ness, intravenous drug addiction, alcoholism, and
other forms of irresponsible behavior that place a
low priority on taking multiple medications daily
for prolonged periods.60
Recommendations for multidrug resistance change
continually.  As of September 1993, suggested
approaches for treatment include the following62:
1.
Patients in communities where the risk of
single-drug resistance is greater than 2%
should be placed on four-drug chemo-
therapy: isoniazid, rifampin, pyrazinamide,
and ethambutol, until the results of drug
sensitivity testing are available (2–5 wk,
optimally).
2.
In high-risk urban areas such as New York
City, where many patients show resistance
to two or more agents, at least five drugs are
necessary.
3.
For patients in high-risk areas with HIV
infection or AIDS, six-drug chemotherapy,
based on local patterns of resistance, may

Cutaneous Tuberculosis
377
TABLE 15-2
TUBERCULOSIS TREATMENT:  DRUGS, DOSES, AND SIDE EFFECTS
*Not available in the United States
PO denotes administration via oral route; IM, intramuscular route; ? denotes not known
Sources: Adapted with permission from (1) Kastrup EK, Olin BR, Connell SI. Drug Facts and Comparisons. St. Louis, Mo: Facts & Comparisons; 1988: 1534. (2) Sehgal V, Wagh
S. Cutaneous tuberculosis: Current concepts. Int J Dermatol. 1990;29:246. (3) Iseman MD. Treatment of multidrug-resistant tuberculosis. N Engl J Med. 1993;329:787.
Table 15-2 is not shown because the copyright permission granted to the
Borden Institute, TMM, does not allow the Borden Institute to grant permis-
sion to other users and/or does not include usage in electronic media. The
current user must apply to the publisher named in the figure legend  for
permission to use this illustration in any type of publication media.

Military Dermatology
378
be indicated until the results of antibiotic
susceptibility testing are known.
4.
Drug dosages and optimal timing of admin-
istration need to be determined for each
patient to achieve maximal serum concen-
trations in the targeted ranges without seri-
ous side effects.  In addition, care should be
taken to assess proper absorption of antitu-
berculosis agents in patients with AIDS, as
they commonly malabsorb these drugs.
The optimal duration of therapy has not been
determined.  Generally, extrapulmonic tuberculo-
sis is treated for the time being as pulmonic.  How-
ever, with miliary tuberculosis or tuberculosis of
the meninges or skeleton, longer courses are re-
quired.26  Patients with pulmonary tuberculosis
whose organisms are resistant to all or most of the
first-line chemotherapeutic agents are treated with
oral medications for 24 months following conver-
sion of the sputum cultures from positive to nega-
tive.  Of those who convert, as many as 20% may
relapse after therapy is discontinued.62
Turning back the clock to the preantibiotic era
in selective patients with cavitary pulmonic
tuberculosis may be beneficial.  Iatrogenic induc-
tion of pneumothorax or pneumoperitoneum, or
surgical crushing of the phrenic nerve to collapse
diseased lobes (because M tuberculosis, being
an obligate aerobe, perishes in anaerobic en-
vironments), has been of some aid in difficult
cases.10  Similarly, where economically feasible,
presurgical chemotherapy and hyperalimentation
combined with pneumonectomy or lobectomy, re-
inforced with a muscular flap to secure the bron-
chial stump, has saved several severely afflicted
patients.  Experience with the latter for multidrug-
resistant pulmonary tuberculosis at National Jew-
ish Center in Denver, Colorado, has been most
gratifying: 49 of 50 long-term survivors have con-
sistently had negative sputum smears and tubercu-
losis cultures.62
PREVENTION
The approach to the prevention of active tuber-
culosis varies from country to country.  In devel-
oped countries such as the United States, where
drug resistance is relatively low, two forms of
isoniazid prophylaxis have been effective tools.
First, in patients who meet the criteria for use, a 6-
to 12-month course of isoniazid (300 mg/d in adults,
5-10 mg/kg/d in children) can reduce the develop-
ment of active disease by 75%.  Second, a multidrug
prophylaxis with isoniazid, streptomycin, rifampin,
and pyrazinamide for 8 weeks resulted in an 81.5%
reduction in the incidence of bacteriologically
proven tuberculosis—a prophylactic course as ef-
fective as 12 months of isoniazid alone.59
In developing countries, where tuberculosis
morbidity and mortality are much greater, disease
prevention is most desirable.  BCG vaccination
against tuberculosis, which is relatively safe, inex-
pensive, and easy to use in the field, has been used
for many years.  Large-scale epidemiological stud-
ies have been attempted, but the interpretation of
their results has been hampered by the biological
variability of available BCG vaccines, difficulties in
case ascertainment and confirmation, and the ne-
cessity for long-term follow-up.  Measured efficacy
of current vaccines in preventing tuberculosis ranges
from nil to 80%.28  Vaccination apparently does not
prevent infection but shows definite protection
against the development of miliary tuberculosis
and meningitis, especially when given to infants
and children.28  Consequently, BCG immunization
should be given as early in life as possible in areas
of high prevalence.  However, it does not seem to
prevent reactivation of latent infections.
One of the probable reasons for the failure of
BCG vaccination is that immunosuppressive fac-
tors present in mycobacterial polysaccharides
depress cell-mediated immunity during active in-
fection through (a) decreased expression of
human lymphocyte antigens–D-group related
(HLA-DR) determinants and (b) increased produc-
tion of interleukin-1.  The consequences of these
immunosuppressive circuits are (a) depression
of tuberculin-induced blastogenesis, (b) produc-
tion of interleukin-2, and (c) generation of
interleukin-2 receptors (ie, natural infection with
M tuberculosis or with BCG may cause immuno-
suppression).63
Thus, worldwide control of tuberculosis appears
improbable unless an effective vaccine is devel-
oped.  One approach is to identify virulence factors
and, through the use of transposon-mediated gene
inactivation, produce mutants that lack these fac-
tors.  Such a strategy can provide important infor-
mation regarding the specific antigens that are im-
portant to the host for protection.  Genetic deletion

Cutaneous Tuberculosis
379
or modification of these virulence factors provides
insight into both the mechanisms of pathogenesis
and the possibilities for the development of live
attenuated vaccines.  Alternatively, individual an-
tigens identified as important for protection by
antibodies and T cells could be used to generate a
vaccine.  Current investigation centers on genetic
engineering techniques to modify and optimize the
antigenic determinants on the tubercle bacillus to
avoid down-regulating the immune system.
The elimination of tuberculosis in countries where
it is highly prevalent, particularly Africa, may be
seriously impeded by patients with AIDS and per-
sons infected with HIV.  It is inevitable that the
number of cases of tuberculosis will increase in
those countries with large numbers of patients with
AIDS.  Indeed, as AIDS increases exponentially in
Africa, tuberculosis continues to keep pace with it.
Many of these patients will succumb rapidly to
their disease, but not before they infect family mem-
bers, friends, coworkers, and others with drug-
resistant organisms.  Infection with M tuberculosis
tends to occur early in the course of AIDS, often
preceding the diagnosis of AIDS by several months.
This is in contrast to infections with an atypical oppor-
tunistic organism such as M avium–intracellulare,
which tends to occur later when immuno-
suppression is more profound.64
Along with the increase in the number of patients
who have both AIDS and tuberculosis, developing
countries face serious epidemiological problems in
the chemotherapy for tuberculosis.  Why?  Because
poor countries tend to rely on intramuscular strep-
tomycin as part of their drug regimens instead of
the more expensive oral alternative, pyrazinamide.
In primitive environments, keeping syringes sterile
to prevent the transmission of AIDS presents a
challenge to native public health services.  Dispos-
able syringes are not the answer due to their cost
and the potential for reutilization.65
A different problem concerns BCG vaccination for
tuberculosis or leprosy in children in countries with a
high prevalence of AIDS: the BCG organism may
become a pathogen in children infected with AIDS.65
TUBERCULOSIS AND ACQUIRED IMMUNODEFICIENCY SYNDROME
Tuberculosis management in refugees and other
displaced persons in temporary settlements poses a
great challenge to the military or to other organiza-
tions that coordinate and provide care and resettle-
ment.  Although we might suspect that the inci-
dence, morbidity, and mortality of tuberculosis
might be worse in war zones, where malnutrition
and physical and emotional stress may be at their
worst, recent evidence from Thailand’s experience
with Kampuchean refugees and Pakistan’s experi-
ence with Afghan refugees suggests that the inci-
dence of tuberculosis in refugees is similar to that in
their respective countries of origin.66
Initial attention to basic needs (nutritional reha-
bilitation, immunization, water supply, and sanita-
tion) is paramount.  This can be followed by treat-
ment of the most infectious patients: those with
active, smear-positive tuberculosis.  Without treat-
ment, 30% to 50% of these individuals will die of
their disease, having first spread their bacilli to
many others in the cramped refugee camps.66
Case-finding is one of the first tasks.  Sputum
samples should be checked on the spot for acid-fast
bacilli in any patient presenting with (a) a history of
3 weeks of cough or chest pain or (b) hematemesis or
significant weight loss.  Those whose sputum tests
are negative for acid-fast bacilli should be rechecked
on two consecutive mornings and observed if sus-
picion remains, but they should not be treated at
this point.  Treatment should be initiated for those
whose sputum tests are positive for acid-fast bacilli,
and additional cases should be sought among fam-
ily members and close contacts.  Among contacts,
children are notorious for having sputum that tests
negative; consequently, if they have symptoms and
signs compatible with tuberculosis, they should be
treated as well.  Tuberculin sensitivity is a poor
predictor of active tuberculosis in child contacts of
known cases.
Basically, however, a rational choice for the pa-
tient with tubercle bacilli that are fully susceptible
to drugs lies between these extremes:
• a 12-month course of isoniazid combined
with thiacetazone (not available in the United
States, due to the high frequency of side
TUBERCULOSIS CONTROL IN REFUGEE CAMPS

Military Dermatology
380
effects seen especially among some Asians),
preferably supplemented by streptomycin
for the first 2 months, which is a very inex-
pensive regimen; and
• a 6-month course of isoniazid combined with
rifampicin (supplemented with pyrazin-
amide, with or without streptomycin for the
first 2 mo), which is an expensive regimen.
Whichever course is selected, patients being treated
should be monitored to ensure compliance with the
treatment regimen, lest interruption of treatment
lead to drug resistance.  This may require retention
of the individual in a medical patient-holding facil-
ity.
Chemoprophylaxis with isoniazid does not play
any significant role for tuberculosis control in a
temporary refugee settlement with a high incidence
of disease.  BCG immunization for infants and small
children is still recommended to slow hematog-
enous spread of tubercle bacilli and the resultant
miliary and meningeal tuberculosis.
The term tuberculid denotes a symmetrical, gen-
eralized exanthem in the skin of a tuberculous pa-
tient due to an allergic or hypersensitivity reaction
to the tubercle bacillus or one of its constituent
parts.
In 1896, Jean Darier reported that patients with
tuberculids have the following key findings67:
• a positive tuberculin skin test,
• tuberculous involvement of lymph nodes or
internal viscera or both,
• absence of tubercle bacilli from skin biopsy
and culture, and
• skin lesions that heal on remission of the
tuberculous infection.
In the modern era, rapid resolution of the skin
lesions invariably follows the institution of
antituberculous antibiotic therapy.67
Tuberculids usually result from hematogenous
spread of mycobacteria in an individual with a
moderate or high degree of immunity (ie, the fluc-
tuation in the immunological state of the patient
determines the development and the features of the
eruption).  Histologically, the morphologic changes
in the skin have a tuberculous character.  Stasis, skin
temperature, and the relative blood supply are re-
sponsible for the pattern of the disease.
Tuberculids have always been rare, even when
tuberculosis was common.  Today, they are so
infrequent that some authorities question whether
they ever existed.  However, their appearance after
the injection of tuberculin, after BCG prophylaxis,
or during the chemotherapy of active tuberculosis
remains the best evidence of their existence.  His-
torically, tuberculids encompassed a host of
conditions, including erythema induratum,
papulonecrotic tuberculid, and lichen scro-
fulosorum.68  Of 400 cases of tuberculosis with
skin manifestations seen in hospitals in Poland dur-
ing the period 1963 through 1987,36 268 (67%) had
tuberculosis of the skin, 113 (28%) had pseudo-
tuberculids, and only 19 patients (5%) had true
tuberculids.  Of the population with true tuberculids,
13 (68%) had erythema induratum and 6 (32%) had
papulonecrotic tuberculid.  No cases of lichen
scrofulosorum were seen.36
Erythema Induratum
Erythema induratum (also called Bazin’s dis-
ease, tuberculosum, tuberculosis cutis indurativa,
nodose tuberculid) is a chronic condition associ-
ated with past or active tuberculosis.  The disease is
characterized by inflammatory cutaneous and sub-
cutaneous nodules that have a tendency to ulcer-
ation and scarring.  It typically occurs on the backs
of women’s legs and is believed to be an allergic or
hypersensitivity reaction to the tubercle bacillus.
Although in recent decades, many investigators
have denied its tuberculous origin and have pre-
ferred the name nodular vasculitis, others have
vigorously defended it.68  Therefore, the term
erythema induratum should be reserved for those
cases in which components of tubercle bacilli are
causative.
Epidemiology
In earlier times when the morbidity of tuberculo-
sis was greater, erythema induratum was frequently
seen.  Today, however, it is rarely diagnosed, its
incidence paralleling the decline of tuberculosis
seen in most industrialized countries.  The disease
tends to favor teenaged or middle-aged women,
especially those with plump extremities and minor
THE TUBERCULIDS

Cutaneous Tuberculosis
381
peripheral circulatory disturbances such as cold
feet, erythrocyanosis, or cutis marmorata.
Etiology and Pathogenesis
The tuberculous cause of erythema induratum
was generally accepted until the discovery of the
tubercle bacillus and the development of Koch’s
three postulates for the diagnosis of tuberculosis:
(1) isolation, (2) culture, and (3) the transfer of the
bacillus.  However, tubercle bacilli have only rarely
been cultured out of the lesions of erythema
induratum.  Additionally, the degree of tuberculin
sensitivity has been variable and the response to
antituberculous therapy inconsistent.  Nonetheless,
researchers68 argued strongly in 1989 for a connec-
tion between tuberculosis and erythema induratum,
after studying a large series of patients who (a) had
strong personal or family histories of tuberculosis,
(b) were extremely tuberculin sensitive, and (c) had
complete resolution of skin lesions after adequate
antituberculosis therapy.
The pathogenic premises for erythema induratum
and papulonecrotic tuberculid are the same: a tu-
berculous stimulus is initiated through either (a)
hematogenous dissemination of a few tubercle ba-
cilli or (b) dissemination of tubercle antigen into a
cooled extremity with disturbed circulation.  The ensu-
ing hypersensitivity reaction, if immune-complex
mediated, may be the cause of cases that show
histological changes consistent with nodular
vasculitis; if cell mediated, they may cause the cases
that show the classic tuberculous histology.  In
support of the latter, researchers69 reporting in 1990
found Leu-1+, Leu-3+, and HLA-DR+ mononuclear
cells (ie, helper T cells) within the lesions, in the
absence of immunoglobulin or C3 deposition—thus
suggesting a cell-mediated immune response to tu-
berculous antigen.  Further, they noted one patient in
whom satellite nodules of erythema induratum de-
veloped in the periphery of a PPD skin test, sup-
porting the concept that the lesions of this tuberculid
can indeed be produced by tuberculous antigen
alone.  Recently, the PCR has been applied to seven
patients with erythema induratum.  Five of seven
patients were positive for M tuberculosis complex
DNA, providing direct molecular confirmation for
this long-debated association of tuberculosis and
chronic nodular eruptions of the lower legs.56
Clinical Features
The eruption of erythema induratum is usually
symmetric, and typically affects the calves of pu-
bertal or adult women.  Rarely are the pretibial
areas affected.  The lesions arise in small numbers
as moderately tender, pea- to cherry-sized lesions,
often platelike, firm, well circumscribed, and elas-
tic.  After some months, these lesions customarily
regress, especially in the summer.  Frequently, the
larger lesions will turn livid red, liquefy centrally,
ulcerate through the skin, and form ulcerations or
fistulae.  The ulcers tend to be ragged, irregular, and
shallow.  The oily or crusted ulceration can remain
for months, but has little or no associated pain.  An
exhaustive search for a deep focus of tuberculosis is
necessary, especially in countries where tuberculo-
sis is prevalent.70
Laboratory Features
Patients with erythema induratum are usually
highly sensitive to PPD, with intradermal Mantoux
test results strongly positive (ie, 20-mm indura-
tion/40-mm erythema, or +++) using the weaker
1:10,000 dilution (1 unit PPD).  (Note: subcutaneous
injection frequently will give a false-negative reac-
tion, and initial skin testing with more concentrated
preparations may result in ulceration.)  Bacterial
cultures are customarily negative.
Histopathology
Often it is necessary to obtain many biopsies to
obtain a definitive diagnosis because there are varia-
tions from biopsy to biopsy and within different
areas of the same biopsy.  In the earliest stages, a
distinctive inflammation occurs in the vessel wall
(usually a vein, but this disease can also involve the
arterioles) with lymphocytic and plasma cell infil-
tration, and with thickening of the adventitia and
media, sometimes with proliferation of the endo-
thelium even to the point of occluding the lumen.  A
variable perivascular infiltrate is the rule at this
stage.  A septal panniculitis is present, which may
overflow into the fat lobules.  In many cases, the
infiltrate is tuberculoid throughout71; in others, it is
more banal.  Fat necrosis and a foreign-body giant
cell reaction may be present.  A lobular gran-
ulomatous reaction in the damaged fatty tissue
leads to Wucher (ie, proliferating) atrophy, wherein
normal fat tissue disappears and is replaced by
fibroblasts and macrophages.71,72  Older lesions may
progress to caseation and liquefaction.  Later, fibro-
sis occurs.  Caseation is always a late feature and
may be seen at biopsy in only 50% of cases.73

Military Dermatology
382
Course
Erythema induratum may wax and wane for
many years, with worsening in the colder months.
New nodules may form, while older nodules and
ulcerations may show only a slight tendency to
heal.  Altogether, a good prognosis can be expected
if no general disease is found.  Careful investiga-
tions can reveal, in a large proportion of cases,
active tuberculosis in an organ or the indication of
past tuberculosis.
Differential Diagnosis
It is important to distinguish erythema induratum
from other conditions affecting the legs.  Erythema
nodosum predominantly affects the pretibial area
and consists of tender, erythematous nodules that
do not ulcerate.  Other conditions to distinguish
include subcutaneous lipogranulomatosis (Roth-
mann-Makai disease), which has a different histol-
ogy (nodular vasculitis/cutaneous periarteritis
nodosa) that can also be present with tuberculosis;
the gummas of tertiary syphilis, which tend to be
asymmetrically located; and nodular pernio, which
has an even greater seasonal predilection, a more
subacute course, and only occurs on the cold-ex-
posed acral regions.  In every case, histological
examination is useful.
Treatment
Combination four-agent antituberculous therapy
given for 6 months is most important in treating
erythema induratum, as one- or two-drug chemo-
therapy may frequently prove inadequate—espe-
cially with the increasing antibiotic resistance to
INH and rifampin currently being seen.59,74  Simple
measures to prevent cold exposure to the legs, and
general measures to improve the peripheral circu-
lation are believed by some investigators24,75 to be
important.  The indiscriminate use of corticoster-
oids for the treatment of nodular vasculitis, which
mimics erythema induratum, may be harmful.
Papulonecrotic Tuberculid
Papulonecrotic tuberculid (also called tubercu-
losis cutis papulonecrotica) is clinically character-
ized as a recurrent, chronic, symmetric eruption of
necrotizing skin papules that appear in crops.  The
lesions tend to heal with varioliform scarring, and
occur in patients with active or past tuberculosis.
The disease may be thought of as a reaction pattern
reflecting a normal protective immune response in
a host with tuberculosis.
Pathogenesis
As a rule, bacteria are difficult to demonstrate in
the lesions of papulonecrotic tuberculid by acid-
fast staining of tissue sections, culture, or guinea
pig inoculation.  But occasionally these investiga-
tions prove fruitful.  A tuberculous etiology is not in
question because
• a large number of cases have an associated
deep focus of tuberculosis,
• tuberculin skin testing is almost always posi-
tive, and
• patients respond rapidly to antituberculous
therapy.
However, rather than direct metastatic spread of
infectious organisms (as is seen in miliary tubercu-
losis), some investigators76 believe the mechanism
of spread in papulonecrotic tuberculid is an Arthus
reaction followed by a delayed hypersensitivity
reaction to mycobacteria in the skin tissue; in other
words, a focus of tuberculosis is believed to release
mycobacteria into the circulation periodically, where
they are opsonized by immunoglobulins and
complement-forming circulating immune com-
plexes.  These complexes then lodge in the walls of
slow-flowing capillaries in the skin.  Phagocytosis
of opsonized bacilli and the resultant destruction of
neutrophils release proteolytic enzymes, which sub-
sequently necrose and destroy the vessels.  Presum-
ably, the ensuing mononuclear cell response then
destroys the bacilli.  Other investigators77 suggest
that the primary insult is either (a) nonspecific or (b)
a subacute lymphohistiocytic vasculitis with
thrombosis and destruction of small dermal ves-
sels, leading to an infarctive lesion with coagulative
necrosis of the overlying dermal tissue.
Most recently, as in erythema induratum, PCR
studies have detected M tuberculosis complex DNA
in lesions of papulonecrotic tuberculid, suggesting
the presence of at least partially intact bacilli within
the skin.57,78
Epidemiology
Girls and young women seem to be more suscep-
tible than men to this particular condition.
Papulonecrotic tuberculid is vanishingly rare in the
industrialized world.79  It occurred in 10 of 222 cases
of tuberculosis in South Vietnam and only 9 times in

Cutaneous Tuberculosis
383
ulcerations occur.  With recurrent crops, fresh pap-
ules and old scars frequently appear side by side.
This results in a characteristic polymorphous clini-
cal picture.  The total number of lesions in any given
patient is highly variable.  Itching and burning
sensations in the lesions may occasionally be present.
Laboratory and Histopathological Findings
Patients often have an exceedingly heightened
sensitivity to tuberculin, with positive intradermal
reactions to PPD in dilutions of 10-8 to 10-9.
A leukocytoclastic vasculitis is present early on.
Later, wedge-shaped necrosis develops, represent-
ing a microinfarct.  Epithelioid and giant cells are
often seen at the periphery of the necrotic zone.
However, well-formed granulomas are not identi-
fied.  Blood vessel involvement is a key feature,
being granulomatous, necrotizing (with fibrin
present in the walls and lumen), and sometimes
obliterative (ie, leading to thrombosis and complete
occlusion of the vascular channels).
Course
The disease may last for years or even decades
with recurrent crops of ulcerations and consequent
varioliform scarring.
Differential Diagnosis
Differentiation from other papulonecrotic pro-
cesses is necessary.  Such entities may include
leukocytoclastic vasculitis, pityriasis lichenoides et
varioliformis acuta (Mucha-Habermann), lympho-
matoid papulosis, acne necrotica, secondary syphi-
lis (rarely), and prurigo simplex–neurotic excoria-
tions.  In all cases, biopsy and tuberculin skin testing
are extremely helpful.
Treatment
Definitive therapy for tuberculosis with four-
drug therapy is indicated.59,74  Occasionally, this is
combined with systemic glucocorticosteroids in
moderate doses in exceptionally extensive cases.
Lichen Scrofulosorum
Lichen scrofulosorum (also called tuberculosis
cutis lichenoides) is a very rare, but distinctive,
lichenoid tuberculid.  The disease, which was origi-
nally recognized by Ferdinand von Hebra in 1860,80
occurs predominantly in children and adolescents
OK to put on the Web
Fig. 15-13. Papulonecrotic tuberculid on the legs of an
elderly woman with active pulmonary tuberculosis.
a 15-year period in the clinic at the Osaka Univer-
sity School of Medicine in Japan.67  Rarely, it follows
BCG vaccination.
Clinical Findings
Typically, symmetrical, loosely disseminated,
grouped eruptions of papulonecrotic lesions arise
in crops, particularly on the extensor surfaces of the
arms and legs, with predilection for the elbows,
knees, backs of the hands, and dorsal surfaces of the
feet (Figure 15-13), as well as on the lower trunk and
buttock region.  The genital region is usually spared.
The eruption tends to worsen in the winter and fade in
the summer months.  The lesions begin as pinhead-to-
pea-sized papules or small nodules and, over the
course of approximately 2 weeks, may become
pustular, vesicular, pemphigoid-like, hemorrhagic,
and necrotic.  After another 3 to 6 weeks, the lesions
heal with varioliform scars.  Rarely, crateriform

Military Dermatology
384
who have either primary complex of tuberculosis or
a secondary organ tuberculosis.
Clinical Features
In lichen scrofulosorum, the sites of predilection
are the sides of the trunk.  The exanthem is very
discrete and consists of symmetrically arranged
groups of tiny papules—often in elongated, oval
arrangements parallel to the skin relaxation lines
(lines of Langer).  The primary lesion is a white, pale
yellow-brown, pale red, or skin-colored follicular
or perifollicular soft acuminate papule, which may
carry a fine scale on its summit.  Rarely, a small
vesicle may be seen.  Occasionally, the small,
pointed, agminated papules are more polygonal
and resemble lichen ruber acuminatus (a form
of lichen planus).  On diascopy, the distinct
yellow-tone tuberculous character of the infiltrate
is easy to miss due to its minimal size.  In addition,
because the eruption is asymptomatic, it may be
overlooked.
Course
After a few months, lichen scrofulosorum erup-
tions customarily resolve spontaneously without
scarring.  Recurrences are possible.  If central vesicle
or pustule formation progresses to an acneform or
necrotic picture, then transformation to papulo-
necrotic tuberculid is assumed to have occurred.
Laboratory and Histopathological Features
The Mantoux skin test for tuberculosis is almost
uniformly positive.  M tuberculosis can occasionally
be cultured from the lesions.81
Typically in lichen scrofulosorum, tuberculoid
granulomas with Langhans’-type giant cells are
seen in the papillary dermis surrounding hair fol-
licles and sweat ducts.  Nonspecific inflammatory
infiltrates may be mixed in with the tuberculous
granulomas.  Caseation necrosis is generally absent.
Differential Diagnosis
The differential diagnosis includes lichen nitidus,
lichen planus, keratosis pilaris, lichenoid second-
ary syphilis, lichenoid drug eruption, lichenoid
sarcoidosis, follicular eczemas, and lichen scorbutus
(scurvy).  A rare possibility, lichenoid syphiliticus
(a small papular, grouped follicular or lichenoid
syphilid), occurs during the course of tertiary syphilis.
Prognosis
In patients whose disease is due to tuberculin
testing or BCG immunization, the prognosis is ex-
cellent.  In other patients, the condition is associ-
ated with lymph node, osseous, pulmonary, or geni-
tourinary tuberculosis.  In patients with normal
immunity and with chemotherapy, the prognosis is
generally good.
Treatment
The spontaneous resolution of the condition in
most patients is no contraindication for treatment
because lichen scrofulosorum is a harbinger of in-
ternal tuberculosis.  Consequently, chemotherapy
for the underlying systemic tuberculosis is indi-
cated and usually clears the skin manifestations in
a matter of weeks; in contrast, the internal disease
may require 6 months or more of therapy.24,59,75
SUMMARY
Tuberculosis is an infectious disease caused by
the bacterium Mycobacterium tuberculosis.  Estimated
to be present in one third of all humans, tuberculo-
sis is again increasing in incidence, particularly in
sub-Saharan Africa, due, in part, to the AIDS epi-
demic.  More alarming has been the progressive
increase in multidrug-resistant strains, particularly
among AIDS patients.  Cases of extrapulmonic tu-
berculosis—and especially cutaneous tuberculosis—
are again being seen in western Europe and in the
United States as a result of the immigration of
peoples from countries with high prevalence of
tuberculosis.  Although cutaneous lesions are
present in fewer than 1% of all tuberculosis pa-
tients, most cutaneous tuberculosis reflects more
serious underlying systemic tuberculosis and can
be seen in patients presenting with HIV infection.
Therefore, prompt recognition of tuberculosis of
the skin is important, as any delay in treatment
may contribute to further spread of disease in the
community.
Patients with cutaneous tuberculosis present with
diverse forms ranging from single, smooth papules
to disseminated, eruptive papules; verrucous or
vegetative plaques; single or multiple ulcerations;
or extensive sinus tracts.  The form of the disease

Cutaneous Tuberculosis
385
depends on the virulence of the strain, the immune
status of the host, the portal of entry, the mode of
internal spread, and the adequacy of initial treat-
ment.  Acute miliary tuberculosis, particularly in
patients who are highly immunosuppressed (eg,
those with AIDS), is generally a harbinger of death
due to overwhelming infection.  Scrofuloderma and
lupus vulgaris are much more common and are
seen in patients who are less immunosuppressed.
Tuberculosis verrucosa cutis is a highly localized
form of cutaneous tuberculosis that is seen in pa-
tients who are immunocompetent.
The clinical diagnosis of cutaneous tuberculosis
is suggested by the presence of apple jelly–colored
dermal infiltrates.  Definitive diagnosis requires
that the organisms be (a) recovered and (b) identi-
fied by either bacterial culture or guinea pig inocu-
lation, or by demonstration of the presence of M
tuberculosis via PCR assays for specific DNA se-
quences.  Compatible histopathology consisting of
granulomatous infiltrates with caseation necrosis
and the presence of acid-fast bacilli in tissue sec-
tions are both suggestive, but are by no means
pathognomonic of tuberculosis.
Tuberculosis can be accompanied by a variety of
hypersensitivity reactions to the bacillus or one of
its constituent parts.  These autosensitization reac-
tions are commonly called tuberculids.  Recent use
of PCR assays for certain M tuberculosis–complex
DNA segments have suggested that the tuberculid
skin lesions contain sizable bacterial fragments of
whole organisms.
The treatment of systemic tuberculosis has be-
come much more complicated during the 1990s.
Administering four-agent chemotherapy for 6
months is standard initial therapy where the inci-
dence of drug resistance is very low.  However,
with the rapid rise of multidrug-resistant strains—
especially in the HIV-infected population—inten-
sive and innovative chemotherapy protocols based
on antibiotic sensitivities need to be custom tailored
to each patient.  The treatment of cutaneous tuber-
culosis in most cases is the same as for pulmonary
tuberculosis, as lesions in the skin often represent
hematogenously or lymphatically dispersed dis-
ease from internal foci of infection.  Rarely will
tuberculosis in the skin be confirmed as strictly a
cutaneous disease.
Militarily, tuberculosis is a serious and growing
health threat in most areas of the world, especially
in Africa, Asia, and the Pacific.  With the increased
emphasis on peacekeeping forces, disaster relief,
and so forth, military personnel are increasingly
involved with refugees in distant, third-world ar-
eas where tuberculosis (and HIV) may have very
high prevalence and incidence.  Thus, the likeli-
hood of exposure is greater.  When coupled with the
possibility that HIV-positive military personnel
could be present, whose natural resistance to the
organism may be significantly compromised, the
stage is set for serious, highly infectious, life-threat-
ening disease.  Therefore, intensive tuberculosis
screening, aggressive treatment, and comprehen-
sive public-health measures are mandatory for pro-
tecting the health of military personnel who are
deployed to these areas.
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Atypical Mycobacterial Diseases
391
ATYPICAL MYCOBACTERIAL DISEASES
Chapter 16
JAMES H. KERR, M.D.* AND TERRY L. BARRETT, M.D.†
*Captain, Medical Corps, U.S. Navy; Chairman, Dermatology Department, Naval Hospital, San Diego, California 92134-5000
†Captain, Medical Corps, U.S. Navy; Pathology and Dermatopathology Consultant, Naval Hospital, San Diego, California 92134-5000
INTRODUCTION
HISTORY
General History
Military History
EPIDEMIOLOGY
Incidence
Sources of Organisms
Distribution
CLASSIFICATION SYSTEMS
HISTOPATHOLOGY
MYCOBACTERIOLOGY
ATYPICAL MYCOBACTERIAL INFECTIONS
Mycobacterium marinum Disease (Group I, Photochromogen)
Mycobacterium kansasii Disease (Group I, Photochromogen)
Mycobacterium szulgai Disease (Group I, Photochromogen/
Scotochromogen)
Mycobacterium scrofulaceum Disease (Group II, Scotochromogen)
Mycobacterium xenopi Disease (Group II,  Scotochromogen)
Mycobacterium gordonae  Disease (Group II, Scotochromogen)
Mycobacterium avium–intracellulare Complex Disease (Group III,
Nonchromogen)
Mycobacterium ulcerans  Disease (Group III, Nonchromogen)
Mycobacterium haemophilum  Disease (Group III, Nonchromogen)
Mycobacterium malmöense  Disease (Group III, Nonchromogen)
Mycobacterium fortuitum–chelonae Complex Disease (Group IV, Rapid
Growers)
Mycobacterium smegmatis Disease (Group IV, Rapid Growers)
ATYPICAL MYCOBACTERIAL INFECTIONS AND ACQUIRED
IMMUNODEFICIENCY SYNDROME
SUMMARY

Military Dermatology
392
The group of acid-fast mycobacteria that do not
cause tuberculosis or leprosy are a diverse collec-
tion of more than 30 facultative pathogens and
saprophytes; they have been called by many names
since first being recognized almost 70 years ago.
Due to the medical importance of tuberculosis at
the turn of the 20th century, designation as
nontuberculous mycobacteria was and still is a com-
mon classification for this group.  However, this
designation was not altogether accurate because
the leprosy bacillus should have been included in
such a group of nontuberculous mycobacteria; none-
theless its exclusion is understandable, as it was not
a culturable organism.  Pseudotubercle bacilli, un-
usual mycobacteria, chromogenic or nonpathogenic
acid-fast bacilli, saprophytic mycobacteria, and
mycobacteria other than tuberculosis (MOTT) were
some of the other terms used for this group of
organisms.  In 1954, Timpe and Runyon1 called
these organisms “atypical acid-fast bacteria” in their
first attempt to classify them.  In a 1959 refinement
of this classification system, Runyon2 referred to
them as “anonymous mycobacteria.”  Thus, in re-
ports about this group of organisms, any of these
terms have been used to refer to what is now almost
universally recognized as the atypical mycobacte-
ria.  This group includes both opportunistic patho-
gens as well as nonpathogenic, saprophytic, acid-
fast mycobacteria; however, if the past is any
indication of the future, some of the mycobacteria
presently classified as nonpathogens will, under
conducive host or environmental conditions, be-
come facultative pathogens and be identified as
such.
INTRODUCTION
General History
The causative organism of leprosy was described
in 1874 by Hansen,3 from whose name the term
Hansen’s disease is derived; however, it was the
identification of the tubercle bacillus as the cause of
tuberculosis by Koch in 18824 that stole the myco-
bacterial disease spotlight for the next 50 years
(Exhibit 16-1).  A great effort was poured into re-
search on epidemiology, diagnosis, and treatment
of tuberculosis, then as now a significant world-
wide medical menace.  However, in many medical
investigations of tuberculous disease, there began
to emerge evidence for the existence of other
“nontuberculous” mycobacterial infections.  Prob-
ably the earliest hint of atypical mycobacterial in-
fection was in 1897, with the description by Sir
Albert Cook of slowly progressive ulcers of skin
and underlying soft tissue in patients in Uganda.5
More than 50 years later, in the Buruli District of
Uganda, reports of multiple cases of Mycobacterium
ulcerans infection would give it one of its eponyms,
Buruli ulcer.
In the early 1900s, there were reports of rapidly
growing, acid-fast organisms (as opposed to slow-
growing tubercle bacilli) that were isolated from
purulent sputum of patients with respiratory-tract
disease.6  Some clinicians called these organisms
HISTORY
pseudotubercle bacilli, but their attempts to culture
them were unsuccessful.  Then, in 1904, came the
report of a chronic injection-site abscess caused by
an acid-fast bacillus.  This organism was cultured
and grew rapidly, in less than 1 week, and probably
was what is presently classified as the group of
rapid-growing atypical mycobacteria of the Myco-
bacterium fortuitum–chelonae complex.  In 1926, My-
cobacterium marinum was described and named as
the cause of disease, not in humans, but in salt-
water fish in the Philadelphia aquarium.7  Years
later, this same organism under a new name, Myco-
bacterium balnei, would be rediscovered as a cause of
a human skin disease associated with swimming
pools.
During the 1930s, further evidence for the exist-
ence of a group of “atypical” mycobacteria began to
accumulate.  In 1931, the Ryan strain, probably M
fortuitum, was isolated from a pleural empyema.
The organism was used to prepare a skin-test re-
agent that was reactive in that patient, who had not
reacted to the usual M tuberculosis tuberculins of
that day.  Clinical laboratories began to isolate yel-
lowish, pigmented, acid-fast organisms that were
completely unlike the nonpigmented cultures of M
tuberculosis or M bovis.  In addition, inoculation of

Atypical Mycobacterial Diseases
393
EXHIBIT 16-1
MILESTONES IN THE HISTORY OF MYCOBACTERIAL DISEASE
Date
Event
1874
Leprosy bacillus is described by Hansen
1882
Tubercle bacillus is identified by Koch
1926
Mycobacterium marinum is identified by Aronson in Philadelphia aquarium fish
1938
M fortuitum is isolated and named by da Costa Cruz
1943
M avium-intracellulare is recovered from silicotuberculosis
1948
M ulcerans is reported isolated from skin ulcers in Australia
1951
M balnei (now called M marinum) is isolated from human skin lesions from swimming pool trauma
1953
M kansasii (“yellow bacillus”) is isolated
1956
M scrofulaceum, so named because it resembled scrofula lymphadenitis in children
1959
Runyon Classification into Rapid Growers and Slow Growers (Groups I-IV) is established
1964
M buruli (now called M ulcerans) is isolated in Buruli District of Uganda
1965
M kansasii is first reported as skin infection
1965
M fortuitum is reported to produce abscesses
1972
M szulgai is first isolated and described
1977
M malmöense is reported as new species
1978
M haemophilum is described and named
1984
First report of skin infection with M gordonae
1984
M ulcerans is discovered in koalas in Australia
1990
M malmöense skin infection is reported
the atypical organisms into guinea pigs produced
only local, self-healing lesions instead of the usual
generalized involvement following M tuberculosis
inoculations of guinea pigs.  The “Mx” (mycobacte-
ria x) strain was isolated from sputum from a lung
abscess, and the “IP” strain originated from a case
of chronic pneumonitis.  Some variants of the “IP”
strain produced pigmented colonies when exposed
to light—again, completely unlike M tuberculosis
colonies.  A  review of the literature published in
1935 revealed more than a dozen instances in which
slow-growing, pigmented strains of acid-fast bacilli
were recovered from humans without associated
disease.8  Then in 1938, da Costa Cruz isolated,
described, and named the rapid-growing, acid-fast
bacillus M fortuitum.9  In that same year, there were
reports of several cases of superficial abscesses from
which rapid-growing, pigmented, acid-fast bacilli
were isolated.  From 1939 on, reports by Hellerström
of facial granulomas, which followed abrasions in a
swimming pool, implicated M tuberculosis as the
cause of disease.6  This was undoubtedly true in
some of these cases, but in others the causative
organism was probably M marinum.  During the
1940s, manifestations of clinical disease were di-
rectly linked to atypical mycobacterial infections.
In 1943, an acid-fast bacillus, later shown to be M
avium–intracellulare, was recovered from a patient
with silicotuberculosis.  During that same year, a
review of multiple pulmonary cases of normal or
clinically nontuberculous patients revealed some
positive M tuberculosis cultures and some “non-
pathogenic” acid-fast bacilli.  It was pointed out
that “nonpathogenicity for animals did not pre-
clude the ability to produce disease in the source
patient.”6(p109)  In 1948, a new mycobacterial disease
in humans was reported from the Bairnsdale dis-
trict of Australia, with the first isolation and identi-
fication of M ulcerans.10  Multiple reports of this
infection in the same area gave it the eponym
Bairnsdale ulcers.  More than a decade later, what
would eventually prove to be the same organism

Military Dermatology
394
was isolated from many patients in the Buruli District
of Uganda with the disease they called Buruli ulcer.
In 1951, self-limited skin lesions thought to be
tuberculous developed in approximately 80 Swed-
ish patients, from whom was isolated acid-fast ba-
cilli that grew at 31°C and produced yellow pig-
ment only after exposure to bright light.  These
culture results made tuberculosis an impossibility,
because M tuberculosis grows at 37°C and produces
no pigment—with or without exposure to light.
The same acid-fast organism was isolated from the
walls of a swimming pool used in common by
several infected patients.  This apparently newly
isolated species of mycobacterium was named M
balnei (from the Latin, meaning “of the bath”).  To
remove all doubt that indeed a new mycobacterial
disease had been discovered, Linell and Norden
inoculated themselves with the organism and pro-
duced identical skin lesions from which the same
mycobacteria were then isolated.  Later in 1959, Bojalil
showed that M balnei was the same species as M
marinum, which had been isolated by Aronson in
1926 from fish in the Philadelphia aquarium.  Thus,
the earlier name took precedence and this organism
officially became M marinum.11  In 1953, two cases of
mycobacterial disease were described that were caused
by the “yellow bacillus,” later identified as M kansasii.12
Three years later, a nontuberculous, acid-fast organ-
ism that produced cervical lymphadenitis in chil-
dren was named M scrofulaceum, because it so re-
sembled tuberculous scrofula.13  A preliminary
report in 1954 on the known facts about nontuberculous
pulmonary disease published the Timpe-Runyon clas-
sification system for these nontuberculous organ-
isms, which were termed “atypical” acid-fast bacte-
ria.  This system was limited to grouping these
organisms into Groups I through III, based on colony
color and texture, and on virulence in mice and
absence of virulence in guinea pigs.  Timpe and
Runyon warned against “discard of an acid-fast
organism isolated from a patient with pulmonary
disease because it fails to fit the cultural or viru-
lence pattern of M tuberculosis.”1(p208)
Then in 1959 came Runyon’s landmark refined
classification system of anonymous mycobacteria
based on both colony pigmentation and growth
rate.2  This was a very detailed, in-depth report on
the epidemiology, culture characteristics varying
with temperature and light, animal pathogenicity,
and drug resistance of more than 400 patient strains
of atypical mycobacteria from 93 laboratories in 30
states.  It provided incontrovertible evidence refut-
ing the dogma that an acid-fast bacillus, unable to
produce disease in guinea pigs, was ipso facto a
saprophyte and not a pathogen.  For, only the year
before, it had been suggested that “atypical vari-
ants” that produce lymphadenitis almost exclu-
sively in children were actually “mutants of M
tuberculosis” that had become predominant because
of their higher drug resistance.14
Into the 1960s, widespread knowledge and ac-
ceptance of the identification of the various atypical
mycobacteria were generally lacking.  In a 1963
report of 12 orthopedic cases that grew out myco-
bacteria, the organisms were identified as “a myco-
bacterium, other than M tuberculosis, M ulcerans, M
balnei, or M leprae.”15(p327)  In other words, these
infections were identified as not due to tuberculo-
sis, Buruli ulcer, swimming-pool granuloma, or lep-
rosy.  The cultures in these cases grew at 22°C to
24°C, 30°C, and/or 37°C, with most colonies pro-
ducing smooth, cream-colored (or, in a few cases,
yellow or orange) growth.  Unfortunately, the time
required for colony growth was not recorded; how-
ever, the nonpigmented ones were probably rapid
growers in the M fortuitum complex, and the orange
colonies, which grew at all three temperatures, may
have been M kansasii from Group I photochromogens
or M szulgai—a temperature-dependent photo-
chromogen/scotochromogen not isolated until 1972.
With all of the culture characteristics, excluding
rate of growth, and without more modern metabo-
lism, seroag-glutination, and chromatography meth-
ods, it is impossible to classify these atypical myco-
bacterial infections precisely.  Use of Runyon’s
classification system, however crude it might ap-
pear by current standards, was and still is helpful in
keying out general groups of organisms.  Even
though the yellow bacillus, M kansasii, had been
isolated from autopsy material more than 10 years
previously, it was not until 1965 that the first skin
infection caused by M kansasii was reported.16  Also in
1965, M xenopi, which has been commonly recovered
from hospital hot-water storage tanks, was recog-
nized first as a pulmonary pathogen.  In that same
year, subcutaneous abscesses due to M fortuitum
were reviewed.  Many reports of M fortuitum infec-
tions of skin, soft tissue, lung, and even the cornea
were documented during this decade.17
The 1970s produced reports of pulmonary infec-
tions by M simiae and skin infections by two new
atypical mycobacteria—M szulgai in 1972 and M
haemophilum in 1978.  In addition, work went for-
ward on serotyping the various groups of atypical
mycobacteria after more widespread use of differ-
ential culture techniques began to demonstrate the

Atypical Mycobacterial Diseases
395
more frequent occurrence of these acid-fast organ-
isms in the production of disease.  Additional bio-
chemical tests were also developed to better differ-
entiate the various species.  Some species with
differing names were found to be the same organ-
ism, while others were split into separate and dis-
tinct species.  The acceptance of the atypical myco-
bacteria as separate and distinct species of
mycobacteria became more widespread; the diag-
nosis of tuberculosis was restricted to slowly grow-
ing mycobacteria that (a) grew at 37°C, (b) did not
produce yellow or orange colonies, (c) did give
positive results for niacin and nitrate reduction,
and (d) were virulent in guinea pigs.
In 1983, M asiaticum, which had been included
among M simiae isolates from primates almost 20
years previously, was implicated as the cause of
pulmonary disease; however, this particular newly
identified organism did not, and has not been shown
to, disseminate to the skin.18,19  In 1984, M gordonae,
a commonly encountered saprophyte in the labora-
tory, which has been referred to as the “tap-water
bacillus” or M aquae in the past, was isolated as the
cause of infection in the hand.13  That same year, M
ulcerans, thought only to infect humans, was iso-
lated from koalas in Australia, thus stimulating
speculation as to the epidemiology and transmissi-
bility of this organism between humans and poten-
tial animal reservoirs.20  Although M malmöense had
been identified in 1977 in Malmö, Sweden, it had
been associated solely with pulmonary disease and
cervical adenitis until 1990, when it was isolated as
the cause of skin nodules in a patient with chronic
myeloid leukemia.21  Prior to development of these
skin nodules, this patient had developed a
supraclavicular node that on biopsy was diagnosed
as tuberculosis but was unresponsive to isoniazid,
rifampicin, and pyrazinamide.
During the decade of the 1980s, increasing num-
bers of cases of atypical mycobacterial infections in
immunocompromised patients, especially those with
acquired immunodeficiency syndrome (AIDS), were
being reported.  Many of these infections occurred
in organs that had not previously been reported as
being involved with atypical mycobacterial infec-
tions.  Thus, it had become apparent that clinicians
and researchers should maintain a high index of
suspicion for unusual presentations of the atypical
organisms, especially in immunocompromised pa-
tients.  Nevertheless, diagnosis is accomplished
through better and more sophisticated diagnostic
classification tests such as thin-layer chromatogra-
phy, plasmid profiling, enzyme-linked immunosor-
bent assay (ELISA), high-pressure liquid chroma-
tography, radiometric culture system, and species-
specific deoxyribonucleic acid (DNA) probes.22–24
Military History
There is no record of a single battle or military
campaign whose outcome was determined by the
presence of atypical mycobacterial infections.  This
is most likely due to their low overall clinical preva-
lence (< 2/100,000 in the United States) and to their
lack of human-to-human or animal-to-human com-
municability.22  Human infection occurs in an op-
portunistic fashion, with repeated or prolonged
exposure of traumatized or compromised skin, soft
tissue, or airway to adequate amounts of patho-
genic, or in some cases, even saprophytic atypical
mycobacteria.  Water and soil appear to be their
most common and most likely sources.22  Therefore,
on the battlefield or on the sea, wounded combat-
ants may have a ready source of opportunistic in-
fection if open wounds are allowed to come into
repeated or prolonged contact with the environ-
ment.  In 1918, chronic pustular skin lesions con-
taining relatively rapidly growing, acid-fast bacilli
were noted in a wounded English soldier who was
being transported by ship.  The ship was then sunk
in the North Sea, which exposed his wounds di-
rectly to seawater.6  The soldier’s subsequent skin
lesions were most likely caused by infection with
organisms from the M fortuitum–chelonae complex
or possibly M marinum.
Almost certainly there were some cases of atypi-
cal mycobacterial infections during World War II,
because tropical areas are endemic for many of the
atypical organisms and wounded soldiers and sail-
ors were undoubtedly directly exposed—sometimes
for prolonged periods—to soil, water, or lush veg-
etation.  However, the seriousness of their wounds,
or the occurrence of more virulent infections in
these wounds, may have displaced concern over
relatively benign-appearing skin lesions, a chronic
cough, or indolent soft-tissue infections such as
might have been seen with atypical mycobacterial
infections.  In fact, if the casualty did survive his
other injuries, many of the skin, pulmonary, or soft-
tissue lesions of atypical mycobacterial infections
would have healed spontaneously, after several
months or even years, despite the lack of standard
wound care.  Some of the atypical mycobacteria
might well have responded to timely debridement,
surgical excision, incision and drainage or, in the
years following World War II, to the administration

Military Dermatology
396
of antituberculous drugs or antibiotics as they be-
came available.  Mortality from these organisms
was apparently small or was attributed to other
types of infections, because during the 1940s, atypi-
cal mycobacteria were only beginning to be sus-
pected as agents of infection.  Usually, pulmonary
disease and soft-tissue and lymphatic involvement
that produced acid-fast bacilli were attributed to
tuberculosis and treated as such.  These treatment
failures were then considered to be unresponsive or
resistant cases of tuberculosis, and, without the
special culture techniques for demonstrating atypi-
cal mycobacteria, their involvement went undetec-
ted.  It was not until after World War II, in 1948, that
M ulcerans was isolated and identified as the acid-
fast bacillus that directly causes progressive ulcer-
ative skin lesions (ie, Bairnsdale ulcers).
With the beginning of the Korean conflict came
the first reports of the isolation of M balnei (the same
organism as M marinum, which had been described
earlier in fish) as the cause of the disease (in several
patients in Sweden) that would later become known
as swimming-pool granuloma.  Little more was
known about atypical mycobacterial infections in
humans, except for suspicions that they might
be secondary pathogens in chronic pulmonary
disease.  Soon after the Korean conflict, Runyon’s
detailed study and classification system for these
organisms was published in 1959.2  Fortunately,
soldiers kept their exposure to water to a mini-
mum during the harsh Korean winter, thereby de-
creasing the chances that casualties with even mi-
nor battle wounds would be contaminated by or-
ganisms such as M marinum or M kansasii.  Certainly
there must have been some soft-tissue infections
with the atypical mycobacteria secondary to con-
tamination associated with shrapnel and bullet
wounds; however, as in World War II, surgical
debridement, excision, incision and drainage,
or amputation would have been curative of many
atypical mycobacterial infections.  Being far from
the tropics, Korea was not an endemic area for
M ulcerans, the cause of Buruli ulcer.  Pulmonary
infections with M kansasii or M avium–intracellulare,
found to be positive for acid-fast bacilli, would have
been treated as tuberculosis, with some success
using antituberculous drugs.  Most likely, these
infections were recognized as somewhat resistant
strains of tuberculosis that, when cultured with the
usual mycobacterial techniques, unlike M tubercu-
losis, produced strangely pigmented yellowish colo-
nies.  For, in this war, as in prior wars, knowledge
about atypical mycobacteria as possible pathogens
was relatively uncommon throughout the medical
community.
Although atypical mycobacterial infections per
se are not mentioned in Lieutenant Colonel Alfred
M. Allen’s landmark volume on dermatology in the
U.S. Army, Skin Diseases in Vietnam, 1965–72,25 sev-
eral reports of that era record infections with these
organisms.  In a report published in 1963,15 12 ortho-
pedic cases were discussed, with atypical mycobac-
terial infections of tendon sheaths in one half of the
patients and involvement of joints in the other half.
Three of the tendon infections followed laceration or
hydrocortisone injections, and three of the six joint
infections followed repeated injections of hydro-
cortisone into the affected joint.  The exact atypical
mycobacteria species in these cases were not iden-
tified, but M ulcerans and M marinum were ruled out
by bacteriological studies; thus, given the culture
growth characteristics, the offending organisms
were most likely M fortuitum, M kansasii, or M szulgai.
One report17 recounted a M fortuitum infection
following multiple gunshot wounds received by a
20-year-old army infantryman while in Vietnam in
1968.  Interestingly, this organism was recovered
from an abscess that developed proximally in the
left thigh some 3 months after the initial wound and
fracture of the left lower leg.  Initial therapy with
isoniazid and pyrazinamide for 2 months had shown
no effect; therefore, extensive debridement,
sequestrectomy of the involved bone, and split-
thickness skin grafting finally produced sustained
healing of the area after 4 more months.  Another
report26 described M fortuitum infections in three
severely wounded Vietnam veterans with deep soft-
tissue abscesses; all eventually healed following
extensive debridement, incision and drainage, and
local wound care.  These three cases were the only
ones found among the large number of injured
patients returning from Vietnam and treated at
Valley Forge (Pennsylvania) General Hospital.  The
low number of cases may have been attributed to
the aeromedical evacuation system that was used
during the Vietnam conflict, which rapidly removed
the accessible wounded from the battlefield, thus
preventing continued contact of open wounds with
water or soil contaminated with atypical mycobac-
teria.  Rapid removal of patients with extensive
open wounds to relatively sophisticated treatment
facilities with good laboratory capabilities is essen-
tial in minimizing delays in diagnosis and effective
treatment of atypical mycobacterial infections.

Atypical Mycobacterial Diseases
397
EPIDEMIOLOGY
TABLE 16-1
PATHOGENIC MYCOBACTERIA ISOLATES
IN THE UNITED STATES (1980)
Adapted with permission from Good RC, Snider, DE. From the
Centers for Disease Control. Isolation of nontuberculous myco-
bacteria in the United States, 1980. J Infect Dis. 1982;146(6):830.
Atypical mycobacterial diseases are not commu-
nicable: human-to-human transmission has rarely,
if ever, been known to occur.  Instead, these dis-
eases occur when an individual made susceptible
by trauma, a deep wound, a surgical procedure—
with or without compromise of the immune sys-
tem—comes in sufficient contact with these
saprophytic organisms.  Atypical mycobacteria can
be found almost worldwide in soil, water, vegeta-
tion, and indigenous animals.  Therefore, the inci-
dence of disease caused by these organisms is rela-
tively low, even rare, unless the scales are tipped in
their favor due to exposure of susceptible tissue to
these organisms in their endemic locales.
Due to their similar clinical, etiologic, and anti-
genic characteristics, two groups of atypical myco-
bacteria are considered together as “complexes.”
For example, M intracellulare and M avium produce
almost identical human pathogenicity and are found
together endemically.  They differ in their ability to
produce disease in animals and can be distinguished
from one another by sophisticated laboratory tech-
niques; however, their human clinical course, his-
tology, and response to treatment are essentially iden-
tical.  They are grouped together as the M avium–
intracellulare complex.  M scrofulaceum is sometimes
included in the M avium–intracellulare complex be-
cause it also produces cervical adenitis—one of the
clinical signs seen in both children and adults with
M avium–intracellulare complex infection.
Although M fortuitum and M chelonae each con-
tain several separate and identifiable subgroups,
the human diseases that they produce have such
similar clinical courses and culture characteristics
that these organisms, too, are usually grouped to-
gether as the M fortuitum–chelonae complex.
Because atypical mycobacteria are ubiquitous,
they were not readily associated with clinical dis-
ease.  However, under circumstances that are pre-
cisely right for them and wrong for the host, these
saprophytes take their place as true pathogens in
the production of human disease.
Incidence
The true incidence of atypical mycobacterial dis-
ease is difficult to ascertain: because they are not
communicable diseases, they are not reportable in
the United States.  However, several laboratory sur-
veys of pathogenic mycobacteria have been reported
(Table 16-1).  One such survey, published in 1982 by
the Centers for Disease Control in Atlanta, Georgia,
suggests that 65.2% of the total mycobacterial patho-
gens isolated were M tuberculosis and 34.8% were
atypical mycobacteria.  Of the atypical mycobacte-
rial isolates, about 60% were M avium–intracellulare
complex; 20% M fortuitum–chelonae complex; 10% M
kansasii; with M scrofulaceum, M marinum, M xenopi,
M szulgai, and M malmöense comprising the remain-
ing 10%.27  In 1990, the overall prevalence of atypical
mycobacterial infections was estimated at about 2/
100,000 population in the United States, with over
one half the cases due to M avium–intracellulare
complex, and the largest population of patients
being white males who are not infected with AIDS.22
If M avium–intracellulare complex infections in AIDS
patients were included, the percentage of infection
in white males would be even higher.  Even though
the M avium–intracellulare complex is the most preva-
lent atypical mycobacterium in the United States
and is also common in western Australia and Japan,
it is rare in Europe: the predominant atypical organ-
isms there are M kansasii and M xenopi.
Sources of Organisms
Mycobacteria exist and probably multiply in a
wide variety of natural sources such as soil, water,
Table 16-1 is not shown because the copyright permis-
sion granted to the Borden Institute, TMM, does not
allow the Borden Institute to grant permission to other
users and/or does not include usage in electronic
media. The current user must apply to the publisher
named in the figure legend  for permission to use this
illustration in any type of publication media.

Military Dermatology
398
and wild and domestic animals and birds; there-
fore, it seems reasonable to believe that most hu-
man disease comes from the environment.6  Even
potable water supplies harbor some of these organ-
isms: M gordonae (the tap-water bacillus) and M
xenopi (isolated almost exclusively from water, es-
pecially from hospital hot-water systems, and called
the hot-water bacillus).13,22
Although M ulcerans has recently been isolated in
Australia from koalas, there have been no isolates
from samplings of soil, water, or vegetation; how-
ever, Buruli (Uganda) and Bairnsdale (Australia)
ulcers, both caused by M ulcerans, are known to be
endemic in tropical or subtropical areas where wet,
marshy terrain produces lush vegetation—usually
without koalas in the environment.20  M marinum is
not only found in both fresh and salt water, it is also
found in fresh- and salt-water fish.  In addition, M
marinum is found in swimming pools, aquariums,
and mud and is capable of multiplying in soil.28
Although not isolated from soil or natural water
supplies, M kansasii has been isolated many times
from tap water and is found in wild and domestic
animals such as cattle and pigs.22,29  Organisms from
the M fortuitum–chelonae complex have been iso-
lated from soil, natural water supplies, tap water,
house dust, distilled water, hemodialysis equip-
ment, and even gentian violet skin-marking solu-
tions.22,30  M scrofulaceum organisms have been found
in soil, water, raw milk, dairy products, and oys-
ters.13  Researchers in one report pooled together
shucked oysters from several oyster beds.  The
oyster homogenate, inoculated on mycobacteria
cultures, grew M scrofulaceum.31
The pulmonary route of infection is probably the
most common for M avium–intracellulare complex.
Interestingly enough, the highest numbers of these
isolates are found aerosolized in air samples when
compared to soil, dust, sediment, or even water
samples (M avium and M intracellulare can remain
viable for years in soil and water).13  Even though
the organisms are known to cause disease in birds,
poultry, pigs, cattle, and monkeys, the disease has
not been shown to be communicable from these
animals to humans.
With the possible exception of pulmonary infec-
tions with M xenopi, human-to-human infections by
atypical mycobacteria do not occur.32
Distribution
Distribution of atypical mycobacteria appears
to be worldwide; however, some organisms
are found only in limited areas (eg, M ulcerans in
Central Africa, Australia, New Guinea, Mexico,
Central America, and South America).  Some
species are common in relatively similar geo-
graphical areas.  For example, although M avium–
intracellulare and M fortuitum–chelonae complexes
are found almost worldwide, in the United States
they are more common in the southeastern and
Gulf-coast states, while M kansasii is more prevalent
in the midwestern and central parts of the coun-
try.22,29  A 1967 report,33 which consolidated data
from two previous reports34,35 on the incidence of
skin-test reactions to specific atypical mycobacte-
rial antigens in healthy U.S. Navy recruits, gave the
following results: in 257,476 recruits, M avium–
intracellulare produced fewer than 30% reactors from
northern, western, and far-western regions, and
approximately 70% reactors from the southeastern
United States.  Similarly, in 31,479 recruits, M
scrofulaceum produced about 30% to 50% reactors in
most areas of the United States, while it produced
more than 80% reactors in the southeastern United
States.33  Likewise, M avium–intracellulare complex
infections are generally more common in rural ar-
eas, while M kansasii is most common atypical my-
cobacterium found in sputum specimens from ur-
ban areas.36
The relatively uncommon occurrence of M
malmöense has been reported only rarely outside a
relatively limited area that includes Sweden, Ire-
land, England, and Wales.13,21  The occurrence of M
scrofulaceum is worldwide, but generally in the more
temperate climatic zones, while M marinum is found
worldwide in association with either fresh or salt
water.13,37  Causing only rare cases of pulmonary
disease, M asiaticum has been found in Queensland,
Australia, and Los Angeles, California.19
CLASSIFICATION SYSTEMS
Due to the variability in organ systems involved
and in the clinical expression of disease in the atypi-
cal mycobacteria group, standardization of a logi-
cal, understandable classification system is difficult
at best.  However, some semblance of order has
developed since 1954, with the first attempt by
Timpe and Runyon to group these organisms into
meaningful categories.  In that first attempt at clas-
sification, organisms were not named by their spe-
cies but instead were placed in Groups I, II, or III

Atypical Mycobacterial Diseases
399
according to their colony color, texture, rate of
growth, virulence in guinea pigs and mice, and how
these characteristics compared with those of organ-
isms from other microbiology laboratories from
around the country.1  Runyon’s much more sophis-
ticated system was proposed in 1959, when he placed
more than 400 atypical strains in the following three
slow-growing groups (ie, Groups I, II and III, which
grew in 3–4 wk), based mainly on colony color and
the effects of light and darkness; and in Group IV,
based solely on how rapidly the colonies grew2:
• Group I: Photochromogens (color forms only
with light),
• Group II: Scotochromogens (color forms even
in darkness),
• Group III: Nonphotochromogens (weak to no
color forms in both darkness and light), and
• Group IV: Rapid Growers (colonies grow
within 48 h, with little to no color).
Additional features that were recorded included
pretreatment drug resistance; strong colony cata-
lase activity; growth at room temperature; lack of
virulence in guinea pigs; and colony characteristics,
including intense pigmentation, smooth surface,
easy dispersion in liquid, and growth within 3 days.
Several of the then-known species of atypical myco-
bacteria were then placed in one of these four simple
groups according to their colony-growth character-
istics; others (eg, M ulcerans) were not placed in the
groups because their features overlapped.
Since then, many additional tests for species sepa-
ration have been developed that can be used by
specialty laboratories to determine (a) the exact
species of atypical mycobacteria causing a specific
disease and (b) its drug sensitivities.  Using readily
available media and incubating at the appropriate
temperatures, a relatively accurate appraisal of sus-
pected atypical mycobacteria can be made, using
tables based on the original Runyon groups.  The
recently identified species have been inserted into
their appropriate groups (Exhibit 16-2) for the
reader’s convenience.  The most commonly isolated
organisms are listed toward the top of each group;
special or unique characteristics are noted in paren-
theses for some species; and, for the more uncom-
mon pathogens, the most significant investigations
are referenced.  Although not included with the
atypical mycobacteria because it was always the
“typical” one, M tuberculosis, if it were listed, would
go into Group III: its colonies are slow growing and
produce no pigmentation.  At present, M leprae is
not culturable by routine methods and therefore is
EXHIBIT 16-2
RUNYON CLASSIFICATION OF
ATYPICAL MYCOBACTERIA
Slow Growers (> 7 d)
Group I, Photochromogens
M marinum*
M kansasii
M szulgai (at 25°C)1
Group II, Scotochromogens†
M scrofulaceum (cervical adenitis with
ulcerations)
M szulgai (at 37°C)1
M xenopi (adenitis, sinus tracts)2
M gordonae3
Group III, Nonchromogens
M avium–intracellulare‡
M ulcerans
M heamophilum (seen in immunocompromised
patients)2
M malmöense 4
Rapid Growers (< 7 d)
Group IV, Buff colored
M fortuitum–chelonae complex (after surgery
and trauma)*
M smegatis (after cardiac bypass surgery)5
*Most commonly seen
†All in this group are rare
‡Seen with increasing frequency with HIV infections
The following are the most significant investigations for
particular organisms:
1. Cross GM, Guill MA, Aton JK. Cutaneous Mycobacte-
rium szulgai infection. Arch Dermatol. February
1985;121:247-249.
2. Woods GL, Washington JA II. Mycobacteria other
than Mycobacterium tuberculosis: Review of microbio-
logic and clinical aspects. Rev Infect Dis. Mar-Apr
1987;9(2):275-294.
3. Shelley WB, Folkens AT. Mycobacterium gordonae in-
fection of the hand. Arch Dermatol. 1984;120:1064-1065.
4. Gannon M, Otridge B, Hone R, Dervan P, O’Loughlin
S. Cutaneous Mycobacterium malmöense infection in an
immunocompromised patient. Int J Dermatol. March
1990;29(2):149-150.
5. Wallace RJ Jr, Musser JM, Hull SI, et al. Diversity and
sources of rapidly growing mycobacteria associated
with infections following cardiac surgery. J Infect Dis.
1989;159(4):708-716.
not placed in a classification group based on colony
characteristics.
Some classification schematics differentiate or-
ganisms solely on their pigment production with-
out reference to the rate of colony growth, while

Military Dermatology
400
others are based on characteristic clinical and radio-
graphic findings and skin tests (eg, purified protein
derivative of tuberculin [PPD]).36  A recently sug-
gested classification system for cutaneous myco-
bacteriosis, which includes mostly tuberculous in-
fections, is based on the clinical source of the
infection: whether exogenous, endogenous, or he-
matogenous.38  A disadvantage of this particular
system is that the atypical mycobacteria can fall into
any of these three categories, and identification of
the particular organism is not the goal of this sys-
tem.  A more recent, clinically useful classification
system divides atypical mycobacterial infections
into clinical disease groups based on the organ
system involved—pulmonary, lymphatic, cutane-
ous, or disseminated.22  In this classification system,
common and unusual etiologic species in each group
are then listed along with their growth rates, colony
pigmentation characteristics, and references to the
medical literature.  One limitation of this system is
that only the more common skin pathogens are
included; therefore, if a patient’s disease is caused
by a rare, atypical organism, it might not be consid-
ered in the clinical or laboratory differential.
One of the main objectives of organism classifica-
tion is to expedite the initiation of effective therapy.
In nonimmunocompromised patients who have
atypical mycobacterial skin infections, time may be
on the side of the patient.  However, should the
infection disseminate or spread to deeper struc-
tures—or, in immunocompromised patients, to soft
tissue—time may be of the essence in preventing
severe morbidity or even mortality.  Additionally,
the ability to rule in certain atypical mycobacterial
infections and to rule out others by culture classifi-
cation is significant in managing these patients with
confidence and effectiveness.  In most cases of my-
cobacterial infection, the histopathology alone will
not be completely diagnostic; therefore, in cases
with borderline or overlapping histopathological
findings, the bacteriological classification of the
involved organism may become vital.
As occurs in M tuberculosis, seven different pat-
terns of reaction may be seen on histological exami-
nation of the atypical mycobacteria (see Chapter 15,
Cutaneous Tuberculosis, for further discussion of
these patterns):
1.
classic tuberculoid granulomas,
2.
abscess formation,
3.
diffuse infiltrate of histiocytes,
4.
panniculitis,
5.
nonspecific chronic inflammation,
6.
sarcoidal granulomas, and
7.
rheumatoid-like nodules.
These patterns are not pure but represent a spec-
trum of changes.  For example, well-formed
granulomas are seen less commonly in atypical
mycobacterial diseases than they are in M tuber-
culosis infections, and a classic tuberculoid
pattern is not commonly seen.  Therefore, instead
of relying on a classic tuberculoid granuloma,
the medical officer should be sufficiently familiar
with the general patterns to suspect a mycobacte-
rial infection in routine stained material, then
obtain special acid-fast stains to identify the caus-
ative organism.  In most atypical mycobacterial
infections, acid-fast organisms are sparse (Fig-
ure 16-1).  However, in early necrotic areas of
Buruli ulcer and in immunocompromised patients,
many organisms—sometimes even clumps—can
be seen.
The features most commonly seen with each spe-
cific atypical mycobacterial infection are discussed
later in this chapter.
HISTOPATHOLOGY
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Fig. 16-1. Note the acid-fast bacillus in the center of this
positive acid-fast stain of atypical mycobacteria.

Atypical Mycobacterial Diseases
401
MYCOBACTERIOLOGY
In 1896, the genus name Mycobacterium was given
to a group of bacteria that grew moldlike pellicles
when cultured on liquid media.39  This genus of
bacteria was already large, and many additional
species, including the atypical mycobacteria, have
been added during the 20th century.  All atypical
mycobacteria are nonmotile, aerobic, nonencapsu-
lated, nonsporulating, usually slender bacilli that
have a waxy coating that resists acid-alcohol decol-
orizing once they are stained, thus their designation
acid fast.
Useful acid-fast stains for these organisms in-
clude Ziehl-Neelsen and Kinyoun, a modified Ziehl-
Neelsen stain that is milder and better suited to
atypical mycobacteria.  The Fite (Fite-Ferraco) stain,
usually used in staining for M leprae, is useful as a
screening acid-fast stain for all mycobacteria.  The
auramine-rhodamine stain using a fluorochrome
technique is approximately 100-fold more sensitive
than the Fite stain and is very useful for detecting
sparse numbers of atypical mycobacteria; M
fortuitum–chelonae organisms, however, do not take
this fluorochrome stain well.  The routine Gram’s
stain is usually positive, to some degree, for atypi-
cal mycobacteria.  The organisms vary in size, rang-
ing from 0.2 to 0.6 µm in diameter and 1.0 to 4.0 µm
in length; however, there may be some variability
even within the same species (eg, M malmöense can
be coccoid to short to moderately long).13
Routine culture media, such as blood or choco-
late agar, will support growth of many of the atypi-
cal mycobacteria including M haemophilum, which
requires a source of hemoglobin or hemin; how-
ever, these media dry out within 5 to 7 days, making
them suboptimal for all except the rapid-growing
group.  Lowenstein-Jensen medium, with contami-
nant-inhibiting antibiotics, is the preferable me-
dium, with 2% ferric ammonium citrate added if M
haemophilum is suspected.  The hemin requirement
of this organism can be met by using standard
chocolate agar, 5% sheep-blood Columbia agar, or
by using the more specialized Mueller-Hinton agar
with Fildes supplement.  The growth of mycobacte-
ria, especially M haemophilum, is stimulated by the
presence of 5% to 10% carbon dioxide during cul-
ture growth.  A new biphasic culture system (Septi-
Chek AFB [SCAFB], manufactured by Roche Diag-
nostic Systems, Nutley, New Jersey) is a specially
designed bottle containing four selected media
(7H11, Lowenstein-Jensen, chocolate agars, and 7H9
broth) for mycobacterial culture that requires only
the addition of the homogenized specimen and then
incubation at the appropriate temperature.  A slow-
release carbon dioxide process is built into the sys-
tem.  Culture results from early testing have given
results as good as or better than those with regular
Lowenstein-Jensen medium.  When an inoculum is
placed on any culture, the surface of the medium
should be scratched to ensure good contact with the
medium and optimum growth conditions.  For the
first 2 weeks, the inoculated surface should be kept
almost horizontal to prevent the colonies from loos-
ening from the medium, and the container cap
should be kept loose to allow circulation of the
carbon dioxide.
Tissue being prepared for culture can be minced
in a sterile Petri dish with a sterile number 10 or
number 15 scalpel blade.  Also available is the hand-
held Sterile Disposable Tissue Grinder (number
3505, manufactured by Sage Products, Inc., Cary,
Ill).  This disposable plastic tissue grinder makes
homogenization of tissue fast and simple.  Great
care must be taken to prevent contamination with
environmental bacteria and ubiquitous saprophytic
atypical mycobacteria, which, under proper condi-
tions, can be opportunistic pathogens and, if grown
out as a contaminant, could cloud the diagnostic
picture.
Overgrowth of cultures by contaminants is a
major problem in culturing of mycobacteria, be-
cause all are relatively slow growers compared to
most bacteria.  Even the rapid growers, which take
only 3 to 7 days to grow, are slow compared to most
other bacterial cultures (which, having no apparent
colonies at 48 h, are called “no growth”).  If any
mycobacterial species are suspected, the laboratory
should be advised to retain the special cultures for
at least 8 weeks, as the usual laboratory procedure
is to dispose of no-growth cultures after 48 to 72
hours.  The laboratory procedures necessary to iso-
late and diagnose atypical mycobacteria can be de-
scribed schematically (Figure 16-2).
Once suspected atypical mycobacterial colonies
do grow, they should be checked for acid-fastness
by using the Kinyoun or auramine-rhodamine stain-
ing technique.  If the culture is acid-fast staining,
the organism is most likely a mycobacterium; how-
ever, Nocardia (a genus of actinomycetes; see Chap-
ter 18, Deep Fungal Skin Diseases) with its uneven
acid-fast staining, could be present.  All suspected

Military Dermatology
402
Fig. 16-2. Algorithm for the laboratory diagnosis and isolation of atypical mycobacteria.
Positive
Negative
(2 foil-wrapped and 1 
unwrapped at each 
temperature)
24°C–25°C
30°C–32°C
35°C–37°C
43°C–45°C
Colony Growth:
Checked weekly for 8–12 wk
Stains:
Kinyoun
Auramine-Rhodamine
Fite
Ziehl-Neelsen
Media:
Lowenstein-Jensen
with antibiotic
with ferric ammonium citrate
7 H10/11
chocolate agar
Carbon dioxide (5%–10%)
Temperatures:
24°C–25°C
30°C–32°C
35°C–37°C
Mycobacteria:
Tuberculosis
Leprosy
Atypical 
Nocardia
Resample or
No acid-fast bacterial infection
Acid-Fast Stain:
Kinyoun
Auramine-Rhodamine
Fite
Ziehl-Neelsen
Mycobacteria:
Tuberculosis
Atypical
Nocardia
Not  mycobacteria
Slow Growers:
Mycobacteria Groups 
I–III and TB
Rapid Growers:
Mycobacteria
Group IV
Determine Growth Rate and
Presence and Type of Pigmentation
Species Identification
Clinically Suspicious Skin Lesion
(papule, plaque, pustule, crusted ulceration, node)
> 7 d
< 7 d
Specimen
(tissue [ground or minced], smear, swab, aspirate)
Acid-Fast Staining
Culture
Positive
Negative
No growth
Growth
Subcultures:

Atypical Mycobacterial Diseases
403
TABLE 16-2
COLONY GROWTH AS A FUNCTION OF TEMPERATURE
Temperature Range (in °C)
Atypical Mycobacteria
24–25
30–32
35–37
42–43
Group I
M marinum
+
+ (7–14)*
N
N
M kansasii
S
S
+ (10–20)*
N
Group II
M szulgai
S
S
+ (12–25)*
N
M scrofulaceum
S
S
+ (> 10)*
N
M xenopi
N
N
+
+ (14–28)*
M gordonae
S
S
+ (20–50)*
N
Group III
M avium-intracellulare
±
+
+ (10–21)*
±
M haemophilum
S
+ (15–30)*
N
N
M ulcerans
N
+ (28–60)*
S
N
M malmöense
S
S
+ (15–60)*
N
Group IV
M fortuitum–chelonae complex
+
+
+ (3–5)*
N
M smegmatis
+
+
+
+ (3–5)*
*number of days necessary for growth at the optimum temperature
+: good growth; ±: growth may or may not occur; S: slow growth; N: no growth
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mycobacterial cultures should be saved under re-
frigeration for sensitivity testing and positive bio-
chemical identification procedures by a specialty
laboratory, or by a referral laboratory such as the
National Jewish Center, Denver, Colorado.
Temperature effects on atypical mycobacterial
growth are crucial for both colony survival and for
differentiation among the various species.  (As dis-
cussed previously, the difference in temperature
requirements and the production of colony pig-
mentation with and without exposure to light are
the two characteristics that originally raised scien-
tific awareness that atypical mycobacteria existed
and were different from the tubercle bacillus.)  With
some species of atypical mycobacteria, colony
growth to any degree hinges on the ambient tem-
perature.  The first objective in culturing is to obtain
some colony growth; therefore, only a few param-
eters require attention.  The properly inoculated
Lowenstein-Jensen cultures are incubated at 25°C
(usual room temperature), at 30°C, and at 37°C,
with a 5% to 10% carbon dioxide atmosphere.  If
colonies appear between 3 to 7 days and are acid-
fast on staining, then rapid-growing atypical myco-
bacteria are most likely present.  If acid-fast colo-
nies appear from 8 days to 8 weeks, then either a
tuberculosis or a slow-growing atypical mycobac-
terium is most likely present.  As mentioned above,
Fig. 16-3. These Lowenstein-Jensen cultures contain orange
scotochromogen (Mycobacterium gordonae) colonies (left)
and buff-colored, nonpigmented, rapid-grower (Mycobac-
terium chelonae) colonies (right). Cultures supplied by Deanne
Harley, Supervisor, Microbiology Section, Laboratory Medi-
cine Department, Naval Hospital, San Diego, California.

Military Dermatology
404
Nocardia can grow on Lowenstein-Jensen medium
and is acid-fast; however, the staining is usually in
an uneven pattern.
To further differentiate the organism, a saline or
broth suspension from the initial culture is inocu-
lated onto Lowenstein-Jensen medium cultures at
24°C, 32°C, 35°C, and 42°C (Table 16-2).  For each
temperature setting, two foil-wrapped and one un-
wrapped Lowenstein-Jensen cultures are used.  After
colony growth is noted in the unwrapped, light-
exposed cultures, one of the foil-wrapped slants
with growth is exposed to a strong light (eg, a 100-
W light bulb at a distance that does not heat the
culture, approximately 50–60 cm).  The other cul-
ture tube remains foil-wrapped and serves as a
control for comparison.  After 3 to 5 hours of expo-
sure to light, the cultures are returned to their
respective incubators and examined at 24, 48, and
72 hours for evidence of yellow or orange colonies
(Figure 16-3) as compared to the covered control.
With this information, using Table 16-2 and Exhibit
16-2, cutaneous atypical mycobacteria may be
grossly classified to guide initial or continuing
therapy.  Positive cultures should always be saved
under refrigeration for later use in definitive classi-
fication and drug sensitivity testing, if necessary.
ATYPICAL MYCOBACTERIAL INFECTIONS
Because its first pathogenic representative was
not identified until 1938, the recorded history of
atypical mycobacterial infections is relatively short.
In comparison with the other mycobacteria, leprosy
and tuberculosis, they pose a much lower risk of
serious disease.  With little or no human-to-human
contagion among the more than 30 species, infec-
tion usually is the result of an opportunistic en-
counter between patient and pathogen.  These soil
and water saprophytes will infect humans only
under certain conducive conditions.  In the opera-
tional military setting, traumatized skin is a portal
of entry for M marinum, M kansasii, M smegmatis,
and possibly M ulcerans.  Penetrating wounds allow
for deep inoculation of organisms such as M gordonae
or M fortuitum–chelonae complex.  Cardiac bypass
surgery has been an avenue for infection by M
smegmatis24; therefore, with cardiothoracic surgery
of any type, whether in the military or civilian
setting, it is prudent to be on guard for infection by
this organism.
Atypical mycobacterial infections are slow in
their progression and, occasionally, slow in regres-
sion.  They can be widely destructive, as seen with
deep infections with M ulcerans and M scrofulaceum.
Having invaded tendons, joints, or even bone, M
kansasii, M szulgai, or M fortuitum–chelonae complex
organisms can be difficult to identify and even more
difficult to eradicate.  With the increasing frequency
of organ transplantation and associated iatrogenic
immunosuppression, the risk for opportunistic in-
fection by several organisms such as M haemophilum,
M xenopi, M avium–intracellulare complex, and even
M marinum has correspondingly increased.  Pa-
tients with AIDS are particularly susceptible to the
M avium–intracellulare complex, which is found at
autopsy in more than half of AIDS victims.40
As noted, mycobacterial infections have not
played a pivotal role in military history.  However,
with the possibility that the military will be de-
ployed anywhere in the world for brief or extended
peacekeeping or combat missions, infections with
these organisms should be kept in mind when mili-
tary planners consider the biological threats in an
operational arena.  Otherwise, the failure to sus-
pect, and thus to diagnose, infections by these or-
ganisms will lead to delayed diagnoses and treat-
ment—with resultant increases in patient morbidity
and even mortality.
Mycobacterium marinum Disease (Group I,
Photochromogen)
The synonyms for M marinum include M balnei, M
platypoecilus (recognized early as the cause of tuber-
culosis in Mexican platyfish), swimming-pool
granuloma, fish-tank granuloma, fish-fancier’s fin-
ger, aquarium granuloma, and oyster-shucker’s
palm.
Epidemiology
Although first isolated from salt-water fish in the
Philadelphia, Pennsylvania, aquarium in 1926, and
named M marinum then, this mycobacterium was
not identified as a human skin pathogen until 1951.7
The overall incidence in the United States is only
about 0.05/100,00041; however, it is the most com-
mon atypical mycobacterium to cause skin disease
in the United States, with about 600 cases reported
since 1951.  The natural habitat is worldwide, in
temperate fresh or salt water (eg, harbors, bays,
rivers, brackish coastal waters, inadequately chlori-
nated pools, aquariums, and even the Dead Sea).

Atypical Mycobacterial Diseases
405
This organism has been readily cultured from ma-
sonry cracks and chinks in pools as well as from the
mud in natural water sources.  It is pathogenic for,
and has been isolated from, marine animals, frogs,
fishes, and even the water flea Daphnia.  Humans
acquire the infection through (a) traumatized skin
lesions exposed to contaminated water or (b) wounds
inflicted by, or in contact with, marine animals or
their products (eg, fish bone).  Occasionally, what
seems to be epidemics of infection have occurred in
patients using the same swimming pool; however,
person-to-person transmission has not been reported
and is assumed not to occur.7
Diagnostic Features
A slightly tender, red, indurated area develops in
the skin within a 1- to 6-week incubation period
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(usually about 3 wk) and then progresses to single
or, occasionally, grouped multiple, brownish red
papulonodules that slowly become violaceous (Fig-
ure 16-4).  The skin lesions may eventually ulcerate
to drain pus or they may form slightly verrucous
papules or plaques resembling psoriasis (Figure
16-5).  These papules are usually located, in de-
creasing order of occurrence, on the elbows (most
common by far), knees, hands, or feet that have
been traumatized during water-related work or lei-
sure activities (Figure 16-6).  Uncommonly in M
marinum infection, underlying bursae, bone, or syn-
ovia may become involved.  Systemic spread occurs
in about 2% of infections, in immunocompromised
or immunocompetent patients.7,42  In about 25% of
cases, tender, red, centrally spreading, secondary
nodules can be seen along the course of the lym-
phatics of the involved extremity in a sporotrichoid
pattern (Figure 16-7).7
Differential Diagnosis.  The differential diagno-
sis for M marinum infection includes sporotrichosis,
nocardiosis, blastomycosis, chromoblastomycosis,
other mycobacterioses, cutaneous leishmaniasis,
coccidioidomycosis, tularemia, foreign body granu-
Fig. 16-5. As an unrecognized, untreated infection with
Mycobacterium marinum becomes chronic, over a several-
week period, a verrucous plaque, like the one shown on
this patient’s knee, develops.
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Fig. 16-4. The early lesion of Mycobacterium marinum
infection appears approximately 3 weeks after exposure to
the organism in a water environment. Here, a brownish red
papulonodule on the wrist is the first sign of infection.

Military Dermatology
406
Fig. 16-6. The feet may be affected if they are traumatized
during water-related work or leisure activities. The en-
larging plaque on this patient’s foot is due to infection
with Mycobacterium marinum. Photograph: Courtesy of
Captain E. C. Oldfield, Medical Corps, US Navy, Naval
Hospital, San Diego, Calif.
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loma, posttraumatic hypertrophic scar, iodine and
bromine granuloma, granuloma annulare, hyper-
trophic lichen planus, sarcoidosis, psoriasis,
ecthyma, favus, syphilis, cutaneous tuberculosis,
warts, and skin cancer.7,43
Histopathology.  In only about 10% of cases does
the histopathology reveal acid-fast bacilli, which are
usually located within histiocytes.  The granulomatous
pattern is that of an epithelioid granuloma that usu-
ally does not exhibit caseation necrosis.
Laboratory Features.  M marinum is one of the
faster slow-growing atypical mycobacteria, such
that in 7 to 10 days, cultures grown in the dark
produce nonpigmented colonies; these then become
yellow-orange within 24 to 48 hours after exposure
to the proper light (see Figure 16-3).  In fact, in early
classification schemata, M marinum was occasion-
ally classified as a rapid grower; however, a more
restricted growth time (ie, < 7 d) now excludes this
organism from the rapid growers.  Culture media
include Middlebrook 7H10 and 7H11, and Lowen-
stein-Jensen with antibiotic.  Temperature control is
a critical factor for growth of this organism since it
typically grows best at 30°C to 32°C and not at the
usual laboratory level of 37°C (see Table 16-2);
however, this organism can show some eventual
growth at 37°C.11,44  If the culture conditions are
optimum, M marinum can be isolated by culture in
about 70% of the involved cases with the earlier
clinical lesions producing the greatest number of
positive cultures.
Course, Treatment, Prognosis, and Prevention
Single skin papules may heal spontaneously in 6
to 36 months; however, some infections have per-
sisted for more than 45 years,45 which makes initia-
tion of therapy a reasonable approach.  In the past,
since this organism is resistant to some antituber-
culous drugs, local destruction of small areas of
involvement was carried out by surgical excision,
cryotherapy, curettage, or radiation.  Fortunately,
over the past 15 years, treatment with oral tetracy-
cline (2 g/d) and, more recently, minocycline or
doxycycline (200 mg/d) for 2 to 4 months has been
quite effective in most cases.46  Oral trimethoprim-
sulfamethoxazole administered twice daily, or
rifampin (600 mg) with ethambutol (15 mg/kg)
administered daily for 3 months, or both, have also
been successful therapy in resistant cases.22  Rarely,
cutaneous dissemination occurs in immunocompe-
tent patients42,47 and, on occasion, dissemination of
infection may be associated with the administration
of systemic corticosteroids.48  Similarly, intralesional
steroid injection may produce enlargement or exac-
erbation or both of the lesion (Figure 16-8).  Dis-
semination or more severe and widespread cutane-
ous infection may occur in immunocompromised
patients with M marinum.48
Preventive measures include adequate chlorina-
tion of swimming pools, protection of traumatized
skin from contaminated water, and reduction of
skin trauma in those exposed to natural water
sources or fish tanks.  For example, in the Chesa-
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Fig. 16-7. As the infection ascends the lymphatics, mul-
tiple inflamed papulonodules develop proximal to the
initial site.  These lesions may ulcerate with time. The
pattern shown here is referred to as “sporotrichoid”
because it resembles the grouping of lesions seen in
sporotrichosis.

Atypical Mycobacterial Diseases
407
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Fig. 16-8. Plaque of Mycobacterium marinum infection on
the elbow. The original lesion began as a verrucous
plaque resembling psoriasis and initially was injected
with intralesional steroid by an unsuspecting civilian
healthcare provider. Photograph: Courtesy of Com-
mander S. J. Walker, Medical Corps, US Navy, Naval
Hospital, San Diego, Calif.
peake Bay area, many commercial fishermen
and watermen wear thick gloves while working
with fish or crabs.  If salt-water wounds occur,
meticulous wound care, with thorough irrigation,
should be performed.  Severe or multiple wounds
may benefit from a short prophylactic 3- to 5-day
course of oral tetracycline or minocycline.49  Infec-
tion with M marinum frequently produces persis-
tent positive cross-reactivity with tuberculin skin
testing; this, however, is not a reliable diagnostic
modality but should be kept in mind when PPD skin
testing is done on patients who work in or around
marine industries.7
Mycobacterium kansasii Disease (Group I,
Photochromogen)
Epidemiology
M kansasii, also known as the yellow bacillus of
Buhler and Pollak, and as the orange bacillus, is
worldwide in distribution but is especially preva-
lent in temperate-climate areas such as the
midwestern and southwestern United States.  This
organism is commonly found in tap water and in
both wild and domestic animals such as cattle and
pigs.  Pulmonary infections are most common and
are probably caused by inhalation of aerosolized
organisms; skin infections are much less common.
Skin infection was reported in 1965,16 with only nine
additional cases reported as of 1987.12  Cutaneous
involvement may occur in normal or previously
traumatized skin, and is commonly seen in patients
with immunodeficiency.
Diagnostic Features
The infection incubation time of M kansasii is
from 15 days to several months.  Clinical manifesta-
tions include red-to-violaceous indurated papules
or plaques; pustular, ulcerated, crusted, or verrucous
papules or nodules; cellulitis; abscesses; joint pain
including arthritis, synovitis, and bursitis; cervical
adenopathy; and a sporotrichoid adenopathy of an
involved extremity (see Figure 16-6).
The clinical differential diagnosis includes pyo-
genic abscess, cellulitis, and sporotrichosis, as well
as the other mycobacterioses.  Exhibit 16-3 not only
presents the variety of diseases that can have a
sporotrichoid pattern of lymphatic spread but also
directs the reader to the most noteworthy descrip-
tion of this clinical presentation.
Histopathology.  Histopathology can show acute
and chronic inflammation alone, or tuberculoid or
epithelioid granulomas with large, cross-barred,
acid-fast bacilli in about 10% of all cases.50
Laboratory Features.  Cultures grow best on
Lowenstein-Jensen medium at 37°C after 10 to 20
days (see Table 16-2), and produce yellow-orange
pigment containing beta carotene crystals after ex-
posure to bright light (see Figure 16-3).  There are no
reliable, routine, specific skin tests or serologic tests
available.
Course, Treatment, Prognosis, and Prevention
Pulmonary M kansasii disease is apparently self-
healing, as evidenced by research studies with pre-
pared PPD-like material showing positive skin tests
in about 50% of the healthy adult population of the
United States.50  In the few skin infections reported,
untreated infections lasting up to 22 years have
been seen.16  For skin infection, successful therapy
has included daily isoniazid (300 mg) plus rifampin
(600 mg), with ethambutol (15 mg/kg for 18–24
mo), with streptomycin added (1 g/d for 2 wk, then
twice weekly for 3 mo).22  The addition of transfer
factor to the treatment regimen has been helpful in
successfully treating immunocompromised pa-
tients.51  Oral therapy with minocycline (200 mg/d)
has also been successful,52 as has surgical excision of
localized cervical adenitis.29  There are no preven-
tive measures known.

Military Dermatology
408
Mycobacterium szulgai Disease (Group I,
Photochromogen/Scotochromogen)
Epidemiology
M szulgai, first recognized in 1972, is a rare patho-
gen with fewer than 20 total cases reported—of
which most have been chronic pulmonary disease
in middle-aged men with fewer than 6 cases involv-
ing skin or soft tissue.13  Apparently, this organism
is distributed worldwide with no known natural
reservoirs.  The incidence of disease reported in
1983 in the United States was 0.01/100,000.41
Diagnostic Features
M szulgai has an array of manifestations.  Red,
tender nodules on the extremities, trunk, or neck
may become fluctuant and drain spontaneously.53,54
Some of these lesions have manifestations of under-
lying osteomyelitis or bursitis with or without ac-
companying pulmonary disease.  Disease has been
seen in immunocompromised and immunocompe-
tent patients.  The differential diagnosis includes
all the causes for carbuncle, cellulitis, subcutan-
eous pyogenic abscess, olecranon bursitis, and
tenosynovitis.
Histopathology.  Histopathology is that of a his-
tiocytic granuloma with multinuclear giant cells
without caseation necrosis.  The presence of acid-
fast bacilli within the granuloma is variable.
Laboratory Features.  Culture characteristics are
both interesting and confusing: this organism is a
photochromogen, with yellow-orange pigment pro-
duction (see Figure 16-3) only after light exposure,
when grown at 25°C; but it is also a scotochromogen,
producing yellow pigment when grown in the dark
at 37°C.  Colonies appear at 2 to 4 weeks, with
slower growth at the lower temperature.
Course, Therapy, Prognosis, and Prevention
Apparently M szulgai disease is progressive, es-
pecially in immunocompromised patients and,
therefore, deserves treatment when it occurs.  In a
prednisone-immunosuppressed patient,53 effective
therapy was achieved with oral administration of
isoniazid (300 mg/d), rifampin (600 mg/d), and
ethambutol (1,200 mg/d for 24 mo); the prednisone
was discontinued over a 3-week period at the begin-
ning of this therapy.  Since prolonged treatment of
this organism is required, it must be distinguished
from the usually more-responsive infections with
M tuberculosis and other atypical mycobacteria.
EXHIBIT 16-3
SKIN INFECTIONS WITH SPOROTRICHOID LYMPHATIC SPREAD
Sporotrichosis1
Nocardiosis1
Atypical mycobacteria
M marinum2,3
M kansasii2,4
M scrofulaceum5,6
M chelonae7
M avium–intracellulare8
M gordonae9,10
Tuberculosis1
Tularemia1
Syphilis1
Yaws1
Scopulariopsis (blochi)1
The following are the most significant descriptions of the clinical presentations of
these organisms:
1. Moschella SL. Diseases of the mononuclear phagocytic system (the so-called reticuloen-
dothelial system). In: Moschella SL, Hurley HJ, eds. Dermatology. Vol 1, 2nd ed.
Philadelphia, Pa: WB Saunders; 1985: 890–999.
2. Glickman FS. Sporotrichoid mycobacterial infections. J Am Acad Dermatol. 1983;8:703–707.
3. Raz I, Katz M, Aram H, Haas H. Sporotrichoid Mycobacterium marinum infection. Int J
Dermatol. 1984;23(8):554–555.
4. Dore N, Collins J-P, Mankiewicz E. A sporotrichoid-like Mycobacterium kansasii infec-
tion of the skin treated with minocycline hydrochloride. Br J Dermatol. 1979;101:75–79.
5. Sowers WF. Swimming pool granuloma due to Mycobacterium scrofulaceum. Arch Dermatol.
1972;105:760–761.
6. Murray-Leisure KA, Egan N, Weitekamp MR. Skin lesions caused by Mycobacterium
scrofulaceum. Arch Dermatol. 1987;123:369–370.
7. Murdoch ME, Leigh IM. Sporotrichoid spread of cutaneous Mycobacterium chelonei
infection. Clin Exper Dermatol. 1989;14:309–312.
8. Wood C, Nickoloff BJ, Todes-Taylor NR. Pseudotumor resulting from atypical myco-
bacterial infection: A “histoid” variety of Mycobacterium avium–intracellulare complex
infection. Am J Clin Pathol. 1985;83:524–527.
9. McIntyre P, Blacklock Z, McCormack JG. Cutaneous infection with Mycobacterium
gordonae. J Infect. 1987;14:71–78.
10. Gengoux P, Portaels F, Lachapelle JM, Minnikin DE, Tennstedt D, Tamigneau P. Skin
granulomas due to Mycobacterium gordonae. Int J Dermatol. April 1987;26(3):181–184.

Atypical Mycobacterial Diseases
409
There are no suggested preventive measures at
present.
Mycobacterium scrofulaceum Disease (Group II,
Scotochromogen)
Epidemiology
In 1956, M scrofulaceum, also called the Gause
strain of mycobacteria, was named because of its
scrofula-like involvement of the cervical lymph
nodes in children.  Most cases involving this organ-
ism still occur in the cervical nodes of children
between 1 and 5 years of age, with rare occurrence
in adults.  Distribution is worldwide in soil, tap
water, raw milk, dairy products, and other prod-
ucts of the environment such as oysters.13  The route
of infection has not been firmly established; how-
ever, oral, oropharyngeal, and hematogenous path-
ways are suspected circumstantially.  The estimated
overall incidence of all M scrofulaceum disease in the
United States was 0.07/100,000 in 1987.41  Due to
similar antigenicity with M avium–intracellulare, M
scrofulaceum is sometimes classified as part of a M
avium–intracellulare–scrofulaceum (MAIS) complex.
An additional organism that causes ulcerative skin
lesions and shares some biochemical characteristics
with both species is classified as M avium–
intracellulare–scrofulaceum intermediate.55
Diagnostic Features
Clinically, M scrofulaceum disease usually occurs
in healthy-appearing children and, rarely, in adults
as unilateral cervical adenopathy high in the neck,
with minimal pain or tenderness.13  Occasionally,
the involved nodes may remain stationary for per-
haps weeks to months13,56,57 and then regress, leav-
ing residual fibrosis and calcification.  More com-
monly, the nodes progress to softening with eventual
rupture and drainage.  This organism also occasion-
ally appears as scattered, multiple, subcutaneous
abscesses and in a sporotrichoid pattern (see Figure
16-7).58  Other manifestations of disease caused by
this organism include pulmonary disease, dissemi-
nated disease, conjunctivitis, osteomyelitis, menin-
gitis, and granulomatous hepatitis.
In adults, the differential diagnosis includes those
entities that produce an expanding neck mass such
as infectious adenitis, dermopathic reactive
lymphadenitis, lymphoproliferative malignancy,
metastatic node, cat-scratch fever, mononucleosis,
salivary gland infection or duct stone, subcutane-
ous or peritonsillar abscess, tuberculosis, or mumps.
In children, the differential includes the causes of
cervical lymphadenitis such as cat-scratch fever,
infectious adenitis, hematological malignancy, re-
actionary inflammatory nodes, deep abscess, or
mononucleosis.  The other skin lesions of M
scrofulaceum resemble pyogenic abscesses or
sporotrichosis (see Exhibit 16-3).
Histopathology.  The histopathological appear-
ance is essentially the same as that of tuberculosis
with varying degrees of caseation necrosis,
granulomatous inflammation, and acid-fast bacilli.
Laboratory Features.  Culture on Lowenstein-
Jensen medium produces buttery, smooth, yellow-
orange colonies in 2 to 4 weeks with the best growth
at 37°C and slow growth at 24°C, 32°C, and 35°C
(see Figure 16-3).  The colony pigmentation occurs
even when grown in the dark (scotochromogen)
and then continues to darken to a deeper orange
with prolonged exposure to light.  No reliable,
diagnostic, skin-test procedure is presently avail-
able for routine testing; and PPD skin testing may
be reactive or nonreactive.
Course, Treatment, Prognosis, and Prevention
M scrofulaceum disease usually progresses; there-
fore, therapy is recommended.  Surgical excision of
the affected lymph node has been successful in
patients who have limited cervical adenitis; how-
ever, incision and drainage alone may result in
chronic draining sinuses and recurrence despite
concomitant drug therapy.13  Successful drug
therapy has included oral rifampin (600 mg/d) plus
isoniazid (300 mg/d) for 9 months despite in vitro
resistance.58  There are no effective preventive mea-
sures yet established.
Mycobacterium xenopi Disease (Group II,
Scotochromogen)
Epidemiology
M xenopi, also called the hot-water bacillus and
M littorale, was first isolated in 1957 and recognized
as a pathogen in 1965.  This organism has been
found in both cold and hot water systems.6  Remark-
ably, it has been recovered from hot water genera-
tors and storage tanks of several hospitals, where it
was linked to pulmonary disease.13  It has been
recovered from bird droppings and, considering
the fact that it has been isolated commonly from the
coastal areas of England, Europe, and the United
States, sea birds are considered possible reser-
voirs.6,13  In the southeastern part of England, M

Military Dermatology
410
xenopi is reported22 to be the most common atypical
mycobacterium recovered in the laboratory since
1977.  Interestingly, M xenopi is common among the
atypical organisms isolated incidentally from ton-
sils.  Although not yet isolated from water mains,
the organism may enter hospital hot-water tanks in
small numbers via the water system and multiply at
its optimum growth temperature of 43°C to 45°C.
Infection may then occur by aerosolization and
absorption via the respiratory tract.22  Not a common
pathogen, its incidence in the United States is esti-
mated as 0.01/100,00041; most occurrences appear as
pulmonary disease in patients with preexisting lung
disease or other debilitating systemic disease.13
Diagnostic Features
Immunocompromised patients with M xenopi
disease may have cutaneous involvement when they
have underlying bone or soft tissue involvement
such as epididymitis, osteomyelitis, lymphadenitis,
arthritis, or sinus tract.13  The rare occurrence of
disseminated disease is usually found in AIDS pa-
tients.  The differential diagnosis of skin manifesta-
tions includes all causes related to the underlying
disease process, and pulmonary disease is clinically
identical to infections with M kansasii and M avium–
intracellulare.
Histopathology.  Histopathology is nonspecific
with collections of epithelioid macrophages,
Langhans’-type giant cells, and acid-fast bacilli
within caseating granulomas.13
Laboratory Features.  In culture, this organism is
a scotochromogen, producing yellow pigment in
the absence of light (see Figure 16-3), and growing
best at the relatively warm temperature of 42°C to
43°C after 3 to 4 weeks.  This is the temperature of
hot-water holding tanks where this organism has
been isolated, giving rise to the name hot-water
bacillus.
Course, Treatment, Prognosis, and Prevention
Infection by M xenopi is opportunistic in
immunocompromised patients and should be
treated when it occurs.  Response to therapy has
been inconsistent; however, some success has been
obtained with combinations of isoniazid, rifampin,
ethambutol, and streptomycin with uniform sus-
ceptibility to cycloserine and ethionamide.13  Pre-
ventive measures might include culturing hospital
hot-water systems in facilities that serve immuno-
compromised patients, thus ensuring an uncon-
taminated hot-water source for drinking, bathing,
hydrotherapy, and wound cleansing.
Mycobacterium gordonae Disease (Group II,
Scotochromogen)
Epidemiology
M gordonae is variously known as the water bacil-
lus, the tap-water bacillus, the tap-water scoto-chro-
mogen, and M aquae.  Rare extrapulmonary postop-
erative infections have been reported since the early
1970s28,59 but the first cutaneous infection was not
reported until 1984,60 and by 1987, only three cases
had been reported.28,61  This organism has been one
of the most common contaminant saprophytes iso-
lated in the laboratory (sometimes approaching 15%
of all mycobacterial isolates) and has been found in
water, mud, water supplies, swimming pools, and in
soil where it has been shown to multiply.13,27,28  Some
wild animals may be reservoirs, since M gordonae
strains have been recovered from the lymph nodes of
wild armadillos in Louisiana.61  An interesting case
report from Belgium involved a patient who devel-
oped cutaneous infection with M gordonae several
months after being bitten by a rat while collecting
frogs in a pond.  Although the animal bite may have
been the source of infection, it may also merely have
been the mode of organism inoculation from an-
other environmental source such as water or soil.61
Diagnostic Features
Cutaneous M gordonae infection occurs as small
tender, red-blue papulonodules 0.5 to 1.5 cm in
diameter with mamillated or ulcerated surfaces and
with or without proximal lymphangitic spread in a
sporotrichoid pattern,61 as was seen in the first
reported skin infections by this organism (see Fig-
ure 16-7).60  Occurring after inoculation from a pen-
etrating wound, infection may produce spreading,
diffuse inflammation, with the wound discharging
serosanguineous material.  The patient can have
localized lymphadenitis but systemic signs of toxic-
ity: fever, chills, malaise, nausea, and vomiting.28
The clinical differential diagnosis includes
sporotrichoid diseases (see Exhibit 16-3), other
mycobacterioses (especially M marinum or M
kansasii), pyogenic infection, sarcoidosis, and other
infectious granulomas.
Histopathology.  Histopathology reveals large
histiocytes, multinucleated giant cells, acute and
chronic inflammation, and a few of the acid-fast

Atypical Mycobacterial Diseases
411
bacilli sometimes described as “plump rods.”  The
inflammatory elements may be intermixed with
areas of fibrosis.60
Laboratory Features.  This organism produces
yellow-orange colonies even when grown in the
dark, thus it is a scotochromogen (see Figure 16-3).
The optimum growth temperature is 37°C.  The
required time for colonies to grow varies from 4 to
8 weeks, with some colonies not seen for 24 weeks
on Lowenstein-Jensen medium (see Table 16-2).
Culture growth is reported to have been enhanced
by decontamination with sodium hydroxide and by
using modified Ogawa medium at pH 6 (versus the
usual Lowenstein-Jensen medium at pH 7).61  Both
tine and Mantonx PPD skin testing with 10 tubercu-
lin units have been reported positive at greater than
5 mm induration at 48 hours.28
Course, Treatment, Prognosis, and Prevention
Therapy has included oral rifampin (300 mg/d)
alone for 6 months, or trimethoprim/sulfa-
methoxazole (320 mg/1600 mg) administered twice
daily with ethambutol (800 mg/d), both given for
24 months, with cycloserine (250 mg/d) added dur-
ing the first 9 months.28,61  Antibiotic disc suscepti-
bility testing may be useful in guiding therapy of
resistant cases of this infection.  In two reported
cases,28,61 all lesions cleared without recurrence
within the treatment periods.  In the initial report of
skin infection by M gordonae,60 the investigator warns
that this organism should not always be assumed to
be a harmless contaminant if isolated from clinical
specimens.  At the present time, no specific preven-
tive measures are recommended.
Mycobacterium avium–intracellulare Complex
Disease (Group III, Nonchromogen)
Epidemiology
The M avium–intracellulare complex is known by
a variety of synonyms including Battey bacillus
(specifically M intracellulare) and M avium complex
(MAC).  As its name suggests, M avium was first
known as a pathogen of chickens, and has been
recognized as such since 1868.  In 1943, the organ-
ism was recognized as a human pulmonary patho-
gen; however, in 1953, a separate but closely related
organism without pathogenicity for chickens was
isolated.  Later in 1957, this organism was found to
be pathogenic in several inpatients of the Battey
State Tuberculosis Hospital in Rome, Georgia, and
was named the Battey bacillus.33  This organism was
later speciated as M intracellulare, but it is so similar
to M avium that for human pathogenicity the two
can be combined into one complex.  With an inci-
dence of about 3.2/100,000 population, approxi-
mately one third that of tuberculosis, M avium–
intracellulare complex became second only to M
tuberculosis in total numbers of mycobacterial iso-
lates in the United States by 1980 (see Table 16-1).27
In the United States, this organism is found most
often in rural areas of the southeastern part of the
country.  This complex is of interest to dermatolo-
gists because of its rare involvement of skin and
lymphatics and because of its rising incidence in
AIDS patients.
M avium–intracellulare complex has been found
in soil, salt and fresh water, house dust, animal
feed, dried plants, and bedding; however, the high-
est number of isolates are found in aerosol samples.
This suggests a likely route for pulmonary infec-
tion.  Although M avium–intracellulare complex is a
cause of disease in such animals as poultry, pigs,
and monkeys, these are not thought to be sources of
human infection.13  This species of atypical myco-
bacteria is discussed in the AIDS section of this
chapter.
Diagnostic Features
In otherwise healthy patients, M avium–
intracellulare complex may be isolated from sputum
without being the cause of disease.  Disease that is
manifest is usually expressed as pulmonary infec-
tion in middle-aged white males with preexisting
lung disease.  In AIDS patients, the presence of M
avium–intracellulare is an ominous sign, especially if
it is found in the urinary or pulmonary tract.  Dis-
semination of disease is usually seen in patients
who are immunocompromised secondary to sys-
temic steroid therapy or AIDS.  Primary skin lesions
are very rare and their presence strongly suggests
immune compromise in any affected patient.  Clini-
cal manifestations of skin involvement include red-
bordered plaques or crusted ulcerations, which
range from limited numbers of lesions to spreading,
extensive lesions.  With dissemination of disease,
multiple granulomas, pustules, ulcerations, and
generalized adenopathy have been reported.29  Other
dermatologic manifestations include cervical
adenitis in children or adults, subcutaneous nod-
ules, sporotrichoid spread (see Figure 16-7),
panniculitis, fascitis, and synovitis.62  The differen-
tial diagnosis can include all reactive, malignant,

Military Dermatology
412
and infectious causes of the above underlying dis-
eases, as well as any chronic granulomatous or
sporotrichoid disease (see Exhibit 16-3).
Histopathology.  Histopathologically, skin and
lymph nodes show either caseating or noncaseating
granulomas with acid-fast bacilli either within or
outside of giant cells.  In AIDS patients, foamy
macrophages containing many intracellular acid-
fast bacilli may be seen.
Laboratory Features.  Culture on Lowenstein-
Jensen medium produces nonpigmented colonies
in the dark or light at 37°C within 2 to 3 weeks (see
Table 16-2).
Course, Treatment, Prognosis, and Prevention
In immunocompetent adult patients with local-
ized disease, surgical debridement plus oral
rifampin (600 mg/d); ethambutol (25 mg/kg/d for
2 mo, then decreased to 15 mg/kg/d); isoniazid
(300 mg/d); and ethionamide or streptomycin (ad-
ministered for several months beyond clearing) are
usually recommended.  An effective role for
isoniazid has not been clearly established.  In chil-
dren with cervical adenitis, recommended treat-
ment is local excision for primary involvement and
limited recurrence.22  Treatment of disseminated
disease in immunocompromised patients is not yet
specific; however, the above adult-disease regimens
with the addition or substitution of amikacin and
clofazimine may offer potential therapeutic advan-
tages.  Prevention lies in reducing or preventing the
causes of immunosuppression in the involved pa-
tient.  At present, the true impact of disseminated M
avium complex disease on the survival of AIDS
patients is not certain, but projections appear
gloomy.22,40
Mycobacterium ulcerans Disease (Group III,
Nonchromogen)
Epidemiology
As previously discussed, the M ulcerans organ-
ism was formerly also known as M buruli6; the
disease is likewise known by several synonyms:
Buruli ulcer (in the Buruli District of Uganda),
Kakerifu ulcer (in Zaire), Bairnsdale ulcer or Searls’
ulcer (in Australia), and Kumusi ulcer (in New
Guinea).
Although large cutaneous ulcers had been de-
scribed in Uganda in 1897 and mycobacterial skin
ulcers had been recognized in 1937 in Bairnsdale,
Australia, not until 1948 was M ulcerans first de-
scribed in patients from Bairnsdale.5,20,63  Later, in
1964, multiple cases of ulcerations, with isolation of
an organism named M buruli, occurred in the Buruli
District of Uganda.6  Subsequently, this organism
was shown to be M ulcerans.  This infection occurs
almost exclusively in tropical or subtropical cli-
mates in areas of lush vegetation or marshy terrain,
with thousands of endemic cases in Uganda and
Zaire and hundreds of cases in New Guinea and
Australia, making it the largest cause of atypical
mycobacterial skin disease worldwide.  Although
the disease is not endemic in the United States,
military physicians should be aware that infection
can be brought in from more tropical climates.  Until
1984, when it was first isolated in koalas,20 this
organism had never been isolated outside the hu-
man body; and although it has been hypothesized63
that M ulcerans resides in soil as a contaminant or on
foliage as a commensal and is transmitted via injury
from the environment, transmission from animals
to humans has not been demonstrated.
Diagnostic Features
Almost all M ulcerans lesions occur on extremi-
ties.  They probably begin as injuries or insect bites
that do not heal but instead become indurated, with
eventual necrosis and spreading ulceration.  Other-
wise, the skin lesion appears as a single, firm, some-
times itchy, papule that becomes more indurated
and fluctuant over several weeks and then breaks
OK to put on the Web
Fig. 16-9. The ulceration of this patient’s lower leg is
due to Mycobacterium ulcerans infection. Note the charac-
teristic undermined borders. The lesion is surprisingly
asymptomatic.

Atypical Mycobacterial Diseases
413
down into a spreading, punched-out ulceration with
classically undermined edges (Figure 16-9).  Mul-
tiple ulcers do appear, but have been reported in
only a few cases.64  There is little pain or tenderness
associated with the ulceration and the skin just
beyond the involved border appears perfectly nor-
mal without physical signs, systemic symptoms, or
lymphangitic involvement.  The ulceration usually
extends only down to muscle, with rare bony in-
volvement (probably due to the organism’s prefer-
ence for cooler growing conditions not usually found
in warm, viable muscle).  It has been hypothesized63
that infection usually occurs on an extremity where
the subcutaneous tissue temperature is lower than
core temperature, thus fostering growth of this or-
ganism.  In addition, if the organism is inoculated
into the skin during the hotter months, it may re-
main dormant in the skin until a prolonged cooling
period occurs, then exacerbate with development of
ulcerations.  According to some experts,63,65 this
disease should be considered in any patient who
presents with a relatively painless, chronic, pro-
gressive skin ulcer on an extremity in a tropical area
where it is endemic.  Indeed, in West Africa, where
hundreds of cases have been seen, Buruli ulcer is a
reliable clinical diagnosis.
Differential diagnosis should include infected
insect bite, pyoderma gangrenosum, brown recluse
spider bite, deep fungal infection, tuberculosis, sup-
purative panniculitis, or self-inflicted injury.
Histopathology.  Histopathology shows coagu-
lation necrosis, septate panniculitis, without
caseation necrosis, but with granulation tissue and
giant cells towards the periphery.  Smears and bi-
opsy material from the necrotic areas almost always
reveal acid-fast bacilli; however, material at the
edge of the ulceration will usually be negative for
organisms and positive for plasma cells—some with
strikingly polynuclear features.  In early skin le-
sions, large, spherical clumps of many acid-fast
organisms can be found extracellularly in the deeper
parts of necrosed, coagulated tissue.10  In recurrent
or chronic disease, acid-fast organisms may be sparse
or difficult to find.  A toxin produced by the organ-
ism is suspected as the necrolytic factor that allows
progression of this necrolytic process.66
Laboratory Features.  Cultures on Lowenstein-
Jensen medium produce nonpigmented colonies at
32°C to 33°C after 6 to 12 weeks, a relatively long
incubation time (see Table 16-2).  At culture tem-
peratures of 25°C, and above 35°C, growth may be
very slow or completely absent.  Tuberculin skin tests
are sometimes positive but not to a reliable degree.
Fig. 16-10. The large, spreading skin ulceration of this
patient’s lower shin is due to infection with Mycobacte-
rium ulcerans. Almost all Buruli ulcers occur on the extremi-
ties and, if untreated, tend to progress slowly in size.
Course, Treatment, Prognosis, and Prevention
If untreated, ulcerations tend to progress over
months to years to involve large areas (Figure 16-
10), sometimes involving an entire extremity, be-
fore healing with residual scarring, deformity, and
lymphedema.  Some rare cases have required am-
putation.67  Small lesions respond to simple surgical
curettage and heal by granulation.63  In addition,
heat application to 40°C to the involved area has
been helpful in some cases.67  The mainstay of
therapy is surgical excision of the entire area with
primary closure or skin grafting.  Drug therapy
consisting of dapsone and streptomycin with or
without ethambutol for a few weeks beyond com-
plete healing is not successful alone, but may be a
helpful adjunct in more limited surgical treatment.13
Other antituberculous drugs have not shown any
consistent efficacy; however, some response has
been seen with trimethoprim-sulfamethoxazole fol-
lowed by rifampin and minocycline.62
Preventive measures are aimed at avoiding
trauma or protecting traumatized extremities from
environmental contact in endemic areas.  Bacille
bilié de Calmette-Guérin (BCG) vaccination may be
somewhat protective for about 6 months.67
Mycobacterium haemophilum Disease (Group
III, Nonchromogen)
Epidemiology
Since its first description in 1978, most of the
dozen reported clinical cases of infection with
Mycobacterium haemophilum have been from Austra-
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Military Dermatology
414
lia or Israel.  Almost all of these cases occurred
in patients with lymphoma or renal transplants,
many of whom were lymphopenic.13,68  Organism
sources and natural reservoirs are unknown at
present.
Diagnostic Features
The skin lesions usually occur in multiple loca-
tions on the extremities and occasionally on the
trunk, with red-to-violaceous papules that gradu-
ally enlarge to become tender, crusted, ulcerated
nodules or abscesses and fistulas draining purulent
material.13,39  Rarely, patients may have bony in-
volvement or, in children, cervical adenitis may be
present.68  The clinical differential includes pyo-
genic abscesses, other mycobacterioses, metastatic
disease, osteomyelitis, and all the causes of cervical
adenitis in children.
Histopathology.  Histopathology reveals
granulomatous panniculitis with a polymorphous
infiltrate, occasional Langhans’-type giant cells, and
usually no caseation necrosis.  Straight, uniformly
staining, acid-fast bacilli are frequently present sin-
gly or in small clusters, and often intracellularly.13
Biopsy material tissue imprints frequently reveal
acid-fast organisms.68
Laboratory Features.  M haemophilum’s most
unique feature is its requirement for hemoglobin or
hemin for growth on culture media.  This require-
ment can be fulfilled with the use of chocolate agar,
5% sheep-blood agar, Mueller-Hinton agar with
Fildes supplement, or most commonly, Lowenstein-
Jensen medium with 2% ferric ammonium citrate.13
Nonpigmented colonies are produced in 2 to 4
weeks, with growth definitely stimulated by the
addition of 10% carbon dioxide.  The optimum
growth temperature is not yet established but ap-
pears to be about 30°C, especially on subculture
(see Table 16-2).  Intermediate and second-strength
tuberculin PPD skin testing have been negative in
patients tested thus far.68
Course, Treatment, Prognosis, and Prevention
It is possible that some patients may recover with
improvement in their immune status; however,
improvement has been seen after only a few weeks
of isoniazid and rifampin.68  Other reports record
resistance to isoniazid.13  Although not usually a
cause of death, M haemophilum infection does pro-
duce considerable morbidity before healing spon-
taneously after months to years.  Prognosis and
preventive measures have not been formulated.
Mycobacterium malmöense Disease (Group III,
Nonchromogen)
Epidemiology
Since the mycobacterium was first isolated in
1977 in Malmö, Sweden, only a few cases of M
malmöense pulmonary or cervical-nodal infections
in children had been reported until 1990, when the
first case of cutaneous infection was reported from
Ireland.21  One earlier case report, in 1989, was that
of an insulin-dependent diabetic who had a cold
abscess of the hand, the infection in which may have
been stimulated or possibly introduced when hy-
drocortisone was injected into a nodule that was
assumed to be a ganglion cyst.69  Most of the previ-
ous noncutaneous cases were reported from rela-
tively small areas of Wales, England, and Sweden,
and a rare case was reported from both Australia
and the United States.  Natural sources and possible
reservoirs for this organism are not known.
Diagnostic Features
A patient with M malmöense disease presented
with cervical adenitis; 6 months later, the patient
developed tender, red, dermal nodules scattered on
the extremities and trunk.21  The differential diag-
nosis can include any condition manifesting as a
tender dermal nodule or as cervical adenitis.
Histopathology.  Histopathology has shown epi-
thelioid granulomas, a few Langhans’-type giant
cells, with caseation necrosis and variable numbers
of acid-fast bacilli.21,69
Laboratory Features.  Nonpigmented colonies
grow in the dark or light in 2 to 12 weeks, with the
shorter times required when pyruvate-containing
media are used.  Optimum temperatures for colony
growth range from 24°C to 37°C, with growth usu-
ally in about 3 weeks at 37°C (see Table 16-2).
Occasionally, cultures may require up to 12 weeks
for growth.  Acid-fast stains of colony material
reveal coccoid, short, or moderately long acid-fast
organisms.
Course, Treatment, Prognosis, and Prevention
The true course of this infection is not yet clear.
Complete healing of skin lesions has occurred with
cycloserine (750 mg/d) and ethambutol (1,200 mg/
d) administered for 2 months.  After 9 months,

Atypical Mycobacterial Diseases
415
sites.17,71  The infection sometimes does not arise
until several months or even years after the caus-
ative surgical procedure.  Rarely, infection may
follow blunt trauma: in one case,72 infection devel-
oped in the hip where, 2 months before, the patient
had been kicked by a horse.  These organisms may
also cause solitary draining cervical lymph-
adenopathy (Figure 16-11), postoperative endo-
carditis, osteomyelitis, and chronic pulmonary dis-
ease.  A sporotrichoid pattern of lymphangitic
spread has been seen with M chelonae infection (see
Figure 16-7).46
The differential diagnosis includes all causes of
postoperative wound infections and injection ab-
medication was stopped, with the patient remain-
ing free of disease for more than 5 years.21  Preven-
tive measures are not yet established.
Mycobacterium fortuitum–chelonae Complex
Disease (Group IV, Rapid Growers)
M fortuitum is also known as M ranae; M minetti;
M fortuitum biovariant fortuitum; biovariant
peregrinum; and third biovariant complex, contain-
ing at least three subgroups.  M chelonae is also
known as M chelonei, M friedmannii, M abscessus, M
runyonii, and M borstelense; and as two subspecies:
M chelonae (abscessus) and M chelonae (chelonae).
Epidemiology
First found as a pathogen in frogs in 1905 and
named M ranae in 1923, M fortuitum was rediscov-
ered as a human pathogen and named by da Costa
Cruz in 1938.9  M chelonae was isolated by Friedman
in 1903 from the lung of a diseased sea turtle (Chelona
corticata).30  Although M fortuitum (with five sub-
groups) and M chelonae (with two subspecies) are
separate species of the genus Mycobacterium, their
very similar clinical manifestations and culture char-
acteristics allow them to be grouped together for
discussion of clinical skin disease.  There are subtle
differences between the two species in their
noncutaneous disease incidence (more than 90% of
the lung disease is due to M chelonae), in some drug
susceptibilities, and in DNA homology.70  These
organisms are distributed worldwide in soil, water
supplies, tap water, surgical basins, hemodialysis
equipment, hydrotherapy pools, gentian violet so-
lution, and even in laboratory distilled water con-
tainers.30  Some disease has been seen in animals such
as rodents and amphibians, but transmission to hu-
mans apparently does not occur.  Overall incidence in
the United States in 1980 was about 0.2/100,000.27
Diagnostic Features
Most M fortuitum–chelonae complex infections
follow trauma or surgery (especially cardiovascu-
lar surgery, intravenous catheter placement, and
injections) and manifest themselves, about 3 to 4
weeks after the initiating event, as tender, red, in-
durated areas or as an inflamed or cold abscess, any
of which may break down and drain.29  Occasion-
ally, firm, red-brown, nontender, subcutaneous
nodules arise at scattered sites in the skin as a result
of dissemination from prior surgery or trauma
OK to put on the Web
Fig. 16-11. The solitary draining cervical lymphadenitis
was due to Mycobacterium chelonae infection in this pa-
tient. Other patients may exhibit sporotrichoid patterns
of subcutaneous nodules due to lymphatic spread up an
extremity, or widespread scattered papulonodules from
hematogenous dissemination. Photograph: Courtesy of
Captain E. C. Oldfield, Medical Corps, US Navy, Naval
Hospital, San Diego, Calif.

Military Dermatology
416
scesses.  In disseminated disease with bacterial
embolization and scattered skin lesions with lym-
phatic involvement, the differential includes tuber-
culosis and all metastatic diseases including
lymphoma.  Sporotrichoid diseases should also be
included in the differential (see Exhibit 16-3).
Histopathology.  Histopathology shows poly-
morphonuclear cells with granulomatous inflam-
mation, necrosis, giant cells, rare caseation, and, in
about one third of the cases, acid-fast bacilli.13  In
addition, the M fortuitum–chelonae complex is the
one type of mycobacteria that does not stain well
with the auramine-rhodamine fluorochrome stain-
ing technique.
Laboratory Features.  Cultures grow in 3 to 5
days on routine culture media and Lowenstein-
Jensen medium at 24°C to 37°C without pigment
production, in darkness or light (see Table 16-2).
Old tuberculin skin testing may be weakly positive.
Course, Treatment, Prognosis, and Prevention
M fortuitum–chelonae complex infections tend to
persist, with only a 10% to 20% remission rate for
cutaneous infections, and a mortality rate of 10% to
20% with disseminated disease.30  Fortunately, all
localized diseases caused by M fortuitum–chelonae
complex organisms appear to be responsive to sur-
gical excision, with or without (depending upon the
severity and extent of disease) systemic treatment
with doxycycline, amikacin, and ciprofloxacin.
Some infections that are secondary to wound con-
tamination or injection may be prevented by (a)
using only sterile surgical equipment, syringes, and
needles and (b) adhering to strict aseptic technique
during surgical procedures, especially those proce-
dures involving deep body cavities or prolonged
tissue exposure.
Mycobacterium smegmatis Disease (Group IV,
Rapid Growers)
Epidemiology
M smegmatis was the second type of mycobacte-
rium to be described following its discovery in
syphilitic chancres and gummas in 1884.  Later, it
was found in chancres and in smegma (normal
genital secretions) and was subsequently named M
smegmatis.73  This organism has been grown from
soil and is known to occur in water and hospital
dust.24  This latter fact may account for the occur-
rence of some of the first isolations of this organism
from postoperative wound infections, mostly from
cardiac bypass surgery, which occurred beginning
in 1980.  These cutaneous infections were first rec-
ognized and reported in 1988.73  Remarkably, none
of the organisms isolated from infections in these
reported cases came from the male genital tract or
from urine isolates.  Distribution of M smegmatis is
probably worldwide but thus far reports of disease
have come only from the United States and Austra-
lia.  This may be in part due to the failure of labora-
tories to consider this organism as a pathogen when
it is isolated from patient specimens.  Disease has
been seen in cats as panniculitis (following injury)
and in cattle as bovine mastitis.
Diagnostic Features
Almost always occurring after surgery, trauma,
or invasive procedures, M smegmatis infections ap-
pear as either (a) cellulitis with redness, swelling,
pain, tenderness, and heat or (b) draining, red, swol-
len areas around wounds, from trauma or surgical
procedures including placement of intravenous
catheters.  The differential diagnosis includes any
cause of posttraumatic or postoperative wound in-
fection.
Histopathology.  Histopathology is nonspecific,
with the following findings: necrosis; presence of
epithelioid cells; a mixed inflammatory infiltrate of
giant cells, polymorphonuclear cells, and plasma
cells; and variable short, coccoid-to–moderately long
acid-fast bacilli.
Laboratory Features.  Cultures grow best on
Middlebrook 7H10 agar, with less growth on
Lowenstein-Jensen medium, at 43°C to 45°C and
always in less than 7 days.  The colonies are buff-
colored at 7 days but some develop yellow-orange
color after 2 weeks’ growth in the dark, with some
intensification of the color on exposure to light.  A
notable characteristic is the ability of this organism
to grow on special MacConkey agar without crystal
violet.  Isolates closely resemble M fortuitum in
the laboratory because both mycobacteria are rapid
growers and have similar-appearing colonies;
however, M smegmatis is distinguished by a nega-
tive 3-day arylsulfatase test, a low semiquantitative
catalase test, and colony growth at 45°C (see Table
16-2).73
Course, Treatment, Prognosis, and Prevention
Infections with this organism produce chronic
draining wounds and abscesses; however, they are

Atypical Mycobacterial Diseases
417
reported to respond well to combinations of
doxycycline, trimethoprim-sulfamethoxazole,
ciprofloxacin, and amikacin.72  Preventive measures
may be aimed at ensuring the adequacy of air filtra-
tion and the strict use of only sterile water and its
containers in operating rooms.24
ATYPICAL MYCOBACTERIAL INFECTIONS IN ACQUIRED IMMUNODEFICIENCY SYNDROME
Like other opportunistic infections, atypical my-
cobacterial infections have a much more severe and
fulminant course in patients with AIDS than in
immunocompetent patients.  The most common
atypical mycobacterial infection seen in AIDS pa-
tients is M avium–intracellulare complex disease.74,75
This may be due to the depression of monocyte and
T lymphocyte function in AIDS patients, an impor-
tant host defense specifically against M avium–
intracellulare complex and M tuberculosis, another
increasingly frequent infection in patients with
AIDS.  In one series,40 approximately 30% of AIDS
patients harbored M avium–intracellulare complex
while alive, and 52% at autopsy.  The researchers
also reported that the mere presence of M avium–
intracellulare complex in urine or respiratory secre-
tions is a sign that dissemination is impending: within
1 to 9 months.  Once dissemination occurs, treatment
has been unsatisfactory, with poor responses to the
usually effective treatment regimens and progres-
sion of disease to a uniformly fatal outcome with a
mean survival time of about 3 months.40
The new macrolides clarithromycin and azithro-
mycin have shown promise in the treatment of
disseminated M avium–intracellulare complex dis-
ease in patients with AIDS.76  In the treatment of
disseminated M avium–intracellulare complex dis-
ease, clinical trials with high-dose clarithromycin
show 98% bacteriological cure initially but with a
25% failure rate by 6 months of treatment.77
Azithromycin substantially reduced M avium–
intracellulare complex bacteremia to 7% of the
untreated level in 30 days of treatment of 21 pa-
tients.78  In vitro studies79 of the susceptibility of M
fortuitum–chelonae to the macrolides clarithromycin,
azithromycin, and roxithromycin suggest the clini-
cal usefulness of these agents against atypical my-
cobacterial infections due to this organism.  An
earlier report80 describes a patient with AIDS who
had 25 months free of M avium–intracellulare com-
plex disease following multiple drug therapy with
amikacin, clofazimine, rifampin, ethambutol, and
ciprofloxacin.  With this regimen, four other pa-
tients had favorable clinical and microbiologic re-
sponses for up to 1 year.80
Like they do in other immunosuppressed pa-
tients (ie, those who have had renal transplants;
have been treated with corticosteroids; or who have
autoimmune disease, leukemia, or lymphoma),
atypical mycobacterial infections have more fla-
grant manifestations in AIDS patients, with the
production of large lesions or extensive involve-
ment.  Individual skin lesions may reveal large
numbers of acid-fast organisms on biopsy, or even
on stained tissue smears of the skin lesion.  If a
tissue smear reveals acid-fast bacilli, specific men-
tion should be made to suspect M haemophilum, a
very rare cause of skin infection, and to include
hemin- or ferric ammonium citrate–enriched media
in culturing for this acid-fast organism.74
In addition, atypical mycobacteria that are cur-
rently classified as saprophytic may, in the future,
become true opportunistic pathogens in the popu-
lation of patients with AIDS.  Vigilance should be
exercised to rule out atypical mycobacterial infec-
tion if a patient with AIDS develops adenopathy or
unusual fulminant skin lesions.
It is apparent that, should a patient manifest
fulminant, widespread, or disseminated involve-
ment from any atypical mycobacterial infection,
especially M avium–intracellulare complex, the phy-
sician must suspect an immunocompromised sta-
tus and pursue the diagnosis.  In any patient, in fact,
even the presence of an atypical mycobacterial in-
fection should raise some suspicion of transient or
early immunosuppression.
SUMMARY
The varied and diverse group of cutaneous
mycobacterial infections arise from a combination
of the low innate pathogenicity of the organisms
and opportune exposures of the hosts.  The
virulence of the particular organism, individual
host susceptibility, and the timing and degree
of exposure all play crucial roles in the acqui-
sition, progression, and duration of the specific

Military Dermatology
418
disease produced.  Although they are classified
together in the same genus of bacteria, the various
atypical mycobacteria have widely varying clinical
manifestations, culture characteristics, histologies,
and responses to therapy.  These very diversities,
however, help to define the specific organism in-
volved and the spectrum of disease produced in
immunocompetent and immunocompromised
patients.
The incidence of these diseases in the military
has been negligible in the past.  Medical officers
should be aware of them, however, especially as the
population of immunocompromised individuals
continues to increase.
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The authors acknowledge the technical advice of Deanne Harley in the preparation of the bacteri-
ology section on atypical mycobacteria.

Superficial Fungal Skin Diseases
423
Chapter 17
SUPERFICIAL FUNGAL SKIN DISEASES
JAMES E. FITZPATRICK, M.D.*
INTRODUCTION
MILITARY HISTORY AND EPIDEMIOLOGY
DERMATOPHYTOSIS
Clinical Features
Diagnosis
Treatment
CANDIDOSIS
Clinical Features
Diagnosis
Treatment
PITYROSPORUM INFECTIONS
Clinical Features
Diagnosis
Treatment
MISCELLANEOUS FUNGAL INFECTIONS
SUMMARY
*Colonel, Medical Corps, U.S. Army; Chief, Dermatology Service, Fitzsimons Army Medical Center, Aurora, Colorado 80045-5001

Military Dermatology
424
INTRODUCTION
In years past, fungi (including molds) were clas-
sified as a subdivision of the plant kingdom.  Tax-
onomists have recently acknowledged that fungi
lack important features of plants (eg, chlorophyll
and differentiation into roots, stems, and leaves)
and therefore merit inclusion in the new kingdom,
Mycota.  This large and diverse kingdom comprises
more than 100,000 recognized species.  Of this large
group, only about 300 species have been identified
as human pathogens; however, more than three
fourths of these pathogens infect primarily the skin
or subcutaneous tissues.
Fungi can be characterized as aerobic, heterophilic
(ie, they require exogenous carbon sources), eu-
karyotic (ie, the nucleus is organized, with associated
subcellular structures), achlorophyllous organisms
that reproduce by sexual or asexual or both means.
Their size and form are highly variable: they can be
unicellular and microscopic (eg, yeast) or multicel-
lular and large (eg, mushrooms).  The cellular mem-
branes of fungi contain ergosterol and zymosterol,
in contrast to mammalian cellular membranes,
which possess cholesterol as their primary sterol.
This is an important distinction because many of
the drugs used to treat fungi (eg, imidazoles and
allylamines) primarily inhibit ergosterol synthesis,
and thus minimally affect the human host.
Fungal infections can be divided into four broad
groups: superficial, localized subcutaneous, sys-
temic, and opportunistic.  The superficial fungal
infections, which are the subject of this chapter,
include those that attack the epidermis, mucosa,
nails, and hair.  While dermatophytes are the most
common cause of superficial infections of the skin
and its appendages, many nondermatophytes can
also produce superficial infections (Exhibit 17-1).
By convention, dermatophytes are defined as fungi
that can utilize keratin as a substrate for growth,
while nondermatophytes use other substrates (eg,
EXHIBIT 17-1
FUNGI CAUSING SUPERFICIAL
CUTANEOUS INFECTIONS
Dermatophytes
Epidermophyton floccosum
Microsporum species
Trichophyton species
Nondermatophytes
Candida species
Pityrosporum orbiculare (Malassezia furfur)
Exophiala werneckii
Piedraia hortae
Trichosporon beigelii
Hendersonula toruloidea
Scopulariopsis brevicaulis
lipids).1  This distinction is somewhat artificial,
however, as the nutritional requirements have not
been clearly established for all species.
Superficial fungal infections are most commonly
acquired from other humans (the anthropophilic
species) but may also be acquired from soil (the
geophilic species) and animals (the zoophilic spe-
cies).  This point is important for medical officers to
remember because soldiers in combat are more likely
to be exposed to and become infected with fungi
that inhabit the soil and infest wild animals.
Although most superficial fungal diseases are
trivial, when they infect military personnel the
morbidity associated with these infections and their
potential effects on military campaigns cannot be
overemphasized.1
Historically, superficial fungal infections have
produced minimal disease in temperate climates
such as seen in European theaters of combat.  The most
severe outbreaks are generally associated with tropi-
cal climates and exposure to new strains of fungi.
The medical report on skin diseases encountered
during World War I in the British Royal Army states
that only 25 of 8,313 (0.3%) cases admitted to a single
general hospital for skin diseases over an 8-mo period
were for “ringworm.”2  This figure is surprisingly low
and invites speculation that some cases might have
been misdiagnosed as inflammatory skin conditions.
MILITARY HISTORY AND EPIDEMIOLOGY

Superficial Fungal Skin Diseases
425
The U.S. Army Medical Department’s official
history of medicine during World War II3 reported
data for the continental United States as well as
for different combat theaters.  For example, only 6%
of soldiers seen for skin disease at Fort Lee, Vir-
ginia, were seen for superficial fungal infections.
As might be expected, the incidence of these infec-
tions was not strikingly different for the European
theater of operations, but warmer climates were
associated with higher attack rates.  Of combat
soldiers seen for skin disease in the Mediterranean
theater, up to 22% had diseases that were attribut-
able to dermatophytic infections.  As expected, rear-
echelon troops experienced a much lower rate of
infection.  In a study of the British Royal Army in
Southeast Asia, investigators methodically exam-
ined the skin of both European and Southeast Asian
troops stationed in the Far East.  They noted that
34% of European soldiers had a tinea infection,
while only 7% of the Southeast Asian troops had
similar infections.4  Besides the high attack rate, the
European soldiers demonstrated widely dissemi-
nated or “florid” disease when compared to the
types of dermatophytic infections normally seen in
the United Kingdom.
The Vietnam conflict provides the best data on
the impact of superficial fungal infections on mili-
tary operations in a tropical climate.  Skin diseases
were the most common cause of outpatient visits
during the war, accounting for 12.2% of visits, and
superficial fungal infections were the most com-
mon skin disease.  In one dermatology clinic, super-
ficial fungal infections accounted for 12.3% of visits;
the most common types were dermatophytosis,
pityriasis versicolor, and candidosis.5  The effect on
combat troops in the forward areas was even more
dramatic: of 142 soldiers in the Mekong Delta who
were studied as they came in for their noonday
meals, 86 had “significant” dermatophytosis—an
incidence of 65%.6  Lieutenant Colonel Alfred M.
Allen, in his seminal book on the skin diseases seen
during the Vietnam conflict, states:
Superficial fungal infections were the most com-
mon and troublesome of all the dermatologic con-
ditions that occurred among U.S. forces in Viet-
nam.  Hardly anyone escaped some form of mycotic
skin infection during his tour of duty in Vietnam,
and a large majority of ground combat troops in
wet, lowland areas developed extensive inflamma-
tory lesions that led to high rates of disability.5(p59)
Although most superficial fungal infections merely
produced discomfort and large numbers of outpa-
tient visits, significant numbers of soldiers were
hospitalized for dermatophytosis or its secondary
complications.  During a 1-year period, the 17th
Field Hospital in Saigon reported 25 admissions
related to dermatophytosis; this accounted for 7%
of all admissions for skin conditions.  Most cases
were successfully managed in Vietnam; even so,
dermatophytosis caused 127 soldiers to be medi-
cally evacuated to the continental United States
from 1965 to 1970.5
Accurate figures regarding the current incidence
of superficial cutaneous fungal infections in sol-
diers stationed in the Zone of Interior during peace-
time are not available.  They would be expected to
parallel those of the civilian population when cor-
rected for age, sex, and geographical location.  In
the best study done to date, investigators examined
and cultured 152 healthy air force recruits in Texas
and demonstrated that 12.5% were infected with
dermatophytes.  In general, the degree of infection
was not as severe as that were seen in Vietnam.7
DERMATOPHYTOSIS
Dermatophytic infections can be organized and
studied either according to their etiology (Exhibit
17-2) or their clinical presentation (Table 17-1).
Because the etiology is usually important only in
epidemiological studies, this chapter is organized
by clinical presentation.  The field of dermatology
has, unfortunately, used different Latin names to
designate infections by the clinical appearance and
site of involvement.  The plethora of terms pro-
duced is confusing to patients and physicians alike,
but the names are too ingrained in the medical
literature to change.
Clinical Features
The clinical presentation of dermatophyte infec-
tions depends on several factors including the site
of infection, the species of fungus, and the host’s
response.  Because dermatophytes utilize keratin
for a substrate, they infect areas of the body with
abundant keratin such as the stratum corneum of
the skin, hair, and nails.  With rare exceptions,
dermatophytes are confined to tissue with keratin
and will not invade living tissue.  Some species have
an affinity for the keratin of hair follicles (eg,

Military Dermatology
426
EXHIBIT 17-2
IMPORTANT DERMATOPHYTOSIS-
PRODUCING SPECIES
Genus Epidermophyton
E floccosum
Genus Microsporum
M audouinii
M canis
M ferrugineum
M gypseum
M nanum
Genus Trichophyton
T concentricum
T mentagrophytes
T rubrum
T schoenleinii
T tonsurans
T verrucosum
Trichophyton tonsurans), while other species have an
affinity for the keratin of skin and nails (eg,
Trichophyton rubrum).  This explains the frequent
limitation of infections to one site.
The host’s response to infection is an important
determinant of the clinical presentation.  Patients
with intense host responses to fungal infections
produce inflammatory lesions that may be
erythematous or even vesiculobullous, while hosts
who have muted responses will produce scaly le-
sions with minimal scaling.
Tinea Capitis
Tinea capitis is primarily a disease of children,
with the peak incidence occurring between the
ages of 2 and 9 years.  In one large study done in
Chicago, 95% of culture-proven patients were un-
der 15 years of age.8  However, no age group is
exempt: patients as old as 64 years were included in
this study.  Recent evidence9 suggests that an a-
symptomatic carrier state may be more common in
adults than previously appreciated.  Tinea capitis is
an uncommon problem in servicemen even under
wartime conditions, but military physicians fre-
quently diagnose and treat this condition in depen-
dent children.
The most common organisms producing tinea
capitis vary in different geographical regions.  In
the United States, the most common organisms are
the fungi Trichophyton tonsurans followed by
Microsporum canis.  Prior to World War II, Microsporum
audouinii was the most common cause of tinea
capitis, but this fungus has almost disappeared in
the United States.  (The author has seen only one
case of tinea capitis produced by this organism
during the last 15 y.)  Trichophyton tonsurans and
Microsporum audouinii are anthropophilic fungi
that are transmitted directly or indirectly from per-
son to person; Microsporum canis is a zoophilic or-
ganism that is often acquired from dogs or cats.
The clinical presentation of tinea capitis may
broadly be divided into noninflammatory and in-
flammatory states; the latter is slightly more com-
mon.  In the most common noninflammatory pat-
tern, patients present with patchy, white scales that
may resemble seborrheic dermatitis (Figure 17-1).
As a rule, a diagnosis of “seborrheic dermatitis” in
a prepubescent child is tinea capitis until proven
otherwise.  Close examination will often reveal the
characteristic hairs broken just above the level of
the skin.  Occasional patients also may demonstrate
dermatophytic infection of other cutaneous sites.
In other patients, broken hairs may predominate,
producing diffuse or patchy alopecia that may re-
semble alopecia areata.  Occasional patients may
present with “black-dot ringworm,” in which areas
of alopecia demonstrate numerous broken, black,
TABLE 17-1
CLINICAL PRESENTATIONS OF
DERMATOPHYTOSES
Infection
Clinical Site
Tinea capitis
Scalp
Tinea favosa
Scalp
Kerion
Scalp, hair
Majocchi granuloma
Hair
Tinea faciei
Face
Tinea barbae
Beard
Tinea corporis
Glabrous skin
Tinea cruris
Groin
Tinea manuum (manus)
Hand
Tinea pedis
Feet
Tinea unguium
Nails

Superficial Fungal Skin Diseases
427
Fig. 17-2. Alopecia and numerous broken hairs (black-
dot ringworm) characteristic of infection with Tricho-
phyton tonsurans.
Fig. 17-4. Kerion with secondary bacterial infection on
the scalp of this young patient. The thick crust and edema
are characteristic.
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Fig. 17-1. A child presented with tinea capitis due to
Microsporum audouinii, which manifested as diffuse scal-
ing with occasional broken hairs. The child acquired the
infection while the family was stationed in Turkey.
Fig. 17-3. Alopecia and scalp abscesses typical of kerion.
Clinicians can easily confuse these with bacterial ab-
scesses.
hair shafts that resemble comedones (Figure 17-2).
In the United States, this pattern is almost
pathognomonic of Trichophyton tonsurans infection,
although in other geographical areas, Trichophyton
violaceum also may produce a similar pattern.
Inflammatory tinea capitis is due to a heightened
host cell-mediated immune response, virulent
strains, or a combination of these two factors.  Milder
cases present as acute folliculitis with minimal in-
duration of the surrounding tissues, while severe
cases present as inflammatory, indurated plaques
containing perifollicular abscesses (Figure 17-3).
This last pattern is termed a kerion.  Clinically, it
may be confused with bacterial pyodermas, and it is
not unusual for patients to be initially treated with
oral antibiotics directed against Staphylococcus
aureus, as secondary impetigo is common (Figure
17-4).  Lymphadenopathy, particularly of the poste-
rior cervical triangle, is frequently present and may
further suggest bacterial infection.  While most pa-
tients do not demonstrate systemic symptoms, se-
vere kerions may be associated with high fevers and
malaise.
Tinea favosa (also called tinea favus) is a rare
variant of tinea capitis produced by T schoenleinii.
This variant is rare in North America, although
small outbreaks have been reported in Quebec and
Kentucky.10  Clinically, tinea favosa is characterized

Military Dermatology
428
OK to put on the Web
Fig. 17-5. Deep, follicular pustules of tinea barbae. These
lesions result from inflammation at the site of the the
organism : the follicular epithelium.
17-5).  It is typically unilateral.  Large, indurated
plaques resembling kerion may be present in the
most severe cases.  As is true with kerions, the
inflammatory and pustular nature of this condition
frequently suggests a bacterial etiology and early
misdiagnoses are common.
Tinea Corporis
Tinea corporis was a major problem for U.S.
troops during the Vietnam conflict, particularly
those assigned to combat units exposed to wet ter-
rain.  In the United States, the most common organ-
ism recovered is T rubrum; however, during the
Vietnam conflict, the most common isolated species
recovered from lesions of tinea corporis and tinea
cruris was a zoophilic strain of T mentagrophytes
that accounted for 73% of fungal infections in com-
bat servicemen.11  Epidemiological studies demon-
strated that the most likely source was native
rats.  Interestingly, native Vietnamese troops and
civilians were not recorded as having infections
with this strain.  The predominant organism identi-
fied from native Vietnamese was T rubrum.  These
data suggest that the American troops had not pre-
viously been exposed to this strain, and were
thus immunologically susceptible to severe infec-
tions, while the native Vietnamese had developed
immunity.  This situation could recur in future
conflicts.
In domestic anthropophilic infections, the sites
of predilection are the neck, trunk, and buttocks,
although any site may be involved.  Most patients
complain of pruritus although occasional patients
are asymptomatic.  The primary lesion is an annu-
Fig. 17-6. Primary lesion of tinea corporis demonstrating
annular morphology and trailing scale.
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by an inflammatory alopecia demonstrating cup-
shaped, honey-colored crusts called scutula, which
are composed of masses of hyphae and serum.
Tinea capitis is a benign disease if quickly diag-
nosed and properly treated.  Patients with
noninflammatory forms and folliculitis will not
demonstrate significant permanent hair loss.  In
patients with the kerion pattern of infection, how-
ever, approximately 50% will eventually recover
normal hair density, approximately 25% will dem-
onstrate focal hair loss that is cosmetically accept-
able, and approximately 25% will demonstrate cos-
metically significant permanent hair loss.
Tinea Barbae
Tinea barbae is the term reserved for fungal in-
fection of the bearded areas of the face and is thus
limited to postpubertal males.  Most patients with
tinea barbae are from rural areas and acquire it from
close contact with animals such as horses or cows.
The most common organisms are zoophilic strains
of T mentagrophytes or T verrucosum.  In years past,
it was called “barber’s itch” because the disease was
commonly acquired from infected hair-cutting in-
struments used in barber shops.  Tinea barbae was
not unusual during the Vietnam conflict, but it
posed considerable diagnostic and management
problems for physicians because it was frequently
misdiagnosed as abscesses, granulomas, or allergic
contact dermatitis.  Attempts at treatment by surgi-
cal drainage resulted in excessive scarring.
Patients with tinea barbae present with severe,
deep, pustular folliculitis of the beard area (Figure

Superficial Fungal Skin Diseases
429
(tinea incognito) that seems to occur with great
frequency.
Majocchi Granuloma.  Majocchi granuloma is a
variant of tinea corporis that is clinically similar to
kerion of the scalp.  The most common organisms are
T rubrum and T mentagrophytes.  The most common
location is the leg, followed by the arm.  Clinically,
patients present with boggy, indurated papules and
plaques that may drain purulent material through
the follicular orifices (Figure 17-8).  More-typical
annular lesions suggesting the correct diagnoses
may or may not be present.12  The patients may demon-
strate systemic symptoms and fever suggesting a sys-
temic infection.  From a histological standpoint, the
name is a misnomer because the primary histologi-
cal process is that of follicular neutrophilic ab-
scesses, although variable granulomatous inflam-
mation is present in mature lesions.
Tinea Imbricata.  Tinea imbricata is a variant
seen in the South Pacific and some regions of South
America.  The etiologic agent is T concentricum.  This
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Fig. 17-7. Extensive tinea corporis in an infantry soldier
acquired at Fort Benning, Georgia.
lar, sharply circumscribed, erythematous ring with
variable white scale that is most pronounced at the
trailing edge of the expanding ring (Figure 17-6).
The areas within the centers of the annular lesions
demonstrate variable clearing with some lesions
demonstrating residual scale, hypopigmentation,
or hyperpigmentation.  Less commonly, multiple
consecutive rings produce a lesion that resembles a
target.  The numbers and sizes of the lesions are
variable; some patients may demonstrate extensive
involvement (Figure 17-7).  Zoophilic strains ac-
quired during combat in Vietnam showed a predi-
lection for areas covered by wet clothing that could
not be easily removed during combat, especially the
buttocks and waist.  Zoophilic strains tend to pro-
duce more-inflammed lesions and frequently show
follicular involvement and secondary bacterial in-
fections.
Tinea Faciei.  Tinea faciei is a regional variant of
tinea corporis that involves the face but does not
affect the beard.  Clinically, the primary lesions are
often circinate and well defined, as they are in other
forms of tinea corporis, but ill-defined erythematous
lesions with indistinct borders is a clinical variant
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Fig. 17-8. This patient’s extensive Majocchi granuloma
was acquired in the Panama Canal Zone. The patient had
fever and malaise and required hospitalization for diag-
nosis and treatment.

Military Dermatology
430
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form of infection is generally restricted to native
populations and it has not been a significant problem
even when American soldiers have operated in en-
demic areas.  Clinically, it is characterized by exten-
sive concentric rings of scale that involve extensive
areas of the body and produce a “geographical”
pattern that resembles the relief scale of a map.
Tinea Cruris
Tinea cruris (ie, jock itch) is almost exclusively
limited to men, although women may, rarely, dem-
onstrate a transient infection.  This is probably the
most common superficial fungal infection seen in
young men.  During the Vietnam conflict, it was the
single most common dermatophytic infection: 33%
of all U.S. combat troops developed tinea cruris.11
In domestic infections, the most common causative
organisms are T rubrum, T mentagrophytes, and E
floccosum.  Epidermophyton floccosum is highly infec-
tious and has a high attack rate when men are
housed together in military barracks, penal institu-
tions, or dormitories, or on athletic teams.  In a
study of Colombian soldiers, investigators reported
that E floccosum accounted for 82% and 78% of cases
of tinea cruris in two separate groups of soldiers.13
During the Vietnam conflict, the most common
organisms were zoophilic strains of T mentagrophytes,
followed by E floccosum.11  In addition to heat and
humidity, the wearing of tight briefs appears to be
a predisposing factor in acquiring and maintaining
tinea cruris.
Clinically, the disease may be unilateral or bilat-
eral.  Tinea cruris is often highly pruritic, and severe
cases may produce pain (due to friction) on
ambulation.  The lesions typically start in a crural
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Fig. 17-9. Chronic tinea cruris demonstrating character-
istic annular border.
Fig. 17-10. Scaly, noninflammatory tinea pedis with con-
centric rings radiating from interdigital space.
fold between the scrotum and upper thigh as
an erythematous papule that demonstrates a typi-
cal, erythematous, annular configuration as it
spreads to the upper thigh (Figure 17-9).  More-
severe lesions demonstrate vesicles, pustules, or
crusting.  Clinical involvement of the scrotum is
uncommon.
Tinea Pedis
Tinea pedis is the term applied to dermatophytic
infections of the feet.  In the United States, this is the
most common form of superficial fungal infection.
The most common organism in domestically ac-
quired infections is T rubrum, followed by T
mentagrophytes and E floccosum.  During the Viet-
nam conflict, the most common organism was, again,
a zoophilic strain of T mentagrophytes.6
Clinically, domestically acquired tinea pedis usu-
ally presents as either toe web infections or demon-
strates diffuse involvement of the soles.  Pruritus
may at times be intense.  The interdigital form is
usually produced by an anthropophilic strain of T
mentagrophytes var interdigitale, while diffuse in-
volvement of the soles (ie, the “moccasin sandal”
form) is more commonly produced by T rubrum.
The typical, interdigital infection demonstrates scale
between the toes on the plantar side, most typically
seen around the fourth toe (Figure 17-10).  Variable
erythema or even vesicles may also be present.
Secondary bacterial overgrowth is typically present
in those lesions that demonstrate macerated, whit-
ish, hyperkeratotic toe webs associated with a foul
odor (Figure 17-11).  Some authorities use the term
dermatophytosis simplex for the former condition and
dermatophytosis complex for the latter variant.14  The

Superficial Fungal Skin Diseases
431
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Fig. 17-11. Macerated, hyperkeratotic tinea pedis. Macer-
ated tinea pedis may become severe enough to inhibit a
soldier’s combat effectiveness.
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Fig. 17-12. Severe, bullous tinea pedis of the instep ini-
tially diagnosed and treated as allergic contact dermatitis.
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mentagrophytes.  The effect of tinea manuum on
military campaigns has been insignificant because
of its low prevalence and minimal morbidity.
Tinea manuum commonly presents as diffuse
scaling of the palms similar to the moccasin-sandal
appearance of tinea pedis (Figure 17-13); variable
erythema and vesicles may be present in patients
with pronounced hypersensitivity.  Most cases of
tinea manuum are unilateral and are associated
with bilateral infection of the feet, producing
the “two-feet-one-hand” syndrome.  This presenta-
tion is virtually diagnostic of dermatophytic
infection.  In cases difficult to differentiate from
other inflammatory dermatoses, the presence of
associated nail involvement may provide a valu-
able clinical clue.
moccasin-sandal pattern is characterized by diffuse
hyperkeratosis and scaling of the entire plantar
surface.  This variant is often asymptomatic and
many patients assume that they have dry feet.  In
severe cases that extend to the instep or over the
dorsal surface, inflammation or vesiculobullous le-
sions may occur (Figure 17-12).  Bullous tinea pedis
is most likely to occur on the instep of patients with
a strong hypersensitivity to fungal antigens; how-
ever, any area of the foot may develop blisters.
During the Vietnam conflict, in addition to toe web
and plantar surface infection, severe infections of
the dorsal surfaces of the feet and ankles were often
present under the wet boots and made marching
uncomfortable or impossible.  Secondary bacterial
pyodermas or cellulitis often complicated these in-
fections.5  Nail involvement is present in a high
percentage of patients with diffuse hyperkeratosis,
and less commonly in patients with interdigital
infection.
Tinea Manuum
Tinea manuum (also called tinea manus) is the
term applied to dermatophytic infections of the
hand.  Tinea manuum is frequently associated with
tinea pedis, but it is much less common.  The most
common organism is T rubrum, followed by T
Fig. 17-13. Tinea manuum demonstrating diffuse
hyperkeratosis of the left palm. The patient had similar
“moccasin sandal” lesions of both feet.

Military Dermatology
432
Tinea Unguium
Tinea unguium is the most precise term for der-
matophytic infections of the nail; the more com-
monly used term onychomycosis encompasses all
fungal infections of the nail, including nondermato-
phytes.  Onychomycosis is the most common cause
of nail diseases presenting to physicians for treat-
ment.15  Dermatophytes are responsible for 27% to
66% of all cases of onychomycosis—depending on
the survey.
As in tinea pedis, tinea unguium is most com-
monly caused by anthropophilic strains of T rubrum
and T mentagrophytes, with the former accounting
for approximately 80% of infections.15  Most cases
are associated with tinea pedis or tinea manuum
and are believed to arise from local extension of
these infections under the nail plate.  Tinea unguium
is not common in active-duty personnel but ap-
pears to be much more common in elderly persons.
Infection of the toenails is more common than infec-
tion of the fingernails, reflecting the higher preva-
lence of tinea pedis.  Usually the infected nail is
asymptomatic, but occasionally the nails may be-
come painful because of trauma or poorly fitting
shoes.
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Fig. 17-15. Tinea unguium demonstrating subungual
hyperkeratosis and onycholysis. This is asymptomatic,
as the surrounding skin is not affected.
Four clinical variants of tinea unguium have been
defined: distal subungual hyperkeratosis, lateral
onychomycosis, proximal onychomycosis, and
leukonychia mycotica.  Distal subungual hyper-
keratosis is the most frequently encountered clini-
cal presentation.  One or more nails demonstrate
subungual hyperkeratosis manifesting as a yellow-
ish white or yellowish gray focal thickening of the
nail that starts at the distal end and progresses
proximally (Figure 17-14).  Ultimately, the entire
nail may be thickened and crumbly, or variable
onycholysis may occur (Figure 17-15).  Lateral
onychomycosis is clinically similar except that it
starts at the lateral edge of the nail.  Proximal
onychomycosis is a very uncommon variant that
may be more common in patients with acquired
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Fig. 17-14. Patients commonly present with tinea unguium
demonstrating subungual hyperkeratosis.
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Fig. 17-16. White, opaque macular lesions of leukonychia
mycotica.

Superficial Fungal Skin Diseases
433
immunodeficiency syndrome.  Leukonychia
mycotica is a somewhat uncommon variant in which
the nail is invaded from its dorsal surface.  Clini-
cally, this manifests as white, opaque macules on
the nail plate (Figure 17-16).15
Diagnosis
The diagnosis of dermatophytic infections is usu-
ally easy but even the most astute clinician may
miss atypical variants.  Establishing the diagnosis
hinges on the demonstration of the organism by
microscopical examination of skin scrapings, cul-
ture, or biopsy material.
The following 10 clinical presentations are all
suggestive of dermatophytosis and the appropriate
investigative studies should be carried out:
1.
children with “seborrheic dermatitis” (ie,
scaly scalps),
2.
children with hair loss,
3.
children with pyodermas of the scalp,
4.
any lesion that is scaly and annular,
5.
any lesion that is red and annular,
6.
any bullous lesion of the hands or feet,
7.
unexplained follicular abscesses, especially
of the legs,
8.
dermatitis of the groin,
9.
dermatitis or scale of the toe webs, and
10.
“dry” feet or one “dry” hand.
It should be emphasized that these are only guide-
lines; atypical variants may be missed even if these
principles are followed.  Once a dermatophytic
infection is suspected, the diagnostic test of choice
is the direct microscopical examination of the sus-
pected site: skin, hair, or nails.  Skin specimens are
best obtained by wetting the surface with an alcohol
wipe or water and scraping the advancing edge of a
lesion with a number 15 scalpel blade.  Some derma-
tologists do not wet the skin; however, this method
is inferior because the specimen does not adhere to
the blade and the resulting sample is smaller and
may be lost in transport.  The specimen is then
smeared on a glass slide and one or two drops of
10% to 20% potassium hydroxide is placed on the
specimen.  The slide is gently heated and examined
under a microscope for the presence of hyphal ele-
ments.  The hyphae of dermatophytes are linear,
branched, demonstrate regular walls, and often
demonstrate a subtle greenish hue (Figure 17-17).  If
dimethyl sulfoxide is included in the potassium
hydroxide, then the heating step is not required.  A
number of other stains and methods are available
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Fig. 17-17. This positive potassium hydroxide examina-
tion of glabrous skin demonstrates the characteristic
branched hyphae of a dermatophyte. However, the spe-
cies cannot be differentiated on the basis of potassium
hydroxide preparations.
but potassium hydroxide examination remains the
standard.  In cases of suspected tinea capitis, the
best results can be obtained when broken hairs can
be plucked and examined using potassium hydrox-
ide (Figure 17-18).  Nails are inherently much more
difficult to sample because the viable hyphae are
often only at the proximal advancing edge.  Ini-
tially, the proximal subungual debris should be
scraped or the distal nail should be cut off for
potassium hydroxide examination.  If this examina-
tion is negative, the advancing edge can be sampled
by carefully drilling a small hole with a large-bore
Fig. 17-18. This positive potassium hydroxide examina-
tion of infected hair demonstrates hyphae and ar-
throspores in a patient with tinea capitis due to
Trichophyton tonsurans (original magnification 100X).
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Military Dermatology
434
needle.  Occasionally, other fungi, including Can-
dida albicans, Scopulariopsis brevicaulis, Hendersonula
toruloidea, Aspergillus species, Alternaria tenuis,
Cephalosporium species, and Scytalidium hyalinum
may produce onychomycosis.15  These infections
can be excluded only by culture.
In most studies, direct microscopical examina-
tion is much more sensitive than culture, but this
depends on the experience of the examiner.  In one
study of 220 patients’ dermatophytic infections,
97% were positive by direct potassium hydroxide
examination and 48% were positive by culture.
Positive cultures were obtained in only 2.7% of
potassium hydroxide–negative specimens.16  Simi-
lar results have been shown in several other stud-
ies.17,18
Cultural confirmation is often used by physi-
cians who lack confidence in their direct micro-
scopical examinations.  Most dermatologists use
cultures to exclude dermatophytic infections when
the diagnosis is still suspected despite repeated
negative potassium hydroxide examinations.  Der-
matophyte test medium is the most frequently used
cultural medium.  The sample is obtained in a fash-
ion identical with that used for potassium hydrox-
ide examinations and inoculated directly onto the
culture medium.  Dermatophytes usually grow
within 7 days and turn the yellowish-orange me-
dium a bright red color.  If the medium turns red
later than 1 week, then the color change was most
likely caused by a contaminant.  Dermatophyte test
medium is not reliable for speciation, and if this is
deemed necessary, the colony can be transferred to
Sabouraud’s agar.  Alternatives to dermatophyte
test medium for initial isolation include Sabouraud’s
agar (Figure 17-19) or Sabouraud’s agar with antibi-
otics (Mycosel, manufactured by Baltimore Biologica
Co., Baltimore, Maryland.)
In cases of suspected tinea capitis, a Wood’s lamp
is useful in cases of fluorescent dermatophytes,
which includes M canis, M audouinii, M ferrugineum,
and T schoenleinii.  The former three organisms will
demonstrate a bluish-white fluorescence of infected
hairs, while T schoenleinii will demonstrate a dull
bluish-white fluorescence.  A negative Wood’s light
examination does not exclude tinea capitis, how-
ever, because T tonsurans, the most common of-
fender, does not fluoresce.
In rare cases, a biopsy may be required to estab-
lish the diagnosis.  This most commonly occurs in
kerions or Majocchi granuloma, when the organ-
isms may be difficult to demonstrate using less
invasive techniques.  The organisms are often diffi-
cult to visualize using standard hematoxylin-eosin
stains; special stains such as periodic acid-Schiff
with diastase or Gomori’s methenamine silver stain
are often required (Figures 17-20 through 17-22).
Treatment
The options available for the treatment of der-
matophytic infections are numerous and confusing
(Exhibit 17-3).  In many clinical situations, the opti-
mal therapy has not been established, and military
physicians rely on anecdotal information and local
availability of antimycotic agents.  Treatment most
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Fig. 17-19. Positive culture on Sabouraud’s agar for
Epidermophyton floccosum, a common cause of tinea cruris.
Sabouraud’s agar is the medium most commonly used
for the culture and identification of dermatophytes.
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Fig. 17-20. This specimen from a biopsy of tinea capitis
demonstrates marked invasion and destruction of the
hair shaft (hematoxylin-eosin stain, original magnifica-
tion 200X).

Superficial Fungal Skin Diseases
435
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Fig. 17-21. This specimen from a biopsy of tinea capitis
demonstrates improved visualization of fungal elements
with special stains (Gomori’s methenamine silver stain,
original magnification 100X).
Fig. 17-22. This specimen from a biopsy of tinea corporis
demonstrates both horizontal and cross sections of hy-
phae (hematoxylin-eosin stain, original magnification
200X).
from the gut approximately twice as efficiently.
The dosages discussed in this chapter are for the
ultramicrosize griseofulvin.  If microsize grise-
ofulvin is used, the listed dosage should be doubled.
The optimal dosage of ultramicrosize griseofulvin
for the treatment of tinea capitis in children has not
been established.  The accepted doses vary—de-
pending on the authority cited—from 3.3 mg/kg to
5.0 mg/kg/d, given in a single daily dose.  Adults
should be treated with a total daily dose of 330 to
750 mg/d, depending on the severity of infection
and tolerance to griseofulvin.  Divided daily doses
produce higher plasma levels and should be used if
compliance is not a problem.19  Treatment should
continue for a minimum of 2 months, or 2 weeks
past the last negative culture.  Twice-weekly sham-
pooing with 2% selenium sulfide is reported to be a
useful adjunctive agent in the treatment of tinea
capitis in children because it is sporicidal and may
decrease the chances for spreading the infection to
other individuals.20  Ideally, other members of the
family, especially children, should be examined as
concurrent infection is not infrequent.  Kerions re-
quire, in addition to antifungal therapy, intralesional
triamcinolone acetonide at a strength of 5 to 10 mg/
mL for limited lesions.  Extensive lesions require
the addition of oral prednisone at a dose of 1 to 2
mg/kg/d for 2 to 4 weeks.
The treatment of tinea corporis depends on the
extent of involvement.  Limited cases are best treated
by twice-daily applications of a broad-spectrum
antifungal cream (eg, one of the imidazoles,
ciclopirox olamine, or naftifine).  Inflamed and scaly
areas should be treated for 2 weeks past the point of
commonly involves the use of specific antifungal
agents, although nonspecific measures are often
used to augment the primary therapy (Figure 17-23).
The treatment of choice for tinea capitis and
other infections that invade hair follicles (eg, tinea
barbae or Majocchi granuloma) is oral griseofulvin.
Griseofulvin is available in both microsize and
ultramicrosize forms, with the latter being absorbed
EXHIBIT 17-3
ANTIMYCOTIC DRUGS
Topical
Imidazoles
Clotrimazole
Econazole
Ketoconazole
Miconazole
Oxiconazole
Sulconazole
Allylamines
Naftifine
Hydroxypyridones
Ciclopirox olamine
Oral
Griseofulvin
Ketoconazole

Military Dermatology
436
Treatment of Dermatophyte Infections
Follicular*
Glabrous‡
Hands/Feet
Nails
1st-Line Drugs
Griseofulvin
Imidazole
Imidazole
Ciclopirox
+
Ciclopirox
Ciclopirox
Naftifine
Selenium sulfide
Naftifine
Naftifine
+/–
Corticosteroids†
2nd-Line Drugs
Ketoconazole
Griseofulvin
Griseofulvin
Griseofulvin
+
+/–
Selenium sulfide
Imidazole§
3rd-Line Drugs
Ketoconazole
Ketoconazole
Ketoconazole
4th-Line Treatment
Avulsion
*Follicular denotes tinea capitis, follicular tinea barbae, or Majocchi granuloma
†Intralesional triamcinolone acetonide for limited lesions and oral prednisone for extensive lesions
‡Extensive cases should be treated with griseofulvin
§Griseofulvin plus topical imidazole for interdigital tinea pedis
Fig. 17-23.  Algorithm for simplified, optimal treatment for dermatophyte infections.
tients experienced irritant reactions, while 15% of
the clotrimazole-treated patients developed ero-
sive irritant reactions.  Until further, similar stud-
ies become available, sulconazole nitrate cream
should be considered the topical imidazole of choice
for tinea cruris in combat conditions, based on its
ease of use and lack of irritancy.  In resistant cases
or in patients unable to tolerate topical antifungal
drugs, oral ultramicrosize griseofulvin should be
given in a dose of 330 to 750 mg/d for a minimum
of 4 weeks, or 2 weeks past the point of total
resolution.  Topical haloprogin is no longer recom-
mended for the treatment of tinea cruris because,
when compared to the less-irritating imidazoles,
its rate of irritation is high and its response rate is
low.22  Switching from briefs to boxer shorts is a
helpful, nonspecific measure.
Tinea manuum and tinea pedis may initially be
treated with topical, broad-spectrum, antimycotic
agents.  Infections of the toe web spaces sometimes
resolution.  Extensive or resistant cases should be
treated with oral ultramicrosize griseofulvin (330–
750 mg/d) for 4 weeks or 2 weeks past the point of
total resolution.  Griseofulvin-resistant cases should
be treated with 200 mg of oral ketoconazole taken in
a single morning dose.  If the patient has not demon-
strated a response at 1 month, the dose should be
increased to 400 mg/d.21
The treatment of choice of tinea cruris is twice-
daily applications of a broad-spectrum antimycotic
agent (eg, an imidazole, ciclopirox olamine, or
naftifine).  Although good comparative irritancy stud-
ies of the various preparations have not been done,
many of the topical preparations produce irritant
reactions in this area, particularly in humid climates.
In a study of 117 Colombian soldiers with tinea
corporis and cruris, researchers report that
sulconazole nitrate cream applied once daily was as
effective as clotrimazole applied twice daily.13  How-
ever, none of the sulconazole nitrate–treated pa-

Superficial Fungal Skin Diseases
437
respond to topical antimycotic therapy alone within
4  to 6 weeks.  At least one study has demonstrated
that a synergistic effect can be achieved by combin-
ing a topical imidazole with oral griseofulvin.23
Infections presenting as diffuse hyperkeratosis are
associated with T rubrum infection and are notori-
ously more difficult to eradicate, often requiring 3
or more months of topical therapy; even then, the
cure rate may be as low as 18%.  Oral ultramicrosize
griseofulvin in a dose of 330 to 750 mg/d for 3
months is probably the drug of choice in the diffuse
plantar hyperkeratotic variant.  The addition of a
topical imidazole does not appear to produce higher
cure rates.  Oral ketoconazole in an oral dose of 200
to 400 mg/d should be reserved for cases of tinea
manuum and pedis that are resistant to griseofulvin.
Erosive or macerated interdigital tinea pedis often
reflects dense colonization with resident bacteria or
Gram-negative organisms.  In these cases, the addi-
tion of a twice-daily application of 30% aluminum
chloride or Castellani’s paint (ie, carbol-fuchsin
paint) may prove helpful.24
Tinea unguium remains the most resistant of
dermatophytic infections, and many cases are es-
sentially not curable using current therapies.  In
general, tinea unguium of the fingernails is more
sensitive to therapy than toenails and should be
treated more aggressively.  Topical antifungal agents
are rarely curative except in leukonychia mycotica
and in occasional cases affecting fingernails.
Although good studies are not available, topical
ciclopirox olamine applied to the nails twice daily is
recommended over the other topical antifungal
agents because its penetration of keratin is excel-
lent.25  Pharmacokinetic studies have also shown
that naftifine penetrates the nail plate, and cures
have been reported in up to 42% of patients treated
with twice-daily applications of naftifine gel.26
Additional, long-term studies will be needed to
confirm these results.  The efficacy of topical
antimycotic agents is improved if the infected kera-
tin is removed by mechanical means such as filing,
clipping, or paring.  Oral griseofulvin is the treat-
ment of choice when systemic antifungal therapy is
used, although the long-term cure rates are low.  In
the author’s experience, 12 months of 750 mg of oral
ultramicrosize griseofulvin results in a 10% cure
rate in toenails and a 60% cure rate in fingernails.
While initial studies suggested that oral keto-
conazole in a dose of 200 to 400 mg/d was highly
effective against tinea unguium, a short-term cure
rate of only 26% was found, with 40% of patients
relapsing within 6 months.27  Removal of infected
nails by either surgical avulsion or urea ointment is
time-consuming and often associated with recur-
rence of infection when the nail regrows.  Avulsion
is indicated when nails become symptomatic or
impede the wearing of shoes.28
In recent years, candidosis has been suggested as
the preferred term to describe infections that occur
as the result of mucocutaneous or systemic infec-
tion by Candida organisms, replacing the terms
candidiasis and moniliasis.  (However, candidiasis is
ingrained in the medical literature and is still used
by many authorities).   Although other species
may produce disease, particularly in immuno-
compromised individuals, C albicans is the most
common pathogen (Exhibit 17-4).  During the Viet-
nam conflict, C albicans accounted for most infec-
tions, although occasional isolates of C tropicalis
were recovered.5
Candida organisms are usually harmless flora of
the skin, mucous membranes, or gastrointestinal
tract; under normal circumstances they do not pro-
duce clinical disease.  Candida species may become
opportunistic pathogens under a variety of circum-
stances including preexisting dermatitis, macera-
tion, diabetes mellitus, antibiotic therapy, or immu-
CANDIDOSIS
EXHIBIT 17-4
PATHOGENIC CANDIDA SPECIES
Candida albicans
C tropicalis
C guillermondii*
C krusei*
C pseudotropicalis*
C stelloidea*
*Rare pathogens
nosuppression.  Unlike the dermatophytes, Candida
organisms do not utilize keratin as a substrate for
growth but prefer areas with high concentrations of

Military Dermatology
438
EXHIBIT 17-5
CLINICAL MANIFESTATIONS OF
CANDIDOSIS
Cutaneous Disease
Intertrigo
Erosio interdigitalis blastomycetica
Paronychia
Onychomycosis
Chronic mucocutaneous candidiasis
Mucosal Disease
Thrush
Perlèche
Balanitis
Vulvovaginitis
Systemic Disease*
*Not discussed in this chapter
The most common sites of infection were the toe
web spaces and the groin.
Clinical Features
Intertrigo
The most common form of candidal infection
experienced by military personnel is intertrigo (ie,
infections of intertriginous areas).  The most com-
mon intertriginous areas affected are the groin,
followed by the toe web spaces, inframammary
crease, and axillae.  Candida albicans prefers high
humidity and a damaged stratum corneum for
growth.  These two requirements are frequently
fulfilled during military campaigns, particularly in
tropical climates where clothes and boots are often
soaked and the stratum corneum is damaged by
other infections or friction.
Symptoms of candidal intertrigo include pruritus
and burning.  Candidosis is more likely to be pain-
ful than dermatophytosis, presumably due to inva-
sion of viable tissue and a brisk host response.  In
the groin and axilla, patients with candidal intertrigo
present with confluent, very erythematous lesions
that demonstrate satellite lesions at the periphery
(Figure 17-24).  Small pustules are frequently present
and central clearing—as seen in dermatophytic in-
fections—is distinctly rare.  Toe web infections dem-
onstrate severe maceration associated with irregu-
lar plaques of white acanthosis.  The surface of the
denuded areas is fiery red and raw.
Erosio interdigitalis blastomycetica is a peculiar,
erosive, hyperkeratotic form of candidal intertrigo
serum or glucose.  This accounts for their predilec-
tion to invade living tissue and the relatively un-
common invasion of nails and hair.  Although
candidosis and candidiasis are terms that encom-
pass all infections, numerous other terms are used
to describe the diverse manifestations (Exhibit 17-
5).  Mucocutaneous candidosis is of interest to mili-
tary medicine; systemic candidosis is not discussed
in this chapter.
Candidosis was not listed as a significant prob-
lem in the military campaigns of World War I2 or
World War II,3 but was a major problem during the
Vietnam conflict.5  It is difficult to imagine that
candidosis was not a problem in tropical areas dur-
ing the Pacific Campaign in World War II, and it is
most likely that the disease was unreported or mis-
diagnosed.  During the Vietnam conflict, candidosis
of the skin and mucosa was estimated to be the
third-most-common cause of skin disease.6  In one
survey, C albicans was isolated from 10% of soldiers
in the Mekong Delta.  These isolations were fre-
quently associated with dermatophytic infections,
suggesting that candidosis was often a secondary
infection.  As in the case of dermatophytosis,
candidosis was more prevalent in combat troops
than in support troops.  An exception to this was
support troops in extremely hot and humid envi-
ronments (eg, cooks and boiler-room workers).5
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Fig. 17-24. Candidosis of the groin demonstrating marked
erythema, satellite lesions, and scrotal involvement; all
features are suggestive of candidosis.

Superficial Fungal Skin Diseases
439
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Fig. 17-25. Erosio interdigitalis blastomycetica demon-
strating characteristic whitish hyperkeratosis. This pa-
tient also had diabetes mellitus, a common predisposing
factor.
that affects the interdigital spaces, particularly be-
tween the third and fourth fingers (Figure 17-25).
This clinical variant is seen in patients whose hands
are immersed repeatedly in water.  Experimental
studies suggest that erosio interdigitalis blasto-
mycetica is a synergistic infection of C albicans and
one or more Gram-negative rods.29
Paronychia and Onychomycosis
Candidal paronychia and onychomycosis are of-
ten present simultaneously.  The role of Candida
organisms in producing paronychia is controver-
sial, as other fungi and bacteria may also be recov-
ered.  Paronychia is strongly associated with per-
sons whose hands are repeatedly immersed in water
(eg, cooks).  The author personally developed
paronychia while working as a bartender; the prob-
lem resolved spontaneously following a change in
occupation.  Clinically, candidal paronychia ap-
pear as erythematous, edematous lesions affecting
the periungual tissues around one or more fingers.
Occasionally, small amounts of purulent material
may be expressed from beneath the proximal nail.
Candidal onychomycosis most commonly occurs
in association with paronychia.  It is generally re-
garded as a secondary process that occurs due to
inflammation of the nail matrix.  Clinically, it pre-
sents as nail dystrophy with horizontal or vertical
furrows.  Occasionally, Candida organisms may be
recovered from the subungual spaces beneath
onycholytic nails.  It is unclear whether this repre-
sents infection or merely colonization of a moist
habitat.
Chronic mucocutaneous candidosis is a rare, pro-
gressive form of infection that occurs in persons
with inherited or sporadic defects in cell-mediated
immunity.  This is a heterogeneous disorder with
anywhere from four to seven subtypes depending
on the classification system used.  Some cases may
be associated with endocrinopathies or thymomas.
In most cases, onset occurs during childhood, with
cutaneous or mucosal infection that is resistant to
normal therapies.  Eventually, the lesions progress
and produce diffuse oral thrush, perlèche, and in-
volvement of virtually any cutaneous surface in-
cluding nails, in which the entire thickness of the nail
plate may be invaded and destroyed (Figure 17-26).
Except for chronic mucocutaneous candidosis,
Candida organisms can affect glabrous skin only
when occluded.  This most commonly occurs in
infants wearing occlusive diapers (Figure 17-27).
While candidosis is only one of many causes of
diaper dermatitis, a correct diagnosis is important
because it affects treatment.  The primary lesions
are usually sharply demarcated areas of erythema
that are confluent in folds that are associated with
satellite erythematous papules or pustules.  In
adults, similar lesions may occur under dressings
(Figure 17-28) and in immobilized hospital patients
(Figure 17-29).
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Fig. 17-26. Chronic mucocutaneous candidiasis demon-
strating onychomycosis, paronychia, and marked
hyperketosis.

Military Dermatology
440
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Fig. 17-27. Marked diaper dermatitis secondary to
candidosis. Note satellite lesions. Photograph: Courtesy
of Bruce Kornfeld, MD, Fort Collins, Colo.
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Fig. 17-29. Marked candidosis can be seen in this immo-
bilized airborne soldier, who fractured both legs during
a training jump.
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Fig. 17-28. Candidosis is limited to the occluded site
beneath the tape. The local heat and moisture afforded by
occlusion predispose to fungal infections.
Candidal vaginitis is a very common infection; it
is usually seen by gynecologists and will not be
discussed here.  However, extension of infection to
the vulva (vulvovaginitis) may occur, particularly
when the patient is pregnant, diabetic, immuno-
compromised, or taking antibiotics.  The most com-
mon symptoms are pruritus or burning.  The find-
ings include a vaginal discharge, erythema of the
introitus and vulva, and characteristic satellite le-
sions on the vulva.  Similar lesions may occur in
men, particularly uncircumcised men, who may
present with erythematous papules, diffuse
erythema (Figure 17-30), or even superficial ero-
sions (Figure 17-31).
Candidosis is the most common fungal infection
of the oral mucosa.30  The most common oral mu-
cosal presentations are perlèche and thrush.  Oral
candidosis most commonly affects newborns, the
elderly, and patients who have diabetes or are
immunocompromised.  The presence of oral
candidosis in a young soldier should precipitate a
search for diabetes mellitus and infection with the
human immunodeficiency virus.  Perlèche (ie, in-
fection of the angles at the corners of the mouth) is
usually but not invariably associated with thrush.
Clinically, patients present with cracks or fissures
at both corners of the mouth; these are associated
with an adherent, white exudate (Figure 17-32).
The hallmark of thrush is the presence of white
patches anywhere within the oral mucosa.  These
areas are composed of white, creamy-to-almost-

Superficial Fungal Skin Diseases
441
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Fig. 17-30. This patient with candidal balanitis presented
with diffuse erythema and edema.
Fig. 17-32. This patient with perlèche presented with
bilateral fissures associated with white exudate.
cheesy exudates that are adherent but easily re-
moved.  The underlying mucosa is brightly
erythematous.  Involvement of the tongue results in
intense erythema and loss of papillae.
Diagnosis
The diagnosis of candidosis is usually suspected
based on the clinical presentation.  In intertriginous
areas or areas under occlusion, the presence of
sharply demarcated erythema associated with small,
brightly erythematous, satellite lesions is candi-
dosis until proven otherwise.  Similarly, leukoplakia
of the oral mucosa that is easily removed with
scraping is most likely candidosis.
The diagnosis is established by demonstrating
the organism either microscopically or by culture.
Fig. 17-31. A soldier stationed in Korea presented with
candidal balanitis manifesting as superficial erosions.
This patient had been incorrectly diagnosed with and
treated for chancroid and genital herpes.
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Fig. 17-33. Positive potassium hydroxide examination of
thrush demonstrating pseudohyphae and yeast forms.

Military Dermatology
442
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Fig. 17-36. This specimen from a biopsy of cutaneous candidosis
demonstrates neutrophilic spongiosis and pseudohyphae,
which are clearly seen between two fragments of keratin
(hematoxylin-eosin stain, original magnification 400X).
Fig. 17-34. Positive Gram’s stain of a pustular lesion of
candidosis demonstrating neutrophils and pseudohyphae.
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Fig. 17-35. Positive culture for Candida albicans on
Sabouraud’s agar demonstrating a typical white, yeasty
colony. Definitive identification usually requires subcul-
ture on cornmeal agar.
yeastlike odor (Figure 17-35)  On Nickerson’s me-
dium, the colonies produced are dark.  Speciation of
C albicans can be confirmed by the demonstration of
chlamydospores on cornmeal agar or the produc-
tion of germ tubes in the presence of serum.  On rare
occasions, candidosis is not suspected and the diag-
nosis is made on biopsy specimens.  Histologically,
hyphal and yeastlike structures are seen in the stra-
tum corneum and upper stratum spinosum.  Neu-
trophils are more commonly associated with
candidosis than dermatophytosis; this may mani-
fest as subcorneal blisters or focal neutrophilic
spongiosis (Figure 17-36).
Treatment
Infection with C albicans responds to the
antimycotic drugs typically used against dermato-
phytes—except tolnaftate and griseofulvin.
Intertrigo, including erosio interdigitalis blasto-
mycetica, is best treated by twice-daily applications
of topical imidazoles, ciclopirox olamine, or
naftifine.  If the lesions are inflammatory or painful,
sulconazole or nystatin are probably preferred due
to their lack of irritancy.  Nystatin, formerly the
antifungal of choice for candidosis, has largely been
replaced by the imidazoles due to the emergence of
both primary and secondary resistant strains of
Candida species.31  Amphotericin B lotion or cream
is also effective but is not recommended because of
its cost.  Nonspecific measures such as reducing
moisture and maceration with a hair dryer and
Using potassium hydroxide examination on cuta-
neous surfaces, the yeast and pseudohyphae of
candidosis are generally more difficult to find than
dermatophytes: the viable pseudohyphae often
penetrate deeper than the stratum corneum and
samples are often too superficial.  Scrapings of
mucosal surfaces are more often positive (Figure
17-33).  Gram’s stain is particularly useful on pustular
lesions that could be either bacterial or fungal because
it will stain both bacteria and Candida organisms
(Figure 17-34).  Scrapings also may be cultured on
either Sabouraud’s or on a Candida-specific medium
such as Nickerson’s.  On Sabouraud’s medium, the
colonies are white or cream-colored and produce a

Superficial Fungal Skin Diseases
443
weight reduction are also helpful.  Paradoxically,
very painful inflammatory lesions can be relieved
with water or Burrow’s solution compresses three
or four times per day.
Candidal paronychia and onychomycosis can
usually be improved by simply having the patient
discontinue wet work if feasible, or using cotton-
lined gloves if water exposure is inevitable.  Women
also should be advised to discontinue the practice
of pushing back the cuticle to allow it to reattach to
the dorsum of the nail plate.  A 3% to 4% solution of
thymol in alcohol applied three times daily to the
paronychial area is an extremely beneficial first-
line therapy.  Resistant cases can be treated with
topical imidazoles, ciclopirox olamine, nystatin, or
naftifine, applied twice daily.  Therapy should be
continued 2 weeks past the point of clinical resolution.
Thrush is best treated with nystatin oral suspen-
sion in a dose of 5 mL (500,000 units) held in the
mouth for several minutes and then swallowed.
This treatment is repeated four times daily for 7 to 10
days.  An alternative approach is dissolving clo-
trimazole troches in the mouth five times daily for
2 weeks.32  Gentian violet (0.5% to 1%) may be applied
to affected areas two or three times daily in resistant
cases, but is infrequently used because of the inevi-
table purplish discoloration.  Perlèche readily responds
to the twice-daily application of a topical imidazole,
ciclopirox olamine, nystatin, or naftifine cream.
The first-line treatment of vulvovaginitis is one
of the imidazole products made for use in this area
including clotrimazole, miconazole, and buto-
conazole.  These treatments have largely replaced
nystatin, which is slightly less effective.  Recurrent
cases may respond to oral ketoconazole in a dose of
400 mg/d for 2 weeks for control.
PITYROSPORUM INFECTIONS
Pityriasis versicolor is the correct term for super-
ficial infections of the epidermis produced by the
yeast Pityrosporum orbiculare.  Many authorities con-
tinue to use the term tinea versicolor, although
“tinea” is incorrect: it denotes infection with a der-
matophyte that uses keratin for a substrate.
Pityrosporum species require lipids for growth and
thus are not dermatophytes.  The taxonomy is also
confusing in that P orbiculare is the taxonomic term
most commonly used for the yeast phase of the
fungus, while Malassezia furfur is the term some-
times used for the pathogenic hyphal phase.  Some
authorities do not make this distinction and one
term or the other is used without explanation.  How-
ever, Malassezia furfur is a confusing term and
should not be used.  From a taxonomic and myco-
logical standpoint, P orbiculare is preferred.33
Pityrosporum species may also produce a charac-
teristic folliculitis (formerly called Malassezia folli-
culitis).  The organism responsible for pityrosporum
folliculitis is probably P orbiculare, although good
cultural studies are lacking.  Some authorities have
stated that P ovale is the etiologic agent; however,
recent morphologic, physiological, and immuno-
logical studies suggest that this species is identical
with P orbiculare.34
Pityrosporum organisms may occasionally
produce systemic infections in the immunocom-
promised host, particularly when intravenous lip-
ids are administered.  This manifestation is beyond
the scope of this chapter and will not be discussed.
Clinical Features
Pityriasis Versicolor
Pityriasis versicolor is a trivial cutaneous infec-
tion.  It has had minimal impact on military cam-
paigns and is infrequently discussed in the medical
histories of previous wars.  The importance of
pityriasis versicolor on the military is related only
to the cost of treatment and time lost from work.
During World War II, a dermatology clinic in
Camp Lee, Virginia, reported that pityriasis
versicolor accounted for 2.4% of visits.3  During the
Vietnam conflict, it frequently caused outpatient
visits, often because soldiers feared that it was a
manifestation of a sexually transmitted disease.
Pityriasis versicolor accounted for 2.7% of visits at
one dermatology clinic, making it the tenth-most-
common dermatologic complaint.5
Pityriasis versicolor is more common in warm,
humid climates, where it may affect up to 50% of
individuals in some areas of the world.35  The inci-
dence is higher in persons such as cooks who work
in hot, humid places (Figure 17-37).  Many patients
do not even regard it as a disease and it is frequently
diagnosed during examination for other diseases.
Pityriasis versicolor often affects multiple members
of the same family, suggesting a genetic susceptibil-
ity to infection.  It is possible that this familial
clustering of infections may be due to more virulent
strains, although this has not been investigated.

Military Dermatology
444
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Fig. 17-38. Characteristic fawn-colored macules of
pityriasis versicolor are present on the abdomen of this
young man.
Fig. 17-37. This patient, a cook in the U.S. military, has
extensive pityriasis versicolor involving almost his en-
tire trunk.
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Fig. 17-39. Hypopigmented lesions of pityriasis versicolor.
Pityriasis versicolor is usually asymptomatic,
although occasional patients may complain of a
burning sensation or mild pruritus.  The primary
lesions are usually tan or fawn-colored macules
that may coalesce into large patches that almost
replace the entire skin.  Close inspection reveals a
fine, branny scale that covers the entire macule or
patch (Figure 17-38).  Annular lesions are distinctly
uncommon, although occasional lesions may be
perifollicular.  Inflammation is usually absent.  The
affected areas usually display a truncal distribu-
tion, although extension to acral areas may occur.
Less commonly, the primary lesions are hypopig-
mented, which apparently is due to the yeast’s
production of biochemical products that interfere
with melanin synthesis and packaging.  This de-
crease in pigmentation is more noticeable when the
patients attempt to develop a tan (Figure 17-39).
Pityrosporum Folliculitis
The prevalence of pityrosporum folliculitis in-
fection in military combat personnel is unknown
because only in recent years has this infection been
defined and accepted as a valid disease process.36
Given the benign nature of this disease, it is un-
likely to have affected military campaigns.
Pityrosporum folliculitis most commonly affects
young and middle-aged persons and has a predilec-
tion for women.  Although most patients are healthy,
this infection may be more common in immuno-
compromised hosts.
The lesions of pityrosporum folliculitis are in-
tensely pruritic; this is often the primary reason that
patients seek medical treatment.  The pruritus may
be aggravated by intense sweating or showers.  The

Superficial Fungal Skin Diseases
445
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Fig. 17-40. Extensive pityrosporum folliculitis of the back.
The clinical picture can closely mimic acne vulgaris.
primary lesions are discrete, follicular papules and
pustules, typically 2 to 4 mm in diameter, and most
commonly located on the upper back, arms, and
chest (Figure 17-40).  Lesions occasionally develop
on acral areas such as the face, arms, and legs.
Variable erythema, excoriations, and wheal-and-
flare reactions also may be present.
Other Pityrosporum Infections
The role of Pityrosporum yeast in the pathogen-
esis of seborrheic dermatitis is controversial.  The
presence of high concentrations of yeast in lesions
of seborrheic dermatitis, combined with a frequent
response to topical imidazole treatment, support
the notion of a potential role.  However, the not-
infrequent failure of imidazoles to improve
seborrheic dermatitis and the presence of high con-
centrations of yeast in clinically normal patients
who have no demonstrable seborrheic dermatitis
both suggest that Pityrosporum organisms may play
a secondary role.  Further studies are needed to
define the role of Pityrosporum in the pathogenesis
of seborrheic dermatitis.
Diagnosis
The diagnosis of pityriasis versicolor can usually
be made based on the clinical presentation alone.
The finding of asymptomatic, branny or whitish
scales that are located primarily on the trunk is
pityriasis versicolor until proven otherwise.  Atypi-
cal cases may be diagnosed by microscopical exami-
nation of skin scrapings that are treated with potas-
sium hydroxide; the examination is performed
exactly like that for dermatophytic infections.  Be-
cause the organism is located superficially in the
stratum corneum, many physicians prefer to obtain
specimens by touching lesions with clear cellophane
tape.  A drop or two of potassium hydroxide is
placed on a slide and the tape is then placed sticky-
side down over the potassium hydroxide.  This
technique is more rapid and less traumatic than the
skin-scraping method.  Alternatively, instead of
potassium hydroxide, a 0.5% to 1% solution of tolui-
dine blue may be used because the yeast preferen-
tially take up this dye.  The diagnosis is made by
finding short, straight hyphae associated with clus-
ters of round, budding yeast, often referred to as
“spaghetti and meatballs” (Figure 17-41).  In con-
trast to dermatophytic infections, the organisms are
so abundant in pityriasis versicolor that a negative
result obtained from a properly performed exami-
nation excludes this diagnosis.
Atypical lesions are sometimes biopsied.  The
biopsies demonstrate a somewhat normal epider-
mis with a mild, superficial, perivascular, lympho-
cytic dermatitis associated with mild hyperkeratosis
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Fig. 17-41. This toluidine blue tape preparation demon-
strates the yeast and short hyphae that are characteristic
of pityriasis versicolor (original magnification 200X).

Military Dermatology
446
that may demonstrate a basket-weave (ie, slightly
compact) appearance.  The organisms are found in
the stratum corneum and are often found in greater
numbers near hair follicles (Figure 17-42).  Occa-
sionally, the organisms are difficult to visualize
with hematoxylin-eosin stain, and special stains
such as Gomori’s methenamine silver or periodic
acid-Schiff stain may be required to demonstrate
them.  Cultures are only required when a diagnosis
of pityrosporum septicemia is suspected.  Routine
dermatologic media such as Sabouraud’s or derma-
tophyte test medium do not support growth; the
medical mycology technician must be informed that
infection with Pityrosporum organisms is suspected
so that a lipid source can be added to the medium.
Pityrosporum folliculitis is diagnosed based on
the clinical presentation combined with a biopsy
showing folliculitis and Pityrosporum yeast.  The
clinical features most suggestive of pityrosporum
folliculitis are the characteristic distribution and
associated pruritus.  Microscopically, the organ-
OK to put on the Web
Fig. 17-42. This biopsy of pityriasis versicolor demon-
strates the characteristic yeast and short hyphae (hema-
toxylin-eosin stain, original magnification 200X).
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Fig. 17-43. (a) This biopsy of pityrosporum folliculitis demonstrates acute folliculitis (hematoxylin-eosin stain, original
magnification 100X). (b) The same tissue, stained with periodic acid–Schiff stain and digested with diastase (original
magnification 200X), demonstrates budding yeast. The organisms are difficult to visualize with routine hematoxylin-
eosin stains.
a
b

Superficial Fungal Skin Diseases
447
isms are always in the yeast phase and the short
hyphae seen in pityriasis versicolor are absent.
Special stains are frequently necessary to visualize
the yeast, as they can be difficult to locate in the
presence of severe inflammation (Figure 17-43).
Treatment
Numerous treatments are reported to be effec-
tive for pityriasis versicolor; however, many topical
therapies have a high rate of clinical relapse.  Pa-
tients with focal or limited disease may be treated
with topical antifungal agents (ie, an imidazole,
ciclopirox olamine, naftifine, or tolnaftate) applied
twice daily for 2 weeks.  The cure rates achieved
with these regimens are in the range of 80% to 90%.37
However, these agents are relatively expensive and
have a high relapse rate.  Patients with extensive
disease are most commonly treated with either sele-
nium sulfide suspension applied daily for 10 to 30
minutes for 7 to 14 days or a zinc pyrithione sham-
poo applied daily for 5 minutes for 14 days.  These
regimens are inexpensive and have high cure rates;
however, both regimens are associated with severe
irritant reactions if the patient leaves the product on
the skin for extended periods of time.  As in the case
of the topical imidazoles, relapses are common.
Other effective topical agents include propylene
glycol, sodium hyposulfite, sodium thiosulfate com-
bined with salicylic acid, salicylic acid prepara-
tions, and retinoic acid cream.
Oral ketoconazole is the most effective treatment
of pityriasis versicolor.  In addition to a high cure
rate, it is associated with a much lower relapse rate.
However, the development of idiosyncratic acute
hepatitis reactions has prevented oral ketoconazole
from replacing topical therapies as the first-line
drug.  Initial studies used 200 to 400 mg/d of oral
ketoconazole for up to 4 weeks and reported high
response rates.  More-recent research has reported
that a single, 400-mg dose cured 100% of patients,
and that recurrences could be prevented by repeat-
ing this treatment on a monthly basis.38  The author
currently utilizes an intermediate dose of 200 mg/
d for 7 days and does not use a prophylactic dose.
Comparative studies are clearly needed to define
the optimal dose.
The treatment options for pityrosporum follic-
ulitis are almost the same as for pityriasis versicolor.
Topical therapy with selenium sulfide lotion, 50%
propylene glycol in water, and econazole cream
have been reported equally efficacious when used
for 3 to 4 weeks; however, if intermittent therapy
was not continued, folliculitis frequently recurred.36
Oral ketoconazole in a dose of 200 mg/d for 4 weeks
is also effective, but the relapse rate approaches
100% and; therefore; it is not recommended for first-
line therapy.39
MISCELLANEOUS FUNGAL INFECTIONS
Tinea Nigra
Tinea nigra is an uncommon superficial dermato-
mycosis produced by the dimorphic fungus
Exophiala werneckii (formerly Cladosporium werneckii).
Exophiala werneckii is a dematiaceous fungus that is
commonly found in the soil and decaying vegeta-
tion.  Tinea nigra is most commonly reported from
subtropical and tropical climates, although occa-
sional cases are acquired in the United States.  This
asymptomatic, rare infection is not important from
a military standpoint.  Other than the cosmetic
appearance, it is only important in that it may be
confused with acral lentiginous melanoma.40
Clinically, tinea nigra is characterized by
asymptomatic gray, tan, brown, or black macular
lesions on the palms or plantar surfaces, although,
rarely, other sites are infected (Figure 17-44).  The
lesions are usually unilateral, although bilateral
infection has been reported.   Spontaneous resolu-
tion usually does not occur.41
The diagnosis is usually suspected based on clini-
cal examination alone.  The diagnosis can be con-
firmed by the demonstration of olivaceous, tortu-
ous, septate hyphae associated with variable
numbers of arthrospores on potassium hydroxide
examinations of skin scrapings (Figure 17-45).  The
diagnosis also can be established by culturing skin
scrapings on Sabouraud’s medium at room tem-
perature.  Typical colonies are initially white or
gray with a smooth surface but quickly turn olive or
black with a downy edge.  Occasionally, lesions are
biopsied to rule out acral lentiginous melanoma.
Histopathological examination reveals variable
hyperkeratosis associated with hyphal elements that
are located primarily in the upper stratum corneum.
A superficial, perivascular, lymphocytic infiltrate
is variably present.
Scraping the affected stratum corneum off with a
surgical blade or abrasive cosmetic pad, followed
by applying a topical imidazole or ciclopirox
olamine, has been recommended as the treatment of

Military Dermatology
448
OK to put on the Web
Fig. 17-44. A grayish-green macular lesion of tinea nigra
can be seen on the palm of this 4-year-old child.
OK to put on the Web
Fig. 17-45. This positive potassium hydroxide prepara-
tion of tinea nigra, taken from the palm depicted in Fig. 17-
44, demonstrates the olivaceous, tortuous septate hyphae.
choice.41  Other effective treatments include epider-
mal stripping, keratolytic agents, and thiabenda-
zole.  Oral griseofulvin does not appear to be an
effective therapy.
Black Piedra
Black piedra is a rare infection of terminal hairs
produced by the dematiaceous fungus, Piedraia
hortae.  Black piedra is endemic in South America,
although it has also been described in other tropical
regions such as Africa and Asia.  Familial infesta-
tions affecting multiple generations have been ob-
served in endemic areas.42  The disease is inconse-
quential in terms of its effect on military personnel.
The primary lesions are small, hard, ovoid, ad-
herent, brown-to-black nodules that affect the scalp
hairs.  Black piedra produces broken hairs and does
not spread to other terminal hairs; this is in contrast to
the presentation of white piedra (discussed below).
The diagnosis can be suspected on the clinical
presentation alone.  The diagnosis can be firmly estab-
lished by microscopical examination of the con-
cretions, which demonstrate intertwined masses of
brown hyphae surrounding an oval ascus that con-
tains eight ascospores.  Cultures on Sabouraud’s agar
demonstrate small, brown-to-black, adherent colonies.
The treatment of choice is removing infected
hairs by either shaving or plucking.  Recurrences
are common in endemic areas.
White Piedra
White piedra (also called trichosporosis) is an
infection of the terminal hair shafts caused by
Trichosporon beigelii (formerly called T cutaneum).
Trichosporon beigelii is a ubiquitous, yeastlike fun-
gus that has been isolated from soil, air, stagnant
water, and sewage.  White piedra is endemic to
tropical areas and formerly was thought to be un-
common in the United States.  However, in a pro-
spective study, researchers were able to isolate T
beigelii in 40% of young men and 14% of young
women in Houston, Texas.43  These data suggest
that white piedra is far more common than was
formerly appreciated.  Although cases have been
reported in military personnel in San Antonio,
Texas,44 white piedra has not been reported to affect
previous military campaigns.
Clinically, the primary lesions are typically white,
although light-gray, red, brown, or greenish vari-
ants have also been observed.  The concretions vary
from distinct, ovoid nodules to coalescent concre-
tions that totally coat the hair shaft.  The nodules are
softer and more easily removed than those seen in
black piedra.  The affected hairs are often straighter
than the unaffected hairs.  Cuticular invasion may
occasionally produce broken hairs.  The most com-
monly affected areas are the scalp, beard, mous-
tache, and genital regions; less commonly affected
areas are the eyelashes, eyebrows, and axillae.  Rare
manifestations of white piedra include onycho-
mycosis and systemic dissemination in immuno-
compromised patients.
The diagnosis of white piedra may be suspected
on the clinical appearance; however, trichomycosis
caused by Cornebacterium tenuis may be clinically
similar.  A distinctive, dull-yellowish fluorescence
is present under Wood’s light examination;
this may be a helpful diagnostic finding.39  The

Superficial Fungal Skin Diseases
449
diagnosis can be confirmed by either a potas-
sium hydroxide–glass-slide mount of an affected
hair, which will demonstrate concretions
composed of hyaline spores, or culture on
Sabouraud’s dextrose agar at room temperature.
Dermatophyte test medium and other media
that contain cycloheximide should not be used
for isolation because cycloheximide will inhibit
growth.  The characteristic colonies are cream-
colored, piled-up, and may demonstrate radial
grooves.
The treatment of choice is shaving the affected
hairs and applying a topical antifungal agent such
as an imidazole or 10% glutaraldehyde.
SUMMARY
Soldiers suffer from superficial cutaneous
infections during both peace and war.  During peace-
time, the infections are mild and rarely
produce significant morbidity; however, during
wartime conditions, soldiers are exposed to more
virulent strains of zoophilic and geophilic dermato-
phytes that are likely to induce an intense host
response.  When superficial fungal infections are
combined with poor hygiene and hot, humid
climates, combat units can be expected to
suffer significant morbidity and loss of effective
fighting strength—as was observed in the Asian
theater during World War II and during the
Vietnam conflict.
Medical officers, who may have to treat superfi-
cial fungal infections under field conditions, need
to be familiar with the myriad of clinical manifes-
tations.  This is particularly important because
adequate diagnostic equipment such as cultures,
microscopes, and potassium hydroxide solution
may not be readily accessible.  Frequently, diagno-
sis and treatment must be initiated based on the
clinical presentation.
The treatment options for the management of
cutaneous fungal infections is becoming increas-
ingly complex as new oral and topical antifungal
agents are developed and released.  Medical offic-
ers need to acquaint themselves not only with
standard therapies but also with alternative thera-
pies for resistant cases.
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1.
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Dermatol. 1987;26:491–499.
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Macpherson WG, Horrocks WH, Beveridge WWO, eds. Skin diseases. In: Medical Services: Hygiene of the War.
London, England: His Majesty’s Stationery Office; 1923: 68–72.
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Pillsbury DM, Livingood CS. Dermatology. In: Havens WP Jr. Infectious Diseases and General Medicine. Vol 3. In:
Anderson RS, ed. Internal Medicine in World War II. Washington, DC: US Government Printing Office; 1968: 568–607.
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Sanderson PH, Sloper JC. Skin disease in the British Army in SE Asia. Part 2. Tinea corporis: Clinical and
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Br J Dermatol. 1953;65:300–309.
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Allen AM. Skin Diseases in Vietnam, 1965–72. In: Ognibene AJ, ed. Internal Medicine in Vietnam. Vol. 1. Washington,
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Blank H, Taplin D, Zaias, N. Cutaneous Trichophyton mentagrophytes infections in Vietnam. Arch Dermatol.
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Davis CM, Garcia KL, Riordon JP. Dermatophytes in military recruits. Arch Dermatol. 1972;105:558–560.
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Bronson DM, Desai DR, Barsky S, Foley SM. An epidemic of infection with Trichophyton tonsurans revealed in
a 20-year survey of fungal infections in Chicago. J Am Acad Dermatol. 1983;8:322–330.
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Babel DE, Baughman SA. Evaluation of the adult carrier state in juvenile tinea capitis caused by Trichophyton
tonsurans. J Am Acad Dermatol. 1989;21:1209–1212.

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Joly J, Delage G. Auger P, Ricard P. Favus: Twenty cases of indigenous cases in the province of Quebec. Arch
Dermatol. 1978;114:1647–1648.
11.
Allen AM, Taplin D. Epidemic Trichophyton mentagrophytes infections in servicemen: Source of infection, role of
environment, host factors, and susceptibility. JAMA. 1973;226:864–867.
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Gentry R, Tribelhorn D, Fitzpatrick JE. Atypical dermatophytosis acquired in the tropics. J Assoc Mil Dermatol.
1988;14:17–18.
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Tanenbaum L, Taplin D, Lavelle C, Akers WA, Rosenberg MJ, Carmargo G. Sulconazole nitrate cream 1 percent
for treating tinea cruris and corporis. Cutis. 1989;44:344–347.
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Leyden JJ, Kligman AM. Interdigital athlete’s foot: The interaction of dermatophytes and resident bacteria. Arch
Dermatol. 1978;114:1466–1472.
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André J, Achten G. Onychomycosis. Int J Dermatol. 1987;26:481–490.
16.
Lefler E, Haim S, Merzbach D. Evaluations of direct microscopic examination versus culture in the diagnosis of
superficial fungal infections. Mykosen. 1981;24:102–106.
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Loenenthal K. Seventy per cent ethyl alcohol as skin cleanser for fungus culture. Arch Dermatol. 1964;89:725–729.
18.
Strauss JS, Kligman A. An experimental study of tinea pedis and onychomycosis of the foot. Arch Dermatol.
1957;76:70–79.
19.
Lambert DR, Siegle RJ, Camisa C. Griseofulvin and ketoconazole in the treatment of dermatophyte infections.
Int J Dermatol. 1989;28:300–304.
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Allen HB, Honig PJ, Leyden JJ, McGinley KJ. Selenium sulfide: Adjunctive therapy for tinea capitis. Pediatrics.
1982;69:81–83.
21.
Robertson MH, Rich P, Parker F, Hanifin JM. Ketoconazole in griseofulvin-resistant dermatophytosis. J Am Acad
Dermatol. 1982;6:224–229.
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VanDersarl JV, Sheppard RH. Clotrimazole vs haloprogin treatment of tinea cruris. Arch Dermatol. 1977;113:
1233–1235.
23.
Zaias N, Battistini F, Gomez-Urcuyo F, Rojas RF, Ricart R. Treatment of “tinea pedis” with griseofulvin and
topical antifungal cream. Cutis. 1978;22:196–199.
24.
Leyden JJ, Kligman AM. Aluminum chloride in the treatment of symptomatic athlete’s foot. Arch Dermatol.
1975;111:1004–1010.
25.
Qadripur SA, Horn G, Höhler T. Aur localwirksamkeit von ciclopiroxolamine bei nagelmykosen. Arzneim
Forsch. 1981;31:1369–1372.
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Klaschka F. Treatment of onychomycosis with naftifine gel. Mykosen. 1987;30(suppl 1):119–123.
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Hersle K, Mobackern H, Moberg S. Long-term ketoconazole treatment of chronic acral dermatophyte infections.
Int J Dermatol. 1985;24:245–248.
28.
South DA, Farber EM. Urea ointment in the nonsurgical avulsion of nail dystrophies—A reappraisal. Cutis.
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29.
Dreizen S. Oral candidiasis. Amer J Med. 1984;77(4D):28–33.

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30.
Rebora A, Marples RR, Kligman AM. Erosio interdigitalis blastomycetica. Arch Dermatol. 1973;108:66–68.
31.
Macura AB. Fungal resistance to antimycotic drugs: A growing problem. Int J Dermatol. 1991;30:181–184.
32.
Kirkpatrick CH, Alling DW. Treatment of chronic oral candidiasis with clotrimazole troches. N Engl J Med.
1978;299:1201–1203.
33.
Fredriksson T, Faergemann J. Semantics—Tinea versus pityriasis versicolor and Pityrosporum orbiculare versus
Malassezia furfur. Which is proper? Int J Dermatol. 1984;23:110–111.
34.
Faergemann J, Fredriksson T. Experimental infections in rabbits and humans with Pityrosporum orbiculare and
P ovale. J Invest Dermatol. 1981;77:314–318.
35.
Pillsbury DM, Hurley HJ. Dermatology. Philadelphia, Pa: WB Saunders; 1975: 621.
36.
Bäck O, Faergemann J, Hörnqvist R. Pityrosporum folliculitis: A common disease of the young and middle-aged.
J Am Acad Dermatol. 1985;12:56–61.
37.
Quiñones CA. Tinea versicolor: New topical treatments. Cutis. 1980;25:386–388.
38.
Rausch LJ, Jacobs PH. Tinea versicolor: Treatment and prophylaxis with monthly administration of ketoconazole.
Cutis. 1984;34:470–471.
39.
Ford GP, Ive FA, Midgley G. Pityrosporum folliculitis and ketoconazole. Br J Dermatol. 1982;107:691–695.
40.
Babel DE, Pelachyk JM, Hurley JP. Tinea nigra masquerading as acral lentiginous melanoma. J Dermatol Surg
Oncol. 1986;12:502–504.
41.
Sayegh-Carreño R, Abramovits-Ackerman W, Girén GP. Therapy of tinea nigra plantaris. Int J Dermatol.
1989;28:46–48.
42.
Adam BA, Soo-Hoo TS, Chong KC. Black piedra in West Malaysia. Aust J Dermatol. 1977;18:45–47.
43.
Kalter DC, Tschen JA, Cernoch PL, et al. Genital white piedra: Epidemiology, microbiology, and therapy. J Am
Acad Dermatol. 1986;14:982–993.
44.
Coquilla BH, Kraus EW. Trichosporosis (white piedra): Four cases in the United States. J Assoc Mil Dermatol.
1983;9:27–29.

Deep Fungal Skin Diseases
453
Chapter 18
DEEP FUNGAL SKIN DISEASES
SCOTT A. NORTON, M.D., M.Sc., M.P.H.*
INTRODUCTION
SYSTEMIC MYCOSES
Histoplasmosis and Histoplasmosis Duboisii
Coccidioidomycosis
Blastomycosis
Paracoccidioidomycosis
SUBCUTANEOUS MYCOSES
Sporotrichosis
Chromoblastomycosis
Mycetoma
Lobomycosis
Rhinosporidiosis
OPPORTUNISTIC MYCOSES AND MISCELLANEOUS INFECTIONS
Cryptococcosis
Entomophthoramycosis
Actinomycosis
Nocardiosis
SUMMARY
*Major, Medical Corps, U.S. Army; Assistant Chief, Dermatology Service, Tripler Army Medical Center, Honolulu, Hawaii 96859

Military Dermatology
454
INTRODUCTION
Fungal infections of humans are divided some-
what arbitrarily into the superficial mycoses and the
deep mycoses.  The superficial mycoses, such as the
dermatophyte infections, are generally confined to
the surface of the skin and hair and are discussed in
Chapter 17, Superficial Fungal Skin Diseases.  The
deep mycoses, discussed here, are fungal infections
that regularly involve the dermis and subcutaneous
tissues, and often other organ systems.  Although
deep fungal infections are seen most often in par-
ticular geographical locations, the diseases’ natural
distributions are not necessarily confined there (Ex-
hibit 18-1).  Even within an endemic focus, a disease
(eg, rhinosporidiosis) may still be uncommon.  Other
diseases (eg, sporotrichosis) are probably ubiqui-
tous but have hyperendemic foci.  Still others (eg,
coccidioidomycosis) are acquired only within their
specific endemic areas.  Our knowledge of the geo-
graphical distributions of mycoses depends to some
extent on the abilities of local laboratories to detect
the pathogens, and on local differences in disease-
reporting requirements.
Deep fungal disease is usually acquired via ei-
ther (a) inhalation of fungal spores or (b) direct
inoculation of the fungus into the skin.  Depending
on the route of entry, some generalizations can
be made on the resulting diseases.  Inhalation of
pathogenic spores may produce a primary pulmo-
nary infection that resembles a transient, flulike
illness.  Patients usually recover uneventfully but
secondary dissemination to skin is not uncommon.
It is from the cutaneous lesions that the diagnosis of
a systemic fungal infection is often made (Figure 18-
1).  Prompt recognition is important because un-
treated disseminated disease is often fatal.  The
other common route of acquisition is direct inocula-
tion of the pathogenic fungus via minor, often
unnoticed, skin trauma.  Again, some generaliza-
tions can be made.  Some fungi produce gran-
ulomatous or verrucous plaques that expand around
the initial site of implantation; other fungi produce
subcutaneous masses that can spread along lym-
phatic channels or cause chronic swelling and de-
f o r m i t y .
Based on their route of entry, deep fungal dis-
eases can be further divided into the systemic
mycoses and the subcutaneous mycoses.  Although
this is an artificial classification, it reflects a clini-
cally useful approach to the diagnosis of the deep
mycoses.  It is important to note that this scheme
ignores true taxonomic relationships among the
fungi.  Indeed, this scheme historically has em-
braced some bacterial diseases under the rubric of
the deep mycoses because of the similarity of their
clinical presentations.  Because pharmacological
therapy of these diseases corresponds more closely
with taxonomy than with the clinical syndromes, it
is important to recognize the discordance between
the clinical and phylogenetic classification systems
in medical mycology.
In the wild, the pathogenic fungi usually dwell in
the soil or on plants as saprophytes.  They are
inconspicuous, usually microscopical, and are of-
ten undetected in their natural state.  Humans are
not essential for the life cycle of any deep fungal
EXHIBIT 18-1
PRINCIPAL GEOGRAPHICAL LOCATIONS
OF DEEP FUNGAL DISEASES
Systemic Mycoses
Histoplasmosis
Mississippi and Ohio River valleys
Panama
Northern South America
Histoplasmosis duboisii
Tropical Africa
Coccidioidomycosis
Southwestern United States
Northwestern Mexico
Blastomycosis
South-central United States
Great Lakes region
Paracoccidioidomycosis
South America, especially Brazil
Subcutaneous Mycoses
Sporotrichosis
Oklahoma
Mexico, Brazil, Japan, South Africa
Chromoblastomycosis
Pantropical
Mycetoma
Mexico, India, northeast Africa
Lobomycosis
Amazon River basin
Rhinosporidiosis
India, Sri Lanka

Deep Fungal Skin Diseases
455
Patient with Cutaneous Lesions
No Systemic Illness
Exophytic Nodules or Masses
Lower Extremities
1.
Chromoblastomycosis: painless, enlarging nodules; flat-topped verrucous plaques
or vegetating nodules; sites of trauma
2.
Mycetoma: swollen tissues, draining sinuses, occasional grains
3.
Lobomycosis: multiple firm, painless, keloidal nodules and plaques
Facial
1.
Lobomycosis: smooth nodules on helices
2.
Rhinosporidiosis: friable, pedunculated polyp on nasal mucosa
Sporotrichoid Lesions
1.
Sporotrichosis: history of trauma; wide differential; obtain culture
2.
Nocardia: history of trauma
3.
Primary inoculation mycosis: known to occur in histoplasmosis, coccidioido-
mycosis, and blastomycosis
4.
Miscellaneous: (eg, cutaneous leishmaniasis or Mycobacterium marinum infection)
Subcutaneous Masses
1.
Entomophthoramycosis: subcutaneous mass on central face or thigh/buttock,
painless and slow-growing
2.
Actinomycosis: indurated submandibular mass, often with draining sinuses; poor
dentition
Subcutaneous Masses with Sinus Tracts
Thoracic
1.
Nocardiosis: severe pleuropulmonary disease
2.
Mycetoma: on backs of laborers who carry wood
3.
Coccidioidomycosis, histoplasmosis, and blastomycosis: from involved bone
Extremities
Eumycetoma and Actinomycetoma: swollen tissues, grains present
Cervicofacial
1.
Actinomycosis: indurated submandibular mass, poor dentition
2.
Paracoccidioidomycosis: cervical adenopathy with sinus, oral mucosal, and
pulmonary involvement
Systemic Illness:
Recent or current,
especially a febrile
pneumonic or flulike illness;
obtain chest radiograph
Fig. 18-1. Algorithm for the clinical diagnosis of deep fungal diseases. The clinical presentation of cutaneous lesions
and any systemic symptoms can be used to suggest a diagnosis. Deep fungal infections that are typically systemic (eg,
histoplasmosis) may occur in a sporotrichoid fashion following an inoculation injury. Conversely, infections that are
usually confined to the skin and subcutaneous tissues (eg, sporotrichosis) occasionally occur as serious systemic
illnesses. Seemingly isolated cutaneous lesions may be the presenting sign of an otherwise subclinical systemic
infection, particularly in blastomycosis. The diagnosis of any suspected deep fungal infection must be confirmed by
identification of the pathogen by direct examination of tissue specimen, biopsy, culture, or serologic assay. In patients
with disseminated histoplasmosis, cryptococcosis, or sporotrichosis, the physician must consider an underlying
immunosuppressive condition (eg, infection with human immunodeficiency virus, chemotherapy, malignancy).
Central Nervous System Involvement
1.
Coccidioidomycosis
2.
Cryptococcosis
Bone Involvement
1.
Blastomycosis
2.
Histoplasmosis duboisii
3.
Coccidioidomycosis
Oral or Mucosal Lesions
1.
Histoplasmosis: ulcer with rolled borders on tongue or buccal mucosa; 1⁄3 to 1⁄2
of persons with disseminated disease
2.
Paracoccidioidomycosis:  oral ulcers with granulomatous bases; periorificial
crusted plaques; prominent cervical adenopathy
Cutaneous Facial Lesions
1.
Blastomycosis: one (or few) irregular plaques, crusted or verrucose expanding
edge, central or trailing scarred region
2.
Paracoccidioidomycosis: (see oral lesions)
3.
Coccidioidomycosis: multiple verrucous nodules and plaques on central face

Military Dermatology
456
pathogen and become infected only incidentally.
Once inside a host, the fungus can undergo a dra-
matic morphologic transformation to cause the con-
ditions described in this chapter.
Several of the systemic mycoses with epidemic
potential have been implicated in occupationally
related outbreaks.  To date, however, the deep
mycoses have not significantly influenced military
operations.  Nevertheless, outbreaks typically oc-
cur in environmentally disturbed areas and there-
fore armies on the move will continue to encounter
some risk from these diseases.
SYSTEMIC MYCOSES
There are four systemic mycoses: histoplasmosis
(including histoplasmosis duboisii), coccidioido-
mycosis, blastomycosis, and paracoccidioido-
mycosis.  Each disease has a distinctive ecological
and geographical distribution (see Exhibit 18-1).
Infections begin when persons inhale fungal spores
into their lungs.  There, the spores convert to their
thermophilic, pathogenic, yeastlike phase, which
causes a primary pulmonary infection.  Initial infec-
tions are often asymptomatic or may cause a tran-
sient, flulike illness.  Unrecognized or subclinical
infections are very common in endemic areas.  Some-
times a severe lung disease develops or the infec-
tion may spread to other organs, with a frequent
predilection for skin.  Indeed, for many years, sev-
eral systemic mycoses were known only from their
cutaneous manifestations.
Histoplasmosis and Histoplasmosis Duboisii
Histoplasmosis is also called Darling’s disease,
spelunker’s disease, cave disease, Ohio Valley dis-
ease, and cytomycosis.  Histoplasmosis duboisii is
also called African histoplasmosis.
Histoplasmosis is probably the most common
systemic mycosis in the world.  In the United States
alone, perhaps 30 to 40 million persons are in-
fected.1  Most infections are clinically inapparent;
however, because of its prevalence, the disease has
the greatest morbidity of any systemic mycosis.
Infection is acquired by inhaling the spores of
Histoplasma capsulatum and is established most im-
portantly in the lungs.  Cutaneous manifestations
arise uncommonly from disseminated infection.
Histoplasma duboisii is the pathogen in central Africa.
Histoplasma capsulatum is a thermally dimorphic
fungus that assumes its mycelial phase in nature
and in culture at room temperature.  In tissue and in
warmer cultures, the yeast form predominates.
Yeast, 2 to 4 µm in diameter, are phagocytized
but not killed by host macrophages.  The apparent
capsule seen on histological sections is an artifact
and the epithet, capsulatum, a misnomer.  The fun-
gus has a sexual (ie, perfect) state, an ascomycete,
Emmonsiella capsulata (synonym Ajellomyces
capsulatus).  Histoplasma duboisii (syn H capsulatum
variety duboisii) has larger yeast, about 7 to 15 µm.2
History
In December 1905, Samuel Taylor Darling, an
American pathologist working for Colonel William
Gorgas at Ancon (later Gorgas) Hospital in the
Panama Canal Zone, first encountered histo-
plasmosis.  While performing an autopsy on a canal
laborer from Martinique, he noted intracellular or-
ganisms in many tissues.  Darling named the organ-
ism Histoplasma capsulata [sic] because of its location
within histiocytes (Histo-), its resemblance to plas-
modia (-plasma), and its encapsulated appearance
(capsulata).3  He later masculinized the specific epi-
thet, capsulatum, to achieve nomenclatural agree-
ment.  Two additional autopsies with similar find-
ings convinced Darling that he had found a new
form of visceral leishmaniasis.4
Mortality rates among canal workers were ex-
traordinary.  Most deaths were caused by pneumo-
nia and the mosquito-borne diseases, yellow fever
and malaria.5  The morbidity of undiagnosed
histoplasmosis among the canal workers remains
undetermined.  Nearly 50 years passed before the
next case of histoplasmosis in Panama was reported,6
although the disease is now known to be common
there.7
After reviewing Darling’s original slides, a Bra-
zilian pathologist, Henrique da Rocha-Lima, deter-
mined that Histoplasma was more akin to yeasts
than to protozoa.8  Its fungal nature was confirmed
by culturing organisms that were recovered from
the blood of an infant dying of an unexplained
febrile illness.9  Until a benign form of the infection
was recognized during the 1940s, histoplasmosis
was considered a uniformly fatal, primarily tropi-
cal, disease.  During the early 1950s, H capsulatum
was detected in calcified pulmonary nodules
resected from healthy soldiers at Fitzsimons Army
Hospital in Colorado.10  The true geographical range,
prevalence, and usual benignity of histoplasmosis

Deep Fungal Skin Diseases
457
were further clarified by skin testing large groups
with histoplasmin and by recovering H capsulatum
from the soil.
Several outbreaks of acute pulmonary histoplas-
mosis have occurred in military units training in
tropical areas but cutaneous manifestations have
not been reported.  While training in Panama, 27 of
47 U.S. soldiers (57%), who had cleaned out and
then slept in an abandoned bunker, contracted acute
pulmonary histoplasmosis.  The bunker, inhabited
by a colony of bats, had several inches of mixed soil
and bat guano (ie, excrement) on the floor.  The
soldiers’ sweeping of the floor had aerosolized the
spores of Histoplasma, which permitted their inhala-
tion.  The severity of the soldiers’ illnesses corre-
sponded roughly to the duration of exposure to the
aerosolized dust.11
During 1977, 8 soldiers in a 35-man engineering
unit who were returning from training exercises in
Panama suddenly developed fevers.  Initial evalu-
ations were unrevealing, leading to a presumptive
diagnosis of an arboviral disease, but histoplasmosis
was confirmed by complement fixation.  The expo-
sure probably occurred while the soldiers cleaned an
abandoned Spanish fort that was inhabited by bats.12
French and Dutch soldiers serving in colonial
French Guiana and Surinam (now Suriname), re-
spectively, occasionally contracted histoplasmosis.
Symptomatic illnesses were usually first diagnosed
as acute pulmonary tuberculosis.  Exposures pre-
sumably occurred in bunkers and old huts where
bat guano had accumulated.13,14
At Chanute Air Force Base, Illinois, there was an
outbreak of acute pulmonary histoplasmosis in 10
persons, most of whom had not lived previously in
endemic areas.  Histoplasma had colonized soil in
the gardens and orchards around their housing
development.15
Distribution and Epidemiology
Histoplasmosis occurs worldwide but is hyper-
endemic along the Mississippi and Ohio River val-
leys (Figure 18-2).  Histoplasmin skin tests and
chest radiographs showing calcified granulomata
suggest nearly universal infection in residents of
these areas.  Additional foci occur in Panama and
northern South America, Australia, Indonesia, In-
dia, South Africa, the Mediterranean, and western
Europe.14  Histoplasmosis duboisii occurs in tropi-
cal Africa.
The organism is a saprophyte found in soil laden
with excreta of bats or birds.  Therefore, habitats
with guano accumulations, for example, caves and
OK to put on the Web
Fig. 18-2. Histoplasmosis is hyperendemic in this North
American region. The distribution corresponds roughly
to the areas drained by the Mississippi and Ohio rivers.
chicken coops, are consistent sources of infection.
Occupations and recreations (eg, chicken farming,
spelunking, pigeon breeding) that expose people to
these niches predispose for infection.  In tropical
areas, bats are the usual reservoir of histoplasmosis.
They, unlike birds, naturally become ill with infec-
tion.  The microenvironment in their caves is suit-
able for the growth of Histoplasma, whereas the
surrounding environment apparently is not.16  In
temperate regions, outbreaks have occurred in resi-
dential areas where excrement from starlings, grack-
les, blackbirds, pigeons, or other birds accumulates
beneath roosting sites.
Clinical Manifestations
Histoplasmosis is acquired when a person in-
hales spores into the lungs, where the spores con-
vert to their yeast forms.  In heavily endemic areas,
perhaps 95% of the population has been infected,
albeit usually with asymptomatic disease or a self-
limited, mild, flulike illness.  The erythema nodosum
and erythema multiforme that sometimes accom-
pany acute disease are probably hypersensitivity
reactions.17  Acute pulmonary infections typically
produce inactive, calcified, pulmonary granulomas
and transient immunity to further bouts of
histoplasmosis.  Persons with underlying lung dis-
orders are susceptible to chronic cavitary histo-
plasmosis.  Its clinical and radiographic features
resemble pulmonary tuberculosis and may be fatal
if untreated.1
Hematogenously disseminated histoplasmosis
occurs in 1 of 2,000 to 5,000 acute infections and has

Military Dermatology
458
a predilection for immunocompromised, elderly, or
very young persons.18  The organisms enter reticu-
loendothelial organs, such as liver, spleen, lymph
nodes, and bone marrow.  Infants, in particular, can
have a fulminant illness with fungemia character-
ized by fever, hepatosplenomegaly, and pancyto-
penia.  Their peripheral smears may reveal yeast
cells.  In adults, disseminated disease has a more
protracted course, often localizing in the bone mar-
row.  Subsequent involvement of the meninges,
endocardium, or adrenal glands is insidious but
potentially lethal.18  Disseminated histoplasmosis
in a person infected with the human immunodefi-
ciency virus (HIV) meets the Centers for Disease
Control and Prevention’s (CDC’s) definition of ac-
quired immunodeficiency syndrome (AIDS).19
Oropharyngeal lesions are the most common
dermatologic sign, found in one third to one half of
disseminated cases (see Figure 18-1).  When present,
they are often the only clinical manifestation of the
disease.  Oral papules or nodules typically erode,
forming ulcers with prominent rolled borders (Fig-
ure 18-3).  In order of their frequency, the affected
sites are the tongue, buccal mucosa, larynx, lip, and
gingiva.1
Skin lesions, none distinctive, occur in only 5% of
patients with disseminated disease (Figure 18-4).
Reported lesions include papules, plaques, ulcers,
abscesses and furuncles, panniculitis, purpura, ec-
zema, and erythroderma.17
African histoplasmosis differs from classic Ameri-
can histoplasmosis because its pulmonary symp-
toms are less severe, whereas bony and skin lesions
are more common.  The most common cutaneous
lesions are hypopigmented, dome-shaped papules
surrounded by hyperpigmented halos, giving them
OK to put on the Web
OK to put on the Web
Fig. 18-4. Granulomatous plaque of cutaneous histo-
plasmosis. Cutaneous lesions of disseminated histoplas-
mosis have varied, nondistinctive morphologies but they
can be diagnostic on either culture or histopathology.
Photograph: Courtesy of William E. Dismukes, MD, Bir-
mingham, Ala.
a targetlike appearance.  These heal with scarring.
Subcutaneous abscesses and draining sinuses aris-
ing from lymph nodes or underlying osteomyelitic
foci are less common but still characteristic of the
disease.20,21
Rare cases of primary inoculation cutaneous
histoplasmosis have followed laboratory accidents
or environmental inoculation.22  A noduloulcerative
lesion arises at the implantation site, followed by
lymphangitis and a chain of lymphocutaneous nod-
ules.  Except for its spontaneous resolution, the
clinical features resemble lymphocutaneous
sporotrichosis.
Diagnosis
H capsulatum can be found within parasitized
macrophages of involved organs (Figure 18-5).  Simi-
larly sized, intracellular parasites also occur in
granuloma inguinale, rhinoscleroma, and leish-
maniasis.  Each may also affect mucocutaneous
regions, but only H capsulatum picks up fungal
stains.  Direct examination of Giemsa- or Wright-
stained smears of sputum, pus, skin or ulcer
scrapings (Tzanck preparation), Buffy-coat smears,
or other materials may reveal Histoplasma.17,23,24
Culture has the highest yield with material aspi-
rated from bone marrow but is often positive when
performed on skin, blood, and other tissues.18  Skin
testing with histoplasmin is useful mainly as an
epidemiological tool, and is often falsely negative
in persons with cutaneous or otherwise dissemi-
Fig. 18-3. This man has disseminated histoplasmosis.
Note the shallow ulcer on his oral mucosa.

Deep Fungal Skin Diseases
459
OK to put on the Web
Fig. 18-5. This photomicrograph shows    infection of the
skin. The yeast forms have been consumed by host mac-
rophages. The unstained rim around the organisms gives
the illusion of a capsule, although a true capsule does not
exist (hematoxylin-eosin stain, original magnification
430X). Photograph: Courtesy of Colonel James E.
Fitzpatrick, Medical Corps, US Army, Aurora, Colo.
nated disease.  Investigational radioimmunoassays
that detect Histoplasma polysaccharide antigen in
the urine are rapid and sensitive.25  Serologic tests
are not the subject of this chapter but are reviewed
in detail elsewhere.18
Treatment
Except in cases of primary inoculation histo-
plasmosis, cutaneous lesions signify disseminated
disease.  Accordingly, these patients require ag-
gressive treatment.  For severe disease, intravenous
amphotericin B should be administered at 25 to 35
mg/d for a total of 2 g over approximately 6 weeks.
Immunocompetent patients with mild infections
that do not involve the central nervous system may
receive the fungistatic agent, ketoconazole, on an
outpatient regimen of 400 mg daily, administered
orally.  Mild, acute, pulmonary infections resolve
spontaneously and require no therapy.18,26,27
Military Implications
Cutaneous histoplasmosis is unlikely to interfere
with military operations.  Outbreaks of acute pul-
monary disease will continue to occur whenever
immunologically naive soldiers enter endemic ar-
eas.  Caution should be exercised on entering caves
and sheltered areas such as old bunkers, especially
in the tropics.  Care not to disturb dusty soil laden
with bat or bird excrement may help prevent out-
breaks of histoplasmosis.24
Coccidioidomycosis
Coccidioidomycosis has a well-recognized eco-
logical and geographical distribution: it is endemic
in certain arid and semiarid regions throughout the
Americas, especially in the southwestern United
States.  Coccidioidomycosis is acquired by inhaling
the arthrospores of Coccidioides immitis or, rarely, by
percutaneous inoculation of the spores.  Primary pul-
monary infections are usually inapparent or produce
a transient, flulike illness.  Disseminated disease is
uncommon but, when present, frequently has cuta-
neous lesions.Coccidioidomycosis is also called San
Joaquin Valley Fever, Posada’s disease, valley fe-
ver, coccidioidal granuloma, and desert fever.
C immitis is a dimorphic fungus that exists in
nature as a soil saprophyte.  The mycelia produce
spores (or arthroconidia) that are easily wind-blown
and are infectious when inhaled.  In tissue, the
organisms develop into specialized, thick-walled
structures called spherules.  Mature spherules are
large, (10–) 30 to 60 (–80) µm in diameter, with
internal septae separating numerous endospores.
When a spherule ruptures, endospores discharge
into surrounding tissue.  External budding, as seen
in other systemic mycoses, does not occur.2
History
Coccidioidomycosis was first described in 1892
in an Argentinean cavalryman stationed in the Gran
Chaco of northern Argentina.  An unexplained sore
developed on his cheek and was unresponsive to
treatment.  The lesion grew more warty so he was
transferred to the University Hospital Clinics in Buenos
Aires.  There, a 21-year-old intern, Alejandro Posadas,
evaluated the patient and discovered the characteris-
tic spherules of coccidioidomycosis, describing them
as protozoa.28  A few years later, the organism was
isolated from several patients in California with wide-
spread, destructive skin lesions.  It was named
Coccidioides for its superficial resemblance to the
avian parasite, Coccidia.  The epithet, immitis, mean-
ing “not mild,” reflects the early impression that
coccidioidomycosis was nearly always fatal.
Further investigations in the San Joaquin Valley
in the 1930s determined that the flulike condition
known locally as valley fever was, in fact, benign
primary pulmonary coccidioidomycosis.29  When the
U.S. Army Air Corps elected to train aviators there,
concerns were raised over bringing nonexposed

Military Dermatology
460
individuals into a highly endemic area.  Despite the
efforts of the military physicians who served as
coccidioidomycosis control officers at each airfield,
the disease caused significant interruptions in train-
ing.  Coccidioidomycosis particularly hampered
preparations for the World War II North Africa
campaign conducted at the U.S. Army’s Desert
Training Center (west of Twenty-Nine Palms, Cali-
fornia, near the Arizona border) and several sites in
southern California and Arizona.  Prisoner-of-war
camps housing Japanese, German, and Italian sol-
diers in Florence, Arizona, and San Luis Obispo,
California, also experienced outbreaks.  The foun-
dation of the modern understanding of coccidioido-
mycosis emerged from the effects of this disease on
the U.S. military during World War II and the medi-
cal departments’ epidemiological and preventive
medicine responses.30
Military installations in Arizona and California
continue to experience high rates of lost man-days
due to pulmonary coccidioidomycosis.31  Active
military bases that have reported disease or sero-
logic evidence of infection include Twenty-Nine
Palms Marine Corps Base, Lemoore Naval Air Sta-
tion, Edwards Air Force Base, and Fort Irwin, all in
California; Chandler Air Force Base, Davis–Monthan
Air Force Base, Luke Air Force Base, and Williams Air
Force Base, all in Arizona; and Fort Bliss, Texas.32–34  In
addition, personnel from the Norwegian, Belgian,
and German military have acquired coccidi-
oidomycosis during training exercises in the Ameri-
can Southwest.35–37
Epidemiology
Approximately 100,000 new cases of coccidioido-
mycosis occur in the United States each year, most
during periods when dry, dusty winds carry the
spores aloft.  Occupational and recreational activi-
ties that expose persons to dusty soils are risk fac-
tors for coccidioidomycosis.  Agricultural workers,
military units, outdoor construction workers, and
archeological teams repeatedly have been involved
in point (ie, localized, single-occasion) outbreaks.38,39
California’s workmen’s compensation laws recog-
nize coccidioidomycosis as an occupational illness.
Risk factors for systemic disease include race,
gender, and, possibly, pregnancy.38,40  The propen-
sity for severe disease is greater in nonwhites than
in whites.  This disparity is severalfold greater for
Mexicans and Native Americans and considerably
more so for blacks and Filipinos.31  The reasons for
this are not well understood.  Socioeconomic factors
(eg, occupational exposures and nutritional status)
do not entirely account for the differences.  In gen-
eral, the disease is more often self-limited in fe-
males than in males.  In contrast, the hormonal
milieu and mild immunosuppression associated
with pregnancy may permit vigorous growth of the
fungus.  Infants, the elderly, and persons with blood
types B or AB also may be at increased risk for
severe disease.31
Distribution
C immitis is tolerant of a wide range of environ-
mental conditions but competes poorly with other
microorganisms in fertile soils.  Therefore, C immitis
is most abundant in soils too dry and dusty for more
fastidious fungi.  Also, once lands are under culti-
vation, other soil fungi displace C immitis.  In North
America, coccidioidomycosis occurs primarily in
the Lower Sonoran life zone, which is characterized
by semiarid conditions; hot summers; mild winters;
and alkaline, sandy soils (Figure 18-6).  Plants typi-
cally found in this habitat include creosote, yucca,
OK to put on the Web
Fig. 18-6. Coccidioides immitis occurs naturally in the dusty
soils of the Lower Sonoran life zone. Ocotillo (the long,
wiry-branched shrub) and several types of cacti (saguaro,
cholla, and prickly pear) typify this ecosystem, seen here in
the Saguaro National Monument near Tucson, Ariz.

Deep Fungal Skin Diseases
461
morbilliform or scarlatiniform erythema may ac-
company the early symptoms in children, adoles-
cents, and 10% of adults.  Several weeks later, a
syndrome (Valley Fever), more common in women
and white people, develops.29  It affects approxi-
mately 25% of infected white women and 10% of
infected white men.38  Erythema nodosum or, less
commonly, erythema multiforme may occur, indi-
cating the host’s strong immunological response
and decreased risk for disseminated disease.
Nonmigratory arthralgias (eg, desert rheumatism)
occur in one third of patients.38
Extrathoracic disease occurs in fewer than 1% of
infections, more commonly in the ethnic groups
noted above.  Target organs for disseminated infec-
tion include skin and subcutaneous tissues, bones,
and the meninges.40  Fatalities, approximately 60
per year in the United States,31 are usually the result
of severe involvement of the lungs or central ner-
vous system.
Skin lesions with recoverable coccidioidomycosis
organisms occur in 15% to 20% of patients with
disseminated disease (Figure 18-8).  Papules typi-
cally evolve into verrucous nodules or plaques.
Plaques frequently occur in the center of the face,
particularly along the nasolabial folds (see Figure
18-1).  Other lesions have considerable variability,
such as subcutaneous cold abscesses or sinuses that
arise from involved bones.41
Primary inoculation coccidioidomycosis has oc-
curred several times after accidental inoculation
during a laboratory or postmortem procedure.
Barbed wire and splinter injuries have also led to
infections.42  In immunologically naive patients, ul-
ceration at the site of trauma is typically followed
by transient lymphangitis and regional lymph-
adenitis.  One case subsequently disseminated, caus-
ing coccidioidal meningitis.42  Another kind of rare
eruption occurs in patients with pulmonary
coccidioidomycosis who develop localized skin lesions
at sites of trauma unassociated with inoculation.43
Diagnosis
The diagnosis of coccidioidomycosis is estab-
lished quickly by finding spherules in touch prepa-
rations of skin lesions or in sputum smears.  The
spherule’s large size, doubly refractile walls, and
numerous endospores are pathognomonic.  Mate-
rial taken from a cutaneous pustule, abscess, or
ulcer should be cleared with potassium hydroxide
and examined by direct microscopy.  Lactophenol
cotton blue or Papanicolaou stain may give supe-
rior results.44  In histological sections, spherules are
OK to put on the Web
Fig. 18-7. The geographical distribution of coccidioido-
mycosis. Infection with Coccidioides immitis is not known
to have occurred naturally outside the Americas.
mesquite, ocotillo, and several types of cacti
(saguaro, cholla, prickly pear).  Hyperendemic foci
are scattered throughout central California’s San
Joaquin Valley, the southwestern United States,
and northwestern Mexico (Figure 18-7).  The dis-
ease also occurs infrequently in several locations in
Central and South America.  The disease is not
transmissible between humans and there are no
reliable reports of coccidioidomycosis acquired
outside the Americas.  Mammals other than hu-
mans are susceptible to infection.31,38
Clinical Manifestations
Coccidioidomycosis follows inhalation of dust
laden with spores of C immitis.  After an incubation
period of 1 to 4 weeks, a primary pulmonary infec-
tion develops.  Perhaps 60% of newly acquired
cases are asymptomatic.40  The others experience
symptoms ranging from a flulike syndrome with
mild fevers to severe pneumonitis with cough, fe-
ver, chest pain, dyspnea, chills, and night sweats.
Typically, symptomatic illnesses completely resolve.
Several nonspecific cutaneous findings are asso-
ciated with early coccidioidomycosis.  A transient

Military Dermatology
462
OK to put on the Web
a
OK to put on the Web
b
c
OK to put on the Web
Fig. 18-8. Patients with cutaneous coccidioidomycosis
present with varied clinical manifestations. (a) This Fili-
pino-American sailor acquired pulmonary coccidi-
oidomycosis after breathing dust that had been stirred
up at a cockfight in southern Arizona. The infection
subsequently disseminated to his skin and appeared as a
cluster of granulomatous papules around his elbow. (b)
This African-American soldier complained of fever,
diplopia, and neck stiffness. He became obtunded and a
skin biopsy of this preauricular lesion showed abundant
spherules of Coccidioides immitis. Despite amphotericin
therapy, the patient soon died. A retrospective history
revealed that his only geographical exposure had oc-
curred 6 months earlier, when he traveled through south-
ern California. (c) Additionally, the skin may become
involved when bony lesions produce draining sinuses.
This man developed fistulous tracts in his chest wall
from rib osteomyelitis caused by C immitis. Photographs:
(b) Courtesy of Lieutenant Colonel Curt P. Samlaska,
Medical Corps, US Army, Honolulu, Hawaii; (c) Cour-
tesy of Captain E. C. Oldfield III, Medical Corps, US
Navy, San Diego, Calif.
apparent with hematoxylin-eosin stain but are en-
hanced by fungal stains (Figure 18-9).
The intradermal skin test is a useful diagnostic
and prognostic tool.  Spherulin, derived from the
pathogenic tissue phase of C immitis, is perhaps
more sensitive to the arthrospore-derived coccidi-
oidin, which was used previously.38,45  Skin tests
turn positive within 3 weeks after onset of pulmo-

Deep Fungal Skin Diseases
463
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b
a
Fig. 18-9. These photomicrographs show cutaneous coccidioidomycosis. (a) Exuberant granulomatous skin lesions are
characterized histologically by pseudoepitheliomatous hyperplasia of the epidermis. Dermal and intradermal abscess
may contain spherules (original magnification 40X). (b) A high-powered view shows many endospores within a
spherule (hematoxylin-eosin stain, original magnification 430X).
ease or failure of therapy.40,41,45  Many medical cen-
ters refrain from routine coccidioidal cultures be-
cause the mycelia have easily dispersed, highly
infectious spores.  Hundreds of medical personnel
have been infected under seemingly innocuous labo-
ratory conditions.31  Therefore, if tissue is sent for
culture, laboratory personnel must be advised to
use appropriate precautions.
Treatment
Most cases of exclusively pulmonary coccidioido-
mycosis are both unrecognized and untreated.  On
the other hand, most persons with cutaneous
coccidioidomycosis require aggressive therapy for
disseminated disease.  After determination of the
extent of disease, usually by bone scan, gallium
scan, and lumbar puncture, a regimen of ampho-
tericin B should be started.  Surgical debridement of
subcutaneous abscesses and underlying bone infec-
tions should be considered.40  Ketoconazole,
fluconazole, and itraconazole are under evaluation
for use either in place of, or as a complement to,
amphotericin.46  As azoles, they are fungistatic and
probably should not be used alone to treat disease
in immunocompromised patients.  Members of eth-
nic groups prone to disseminated disease should be
evaluated with extra concern.
Prevention
Most attempts to prevent coccidioidomycosis are
impractical because the infectious particles are borne
by wind-blown dust.  Dust-control measures in-
nary symptoms.  A positive test confirms infection
in previous nonreactors and, presumably, in per-
sons who have never before lived in endemic areas.
False positives may indicate previous infection with
histoplasmosis, blastomycosis, or paracoccid-
ioidomycosis.  False negatives may indicate the
host’s poor immunological response to infection
and signal susceptibility for disseminated disease.38
Furthermore, persons with persistent negative skin
tests during therapy are at increased risk for relapse
if therapy is discontinued.
In endemic areas, the most common cause of
erythema nodosum in white patients is coccidi-
oidomycosis.  It signifies a vigorous immunological
response.  If skin testing is conducted on these
individuals, a dilute strength (1:1000 or 1:10,000)
of spherulin should be used to prevent an intense
reaction such as local necrosis or erythema
multiforme.41
Patients with symptomatic primary pulmonary
coccidioidomycosis often have chest radiographs
showing infiltrates, hilar adenopathy, or pleural
effusions.  Mild peripheral eosinophilia is frequently
present and may reach 80%.
Serologic assays are valuable adjuncts in the di-
agnosis and management of coccidioidomycosis.
Tests that detect immunoglobulin (Ig) M antibodies
(eg, tube precipitin, latex particle agglutination, or
concentrated immunodiffusion) help confirm acute
coccidioidomycosis, whereas complement fixation
is more valuable in cases of long-standing or dis-
seminated disease, including cutaneous coccid-
ioidomycosis.  A high (> 1:16) or rising complement
fixation-titer suggests either dissemination of dis-

Military Dermatology
464
clude watering down or oiling airstrips, planting
lawns or vegetation, encouraging cultivation, and
restricting activities downwind of disturbed sites.32,47
Archaeologists working in the Southwest have tried
wearing masks and wetting the ground in their
work areas to lessen the dusty conditions.  Suscep-
tible persons from nonendemic areas should prefer-
ably avoid dusty activities, such as road grading.48
Efforts to develop an effective vaccine continue.
Blastomycosis
Blastomycosis, caused by Blastomyces dermatitidis,
is principally a pulmonary infection that involves
the skin after rare dissemination.  Even more rarely,
skin lesions follow percutaneous inoculation of the
pathogen.  Synonyms include North American
blastomycosis, Gilchrist’s disease, Chicago disease,
Namekagon fever, and blastomycetic dermatitis.
A thermally dimorphic fungus, B dermatitidis
exists in a mycelial phase in nature and in culture at
25°C.  A pathogenic yeast phase grows at body
temperature.  Yeast cells are spherical, approxi-
mately 8 to 15 (–30) µm in diameter, and possess a
thick, doubly refractile cell wall.  Yeast reproduce
by forming single buds attached to the parent cell
by a broad base.  The sexual stage is Ajellomyces
dermatitidis.
History
Blastomycosis was identified in 1894 by Thomas
Caspar Gilchrist, a dermatologist at The Johns
Hopkins Hospital, Baltimore, Maryland, and later
president of the American Dermatologic Associa-
tion.  His 1894 report was titled “Protozoan Derma-
titis,”49 despite his recognition that the organism
was a hitherto-unknown fungus.50  The epithet,
dermatitidis, reflects Gilchrist’s appreciation for the
organism’s affinity for skin.  Before self-limited
forms of blastomycosis were recognized, the dis-
ease was believed nearly always fatal.51
Epidemiology
The epidemiology of blastomycosis is poorly
defined because clusters of human disease rarely
occur.  Moreover, it was 1984 before B dermatitidis
was recovered from a location where human dis-
ease had occurred: half of the approximately 100
members of a Wisconsin school group that visited a
beaver lodge acquired blastomycosis.52  The organ-
ism was found in the moist, excrement-laden soil
surrounding the lodge.  Apparently, a microfocus
of damp or swampy, nitrogen-rich soil with an acid
pH and high organic matter content provides a
suitable habitat for the fungus.53  Persons whose
occupational or recreational activities (eg, forestry,
hunting, camping) expose them to this ecological
niche are at risk for infection.  Even so, the disease
is unlikely to be contracted more than once in any
particular location.  One third of foresters in north-
ern Wisconsin and Minnesota have serologic evi-
dence of prior infection.54
Sporadic disease affects mostly men, reflecting
occupational exposures, but epidemic disease af-
fects the sexes equally.51  Although the disease is not
considered contagious, women have acquired en-
dometrial blastomycosis after sexual contact with
partners who had genitourinary disease.55  In North
America, other mammals, most notably dogs, natu-
rally acquire blastomycosis.  The geographical range
of canine blastomycosis parallels that of human
disease,56 except in Africa where canine disease has
not been diagnosed.57
Distribution
Blastomycosis is principally a North American
disease, endemic in the southeastern United States
(particularly Kentucky, Mississippi, and Arkansas),
the Great Lakes region, and the drainage basins of
the Mississippi and St. Lawrence rivers (Figure 18-
10).  Many cases of autochthonous infection have
occurred in Zimbabwe and South Africa.57  Fewer
cases are reported from other parts of Africa, South
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Fig. 18-10. The North American region where blasto-
mycosis is endemic. Like histoplasmosis, its distribution
follows the parts of the Mississippi and Ohio River val-
leys. Note that the range of blastomycosis extends into
the upper Midwest and along the St. Lawrence River.

Deep Fungal Skin Diseases
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c
d
a
b
Fig. 18-11. These individuals have cutaneous blastomycosis. The mid-face (a, b, and c) and distal extremities (d) are
typical locations for cutaneous disease. The appearance of these lesions is quite suggestive of blastomycosis: typical
granulomatous plaques with expanding, verrucous borders surmounted by fine, dark puncta.
Systemic Blastomycosis.  Hematogenous spread
from the lungs produces systemic blastomycosis.
The skin is the most commonly affected extrathoracic
organ, involved in perhaps 50% of disseminated
cases.  Bones, the genitourinary system (particu-
larly the prostate), and the central nervous system
also are involved frequently.58  In addition, there is
a less aggressive form of systemic blastomycosis in
which infection spreads exclusively to skin.59  About
40% of patients with disseminated blastomycosis
have inactive pulmonary disease.27
Skin lesions are usually few or solitary and are
located on exposed skin, often the face (Figure 18-
11).  They begin as inflammatory nodules that sub-
sequently break down to form expanding granulo-
matous ulcers and plaques.  Borders are raised and
have an annular, arcuate, or serpiginous pattern.
Lesions often expand asymmetrically with an exu-
berant, verrucous, active edge.  When the crusted
edges are removed, a granulomatous base studded
with minute pustules is revealed.  Central healing
may leave a depigmented, atrophic scar.  Oral and
America, and Asia.  Indigenous disease in Europe
and the Far East is unknown.
Clinical Manifestations
There are three clinical forms of disease: primary
pulmonary blastomycosis, systemic blastomycosis,
and primary cutaneous inoculation blastomycosis
(see Figure 18-1).  The first form is the most com-
mon.
Primary Pulmonary Blastomycosis.  Primary
pulmonary blastomycosis starts with the inhalation
of spores.  The usual incubation period is 40 to 50
days53 but may range from 21 to 106 days.52  Most
infections are asymptomatic but patients can present
with mild pneumonia; both conditions usually re-
solve without sequelae.  Erythema nodosum may
accompany a syndrome of fever, chest pain, and
productive cough.  Symptomatic conditions also
include a fulminant presentation and a chronic,
progressive, pulmonary disorder, with or without
dissemination.

Military Dermatology
466
mucocutaneous ulcers also can occur.  Bone infec-
tions sometimes produce fistulae extending to the
skin.51
The differential diagnosis of cutaneous blasto-
mycosis includes other deep fungal infections, tu-
berculosis verrucosa cutis, halodermias, pyoderma
gangrenosum, and squamous cell carcinoma.50
Primary Cutaneous Inoculation Blastomycosis.
Several cases of primary cutaneous inoculation
blastomycosis have followed autopsy or laboratory
accidents60 or dog bites.61  A chancriform syndrome,
with regional lymphadenopathy and a chain of
subcutaneous nodules, generally resolves on its
own within several months.60
Diagnosis
Direct examination of a smear of pus or sputum
is a simple, quick way to diagnose blastomycosis.
Smears are positive in more than half the cases.
After the crust has been lifted off an active border,
swabbed material from a micropustule should be
smeared on a glass slide.  A bit of necrotic tissue
crushed between two slides is also suitable.  After
debris is cleared with potassium hydroxide, micro-
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Fig. 18-12. These photomicrographs show the histology
of cutaneous blastomycosis. (a) The granulomatous
plaques are characterized histologically by pseudo-
epitheliomatous hyperplasia of the epidermis (hema-
toxylin-eosin stain, original magnification 25X). There
are dermal and intraepidermal abscesses that, when
passed through the epidermis, appear as the superficial
dark puncta seen clinically. (b) The typical broad-based
budding of blastomycosis can be seen in the high-power
view (Gomori’s methenamine-silver stain, original mag-
nification 430X).
b
a
scopical examination will show yeast with doubly
refractile walls (accentuated by lowering the con-
denser) and distinctive, single, broad-based buds.
Biopsied skin specimens prepared with fungal
stains show pseudoepitheliomatous hyperplasia,
microabscesses, giant cells, and the characteristic
organisms (Figure 18-12).51  The organism may be
cultured, on Sabouraud’s agar at 25°C to 30°C, from
pus, skin scrapings, or biopsy specimens.2,51
Blastomycin skin tests are insensitive, lose reactiv-
ity over time, and are often falsely positive in pa-
tients with histoplasmosis.54  Investigational enzyme
immunoassay and in vitro lymphocyte stimulation
assays show greater reliability than the two more
widely available serologic tests, immunodiffusion
and complement fixation.52–54
Treatment
Because most cases of acute pulmonary blasto-
mycosis probably resolve spontaneously, whether
all persons should receive treatment remains unre-
solved.58,62  If untreated, pulmonary blastomycosis
can reactivate years later.  In general, patients with
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Deep Fungal Skin Diseases
467
should receive therapy.63  An outpatient regimen of
ketoconazole (400 mg daily for at least 6 mo) is
generally effective.26,53  If the disease worsens, the
dose should be increased to 600 to 800 mg daily.
Because ketoconazole is distributed poorly in the
central nervous system and is not excreted by the
kidneys, it is not recommended for treating
meningeal or genitourinary blastomycosis.27  Intra-
venous amphotericin B (2-g regimen over 6 wk) is
recommended for immunocompromised patients
or those with fulminant, refractory, or meningeal
disease.  The triazole antifungal agent, itraconazole,
has shown promise in preliminary investigations.63
Military Implications
Few clusters of human blastomycosis have oc-
curred,52,62 suggesting that the disease has little epi-
demic potential.  Military exercises may expose
soldiers to the habitats of B dermatitidis but the
appearance of skin disease, other than in solitary
cases, is unlikely.  Because dogs are more suscep-
tible to infection than are humans, close coopera-
tion with veterinary staff may be required.56
Paracoccidioidomycosis
Paracoccidioidomycosis (also called South Ameri-
can blastomycosis, Brazilian blastomycosis, Lutz-
Splendore-Almeida’s disease, and paracoccidioidal
granuloma) is a chronic, progressive, potentially
fatal, systemic mycosis.  It is principally a pulmo-
nary infection but may secondarily involve skin
and mucosal surfaces.  The causative organism is
Paracoccidioides brasiliensis.  The disease occurs only
in South and Central America, where in many areas
it is the most prevalent and serious systemic fungal
disorder.  Paracoccidioidomycosis occurs sporadi-
cally and therefore poses little risk to military units.
P brasiliensis is a thermally dimorphic fungus
whose pathogenic yeast forms have a diameter of 6
to 40 µm.  In tissue, a spherical yeast cell sur-
rounded by narrow-based progeny cells gives the
distinctive appearance of a ship’s pilot wheel or, if
fewer buds are present, a Mickey Mouse head.
History
A mummified woman who died circa AD 290,
excavated from northern Chile, was found to have
paracoccidioidal pulmonary infection.64  The first
patients described in modern times presented with
oral lesions and were reported in 1908 by Adolpho
Lutz, director of the São Paulo Bacteriological Insti-
tute.  Lutz demonstrated the dimorphism and patho-
genicity of the fungus, yet its distinction from
Blastomyces and Coccidioides remained in dispute.
In the late 1920s, Almeida convincingly differenti-
ated the organisms and provided the name
Paracoccidioides brasiliensis.65  Paracoccidioido-
mycosis is not known to have hampered military
operations.
Epidemiology and Distribution
Paracoccidioidomycosis is restricted to the Ameri-
cas, occurring as far north as Mexico (Figure 18-13).
Brazil, in particular the São Paulo region, has the
highest incidence of disease.66  The disease occurs
primarily in forested tropical and subtropical re-
gions, although the ecological niche of the fungus
remains unknown.67  Young and middle-aged men
who work outdoors are at greatest risk for infection.
Women are rarely affected, probably due to the
suppressive effects of active estrogens on mycelial-
to-yeast transformation.68  The theory that cleaning
one’s teeth with contaminated twigs causes gingi-
val inoculation remains unproven.
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Fig. 18-13. This map shows the geographical distribution
of paracoccidioidomycosis. The disease is most preva-
lent in coastal regions of Brazil but can occur throughout
South America and Central America.

Military Dermatology
468
Clinical Manifestations
The clinical manifestations and natural history of
paracoccidioidomycosis are poorly understood.
Presumably infectious organisms are inhaled, caus-
ing a primary lung infection that is characterized by
productive cough, dyspnea, fever, and weight loss.69
Asymptomatic pulmonary infections, similar to
those of histoplasmosis, occur infrequently70 but
may recrudesce after years of dormancy.71  One half
of infected individuals develop oral lesions, often
accompanied by nasal and pharyngeal ulcers (see
Figure 18-1).  Mucosal ulcers have granulomatous,
often exuberant, bases.  The patient may complain
of dysphagia or hoarseness.  Periorificial, crusted,
granulomatous plaques may encroach onto and
destroy facial structures (Figure 18-14).  Affected
gingivae may lose teeth.  Involvement of lymphoid
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Fig. 18-14. Cutaneous lesions of paracoccidioidomycosis typically appear in or around the mouth. These patients have
(a) periorificial granulomatous plaques and (b) granulomatous infiltration of the tongue and (c) labial mucosa. (d)
Cervical adenopathy resembling tuberculous adenopathy commonly occurs in paracoccidioidomycosis. The lymph
nodes may suppurate and form draining sinuses. Photographs: Courtesy of Professor Angela Restrepo-M., Medellin,
Colombia.
a
b
d
c

Deep Fungal Skin Diseases
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Fig. 18-15. The histopathology of cutaneous paracoccid-
ioidomycosis. (a) Pseudoepitheliomatous hyperplasia
with dermal and intraepidermal abscesses (40X original
magnification). (b) A closer view of an intraepidermal
abscess shows twin buds arising from a parent organism,
giving the appearance of a Mickey Mouse head (hema-
toxylin-eosin stain, original magnification 430X). (c) On
this touch preparation, the multiple narrow-based buds
arising from parent organisms give the appearance of a
ship-pilot’s wheel. No other systemic fungal pathogen
has this morphologic appearance. Photographs: Cour-
tesy of Colonel James E. Fitzpatrick, Medical Corps, US
Army, Aurora, Colo.
c
a
b
tissues is especially common in children.  Cervical
lymph nodes draining oral lesions may be painful
and massive.  Invasion of mesenteric lymphoid
tissue may cause bowel obstruction and symptoms
of an acute abdominal emergency.71
Cutaneous lesions do not resolve spontaneously.
Untreated paracoccidioidomycosis is often fatal,
due mainly to extensive pulmonary fibrosis or ad-
renal gland invasion.  Dormant infections may be
reactivated after a 30-year latency.72
The differential diagnosis includes mucocutane-
ous leishmaniasis, fixed cutaneous sporotrichosis,
histoplasmosis, lymphoma, and scrofula.  Coexist-
ing tuberculosis has been noted often.  Blastomyces
blastomycosis more commonly affects skin instead
of mucosa, often heals centrally with atrophic scars,
and lacks both gingival involvement and regional
lymphadenopathy.
Diagnosis
Evaluation for paracoccidioidomycosis is war-
ranted in patients from endemic regions who have
respiratory symptoms and oral lesions.  The diag-
nosis is confirmed by culture or by finding charac-
teristic, multiply budding yeast in tissue (Figure
18-15).  Skin biopsies show areas of pseudo-
epitheliomatous hyperplasia and microabscesses
containing the organisms.  A potassium hydroxide
preparation of lesional scrapings, sputum or lung-
lavage fluid, or pus from draining sinuses may
reveal the organisms.  The thinner cell wall, in-
creased number of buds, and narrow bud stalks
distinguish P brasiliensis from B dermatitidis.
Cultures grow slowly but are diagnostic.  Several
immunological assays, in particular immunodiffu-
sion, are potentially valuable diagnostic adjuncts
and are being evaluated in endemic areas.73,74
Paracoccidioidin skin tests are unreliable.67,72
Treatment
Paracoccidioidomycosis must be treated because
it rarely resolves on its own.  Therapy with
itraconazole for 6 months or more generally is effec-
tive for both pulmonary and cutaneous disease.75,76

Military Dermatology
470
SUBCUTANEOUS MYCOSES
The subcutaneous mycoses comprise sporotri-
chosis, chromoblastomycosis, mycetoma, lobomy-
cosis, and rhinosporidiosis.  They are united by
their similar onset after percutaneous inoculation
of the pathogen—usually a soil or plant saprophyte.
The resulting disease is usually confined to the skin
and subcutaneous tissues, and rarely invades deeper
or disseminates.  The subcutaneous mycoses are
most common in tropical or warm temperate re-
gions (see Exhibit 18-1).
Sporotrichosis
Sporotrichosis has a nearly worldwide distribu-
tion and is perhaps the deep mycosis that military
dermatologists most frequently encounter.  Sporotri-
chosis nearly always results from traumatic im-
plantation of the pathogen Sporothrix schenckii into
the skin.  Infection is generally limited to cutaneous
and subcutaneous tissues.
S schenckii, a thermally dimorphic fungus, is
the sole member of its genus.  It is a common
saprophyte, associated with live and decaying
vegetation, plant products, and soils.  It infects
humans and other mammals but simply colonizes
the host plants.  In nature and in cooler cultures, the
mycelial phase predominates.  In infected tissues
and in culture at 37°C, S schenckii assumes its yeast
phase.
Sporotrichosis poses risks to individuals world-
wide but has little epidemic potential.  There are
no reports of sporotrichosis hampering military
operations.
History
Sporotrichosis was first described in 1898
by Benjamin Robinson Schenck, then a second-
year medical student at The Johns Hopkins Univer-
sity, Baltimore, Maryland.77,78  Most cases
of sporotrichosis are solitary, although clusters of
infection have occurred.  The largest outbreak
was among South African gold miners in the
1940s.  Nearly 3,000 Bantu mine workers
developed lymphocutaneous sporotrichosis after
wounding themselves on the Sporothrix-laden tim-
bers that were used to shore the mine tunnels.79
Such outbreaks can be controlled by discontinuing
the use of local timber or treating the wood with
antifungals.
Epidemiology and Distribution
Sporotrichosis results from minor, often unno-
ticed, traumatic implantation of the organism into
the skin.  Occupations typically at risk for
sporotrichosis are those exposed to injuries from
plant materials, such as florists, plant nursery and
forestry workers, and farmers.  Rosebushes, hay,
and sphagnum moss have been implicated repeat-
edly as sources of infection.80  Hands and fingers are
typically involved, except in regions where bare-
foot farmers get foot infections.  Transmission to
humans from animals, particularly cats, may cause
sporotrichosis even without a clear history of an
animal bite or scratch.81  No clear gender or racial
predilections have been identified.  Sporotrichosis
is not transmitted from person to person.
Sporothrix and sporotrichosis occur in tropical
and warm, humid, temperate regions worldwide.
Mexico, Brazil, Japan, and Oklahoma have espe-
cially high incidences of disease.80,82,83
Clinical Manifestations
Sporotrichosis has several clinical forms but rarely
causes systemic disease.  Classically, inoculation
occurs on a distal extremity, and, after an incuba-
tion period of several weeks, a violaceous, firm,
granulomatous papule or plaque develops.  The
initial site often remains painless, although it may
suppurate, ulcerate, or become verrucous.
Lymphocutaneous sporotrichosis constitutes
approximately 75% of cases (Figure 18-16).  An
ascending chain of painless, subcutaneous nodules
develops along lymphatic drainage, causing
lymphangitis and regional lymphadenopathy (see
Figure 18-1).  The nodules may form cold abscesses
and ulcerate.  Untreated infections have an indolent
course and rarely disseminate.
Fixed cutaneous sporotrichosis (approximately
20% of cases) also follows trauma but lacks lym-
phatic involvement (Figure 18-17).  Persistent
granulomatous papules or plaques develop at the
site of implantation.  In particular, children with
facial lesions typically present this way.  Fixed cutane-
ous sporotrichosis may resolve spontaneously.
The differential diagnosis for lymphocutaneous
sporotrichosis includes other deep fungal infec-
tions, atypical mycobacteriosis (eg, from Mycobacte-
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Deep Fungal Skin Diseases
471
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a
b
Fig. 18-16. Lymphocutaneous sporotrichosis arises after traumatic inoculation of Sporothrix schenckii. (a) A veterinary
assistant developed dermal nodules on the dorsa of her hands after being scratched by an infected cat. Culture of
Sabouraud’s medium confirmed the diagnosis 1 week later, and she was successfully treated with a potassium iodide
preparation. (b) As Sporothrix infection spreads along subcutaneous Iymph nodes, the characteristic sporotrichoid
appearance develops.
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cat-scratch disease, anthrax, pyodermas, botryo-
mycosis, and Nocardia brasiliensis infection.  When
evaluating fixed cutaneous sporotrichosis, pyo-
dermas, syphilis, other deep fungal infections,
cutaneous tuberculosis, and sarcoidosis should
be considered.80
Extracutaneous sporotrichosis arising from a pri-
mary cutaneous infection is rare.  The typical pa-
tient with systemic sporotrichosis is immunosup-
pressed by chronic alcoholism, hematological
malignancies, diabetes mellitus, or chronic corti-
costeroid therapy.84  Extracutaneous infection com-
monly involves joints, causing monoarticular or
oligoarticular arthritis that often eludes diagnosis
for some time.82  Several patients with chronic
Sporothrix meningitis had concomitant primary cu-
taneous lesions.  Meningeal disease is uncommon
but usually fatal if untreated.82,84
Pulmonary sporotrichosis follows inhalation of
spores and may range from an inapparent to a
tuberculosis-like illness.  In some regions, skin tests
show a high prevalence of infection, suggesting that
asymptomatic pulmonary infection is more com-
mon than is ordinarily suspected.  Rare hematog-
Fig. 18-17. This young girl developed fixed cutaneous
sporotrichosis on her face after suffering a cat scratch on
her left malar region. Photograph: Courtesy of Colonel
M. J. Schleve, Medical Corps, US Army, Aurora, Colo.

Military Dermatology
472
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Fig. 18-18. Immunocompromised patients may develop
disseminated sporotrichosis. This soldier, debilitated
from alcohol abuse, presented with the fever, weight
loss, and skin nodules. This picture shows ulceration of
dermal and subcutaneous nodules. Sporothrix schenckii
was cultured from several skin sites. His sporotrichosis
may have started as a primary pulmonary infection.
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Delayed-hypersensitivity skin tests with sporo-
trichin are often positive in inhabitants of endemic
areas, ranging from 10% in Louisiana and Arizona
to more than 90% in parts of Japan.  Direct immuno-
fluorescence and serologic tests have varying
degrees of sensitivity, specificity, rapidity, and
 availability.80,84
Treatment
Most cases of purely cutaneous disease may be
treated simply and inexpensively with supersatu-
rated potassium iodide (SSKI).  SSKI (5 drops in
juice) is consumed three times daily, increasing the
amount by 1 drop per dose per day until a dose of 40
drops three times daily is achieved.85  Administra-
tion is continued until 4 weeks after clinical resolu-
tion.  SSKI’s mechanism of action is uncertain.  The
untoward side effects of iodides include an acneform
a
b
enous dissemination may produce skin lesions (Fig-
ure 18-18) or involve joints, tendons, bones, or the
brain.80
Diagnosis
The clinical picture of an extremity with a pain-
less ulcer and ascending lymphocutaneous nodules
is characteristic of sporotrichosis.  The diagnosis is
strongly supported by (a) the history of onset after
plant-related trauma and (b) the lack of response to
presumptive antibacterial therapy.  Confirmation
requires identification of the organism by culture or
microscopy.  On histological sections, the organ-
isms appear round to oval and are approximately 4
to 6 µm in diameter (Figure 18-19).  Larger, cigar-
shaped bodies, 8 µm in length, and asteroid bodies,
although characteristic of sporotrichosis, occur in-
frequently.  Rarely, the fungus can be identified on
microscopical examination of smears of pus from a
lesion, stained with periodic acid–Schiff or Gram’s
stain.  Histological confirmation is often difficult
because the organisms are scarce and small.59
On the other hand, Sporothrix grows rapidly on
Sabouraud’s agar.  Material for culture can be ob-
tained from ulcer scrapings, an aspirated subcuta-
neous nodule, or macerated biopsy material.  After
3 to 7 days at 25°C to 30°C, smooth, moist, cream-
colored colonies develop.  As aerial hyphae de-
velop, the colonies typically become brown and
velvety.
Fig. 18-19. (a) Typical skin lesions of sporotrichosis show
pseudoepitheliomatous hyperplasia and intraepidermal
abscesses (hematoxylin-eosin stain; original magnifica-
tion 25X). (b) A closer view shows the characteristic oval-
shaped budding yeast (periodic acid–Schiff stain; origi-
nal magnification 430X).

Deep Fungal Skin Diseases
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eruption, brassy taste, gastrointestinal distress,
hypothyroidism, parotid swelling, and increased
salivation and lacrimation.86  Local heat therapy is a
useful adjunct because Sporothrix is intolerant of
temperatures above 38.5°C.  Applications of hot
(42°C), moist compresses for 30 minutes twice daily
will enable the heat to reach subcutaneous infec-
tions.80
Currently, intravenous amphotericin B is the drug
of choice for extracutaneous infections and for re-
fractory, widespread, or debilitating cutaneous dis-
ease.  Because amphotericin is nephrotoxic and
requires intravenous administration, other antifun-
gal agents are being evaluated.  Itraconazole, but
not ketoconazole, is effective at a daily dosage of
100 to 200 mg, administered orally for 3 to 5
months.82,87
Chromoblastomycosis
Chromoblastomycosis designates a group of
chronic cutaneous and subcutaneous mycoses
caused by several species of dematiaceous fungi.
Common pantropically in rural areas, the disease is
also called chromomycosis, verrucous dermatitis,
Pedroso’s disease, Fonseca’s disease, and Lane and
Pedroso’s mycosis.
Chromoblastomycosis occurs sporadically and
lacks epidemic potential.  In tropical areas, shoes
and leg coverings protect individuals from the mi-
nor penetrating trauma that inoculates the pathogens.
Several species of dematiaceous (darkly pig-
mented) fungi cause most cases of chromo-
blastomycosis.  These include Fonsecaea pedrosoi (the
major pathogen), Fonsecaea compacta, Phialophora
verrucosa, Cladosporium carrionii, and Rhinocladiella
aquaspersa.88  Each species has more than one
morphologic strain, compounding the nomencla-
tural disarray.  The related genera produce similar,
dark brown, sclerotic bodies in tissue and form
pigmented colonies on culture.  Because these fungi
reproduce by internal septation rather than by bud-
ding, some89 have argued that -blasto- should be
deleted from the name of the disease.
History
Early in the 20th century, several workers de-
scribed patients with chromoblastomycosis and iso-
lated the pathogens.89  Controversy persists over
priority of description, name of the disease, and
nomenclature of the causative fungi.89,90  There are
no reports of chromoblastomycosis having ham-
pered military operations.
Epidemiology and Distribution
Although found worldwide, chromoblasto-
mycosis occurs mainly in the humid tropics and
subtropics.  The causative fungi are saprophytes
and are recoverable from soil, rotting wood, and
other plant debris.  Their spores enter the skin via
minor penetrating trauma.  Barefooted rural farm-
ers, therefore, have the greatest occupational risk.91
The disease occurs overwhelmingly in men aged 25
through 50, except in Japan where men and women
are affected equally.92  Fonsecaea pedrosoi is the major
pathogen, although regional variations exist.
Clinical Manifestations
Chromoblastomycosis starts as painless, skin-
colored papules typically on the lower legs or the
lateral aspects of the feet (see Figure 18-1).  Enlarg-
ing lesions develop into nodules or plaques.  Their
surfaces can be verrucous, papillomatous, scaly,
sclerotic, or a combination of these.  Flat, rough-
surfaced plaques often heal with central atrophy,
scarring, or keloid formation (Figure 18-20).  Else-
where, satellite lesions or peripheral expansion
along serpiginous borders may develop.91,93
After many years, some lesions evolve into cau-
liflower-like lobulated vegetations (Figure 18-21).
Frequently, secondary bacterial infections cause fi-
brosis of superficial lymphatics and subsequent
lymphedema or elephantiasis.  The fungi do not
invade underlying muscle and bone.
Morbidity in chromoblastomycosis arises from
the disfigurement or disability of an affected part,
secondary infections, or, rarely, a supervening squa-
mous cell carcinoma.  Rare hematogenous spread
may lead to cerebral chromoblastomycosis even if
cutaneous lesions are absent.93
The differential diagnosis includes other deep
fungal infections (such as blastomycosis, sporotri-
chosis, and mycetoma), tuberculosis verrucosa cu-
tis, cutaneous leishmaniasis, and treponemal dis-
eases (eg, yaws and tertiary syphilis).
Diagnosis
Diagnosis of chromoblastomycosis requires both
detection of sclerotic bodies from lesional material
and a fungal culture.  Sclerotic bodies (ie, “copper
pennies” or Medlar bodies) are 6- to 12-µm, dark-
walled, polyhedral structures (Figure 18-22).  Inter-
nal cross-walls (ie, septae), produced by intracellu-
lar reproduction, give the cells a muriform
appearance.89  They are often seen in potassium

Military Dermatology
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Fig. 18-20. Chromoblastomycosis most commonly ap-
pears as granulomatous plaques with serpiginous bor-
ders. These photographs (a and b) show the proximal
pretibial surface of a woman from Yap, Federated States
of Micronesia. She presumably acquired the infection by
kneeling on contaminated wooden planks in her tradi-
tional home. (b) The scattered dark puncta are found in both
blastomycosis and chromoblastomycosis, but the lesion’s
location on a surface exposed to minor trauma and the
tropical setting make the clinical diagnosis straightfor-
ward. Chromoblastomycosis can remain indolent for de-
cades. (c) This man acquired his infection 50 years earlier
during World War II when he was stationed on Manus
Island, north of New Guinea. A log fell on his upper back
while he was working on a construction project.
c
b
a
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Fig. 18-21. Chromoblastomycosis can also progress into a
vegetative form, as seen in this disfiguring vegetative
chromoblastomycosis of the leg.

Deep Fungal Skin Diseases
475
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hydroxide preparations of exudate or surface
scrapings.  Punctate black dots found on the surface
of exuberant lesions are often composed of
transepidermally eliminated sclerotic bodies.  Skin
biopsies show pseudoepitheliomatous hyperplasia,
multinucleated giant cells, microabscesses, and scle-
rotic bodies.  Sclerotic bodies, easily seen with he-
matoxylin-eosin staining, appear singly or in clus-
ters, and are most numerous in vegetative growths.94
Material grown on Sabouraud’s agar forms gray-
green or black colonies.  Species identification is
based on sporulation patterns.
Treatment
Treatment regimens for chromoblastomycosis
have been disappointing.  Physical measures in-
clude wide surgical excision, Mohs’ surgery, car-
bon dioxide laser, radiation, local heat, and
cryotherapy.  Curettage and electrodesiccation may
promote lymphatic spread and should be avoided.
Chemotherapeutic approaches include potassium
iodide, intralesional amphotericin, ketoconazole,
itraconazole, thiabendazole, and 5-fluorocy-
tosine.91,95  Small, early lesions may be excised suc-
cessfully.  More extensive disease requires long-
term treatment with itraconazole alone or with a
regimen combining 5-fluorocytosine and ampho-
tericin.96,97  Limbs disabled or deformed from refrac-
tory infections may require amputation.
Mycetoma
Mycetoma is also called maduramycosis, Madura
foot, eumycetoma, eumycotic mycetoma, actinomy-
cetoma, and actinomycotic mycetoma.  The word
mycetoma means “fungal tumor” but most cases
are caused by bacteria.  Perhaps 20 different patho-
gens cause mycetoma, the main ones being
Pseudallescheria (syn Allescheria, Petriellidium,
Monosporium, Scedosporium) boydii in the United
States, Nocardia brasiliensis in Mexico, and Madurella
mycetomatis in India and Africa (Table 18-1).  The
organisms are saprophytes, recoverable from soil
and plant debris.  Ecological conditions influence
their distribution and medical importance so that,
for example, in Central and South America the
overwhelming majority of cases are due to Nocardia
brasiliensis, a less important pathogen elsewhere.98
Mycetoma is a chronic, progressive infection of
skin and subcutaneous tissues and is found mostly
in the tropics.  Infection follows traumatic implan-
tation of pathogenic true fungi (eumycetoma) or
filamentous bacteria (actinomycetoma).  The two
forms are similar clinically.  Mycetomas frequently
affect the lower extremities and may invade deeper
structures.  Infection is characterized by swollen
tissues and destructive sinuses from which drains
pus containing characteristic granules.
In hyperendemic tropical regions, soldiers should
protect themselves from minor trauma by wearing
footgear and uniforms.  Activities during which
implantation could occur, such as carrying locally
obtained wood on bare shoulders or backs, should
be avoided.
History
Royal Army physicians stationed in the Madura
region of India first described mycetomas in the
a
b
Fig. 18-22. (a) A potassium hydroxide preparation of the dark puncta seen in Fig. 18-20 b revealed the diagnostic
copper-colored sclerotic bodies of chromoblastomycosis. (b) More sclerotic bodies are seen in tissue with a photomicro-
graph of her skin biopsy (hematoxylin-eosin stain; original magnification 430X). The culture grew Fonsecaea pedrosoi.

Military Dermatology
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TABLE 18-1
MAJOR PATHOGENS IN MYCETOMA: THEIR DISTRIBUTION AND GRANULE COLOR
Location
Pathogen
Eur
USA
Mex
SAm
WAf
EAf
Ind
Eumycetoma (Ascomycetes and deuteromycetes)
Pseudallescheria boydii
Y-W
Y-W
Madurella grisea
B
Madurella mycetomatis
B
B
B
Leptosphaeria senegalensis
B
B
Actinomycetoma (Actinomycetes and streptomycetes)
Streptomyces somaliensis
Y
Y
Streptomyces (Acremonium) pelletieri
R
R
Actinomadura (Nocardia) madurae
W
Nocardia brasiliensis
C-W
C-W
C-W
Eur: Europe, USA: United States; Mex: Mexico; SAm: South America; WAf: West Africa; EAf: East Africa; Ind: India; Y: yellow; W:
white; B: black; R: red; Y-W: yellow-to-white; C: colorless; C-W: colorless-to-white
Data sources: (1) Magaña M. Mycetoma. Int J Dermatol. 1984;4:221–236. (2) Gumaa SA, Mahgoub ES, El Sid MA. Mycetoma of the head
and neck. Am J Trop Med Hyg. 1986;35:594–600. (3) Develoux M, Audoin J, Tregeur J, Vetter JM, Warter A, Cenac A. Mycetoma in the
Republic of Niger: Clinical features and  epidemiology. Am J Trop Med Hyg. 1988;38: 86–90. (4) McGinnis MR, Fader RC. Mycetoma:
A contemporary concept. Infect Dis Clin North Am. 1988;2:939–954. (5) Zaias N, Taplin D, Rebell G. Mycetoma. Arch Dermatol.
1969;99:215–225.
local population in the 1840s.  Vandyke Carter,
surgeon in the British India Army in Bombay, rec-
ognized the fungal etiology and coined the name
“mycetoma.”99  Military health reports from India
did not include mycetoma as a significant problem
for British forces there.
Epidemiology and Distribution
Although it is a cosmopolitan disorder, mycetoma
is important only in the tropics and subtropics.
Adult males engaged in outdoor work are at great-
est risk.  The site of infection corresponds to the
body parts exposed to trauma: barefoot laborers
have foot and leg infections, whereas persons who
carry contaminated wood and other plant products
on their heads, upper backs, and shoulders develop
mycetomas there.  The infections are not contagious.
Infections occur more often in moist regions,
although some organisms, notably Nocardia
brasiliensis and Streptomyces pelletieri, are common
in dry areas.  Incidence is highest in Mexico, India,
and parts of Africa (Sudan, Somalia, Senegal).98,100,101
Clinical Manifestations
Mycetoma is characterized by the clinical triad of
swollen tissues, draining sinuses, and extrusion of
grains.102  Mycetomas principally occur on the foot,
ankle, leg, hand, and upper trunk, although any
exposed area is susceptible (see Figure 18-1).  After
the pathogen is implanted, there is a several-month
incubation period.  Early lesions are painless, indu-
rated, subcutaneous nodules that grow slowly, coa-
lescing into large plaques or tumors (Figure 18-23).
These subsequently form necrotic abscesses and
draining sinuses.  Grains, usually 0.5 to 2.0 mm in
diameter, which are actually colonies of organisms,
can be recovered in the seropurulent drainage.  In-
vasion into subcutaneous tissues causes more swell-
ing and induration, often destroying fascia and
muscle, and producing chronically draining fistu-
lae.  Further extension occurs by direct invasion
along fascial planes or by coalescence of abscesses
and sinus tracts.  Bone involvement leads to
periostitis, chronic osteomyelitis, and osteolysis.
Mycetomas do not self-heal.  Infections progress
relentlessly, ultimately leading to deformity and
disability.  Encroachment into the central nervous
system has been reported, although mortality is
generally low.98,100,103–105
The differential diagnosis for mycetoma includes
other deep fungal infections, tuberculous and bacte-
rial osteomyelitis, actinomycosis, botryomycosis,

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Fig. 18-23. The swollen tissues and draining sinuses of a
mycetoma are apparent in this photograph. The feet and
lower legs are the most common sites for mycetomas
because those sites suffer the most minor trauma, espe-
cially in individuals who go barefoot.
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an actinomycete causes a mycetoma so that appro-
priate therapy can be started.  Preliminary identifi-
cation can be made from clinical assessment,
the patient’s travel history, and, most importantly,
examination of the grains (see Table 18-1).  Grains,
particularly dark ones, are often visible to the
naked eye but may be found by diluting purulent
exudate with sterile saline.  Grains should be exam-
ined grossly for color and texture and microscopi-
cally for hyphae or filaments.  Black grains (Figure
18-24) are produced exclusively by eumycetomas.
Pale (colorless, white, or yellow) granules are
produced by most actinomycetes but only by one
eumycete, Pseudallescheria boydii.  Red granules
 are formed by Streptomyces pelletieri.  A hard, brittle
texture characterizes Madurella species’ grains.  Ex-
tensive details on mycetoma grains can be found
elsewhere.98,106
Crushed granules should be examined with
Gram’s stain and potassium hydroxide prepara-
tions.  Eumycotic grains will reveal Gram-negative
septate hyphae.  Actinomycotic grains have Gram-
negative centers with Gram-positive, fine, radiat-
ing fringes.  Also, preparations with potassium
hydroxide or lactophenol cotton blue demonstrate
the delicate (1 µm thick), branching filaments of
Kaposi’s sarcoma, tertiary syphilis, yaws, leprosy,
and cutaneous leishmaniasis.106
Laboratory Diagnosis
It is essential to determine whether a fungus or
a
b
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Fig. 18-24. Histopathology of eumycetoma. (a) This skin
biopsy of a eumycetoma shows fibrosis, deep abscess,
and two dark granules (hematoxylin-eosin stain, original
magnification 10X). (b) A closer view of the same biopsy
tissue (hematoxylin-eosin stain, original magnification
40X).

Military Dermatology
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actinomycetes and the larger (4-5 µm) septate hy-
phae of eumycetes.103,107
Skin biopsies show dermal inflammation and
microabscesses surrounded by a polymorphous in-
filtrate.  The grains of botryomycosis and actino-
mycosis resemble those of mycetoma.  Often the
organism can be identified by histopathological
examination alone.  True fungi are enhanced with
periodic acid–Schiff or Gomori’s methenamine-sil-
ver stains, whereas Nocardia is partly acid-fast.
Culture of the pathogen permits a determination
of drug sensitivities.  Grains should be either washed
in sterile saline to remove contaminants or obtained
from deep sites.103  They should be minced into a
suspension for plating onto an appropriate agar
(eg, Sabouraud’s with and without antibiotics).
Growth requirements for the various organisms are
discussed elsewhere.107,108
Serologic tests and immunoassays are under in-
vestigation but are not widely available.  Radio-
graphs of affected parts will help assess extent of
bony destruction.105
Treatment
Therapy for mycetoma depends on the organism,
the site of the infection, and the degree of invasion.
The prognosis for actinomycetoma is better than for
eumycetoma but therapies for both are often disap-
pointing.  Actinomycetoma may be treated with
long-term combinations of oral antibiotics, such as
streptomycin with either dapsone or co-trimoxazole.
Eumycetomas are resistant to amphotericin and
griseofulvin but on occasion respond to imidazoles.
Small, solitary nodules can be excised but that must
be followed by chemotherapy to prevent relapses.
Larger nodules can be debrided and abscesses
drained.  Advanced disease should receive com-
bined surgical and chemotherapeutic measures.
Limbs with refractory, destructive disease may re-
quire amputation, although stump recurrences are
common.98,103,105
Lobomycosis
Lobomycosis is a chronic, cutaneous mycosis of
the New World tropics.  It typically appears as
multiple, smooth, firm nodules of skin only, spar-
ing mucosa and viscera.  The disease is also called
Jorge Lobo’s disease and keloidal blastomycosis.
Jorge Lobo first described the cutaneous lesions
of lobomycosis in 1931 in a patient from the Ama-
zon basin.109  The fungus is recoverable only from
cutaneous lesions.  It has neither been isolated from
nature nor grown satisfactorily in culture.  Taxono-
mists have never been sure of the proper affinities
of this fungus, and in the early literature, it was
included at times in several genera, such as
Paracoccidioides, Blastomyces, Glenospora, Gleno-
sporella, and Lobomyces.  Until its taxonomic affini-
ties are better determined, the organism, Loboa loboi,
is best regarded as the sole member of its genus.110
Lobomycosis is rare even in endemic areas and
poses little risk to military units.  Individuals may
become infected in the dense lowland forests of
Central and South America, but, owing to the lengthy
incubation period, clinical manifestations will be
inapparent for months.  No military activities are
known to have been hampered by this disease.
Several Atlantic bottle-nosed dolphins on duty with
the U.S. Navy have been afflicted with lobomycosis.
Distribution and Epidemiology
Lobomycosis occurs only in South and Central
America, where it is, nevertheless, rare (Figure 18-25).
It occurs mostly in densely forested humid areas,
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Fig. 18-25. The distribution of human lobomycosis, which
occurs principally in the Amazon River basin. Dolphin
lobomycosis is found more northward, along the Caribbean
coast of South America and the coast of southern Florida.

Deep Fungal Skin Diseases
479
such as the Amazon basin of Brazil, and less often in
contiguous countries from French Guiana to Costa
Rica.  Farmers, miners, workers on rubber planta-
tions, and Brazil’s Cayabi Indians are most fre-
quently affected.111,112  Presumably, the fungus en-
ters the skin by minor trauma or via arthropod
bites.112  Another enigma is that lobomycosis natu-
rally occurs in dolphins found along the coasts of
Florida (Atlantic bottle-nosed dolphin, Tursiops
truncatus) and an estuary in Suriname (Guyana
River dolphin, Sotalia guianensis).109
Clinical Manifestations
The incubation period of lobomycosis is prob-
ably months to years.  Skin lesions begin as
multiple, painless, firm, violaceous nodules that
coalesce into variably sized keloidal plaques (Fig-
ure 18-26).  Although their surfaces are usually
smooth and shiny, they may instead show epider-
mal atrophy or warty changes.  Lobomycosis
principally involves the face and ears, distal ex-
tremities, and buttocks (see Figure 18-1).  This dis-
tribution and the relative sparing of the back sup-
port the idea that the disease is acquired initially by
minor trauma and spread subsequently by
autoinoculation.  Lesions also may spread locally
by direct extension or via the superficial lymphat-
ics.  Sequelae include ulcers, fistulae, and, rarely,
squamous cell carcinoma.111
Helical lesions must be distinguished from
lepromatous leprosy, sarcoidosis, cutaneous
Fig. 18-26. (a) Human and (b) dolphin lobomycosis. The smooth, whitish, warty excrescences of lobomycosis are
similar in both species. This Atlantic bottle-nosed dolphin was captured in an estuary in central Florida. For over a
decade, the dolphin has been an active member of the US Naval Command Control Ocean Surveillance Center research
facility, formerly at Kaneohe Marine Corps Air Station, Hawaii. The lesions are unresponsive to imidazole therapy but
they do not seem to hamper the dolphin’s life or performance of its duty. Photograph (a): Courtesy of Professor Angela
Restrepo-M., Medellin, Colombia.
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a
b
leishmaniasis, and true keloids.  Verrucous plaques
of the legs may resemble other deep mycoses, such
as chromoblastomycosis.112
The disease is chronic and spreads slowly, though
the patient remains generally well.  Morbidity is a
consequence of disability or disfigurement.
Diagnosis
The diagnosis of lobomycosis must be confirmed
histopathologically.110  The dermis is nearly replaced
by an infiltrate of macrophages and multinucleate
giant cells.  Abundant fungal spores, averaging 8 to
10 µm in diameter, appear within and freely
between the giant cells.  The organisms stain
poorly with hematoxylin-eosin, producing a
characteristic sievelike pattern (Figure 18-27).59  Fun-
gal stains, such as periodic acid–Schiff, reveal chains
of thick-walled organisms with tubular intercon-
nections.  Single buds are seen occasionally.  Skin
tests, serologic tests, and attempts to culture the
pathogen are not useful in the evaluation of
lobomycosis.
Treatment
Lobomycosis does not resolve spontaneously nor
is there any satisfactory treatment.  Medical inter-
vention, even with amphotericin and ketoconazole,
has been uniformly unsuccessful.  Small lesions
may be excised but recurrences are common.112

Military Dermatology
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Fig. 18-27. The characteristic histology of Loboa loboi infection in a human. (a) The low-power view shows dermal
fibrosis and a sievelike pattern created by numerous organisms. (b) Chains of L loboi are seen on closer view
(hematoxylin-eosin stain, original magnification 430X).
a
b
Details of transmission remain largely speculative,
but infection seems to follow exposure to contami-
nated water.  Paddy cultivators and persons who
bathe in waters frequented by large farm animals
are at increased risk.  Young men are most often
affected, but this may reflect occupational expo-
sure.  The disease also occurs in horses, mules,
cattle, goats, dogs, and birds.116,117
Clinical Manifestations
In 70% of cases, patients with rhinosporidiosis
present with a friable, usually pedunculated, polyp
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Fig. 18-28. Although most patients with rhinosporidiosis
present with nasal lesions, other mucosal sites such as the
conjunctiva may also be affected. The glistening, red,
pedunculated lesion may have the appearance of a pyogenic
granuloma. Photograph: Courtesy of Colonel William D.
James, Medical Corps, US Army, Washington, DC.
Rhinosporidiosis
Rhinosporidiosis is a chronic, painless, mucosal
infection caused by Rhinosporidium seeberi.  Typically,
an intranasal papule evolves into a hyperplastic
polyp.  Lesions may obstruct the nares and impair
breathing, cause nasal bleeding, or, if the oral mucosa
is involved, compromise speech and digestion.
In infected tissues, R seeberi appear as abund-
ant spores and sporangia.  Immature spores
(7–10 µm) enlarge and undergo repeated mitotic
divisions, forming thick-walled sporangia
(100–350 µm).113–115
Solitary cases of rhinosporidiosis may occur after
individuals are exposed to fresh water in India and
adjacent countries.  No cases were reported among
U.S. soldiers in Vietnam.  The disease lacks epi-
demic potential.
History
Rhinosporidiosis was first described in 1896 in
Argentina, where few cases have been reported
since.  Guillermo Seeber, a medical student in Buenos
Aires, described a 19-year-old farm worker whose
breathing was impaired by a nasal mass.  The patho-
gen was considered a coccidia-like protozoan, but
in 1923, Ashworth determined it was a fungus and
established the current name.116
Epidemiology and Distribution
Nearly 90% of cases of rhinosporidiosis are from
India and Sri Lanka.  The disease has been reported
worldwide except in parts of Europe and Oceania.

Deep Fungal Skin Diseases
481
emerging from the nasal mucosa (see Figure
18-1).  The surface of lesions appears vascular and has
sharply defined white dots corresponding to visible
sporangia.  Usually only one nostril is involved, though
both may be.  Mucosal sites involved less frequently
include the palpebral conjunctiva (Figure 18-28),
oropharynx and nasopharynx, external ear canal,
and genitalia.  Visceral dissemination has been re-
ported several times.113,114,116–118
Diagnosis
Histopathological demonstration of the charac-
teristic thick-walled, giant sporangia is diagnost-
ic.  The organisms are abundant and appear in
various sizes and stages of development.118  Re-
cently, R seeberi has been cultivated successfully in
vitro in a human epithelial cell culture.119
The technique is not suitable for routine diagnostic
work.
Treatment
Medical management is inadequate.  Excision of
the polyps is necessary, although recurrences are
common.117
OPPORTUNISTIC MYCOSES AND MISCELLANEOUS INFECTIONS
In addition to the systemic and subcutaneous
mycoses, deep fungal skin diseases also include the
opportunistic mycoses and miscellaneous infec-
tions.  Cryptococcosis was formerly an uncommon
opportunistic infection, but it is seen frequently
now in HIV-infected persons.  Entomophthor-
amycosis is a rare, tropical fungal infection of deep
subcutaneous tissues of immunocompetent hosts.
Actinomycosis and nocardiosis are traditionally
placed with the deep fungal infections although
they are caused by related, true bacteria.
Cryptococcosis
Cryptococcosis, also called Busse-Buschke’s dis-
ease, torulosis, and European blastomycosis, is an
opportunistic infection that has its most severe
effects on the central nervous system.  Cutaneous
cryptococcosis occurs in approximately 15% of pa-
tients with disseminated disease.
The disease is caused by Cryptococcus neoformans,
the only basidiomycete known to cause deep fungal
infections.  The organism has a perfect state
(Filobasidiella neoformans) but lacks thermal dimor-
phism.  The pathogenic form is a unicellular, round-
to-oval, thin-walled yeast that reproduces by
budding.  In tissue, C neoformans often acquires a
thick, mucoid, polysaccharide capsule, assuming a
size of 4 to 12 µm.  Differences in capsular antigenic-
ity produce four serotypes (A, B, C, and D), of
which types A and D are most common in the
United States.120,121  Capsular features influence viru-
lence, although the patient’s immune status deter-
mines the course of the disease.  Two varieties, C
neoformans var neoformans and C neoformans var
gattii, but rarely other cryptococcal species, cause
disease.120
Epidemiology and Distribution
Cryptococcosis, a cosmopolitan disease, is re-
ported most frequently from temperate regions.  C
neoformans is ecologically associated with birds,
especially pigeons, because it thrives in their ex-
creta.  The organism passes harmlessly through the
bird’s gut.  Pigeon fanciers often have antibodies,
indicating frequent exposure, but do not have an
increased rate of infection.  C neoformans is easily
recovered from pigeon excrement but is rapidly
cleared from soil by Acanthamoeba organisms.
In Australia, Cryptococcus neoformans var gattii is
closely associated with Eucalyptus camaldulensis, one
of the few trees on which koalas feed.  Koalas pass
the yeast fecally (in the same ecological role served
by pigeons elsewhere) but also contract cryptococ-
cosis occasionally.122  Serious infections caused by
Cryptococcus neoformans var gattii have been found
not only in immunocompromised but also in immu-
nocompetent patients.123
Persons at increased risk for infection are those
with impaired cell-mediated immunity from, for
example, chronic corticosteroid therapy, lupus
erythematosus, sarcoidosis, or iatrogenic immuno-
suppression associated with organ transplanta-
tion.121  Cryptococcal infection in an HIV-infected
person meets the CDC definition for AIDS.  Indeed,
the unexpected diagnosis of cutaneous crypto-
coccosis requires prompt evaluation for other in-
volved organs and for underlying immunodefi-
ciency.
Clinical Manifestations
The primary infection in cryptococcosis is pul-
monary, but involvement of the central nervous

Military Dermatology
482
Fig. 18-29. Disseminated cryptococcal infection usually  occurs in immunocompromised individuals. (a) Most lesions
of cutaneous cryptococcosis are not distinctive. (b) However, in an individual infected with the human immunodefi-
ciency virus, the lesions may resemble those seen in patients with molluscum contagiosum. Photograph (b): Courtesy
of Colonel Richard Gentry, Medical Corps, US Army, Aurora, Colo.
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a
b
within macrophages and giant cells.59  Mucopolysac-
charide capsules are enhanced with Meyer
mucicarmine stain but the organisms within are
better seen with periodic acid–Schiff stain.  Gram’s
stain, India ink, and Tzanck preparations on aspi-
rated or biopsied material also may reveal the or-
ganisms.125  Culture of skin, sputum, and cerebrospi-
nal fluid should be set up on Sabouraud’s agar.121
Cryptococcal infections of the meninges are tra-
ditionally diagnosed by examining a cerebrospinal
fluid–India ink preparation, which has only 50%
sensitivity.  Latex agglutination tests for cryptococ-
cal antigens are more sensitive.  Serologic tests may
demonstrate antibodies.
Treatment
Disseminated cryptococcosis is usually fatal if
untreated.  Combination therapy with flucytosine
and amphotericin is the treatment of choice for
cryptococcal meningitis.121,132  Fluconazole is prov-
ing increasingly valuable in managing cryptococ-
cosis in patients with AIDS.
Entomophthoramycosis
Entomophthoramycosis (also called entomoph-
thoromycosis, 
subcutaneous 
zygomycosis
or phycomycosis, rhinophycomycosis, and rhino-
entomophthoromycosis) comprises two rare infec-
tions, conidiobolomycosis and basidiobolomycosis,
that are caused by the related zygomycetes
Conidiobolus coronatus and Basidiobolus ranarum, re-
spectively.  Both diseases occur mainly in forested
system is the most common and serious complica-
tion.  Cutaneous manifestations appear in approxi-
mately 15% of persons with disseminated disease,
occasionally before the start of life-threatening
meningeal involvement (see Figure 18-1).124  The
clinical diagnosis of cutaneous cryptococcosis is
difficult because the manifestations are diverse and
nonspecific (Figure 18-29).  Most often, painless
papules arise on the head or neck and then evolve
into nodules, pustules, abscesses, grouped vesicles,
purpura, vasculitis, plaques, or ulcers.125–127  Two
uncommon but well-described cutaneous presenta-
tions are cryptococcal cellulitis in prednisone-
treated patients who have had renal transplants125,128
and molluscum-like facial papules in patients with
AIDS.124  More rarely, the lesions resemble pyoderma
gangrenosum or Kaposi’s sarcoma.  Primary inocula-
tion cryptococcosis is extremely rare129–131 and it is best
to consider a cutaneous lesion evidence of dissemi-
nated cryptococcosis until proven otherwise.126
Diagnosis
The clinical diagnosis may be difficult but the
histological diagnosis is not.  Two patterns—gelati-
nous and granulomatous—are seen in biopsy speci-
mens.  The gelatinous pattern demonstrates many
organisms with minimal host response.  The thick,
mucopolysaccharide capsules do not stain with
hematoxylin-eosin, producing a sievelike appear-
ance (Figure 18-30).  The granulomatous pattern
has fewer organisms, which measure 2 to 4  µm in
size, with inconspicuous capsules.  In this type, the
host response is vigorous and organisms are seen

Deep Fungal Skin Diseases
483
OK to put on the Web
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c
b
a
Fig. 18-30. These photomicrographs show a gelatinous
response to cutaneous infection with Cryptococcus
neoformans. In both (a) the low-power (original magnifi-
cation 40X) and (b) the high-power (original magnifica-
tion 430X) views of hematoxylin-eosin–stained material,
the organisms have a shadowy appearance within clear
capsular spaces. (c) Mucicarmine-stained tissue accentu-
ates the organisms (original magnification 250X).
tropical regions even though the causative fungi are
ubiquitous.  Conidiobolus coronatus naturally occurs
both as a plant saprophyte and as a pathogen
of several arthropods.  Basidiobolus ranarum is
frequently recovered from the digestive tracts of
reptiles and amphibians.133  Their portal of entry
and incubation period in humans is unknown.
Neither organism is opportunistic.  Some generali-
zations regarding each infection can be made (see
Figure 18-1).
Conidiobolomycosis is usually confined to sub-
cutaneous tissues of and surrounding the nose.  The
disease usually occurs in adult males, starting as a
swelling of the inferior nasal turbinates with subse-
quent bilateral invasion of perinasal structures (such
as the sinuses and upper lip).  The resulting masses
are firm, mobile, nontender, and profoundly disfig-
uring but rarely lethal.133–135  The patient generally
remains otherwise healthy, a feature that clinically
distinguishes this condition from rhinocerebral
mucormycosis.  Basidiobolomycosis occurs as large,
indurated, subcutaneous masses on the proximal
extremities, buttocks, or trunk of healthy children.
Biopsy specimens of both organisms show broad
hyphae with infrequent septae and no vascular
invasion.  The hyphae are surrounded by eosino-
philic debris (the Splendore-Hoeppli phenomenon).
Treatment consists of oral potassium iodide.135
Amphotericin alone is ineffective but ketoconazole
has shown some promise.136
Actinomycosis
Infections caused by actinomycetes (also called
ray fungi) are traditionally placed with fungal dis-
orders despite their proper position among true
bacterial diseases.  Synonyms include lumpy jaw,
leptothricosis, and streptothricosis.  The source of
infection is the normal oral flora harboring Actino-
myces israelii.  Several clinical forms of actinomycosis
are recognized: cervicofacial (the most common),
thoracic, and abdominal.  Another form, pelvic, was
linked with endometritis associated with intrauter-
ine devices.137
Years ago, actinomycosis was commonly diag-
nosed but it is rare in the United States now because
of improved oral hygiene.137  During World War II,
there were approximately 230 cases of actino-
mycosis in U.S. troops.  Of these, four died of com-
plications of their infections.138

Military Dermatology
484
aggregates of mycelia.140  The swellings are charac-
teristically woody in their firmness.  Mandibular
periostitis and osteomyelitis may ensue.  Abdomi-
nal and thoracic infections follow aspiration or in-
gestion of oral material.  Their cutaneous manifes-
tations also appear as sinuses draining to the
exterior.137,139,140
The diagnosis is confirmed by detecting organ-
isms by culture, biopsy, or tissue examination.
Gram’s stain of a crushed granule shows thin (ap-
proximately 1 µm), Gram-positive filaments radiat-
ing and intertwining along the periphery.139  Biopsy
specimens stained with hematoxylin-eosin show
that the centers of grains are basophilic and the
fringes are eosinophilic (Figure 18-32).  Actinomyces
may be distinguished from Nocardia by their lack of
acid-fastness and by specific fluorescent antibody
stains.  Culture has special requirements so prior
consultation with a laboratory officer is necessary.140
OK to put on the Web
Fig. 18-31. This Fijian soldier developed cervicofacial
actinomycosis after repeated dental procedures on an
abscessed tooth. On palpation, the mass was woody and
adherent to the mandible. Exploratory surgery showed
five yellow-green sulfur granules, each approximately
2 mm in diameter.
Fig. 18-32. Histology of actinomycotic granule. (a) Baso-
philic center and eosinophilic periphery (hematoxylin-
eosin stain, original magnification 100X). (b) Radiating
fringe of filamentous organisms from the same tissue
(hematoxylin-eosin stain, original magnification 250X).
Actinomyces israelii is the most common cause of
human actinomycosis.  Several congeners and mem-
bers of related genera (Arachnia, Bifidobacterium)
have also been implicated.  They are anaerobic,
Gram-positive, filamentous bacteria that grow best
under anaerobic conditions.  Actinomyces bovis causes
actinomycosis of cattle, commonly presenting as
woody tongue disease.139
The clinical forms of actinomycosis are charac-
terized by chronic suppuration.  Predisposing fac-
tors to cervicofacial infection include accidental
trauma to the area, dental extraction, caries, or
other evidence of poor oral hygiene.  Patients with
cervicofacial actinomycosis typically present with a
painless, indurated mass growing insidiously along
the jawline (Figure 18-31).  The masses consist of
deep nodules that coalesce and form sinuses drain-
ing to the exterior (see Figure 18-1).  The discharge
often contains minute, yellow spherules (1–5 mm in
diameter) called sulfur granules.  They contain no
sulfur but are colonies of organisms that form dense
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b
a

Deep Fungal Skin Diseases
485
Cervicofacial infection requires long-term anti-
biotic therapy, usually 6 months or more, often
coupled with surgical debridement of indurated
masses.  Penicillin is the drug of choice and should
be given parenterally during the initial weeks of
therapy.140
Nocardiosis
Several forms of nocardiosis involve the skin.
The most common and serious form mostly affects
debilitated hosts and is caused by Nocardia asteroides.
It usually causes a pleuropulmonary disease re-
sembling tuberculosis.  Secondary involvement of
the skin is due to hematogenous spread or the
formation of thoracic sinuses.  Its most serious com-
plication is metastatic cerebral infection.141  Primary
cutaneous nocardiosis is caused by Nocardia
brasiliensis, the organism also responsible for most
New World actinomycetomas.  This form typically
follows plant-associated percutaneous injuries to
the hands, followed by a chain of nodules ascend-
ing along lymphatic channels (see Figure 18-1).  By
history and examination, primary cutaneous
nocardiosis may be clinically indistinguishable from
lymphocutaneous sporotrichosis.142  Diagnosis re-
quires identification of the organism because there
are no pathognomonic clinical features.143  Nocardia
grows slowly on a wide range of culture media.
Gram’s stain of purulent material shows Gram-
positive filaments that also are partially acid-fast.
Granules, as seen in nocardial actinomycetoma, are
absent.  Initial therapy should be with co-
trimoxazole or other sulfa derivatives.  Because
long-term treatment is necessary, antibiotic sensi-
tivity studies should be conducted.  Other unre-
lated agents, such as minocycline and amikacin, are
often effective.141,142  Incision and drainage or exci-
sion of lymphocutaneous abscesses also may be
indicated.143
and California.  Military physicians continue to
see patients with systemic coccidioidomycosis
acquired during duty in the southwestern United
States.
Several of the deep mycoses are uncommon or
unreported in the U.S. armed forces or, for that
matter, in personnel of any military.  The endemic
foci of several diseases are in areas where armies
have rarely deployed.  As the missions of the U.S.
military evolve and as populations migrate, how-
ever, it behooves medical officers to know the epi-
demiology and clinical manifestations of even the
uncommon deep mycoses.
SUMMARY
Deep fungal infections can involve a number of
organ systems, and patients can present with a
broad range of clinical signs and symptoms.  Often,
it is the cutaneous aspects of an illness that allow
clinicians to make a diagnosis, whether by physical
examination, biopsy, or culture.
Many pathogenic fungi have distinctive environ-
mental or geographical predilections.  Conse-
quently, the diseases they cause also have environ-
mental or geographical distributions.  Our
knowledge of coccidioidomycosis, for example,
comes largely from the problems the disease
posed during World War II exercises in Arizona
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Benenson AS. Chromoblastomycosis. In: Control of Communicable Disease in Man. 15th ed., Washington, DC:
American Public Health Association; 1990: 94–95.
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Magaña M. Mycetoma. Int J Dermatol. 1984;4:221–236.
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Chalmers AJ, Archibald RG. A Sudanese maduramycosis. Ann Trop Med. 1917;10:169–214.
100.
Gumaa SA, Mahgoub ES, El Sid MA. Mycetoma of the head and neck. Am J Trop Med Hyg. 1986;35:594–600.
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Develoux M, Audoin J, Tregeur J, Vetter JM, Warter A, Cenac A. Mycetoma in the Republic of Niger: Clinical
features and epidemiology. Am J Trop Med Hyg. 1988;38: 86–90.
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Vanbreuseghem R. The early diagnosis of mycetoma. Dermatol Int. 1967;6:123–140.
103.
Palestine RF, Rogers RS III. Diagnosis and treatment of mycetoma. J Am Acad Dermatol. 1982;6:107–111.
104.
McGinnis MR, Fader RC. Mycetoma: A contemporary concept. Infect Dis Clin North Am. 1988;2:939–954.
105.
Magaña M, Magaña-Garcia M. Mycetoma. Dermatol Clin. 1989;7:203–217.
106.
Mariat F, Destombes P, Segretain G. The mycetomas: Clinical features, pathology, etiology and epidemiology.
Contrib Microbiol Immunol. 1977;4:1–39.
107.
Barnetson RStC, Milne LJR. Mycetoma. Br J Dermatol. 1978;99:227–231.
108.
Zaias N, Taplin D, Rebell G. Mycetoma. Arch Dermatol. 1969;99:215–225.
109.
Caldwell DK, Caldwell MC, Woodard JC, et al. Lobomycosis as a disease of the Atlantic bottle-nosed dolphin
(Tursiops truncatus Montagu, 1821). Am J Trop Med Hyg. 1975;24:105–114.
110.
Rippon JW. Lobomycosis. In: Mycology: The Pathogenic Fungi and the Pathogenic Ascomycetes. 2nd ed. Philadel-
phia, Pa: WB Saunders; 1982: 315–324.
111.
Baruzzi RG, Rodrigues DA, Michalany NS, Salomão R. Squamous-cell carcinoma and lobomycosis (Jorge Lobo’s
disease). Int J Dermatol. 1989;28:183–185.
112.
Fuchs J, Mibradt R, Pecher SA. Lobomycosis (keloidal blastomycosis): Case reports and overview. Cutis.
1990;46:227–234.
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Binford CH, Dooley JR. Rhinosporidiosis. In: Binford CH, Connor DH, eds. Pathology of Tropical and Extraordi-
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114.
Lasser A, Smith HW. Rhinosporidiosis. Arch Otolaryngol. 1976;102:308–310.

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Easley JR, Meuten DJ, Levy MG. Nasal rhinosporidiosis in the dog. Vet Pathol. 1986;23:50–56.
116.
Karunaratne WAE. Rhinosporidiosis in man. London, England: Athlone Press; 1964.
117.
Samaddar RR, Sen MK. Rhinosporidiosis in Bankura. Indian J Pathol Microbiol. 1990;33:129–136.
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Thianprasit M, Thagerngpol K. Rhinosporidiosis. Curr Top Med Mycol. 1989;3:64–85.
119.
Levy MG, Meuten DJ, Breitschwerdt EB. Cultivation of Rhinosporidium seeberi in vitro: Interaction with epithelial
cells. Science. 1986;234:474–476.
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Pincus DH, Salkin IF. Human infections caused by yeastlike fungi. In: Wentworth BB, ed. Diagnostic Procedures
for Mycotic and Parasitic Infections. 2nd ed. Washington, DC: American Public Health Association; 1988: 239–269.
121.
Diamond RD. Cryptococcus neoformans. In: Mandel GL, Douglas RG Jr, Bennett JE. Principles and Practice of
Infectious Diseases. 3rd ed. New York, NY: Churchill Livingstone; 1990: 1980–1989.
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Ellis DH, Pfeiffer TJ. Ecology, life cycle, and infectious propagule of Cryptococcus neoformans. Lancet. 1991;
336:923–925.
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Levitz SM. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev Infect Dis.
1991;13:1163–1169.
124.
Rico MJ, Pennys NS. Cutaneous cryptococcosis resembling molluscum contagiosum in a patient with AIDS. Arch
Dermatol. 1985;121:901–902.
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Hall JC, Brewer JH, Crouch TT, Watson KR. Cryptococcal cellulitis with multiple sites of involvement. J Am Acad
Dermatol. 1987;17:329–332.
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Barfield L, Iacobelli D, Hashimoto K. Secondary cutaneous cryptococcosis: Case report and review of 22 cases.
J Cutan Pathol. 1988;15:385–392.
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Hernandez AD. Cutaneous cryptococcosis. Dermatol Clin. 1989;7:269–274.
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Carlson KC, Mehlmauer M, Evans S, Chandrasoma P. Cryptococcal cellulitis in renal transplant recipients. J Am
Acad Dermatol. 1987;17:469–472.
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Baes H, Van Cutsem J. Primary cutaneous cryptococcosis. Dermatologica 1985;171:357–361.
130.
Glaser JB, Garden A. Inoculation of cryptococcosis without transmission of the acquired immunodeficiency
syndrome. N Engl J Med. 1985;313:266.
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Sussman EJ, McMahon F, Wright D, Friedman HM. Cutaneous cryptococcosis without evidence of systemic
involvement. J Am Acad Dermatol. 1984;11:371–374.
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Sugar AM, Stern AM, Dupont B. Overview: Treatment of cryptococcal meningitis. Rev Infect Dis.
1990;12(Suppl):S338–348.
133.
Rippon JW. Entomophthoromycosis. In: Mycology: The Pathogenic Fungi and the Pathogenic Ascomycetes. 2nd ed.
Philadelphia, Pa: WB Saunders; 1982: 303–314.
134.
Segura JJ, Gonzalez K, Berrocal J, Marin G. Rhinoentomophthoromycosis: Report of the first two cases observed
in Costa Rica (Central America), and review of the literature. Am J Trop Med Hyg. 1981;30:1078–1084.
135.
Herstoff JK, Bogaars H, McDonald CJ. Rhinophycomycosis entomophthorae. Arch Dermatol. 1978;
114:1674–1678.

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Towersey L, Wanke B, Estrella RR, Londero AT, Mendonça AMN, Neves RG. Conidiobolus coronatus infection
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1984;94:1198–1217.
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Smith DT. Actinomycosis. In: Hoff ED, ed. Communicable Disease Transmitted Through Contact or by Unknown
Means. Vol 5. In: Coates JB Jr, ed. Preventive Medicine in World War II. Washington, DC: Medical Department, US
Army, Office of The Surgeon General; 1960: 1–2.
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Lerner PI. The lumpy jaw: Cervicofacial actinomycosis. Infect Dis Clin North Am. 1988;2:203–220.
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Smego RA Jr, Gallis HA. The clinical spectrum of Nocardia brasiliensis infection in the United States. Rev Infect
Dis. 1984;6:164–180.

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493
Chapter 19
SEXUALLY TRANSMITTED DISEASES
PAUL M. BENSON, M.D.*
*Lieutenant Colonel, Medical Corps, U.S. Army; Dermatology Service, Walter Reed Army Medical Center, Washington, D.C. 20307-5001
INTRODUCTION
MILITARY IMPACT OF SEXUALLY TRANSMITTED DISEASES
SYPHILIS
Magnitude of the Problem
Clinical Manifestations
Laboratory Diagnosis
Treatment
GONORRHEA
Clinical Manifestations
Laboratory Diagnosis
Treatment
CHANCROID
Clinical Manifestations
Laboratory Diagnosis
Treatment
GRANULOMA INGUINALE
Clinical Manifestations
Complications
Laboratory Diagnosis
Treatment
LYMPHOGRANULOMA VENEREUM
Clinical Manifestations
Laboratory Diagnosis
Treatment
GENITAL HERPES INFECTION
Clinical Manifestations
Laboratory Diagnosis
Treatment
GENITAL WARTS
Clinical Manifestations
Clinical Diagnosis
Treatment
MOLLUSCUM CONTAGIOSUM
Clinical Manifestations
Complications
Diagnosis
Treatment
SUMMARY

Military Dermatology
494
INTRODUCTION
Field medical officers are likely to encounter
sexually transmitted diseases (STDs)—a diverse
group of infections caused by bacterial, chlamydial,
and viral pathogens—in an active-duty population
of men and women.  Worldwide, STDs account for
millions of patient visits to health clinics and seri-
ous perinatal complications, and expose sexual part-
ners to the risk of infection with the human immu-
nodeficiency virus (HIV).  STDs share several
common characteristics1:
• they are infectious,
• they spread predominately by sexual activ-
ity,
• the usual presentation is in the anogenital
area, and
• infection does not confer lifelong immunity.
Genital ulcer disease is a subset of STD in which
patients present with ulcers on the genitalia or
perineum.  This subset includes syphilis, chancroid,
granuloma inguinale, lymphogranuloma vener-
eum, and genital herpes.  In the United States,
genital herpes is the most common cause of genital
ulcer disease, accounting for 60% to 70% of ulcer
disease in patients attending an STD clinic.  In 1991,
there were more than 250,000 visits to healthcare
providers for genital herpes.  Syphilis, the second-
most-common cause of genital ulcer disease, was
responsible for 10% to 20% of visits to STD clinics.
In 1991, approximately 43,000 cases of primary and
secondary syphilis were reported.  Fewer than 10%
of STD visits were for chancroid, with the remain-
ing visits due to infection with lymphogranuloma
venereum, granuloma inguinale, and miscellaneous
conditions.2
Elsewhere in the world, chancroid accounts for
more than half of all cases of genital ulcer disease,
and the disease is closely linked to prostitution and
drug abuse.  Syphilis accounts for 10% to 20% of
cases; genital herpes for fewer than 10%; and
lymphogranuloma venereum, granuloma inguinale,
and others account for the remainder.2
The evaluation of genital ulcer disease is difficult
even for experienced clinicians, and the limited
diagnostic tests and laboratory support in dispen-
saries and field medical units make accurate diag-
nosis even more difficult.  However, important
clinical clues can enable medical officers to be
more certain of their diagnoses (Table 19-1 and
Figure 19-1).
Many of the bacterial and vial pathogens in-
volved in STDs are able—by mechanisms that re-
main to be elucidated—to successfully evade the
host’s (ie, the individual human’s) immune system.
This may lead to chronic, progressive disease, as in
lymphogranuloma venereum or tertiary syphilis;
recurrent episodes of disease, as in genital herpes;
or asymptomatic carrier states, as in gonorrhea and
chancroid.  Additionally, persistence of infection
my be due to many factors, including antibiotic
resistance, ineffective or inappropriate treatment,
an immunologically impaired host, or lack of avail-
able treatment.
Risk factors and risk behavior have replaced the
term risk groups to describe an activity or behavior
that has a significant association with the acquisi-
tion of STD (Exhibit 19-1).  The worldwide spread of
infection with HIV has focused much attention on
these behaviors because unprotected sexual inter-
course, multiple sexual partners, prostitution, and
intravenous drug abuse significantly increase the
risk of transmission of the HIV virus.1  It is the
responsibility of healthcare providers to do more
than simply treat STDs.  Not only individual sol-
diers but also the chain of command must be edu-
cated and reeducated on risk factors and behaviors
and, when necessary, must make attempts to modify
them.
International travel permits rapid mobility of
large groups of individuals, with the result that
diseases previously thought to be local or regional
phenomena suddenly appear in areas far removed
from the source.  Likewise, microorganisms carry
their antibiotic susceptibility profiles with them; as
a result, an antibiotic-resistant strain of diseases
such as gonorrhea or chancroid from the Philip-
pines or the Middle East may appear abruptly.
Clearly, a thorough history, careful contact tracing,
laboratory confirmation of antibiotic sensitivities,
and follow-up cultures are essential to ensure that
appropriate therapy is provided and that the dis-
ease is eradicated.
This chapter does not address acquired immuno-
deficiency syndrome (AIDS) and HIV infection as
STDs per se for the following reasons:

Sexually Transmitted Diseases
495
TABLE 19-1
RELATIVE FREQUENCY OF CLINICAL FEATURES OF GENITAL ULCER DISEASE
1+: 0%–25%; 2+: 25%–50%; 3+: 50%–75%; 4+: 75%–100%; 1°: primary; 2°: recurrent.
Reprinted with permission from Jessamine PG, Ronald AR. Chancroid and the role of genital ulcer disease in the spread of human retroviruses. Medical Clinics of North America.
Philadelphia, Pa: WB Saunders; 1990;74(6):1423.
Table 19-1 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does not
include usage in electronic media. The current
user must apply to the publisher named in the
figure legend  for permission to use this illustra-
tion in any type of publication media.

Military Dermatology
496
Painful ulcers?
Grouped, fluid-filled
vesicles?
Ulcers on genitalia?
Firm, skin-colored
papules?
Molluscum
Contagiosum
1° Syphilis
D, RPR, VDRL,†
FTA-ABS
Ragged, yellow-gray
base, (+)  adenopathy?
Single/multiple
ulcers, (+) lymph
nodes?
Shallow, grouped,
clean erosions?
Chancroid
G, C
Yes
No
No
Yes
Yes
No
Yes
Yes
No
Yes
No
Yes
*patients with genital herpes infection can present both with and without ulcers
†RPR and VDRL may be negative in early syphilis
(+):  positive
C: culture
D: dark-field microscopy
DFA: direct fluorescent antibody
FTA-ABS: fluorescent treponemal antibody absorption
G: Gram’s stain
L: serology for lymphogranuloma venereum
RPR: rapid plasma reagin test
Tz: Tzanck prepreparation
VDRL: Venereal Disease Research Laboratory test
Fig. 19-1. A field algorithm for diagnosing genital ulcer disease.
Lymphogranuloma
Venereum
L
Genital Herpes
Infection*
Tz, C, DFA
Genital Herpes
Infection*
Tz, C, DFA
No lesion
(+) tender inguinal
lymph nodes?

Sexually Transmitted Diseases
497
EXHIBIT 19-1
RISK FACTORS AND RISK BEHAVIORS FOR SEXUALLY ACQUIRED DISEASES
Reprinted with permission from Eichmann AR. Sexually transmitted diseases. In: Fitzpatrick TB, Eisen AZ, Wolff K,
Freedberg IM, Austen KF, eds. Dermatology in General Medicine. 4th ed, Vol 2. New York, NY: McGraw-Hill; 1993: 2701.
• HIV-positive military personnel are not de-
ployed;
• there are no recognizable cutaneous signs
and symptoms of early HIV infections;
• the cutaneous manifestations of AIDS are
usually late signs (this chapter focuses on
acute, treatable STDs that have signs and
symptoms that allow the medical officer to
make a definite or probable diagnosis); and
• because HIV infection and AIDS are compli-
cating and exacerbating factors in other STDs
and also in other cutaneous diseases (eg, tuber-
culosis and leprosy), they are discussed briefly
in this and other chapters throughout the book.
MILITARY IMPACT OF SEXUALLY TRANSMITTED DISEASES
sulphonamide-resistant gonorrhea.  The average
rate of cure with the sulphonamides was falling
below 75 percent, owing to the development of
sulphonamide-resistant strains of the gonococcus
and to the substantial number of chronic cases that
probably represented relapse after inadequate self-
administered treatment.  Every station and general
hospital had a mounting backlog of patients with
chronic gonorrhea for whom the only prospect of
cure and return to duty at that time lay in treatment
with fever [therapy].4(p412)
During the years 1946 to 1950, the incidence of
STDs doubled to more than 82 cases per 1,000 ser-
vice personnel.  During the years 1951 to 1955 of the
Korean conflict, the case rate more than doubled
again to 184/1,000.3
During the Vietnam conflict, STDs were the num-
ber one medical diagnosis in the theater, and ap-
proximately 90% of this caseload was caused by
gonorrhea.  The overall incidence of STDs exceeded
260/1,000/y during the period 1963 to 1972.  De-
Among U.S. Army personnel during World War
I, STDs accounted for 6,804,818 lost duty days and
the discharge from active duty of more than 10,000
men.3  As a cause of disability and absence from
duty, STDs ranked second only to influenza in this
conflict.  During World War II,  the different the-
aters varied widely in the impact of STDs on mili-
tary personnel.  Worldwide, between the years 1941
and 1945, the incidence of STDs in U.S. Army per-
sonnel was about 43 cases per 1,000 individuals.4
The impact of these figures can be appreciated in a
report issued early in World War II that addresses
the critical problem of sulfonamide-resistant gon-
orrhea among U.S. military personnel during the
early period of the war:
Circular Letter No. 86, Office of The Surgeon Gen-
eral, 18 August 1942, … designated eight named
general hospitals as fever therapy centers....
These eight hospitals soon proved to be insufficient
to care for the mounting load of patients with
Exhibit 19-1 is not shown because the copyright permission granted to the Borden Institute, TMM, does
not allow the Borden Institute to grant permission to other users and/or does not include usage in elec-
tronic media. The current user must apply to the publisher named in the figure legend  for permission to
use this illustration in any type of publication media.

Military Dermatology
498
spite the high prevalence of STDs, however, fewer
than 1% of individuals required admission to the
hospital for therapy.3
Much has changed since World War I, when
patients with STDs were admitted to hospitals and
treated with painful and often dangerous medica-
tions.  Treatment now is rational and safe, state-of-
the-art medical facilities can be transported quickly
to the front, and hospitalization with prolonged
convalescence is almost never necessary.  Nonethe-
less, the inability of the military’s extensive public
health procedures to curb the enormous incidence
of STDs among its personnel, especially in wartime,
means that military physicians need to attain and
maintain clinical competence in the diagnosis and
treatment of STDs.
SYPHILIS
with urethral exudate from a patient with gonococ-
cal urethritis.  In fact, the patient had both syphilis
and gonorrhea.  Hunter developed both a chancre
and urethritis, and he erroneously concluded that
the two diseases were disparate manifestations of
the same infection.11  Not until 1838 was the sepa-
rate nature of gonorrhea and syphilis established.
A dramatic increase in the incidence of primary,
secondary, and congenital syphilis in the United
States has prompted a resurgence of interest in this
ancient disease.  The populations most at risk—
urban, heterosexual, black and Hispanic men and
women with limited access to medical care—are the
Syphilis is a venereal disease that is caused by the
bacterial spirochete Treponema pallidum and is trans-
mitted by direct contact, usually sexual intercourse.
Among the STDs, syphilis has occupied a unique
place in medical literature and lore since the late 15th
century.  Various theories attempt to explain the ori-
gins of syphilis and reasons for the rapid spread and
increased severity of the disease among European
populations, who knew the disease as the “Great
Pox.”  The Columbian theory proposes that, on re-
turning to Europe in 1493, Columbus’s crew brought
syphilis with them, having acquired it from natives in
the West Indies.  However, there are inconsistencies in
this theory: syphilis has not been described in early
Native Americans, and ancient Chinese writings
are known that describe an illness similar to late
cutaneous syphilis.  Others postulate that syphilis
was endemic to European populations during the
time of Columbus.  At that time, Europe was em-
broiled in long, protracted wars and syphilis, al-
ready present at a low background level, may have
become epidemic as a result of the movement of
troops and the migration of civilian populations.5,6
A newer idea, known as the environmental or
unitarian theory, proposes that syphilis, yaws, pinta,
and nonvenereal endemic syphilis (ie, bejel) are all
variants of the same disease and that they arose
from a single ancestral saprophytic treponeme (Fig-
ure 19-2).  According to this theory, the various
expressions of spirochetal disease reflect the influ-
ence of temperature, environment, and other fac-
tors on pathogenicity and clinical manifestations.7,8
The relatively benign African diseases yaws and
bejel may have been transformed in the susceptible
population of Europe into a highly virulent disease
with high mortality rates.9,10
The venereal nature of the transmission of syphi-
lis was not recognized until the 18th century, and
confusion reigned whether gonorrhea and syphilis
represented different manifestations of the same
disease or were two different diseases.  To resolve
the issue, in 1767, John Hunter inoculated himself
Fig. 19-2. Syphilis, yaws, pinta, and nonvenereal syphilis
may all have evolved from one ancestral saprophytic
spirochete. This photomicrograph of Treponema pallidum,
the spirochete that causes syphilis, shows the character-
istic helical coils. These thin, highly motile microorgan-
isms must be viewed through a dark-field microscope,
which uses light reflected off the specimen. Photograph:
Reprinted with permission from Smith JL. Spirochetes in
Late Seronegative Syphilis, Penicillin Notwithstanding.
Springfield, Ill: Charles C Thomas; 1969: 317.
Fig 19-2 is not shown because the copyright
permission granted to the Borden Institute, TMM,
does not allow the Borden Institute to grant
permission to other users and/or does not
include usage in electronic media. The current
user must apply to the publisher named in the
figure legend  for permission to use this illustra-
tion in any type of publication media.

Sexually Transmitted Diseases
499
same groups experiencing a dramatic increase in
the rates of HIV infection as a result of intravenous
drug use and sex-for-drugs prostitution.12  In addi-
tion, syphilis in individuals who are infected with
HIV may behave in a biologically different manner
resulting in serologic aberrations,13 an increased
risk of symptomatic neurosyphilis,14 and failures
with traditional antibiotic regimens.15
Syphilis, the “great imitator,” will continue to
present clinicians and public health officials with
major diagnostic and therapeutic challenges in this
decade.  The medical officer in a field unit or on
board a ship may find himself or herself with a lack
of resources and trained personnel to accurately
diagnose syphilis in any stage of the disease.  Dark-
field microscopy, the principal means of diagnos-
ing primary syphilis, is usually unavailable.  A new
test utilizing direct immunofluorescent staining of
dried ulcer exudate (discussed later in this chapter)
may allow more accurate and timely diagnosis.  The
cutaneous and mucosal lesions of secondary and
tertiary stages of syphilis may be confused with
numerous similar skin eruptions.  Pitfalls in the
interpretation of serologic tests cause a small but
significant number of false-positive and false-nega-
tive test results.  The legal requirement to report
syphilis and the potential embarrassment of contact
tracing may lead to less-than-honest answers by
patients regarding their sexual exposure and sexual
behavior.
A rational approach to the clinical and laboratory
diagnosis of primary and secondary syphilis will be
presented, geared to the resources available to the
field medical officer.  Late, or tertiary, syphilis will
be discussed briefly; congenital syphilis and syphi-
lis during pregnancy will not; interested readers
can find several excellent discussions16,17 of these
subjects.  Lastly, the impact of HIV infection on the
current syphilis epidemic will be discussed as it
relates to changes in diagnosis and treatment.
Magnitude of the Problem
In 1990, the Centers for Disease Control (CDC),
Atlanta, Georgia, reported that between the years
1981 to 1989 the incidence of primary and second-
ary syphilis increased an alarming 34% in the United
States.12  This represents the highest incidence of
syphilis in the general population since 1949.  In
1993, there were 26,279 projected cases of primary
and secondary syphilis (10.6/100,000) reported to
the STD Surveillance Department of the CDC.  In
reviewing the data among various population
groups, several striking trends are apparent12:
• Among white men, the incidence of syphilis
actually decreased by 69% during this pe-
riod, to 3.2/100,000.
• However, among heterosexual black men
and women, the incidence of syphilis ap-
proached 122/100,000.  This is almost a 50-
fold difference between black and white
populations.
• Incidence rates for Hispanic men and women
were intermediate between the rates for
whites and blacks.
• The increase in syphilis is most acute for
women, regardless of their racial or ethnic
background.
• The male-to-female ratio has declined to just
below 2:1.
This shift of disease—from homosexual men in
the 1970s to heterosexual black men and women in
the 1980s—foreshadows a potential public health
catastrophe with regard to human HIV infection.
Several reports from Africa18,19 demonstrate that
genital ulcer disease, including syphilis, facilitates
the sexual transmission of HIV infection.  This sug-
gests that segments of the population in the United
States, especially urban blacks, may be at great risk
of suffering the rapid spread of HIV disease that has
been seen among heterosexuals in Africa.
As a result of changes in sexual practices be-
tween 1981 and 1989, the largest decrease in syphi-
lis rates occurred among white homosexual and
bisexual men (Figure 19-3).  However, among black
Fig. 19-3. Anal chancre in a man who is also infected with
the human immunodeficiency virus.  Primary lesions of
syphilis are usually asymptomatic and are frequently
overlooked by the patient. Such a lesion might mimic a
perirectal abscess.
OK to put on the Web

Military Dermatology
500
heterosexuals, especially black women, the enor-
mous increase in rates of syphilis and gonorrhea
can be traced to the use of illegal drugs—in particu-
lar, crack cocaine.12
There has also been a resurgence in cases of
congenital syphilis that parallels the increase in
syphilis among women.  During 1989, for example,
1,747 cases of congenital syphilis were reported to
the CDC.  The majority (1,017 cases) were reported
from New York City.20
Clinical Manifestations
Syphilis is not a highly contagious STD.  About
30% of individuals exposed to an infected partner
will develop syphilis, based on a study21 that deter-
mined the efficacy of antibiotics to abort syphilis
infections in individuals exposed to known con-
tacts.  Another study22 demonstrated that about one
half of the contacts of individuals with early syphi-
lis developed infection.  Transfusion-associated
syphilis has been virtually eliminated in the United
States as a result of serologic screening of all blood
prior to transfusion.  However, in developing coun-
tries where screening of donated blood is inconsis-
tent, transfusion-associated syphilis still occurs.  The
practice in the United States of using refrigerated
stored components is also advantageous, as T
pallidum is killed by storage at 4°C.11
Syphilis is almost exclusively sexually transmit-
ted and direct contact with skin or mucous mem-
branes, from an infected to an uninfected person, is
required for transmission.  The organism will pass
through mucous membranes and abraded skin.
However, it is quite sensitive to a variety of physical
and chemical agents and is inactivated by heat,
cold, drying, and soap and water.23  The site of
inoculation is usually on the genitalia, although the
lips may be involved through kissing, and other
areas of the skin may be infected through abrasions.
Healthcare workers can be infected if they fail to use
gloves when examining lesions or handling infec-
tious exudates or specimens.9
Following exposure, T pallidum incubates for a
variable period ranging from 10 to 90 days (average
21 d).  The length of the incubation period is in-
versely proportional to the size of the inoculum (eg,
the larger the inoculum, the shorter incubation pe-
riod).24  In the primary stage of syphilis, a chancre
develops at the site of inoculation.  If untreated, the
chancre spontaneously resolves within 3 to 6 weeks.
In 60% to 90% of patients, secondary syphilis devel-
ops, typically 4 to 10 weeks following the develop-
ment of primary syphilis.  A chancre is still present
in 18% to 34% of patients who present with second-
ary syphilis.11  Almost 25% of patients with second-
ary syphilis do not recall a primary lesion: lesions
are often on the cervix or vaginal wall in women, or
in the anal canal in women and homosexual men.23
With resolution of the secondary stage, the pa-
tient enters the latent phase, where there are no
clinical signs or symptoms of the disease.  For treat-
ment purposes, the U.S. Public Health Service de-
fines early latent syphilis as syphilis of less than 1
year’s duration after the primary lesion, and late
latent syphilis as syphilis of longer than 1 year’s
duration after the onset of the chancre.25
After a period ranging from 2 to more than 40
years, clinical signs of late, or tertiary, syphilis may
develop in about one third of untreated patients.11
Tertiary syphilis is now rare in this country because
of widespread serologic testing and the availability
of antibiotics.  However, infection with HIV ap-
pears to alter the biological behavior of the spiro-
chete and its responsiveness to therapy.26  Persis-
tence of spirochetes has been reported27 in the
cerebrospinal fluid of patients who (a) are infected
with HIV and (b) have been treated with the doses
of penicillin recommended for early syphilis.  The
treatment guidelines for managing all stages of
syphilis in the HIV-infected population will un-
doubtedly change.
Primary Syphilis
The primary lesion of syphilis is the chancre,
which develops 10 days to 3 months (average 3 wk)
after exposure to the spirochete.  The classic chancre
begins as a painless, firm, rubbery, elevated papule
that progresses to develop a central ulceration (Fig-
ure 19-4).  The base of the ulcer is clean and smooth
with a thin, serous exudate present.  In men, the
chancre is found on the inner aspect of the foreskin,
near the frenulum, in the coronal sulcus, and occa-
sionally on the glans or penile shaft.  In women, the
primary lesion may go unnoticed.  It occurs on the
cervix, vaginal wall, vulva, and periurethral and
perianal areas.  Although they are classically de-
scribed as nontender, occasional chancres are pain-
ful owing to secondary infection with bacteria.28
Atypical lesions commonly occur.  Multiple chan-
cres may be found in up to 25% of patients.29  In the
perianal area, the primary lesion may resemble an
anal fissure.  Extragenital chancres may be found on
the oral mucosa, lips, tonsils, and pharynx of homo-
sexual men or individuals who practice orogenital
sex.  Anal and rectal chancres also occur and may be
asymptomatic, may present as an acute proctitis, or

Sexually Transmitted Diseases
501
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Fig. 19-4. This painless, clean-based ulcer with rolled
borders is typical of primary syphilis.
syphilis.  Pruritus is usually absent but has been
reported in a minority of patients; the presence or
absence of pruritus is not a reliable clinical sign in
the evaluation of possible syphilitic exanthems.28
Papular lesions are dull red-to-ham colored but
may only appear as elevated areas of hyperpigmen-
tation in dark-skinned patients.  Macules and pap-
ules are often found together as symmetrically dis-
tributed, discrete lesions with a predilection for the
palms and soles (Figure 19-6).  Various investiga-
tors have emphasized the “uniqueness” of palmar
and plantar lesions.  However, dermatologists are
well aware that drug eruptions, viral illnesses, and
rickettsial infections (ie, Rocky Mountain spotted
fever) may also be important causes of lesions in
these areas.  Scaling overlying the lesions may be (a)
minimal to absent, (b) suggestive of psoriasis, or (c)
very thickened and keratotic (ie, lues cornee).  Cen-
tral clearing of papular lesions results in annular
lesions (also called annular syphilid) that are com-
monly seen on the face of dark-skinned individuals.
Split papules are common, especially at the corners
of the mouth and nostrils in dark-skinned individu-
als.31  Less-common secondary lesions include pus-
tules; acneform lesions; follicular or miliary syphilid
consisting of small, discrete follicular papules;
corymbose (ie, bombshell) syphilid with a large
central papule surrounded by smaller lesions (Fig-
ure 19-7); and a highly destructive, necrotic, ulcer-
ative form known as lues maligna, which is associ-
ated with fever and malaise (Figure 19-8).28
may be misdiagnosed as a carcinoma.  Intraurethral
chancres may produce signs and symptoms of
urethritis.  Lesions in other areas such as fingers are
rare (Figure 19-5).10
Inguinal lymphadenopathy usually develops
within a few days of the appearance of the chancre,
if it is located on the external genitalia.  Lymphaden-
opathy may be unilateral or bilateral.  The lymph
nodes are firm, discrete, and painless unless the
chancre is secondarily infected.  With extra-genital
infection, the lymphadenopathy is more commonly
unilateral.10
If no treatment is sought or if the chancre is
inconspicuous, it heals uneventfully in 3 to 6 weeks.
Secondary Syphilis
Secondary syphilis develops in 60% to 90% of
untreated patients from 4 to 10 weeks after the
initial appearance of the chancre.  As noted previ-
ously, up to one third of patients may still have a
chancre present at the time of onset of lesions of
secondary disease.11,30  The characteristic rash,
present in 75% to 100% of patients, is typically
found on the trunk, extremities, palms, and soles.
Condylomata lata lesions are found on mucous
membranes and other moist areas such as the
inframammary and axillary areas.  The cutaneous
lesions are polymorphous, and numerous colorful
terms have been used to describe the clinical find-
ings.  Lesions may be macular, papular, papulo-
squamous, follicular, annular, pustular, or nodu-
lar—the most common presentations are variants of
papular lesions.  Vesiculobullous lesions do not
occur in adults but are frequently seen in congenital
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Fig. 19-5. Syphilitic chancre on a patient’s index finger.
This chronic, ulcerative lesion mimics many other infec-
tious and inflammatory processes such as tuberculosis,
deep fungal infections, or malignancy.

Military Dermatology
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Fig. 19-6. Papulosquamous lesions of secondary syphilis on (a)
the hands and (b) the feet, which are frequently involved in
secondary syphilis. The lesions are asymp-tomatic, pink-to-
red papules with slight overlying scale. These eruptions are
frequently overlooked by the patient or misdiagnosed as viral
exanthems or drug eruptions. Photograph: Courtesy of C.
Kalter, MD, Bethesda, Md.
Fig. 19-8. Lues maligna showing destructive papulo-necrotic
lesions of the face and scalp. This rare, destructive form of
secondary syphilis is associated with severe constitutional
symptoms and ulcerative lesions.  Photograph: Courtesy of
Walter Reed Army Medical Center Dermatology Service slide
file, Washington, DC.
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a
b
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Fig. 19-7.  Rupial lesions are uncommon manifestations of
secondary syphilis. They are elevated, often with thick, over-
lying scale-crust. Photograph: Courtesy of C. Kalter, MD,
Bethesda, Md.
Fig. 19-9.  These grayish white, smooth papules of condylomata
lata of the glans penis resemble genital warts. When lesions
like this are seen, healthcare personnel should look elsewhere
on the patient’s body for telltale signs of secondary syphilis.
Photograph: Courtesy of C. Kalter, MD, Bethesda, Md.

Sexually Transmitted Diseases
503
Lesions in the mucous membranes are common
and are known as (a) condylomata lata when found
in moist intertriginous areas (eg, groin and perianal
area) and (b) mucous patches when located in the
mouth or on the lips.  The lesions are asymptomatic,
white-to-grayish, flat-topped papules or plaques,
with a mucoid exudate on the surface (Figure 19-9).
The lesions may become large, malodorous vegeta-
tions.  The moist environment in which they de-
velop permits large numbers of spirochetes to sur-
vive, and the lesions are highly infectious.28
Other reported cutaneous findings include a
“moth-eaten,” patchy alopecia, or a diffuse hair
loss; hyperpigmentation and hypopigmentation,
often as a result of previous inflammation; and
syphilitic paronychia.28
Constitutional signs and symptoms are variable,
although generalized, asymptomatic, nontender
lymphadenopathy is present in virtually every pa-
tient with secondary syphilis.  Signs and symptoms
vary from mild to severe and include low-grade
fever, headache, myalgias, sore throat, and loss of
appetite.  Anemia, elevated sedimentation rate, and
lymphocytosis may be found on routine blood tests.
Almost any organ may be involved during the sec-
ond stage of syphilis, and clinical and laboratory
findings referable to this involvement should be
sought.  Major organ involvement includes the fol-
lowing31:
• syphilitic hepatitis (elevated alkaline phos-
phatase, rarely jaundice);
• renal involvement (proteinuria, nephrotic
syndrome, glomerulonephritis);
• ocular disease (anterior uveitis, photophobia,
lacrimation, and rarely chorioretinitis);
• syphilitic myocarditis with electrocardio-
graphic abnormalities; and
• central nervous system involvement, which,
although uncommon, may include cranial
nerve palsies, acute meningitis, transverse
myelitis, neural deafness, or thrombosis of
spinal arteries.
Recently, patients with HIV infection have been
reported to develop lesions of secondary syphilis in
the absence of confirmatory serologic tests (eg, the
Venereal Disease Research Laboratory [VDRL] test
and the fluorescent treponemal antibody absorp-
tion [FTA-ABS] test).13  Therefore, in any patient
with clinical signs or symptoms that may be those of
syphilis, laboratory tests—and even skin biopsy—
should be done early and routinely.
If secondary syphilis is not treated, the lesions
spontaneously resolve in 1 to 3 months, with sec-
ondary relapses occurring in as many as 25% of
patients,32 usually during the first year after infec-
tion.  After resolution of the secondary lesions, the
patient enters either the early or the late latent
disease phase.  This division has important medical
implications, as patients with early latent disease
(a) may have relapses of secondary lesions during
this time and (b) are potentially infectious to their
sexual partners.  Individuals in the late latent phase
are generally not infectious.11
Tertiary Syphilis
Tertiary syphilis is now a rare disease in the
United States.  About 70% of patients with un-
treated syphilis will remain asymptomatic; the
remainder will progress to tertiary disease and may
present with late benign gummata (16%),
cardiovascular syphilis (9.6%), neurosyphilis (6.5%),
or involvement of bone or virtually any other
organ.28
Gummata (ie, superficial or deep, destructive
granulomatous lesions that involve skin, subcuta-
neous tissues, or bone) tend to occur on the extremi-
ties, especially at the sites of trauma and in the
head and neck.  The lesions, which are asymp-
tomatic, begin as nodules or subcutaneous masses
that often ulcerate and coalesce to form large ir-
regular plaques with annular borders.  The skin
may be secondarily involved by direct extension
from underlying bony gummata.  The lesions heal
slowly with atrophy and pigmentary changes.  Dif-
ferential diagnosis includes malignancy, tuberculo-
sis, leprosy, cutaneous lymphomas, and deep
mycoses, among others.11,28
The clinical presentation of syphilitic involve-
ment of the central nervous system has changed
recently, for unknown reasons.  General paresis
and tabes dorsalis are much less common than
in previous times and seizure disorders and
neuro-ophthalmic findings are more often encoun-
tered.28  A discussion of neurosyphilis is beyond
the scope of this chapter; however, recent experi-
ences with late syphilis in patients infected with
HIV suggest that current treatment regimens
are inadequate to prevent this complication in
this population.  Two groups of investigators26,33
have reported development of symptomatic
neurosyphilis in patients infected with HIV despite
treatment with recommended doses of benzathine
penicillin.

Military Dermatology
504
Laboratory Diagnosis
Culture
Culture of treponemes is both unavailable and
impractical for the rapid diagnosis of syphilis.
However, the recent confirmation that T pallidum
can successfully be propagated in vitro will un-
doubtedly increase knowledge of both the molecu-
lar biology and the spirochete–host interaction that
leads to infection.
T pallidum, a spirochete, the causative organism
of syphilis, is a motile, flexible, rod-shaped bacte-
rium with 8 to 14 helical coils that gives the tre-
poneme its characteristic shape.  The genus Tre-
ponema (from the Greek words trepo and nema
meaning “turning thread”) contains the spirochetes
that cause syphilis, yaws, pinta, and nonvenereal
syphilis; the species are indistinguishable both
morphologically and serologically.  Differentiation
of the pathogenic spirochetes is based solely on
their mode of infection, the severity of the infection,
and the infectivity for laboratory animals.  As a
result, the nomenclature has been changed to reflect
the close relatedness of the treponemes9:
• Treponema pallidum (which causes syphilis)
is now called T pallidum (subspecies pallidum);
• Treponema pertenue (which causes yaws) is
now called T pallidum (pertenue); and
• the Treponema pallidum variant that causes
endemic syphilis is now called T pallidum
(endemicum).
In the laboratory, T pallidum is usually main-
tained in rabbit testes.  Until recently, the spirochete
had never been cultured outside a human or animal
host.  Using special tissue culture techniques, the
organism has been shown to multiply through sev-
eral generations in rabbit epithelial cells.  Tre-
ponemes were found to attach and replicate on the
surface of tissue culture cells—tissue culture ap-
pears to be essential for successful in vitro cultiva-
tion.  However, although virulence has been main-
tained in culture, it has not been possible to pass the
organisms serially.9,34
Dark-Field Microscopy
T pallidum is too narrow to be seen well by ordi-
nary light microscopy, and dark background illu-
mination (ie, dark-field microscopy) is necessary to
visualize the organism (see Figure 19-2).  Dark-field
microscopy is the principal means of diagnosing
primary syphilis, as serologic tests are often nega-
tive when patients are first seen.10  Except from the
moist condylomata lata, organisms are difficult to
obtain from lesions of secondary syphilis.  Non-
pathogenic treponemes are found in the mouth and
along the gingival margins in normal individuals.
Therefore, dark-field microscopy is unreliable for
diagnosis of primary or secondary lesions occur-
ring in the oropharynx.
Dark-field microscopy requires a dark-field con-
denser, trained personnel, and knowledge of the
technical difficulties in preparing a specimen and
interpreting the findings.  Pitfalls often encoun-
tered include (a) the age or condition of the lesion,
(b) inadequate or improper collection of specimens,
(c) recent use of topical or oral antibiotics by the
patient, and (d) failure to distinguish artifacts and
nonpathogenic treponemes from T pallidum.
For those interested in the technique and materi-
als required for dark-field microscopy, the CDC has
an excellent publication available free of charge.35
Direct Fluorescence Microscopy
A fluorescein-tagged monoclonal antibody that
is specific for T pallidum has been developed and
can be used to detect the presence of the organism
on dried exudate from lesions.  A smear of lesional
material is applied to a glass microscope slide, air-
dried, fixed in acetone, and sent to the laboratory.
The slide can be sent by mail to a reference labora-
tory if the test cannot be done locally.  If specimens
are to be mailed, the smears should be air-dried
only and not fixed.36  Initial results of the fluores-
cein-tagged monoclonal antibody indicate that it is
both sensitive and specific.10,37
Lesional material may also be collected in hep-
arinized, microhematocrit capillary tubes, then
sealed and stored at 4°C to 8°C until slides are to be
prepared.  Capillary tubes may be mailed to a refer-
ence laboratory without refrigeration.36
Serologic Tests
Serologic testing, despite its limitations and pit-
falls, remains the workhorse for the laboratory di-
agnosis of syphilis.  Unfortunately, these tests are
neither inexpensive nor rapid, and delays of days to
a week or more may cause treatment to be delayed
in a potentially infectious individual.  Two types of
serologic tests for syphilis are currently in use or are
being evaluated for use: the nontreponemal tests,
which are discussed below, and treponemal tests.
Treponemal tests employ spirochetal antigen and

Sexually Transmitted Diseases
505
standard VDRL microscopical flocculation test and
various modifications including the rapid plasma
reagin (RPR) 18-mm–circle card test; automated
reagin test (ART); unheated serum reagin (USR);
and toluidine red unheated serum test (TRUST),
which is an investigational test.
All nontreponemal tests measure antilipid im-
munoglobulin (Ig) G and IgM antibodies.  The test
antigen is mixed with the patient’s serum on a card,
rotated for a specified number of minutes, and then
read.  The tests are reported as either reactive or
nonreactive; the VDRL and USR tests are also re-
ported as weakly reactive (Table 19-2).36
In general, quantitative tests indicating tube di-
lutions (ie, 1:32) are more useful in evaluation of
serologic status and response to treatment.  Active
disease will show a rising titer, adequately treated
disease will show a drop in titer, and serofast pa-
tients will have no change in titer on serial testing.28
The nontreponemal tests usually become posi-
tive within 10 to 14 days after the chancre has
appeared, but up to 4 weeks may be required in
some individuals.10  In primary syphilis, the titers
may be negative, low, or occasionally 1:32 or higher.
They are usually high (> 1:32) in secondary syphi-
lis.28  Sera from about 30% of patients with cardio-
vascular syphilis or with neurosyphilis are
nonreactive with the VDRL test.38  In a small num-
ber of patients with secondary syphilis, a false-
negative or weakly reactive test (ie, the prozone
phenomenon) may occur in the presence of high
antibody titers.  Most laboratories perform dilu-
tions on specimens to distinguish false-negative
results from this phenomenon.17
Biological false-positive reactions occur in 1% to
2% of the population and increase to more than 10%
of intravenous drug abusers.  Most titers are usually
1:8 or less; however, low titers may also be seen
in the later stages of syphilis.  All reactive
nontreponemal tests must be confirmed with a
treponemal test.36
Treponemal Tests.  Patients with reactive
nontreponemal tests must have the reactivity con-
firmed with one of the four currently available
treponemal antibody tests: (1) fluorescent trepone-
mal antibody absorption (FTA-ABS); (2) fluores-
cent treponemal antibody absorption double-stain-
ing (FTA-ABS DS), a recent modification using a
fluorochrome-labeled counterstain; (3) hemagglu-
tination treponemal test for syphilis (HATTS); and
(4) microhemagglutination assay for antibodies to T
pallidum (MHA-TP).
The FTA-ABS is still the most widely used test
and is an indirect immunofluorescent technique
are reliable indicators of syphilitic infection, present
or past.  However, they do cross-react with other
treponemes and therefore are not entirely specific.9
It is incumbent on the medical officer to appreciate
the sensitivity and specificity of the test that is being
ordered, and to consider false-negative and false-
positive results, prior infection (serofast), possible
reinfection or relapse, and treatment failures in the
evaluation of the patient (Exhibit 19-2).
Nontreponemal Tests.  The word nontreponemal
means that the test antigen is derived from a source
other than a spirochete.  This test antigen is
cardiolipin-lecithin-cholesterol (reagin), which is a
beef-heart extract.  Reagin is a phospholipid also
found in human tissue and is present in minor
amounts in spirochetal membranes.36  Non-
treponemal tests currently available include the
EXHIBIT 19-2
DIAGNOSTIC TESTS FOR SYPHILIS
Exhibit 19-2 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does not
include usage in electronic media. The current
user must apply to the publisher named in the
figure legend  for permission to use this illustra-
tion in any type of publication media.
Adapted with permission from Larsen SA, Hunter EF,
Creighton ET. In: Holmes II, Mårdh P-A, Sparling PF, et
al, eds. Sexually Transmitted Diseases. New York: McGraw-
Hill; 1990: 928.

Military Dermatology
506
TABLE 19-2
SENSITIVITY OF SEROLOGIC TESTS IN UNTREATED SYPHILIS
VDRL: Venereal Disease Research Laboratory
FTA-ABS: fluorescent treponemal antibody absorption
MHA-TP: microhemagglutination assay for antibodies to Treponema pallidum
Adapted with permission from  Jaffe HW, Musher DM. In: Holmes II, Mårdh P-A, Sparling PF, et al, eds. Sexually Transmitted Diseases.
New York: McGraw-Hill; 1990: 935.
improvement over the treatment used during the
Civil War by Assistant Surgeon E. A. Tompkins,
Fourth Cavalry, Fort Yamhill, on 1 April 1863:
The patient contracted syphilis ... a short time be-
fore I arrived at this post.  He was relieved by the
use of iodide of potassium in syrup of sarsaparilla.
Small doses of corrosive sublimate were given and
lunar caustic was applied to the chancres.  A con-
tinuance of this treatment for three weeks enabled
him to return to duty, although not entirely
well.40(p893)
T pallidum has remained sensitive to penicillin
since the drug was first used for the treatment of
syphilis in 1943.  However, because of the organism’s
long dividing time, prolonged, moderately low lev-
els are required for complete killing of the organ-
isms present.11  The current treatment guidelines for
adults recommended by the CDC are presented
below.  Controversy exists regarding therapy of
patients with HIV infection, and they may require
alternative regimens.  Consultation with an infec-
tious disease specialist is advised, as numerous
investigational protocols are currently underway.
The treatment of syphilis in pregnant women and
children is not discussed in this chapter.
Primary, Secondary, and Early Latent Syphilis
The recommended regimen for treatment of pri-
mary, secondary, and early latent syphilis25 is
benzathine penicillin G 2.4 million units, adminis-
tered intramuscularly, in one dose.  There are two
alternative regimens for nonpregnant, penicillin-
allergic patients:
that utilizes a fluorescein-labeled antihuman anti-
body to detect host antibodies against T pallidum.  A
sorbent, which removes antibodies to nonpathogenic
Reiter treponemes (hence the word “absorption”),
is first utilized.36
The other two tests, the HATTS and MHA-TP, do
not require a fluorescent microscope and can be
performed more quickly.  However, they are less
sensitive in primary syphilis and cross-reactions
may occur.36
The treponemal tests become reactive earlier in
primary syphilis than the nontreponemal tests.  Still,
approximately 20% of patients who present with
primary syphilis will be nonreactive on the FTA-
ABS test.  Therefore, the FTA-ABS test should be
performed and may provide important information
in suspect cases where the RPR test is negative.  The
treponemal tests remain positive throughout an
individual’s life.  However, the CDC reports25 that
15% to 25% of patients who are treated during the
primary stage may revert to being seronegative on
the treponemal tests after 2 to 3 years.  The false-
positive rate in the general population is about 1%
(Exhibit 19-3).11
The FTA-ABS test has several drawbacks: it re-
quires special equipment and trained personnel, is
time-consuming to perform and technicians find
the repetitive reading of tests tiresome, and is some-
what expensive.  It should be used principally as a
confirmatory test.39
Treatment
Penicillin, the treatment of choice for all patients
in any stage of syphilis today, is a considerable
Table 19-2 is not shown because the copyright permission granted to the Borden Institute, TMM,
does not allow the Borden Institute to grant permission to other users and/or does not include
usage in electronic media. The current user must apply to the publisher named in the figure
legend  for permission to use this illustration in any type of publication media.

Sexually Transmitted Diseases
507
EXHIBIT 19-3
FALSE-POSITIVE REACTIONS TO NONTREPONEMAL AND TREPONEMAL TESTS FOR SYPHILIS
Adapted from (1) Hutchinson CM, Hook EW. Syphilis in adults. Med Clin N Am. 1990;74(6):1405. (2) Rhodes AR, Luger AFH.
Syphilis and other treponematoses.  In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, eds. Dermatology in
General Medicine. 3rd ed. New York, NY: McGraw-Hill; 1987: 2424, 2426.
Exhibit 19-3 is not shown because the copyright permission granted to the Borden Institute, TMM, does not
allow the Borden Institute to grant permission to other users and/or does not include usage in electronic
media. The current user must apply to the publisher named in the figure legend  for permission to use this
illustration in any type of publication media.

Military Dermatology
508
1.
doxycycline 100 mg, administered orally
twice daily for 2 weeks, or
2.
tetracycline 500 mg, administered orally four
times daily for 2 weeks.
There is less clinical experience with doxycycline
than with tetracycline, but compliance may be bet-
ter with doxycycline.
Similarly, two options are available for treating
patients who are unable to tolerate tetracycline or
doxycycline25:
1.
the patient should have skin-testing for peni-
cillin allergy and be desensitized, if neces-
sary; or
2.
erythromycin 500 mg should be adminis-
tered orally four times daily for 2 weeks.
Erythromycin is less effective than other recom-
mended regimens.  Single-dose ceftriaxone is not
effective for treating syphilis.25  Optimal dose and
duration have not been established for ceftriaxone.
Persons Exposed to Syphilis.  Persons who have
been exposed to syphilis within the preceding 90
days should have clinical and serologic examina-
tions, and the patient should be treated presump-
tively even if seronegative.  Evidence of other STDs
should be sought in every individual.25
Follow-Up.  Following treatment, the CDC rec-
ommends that patients be reexamined clinically
and serologically at 3 and again at 6 months.  Treat-
ment failures can occur with any regimen.  The CDC
currently recommends that patients who are in-
fected with HIV, and who are also being treated for
syphilis, should have more frequent serologic test-
ing at 1, 2, 3, 6, 9, and 12 months.25
Latent Syphilis of Unknown Duration, Late
Latent Syphilis, and Tertiary Syphilis
Patients with late latent or symptomatic tertiary
syphilis need more extensive evaluation that is be-
yond the scope of this discussion.  For therapeutic
guidelines, see the CDC guidelines for dosage and
routes of administration of penicillin or alternative
regimens.25
GONORRHEA
Gonorrhea, caused by the Gram-negative diplo-
coccus bacterium Neisseria gonorrhoeae, is the most
commonly reported communicable disease in the
United States.  In 1993, there were 419,711 projected
cases (169/100,000) reported to the CDC,41 although
many more cases go unreported.  Important shifts
in the epidemiology, populations at risk, and anti-
biotic susceptibility of the organism have resulted
in significant and rapid changes in treatment guide-
lines and strategies for public health intervention.
The military has figured prominently in epidemio-
logical studies of gonorrhea because of the large
numbers of young, sexually active individuals who
can be followed prospectively for long periods of
time.
Gonorrhea is transmitted almost exclusively by
sexual contact and is common in both developed
and developing countries.  Globally, almost 200
million cases are reported annually, evidence of the
enormity of the problem and the necessity for im-
proved public health measures for control.  Early
and accurate diagnosis of gonococcal infection fol-
lowed by an effective treatment that ensures a high
level of patient compliance are crucial to any suc-
cessful control program.42
The spectrum of disease caused by N gonorrhoeae
includes42:
• genital infection including acute anterior
urethritis in men, acute endocervicitis in
women, and asymptomatic urethral infections;
• rectal infection;
• pharyngeal infection;
• local complications including acute salping-
itis (pelvic inflammatory disease) and
Bartholin’s gland abscess in women; and
epididymitis, prostatitis, and other perineal
complications in men;
• disseminated gonococcal infection, includ-
ing the arthritis-dermatitis syndrome and
meningitis; and
• infections in infants and children, frequently
a sign of sexual abuse (although gonorrhea
can be acquired during birth).
Clinical Manifestations
Acute Anterior Urethritis in Men
Epidemiological studies have revealed that fol-
lowing a single exposure to an infected woman,
about 20% of exposed men will become infected.43
The incubation period for acute gonococcal urethritis
averages 2 to 5 days following exposure, with a
range of 1 to 14 days.

Sexually Transmitted Diseases
509
Approximately 85% of infected men will develop
an acute urethritis syndrome consisting of pain,
dysuria, and a urethral discharge (Figure 19-10).44
The discharge is initially scant and mucoid to
mucopurulent, but within 24 hours becomes frankly
purulent and profuse.45  The urethral discharge has
been reported to be purulent in 75% of cases, white
or cloudy in 20%, and clear to mucoid in the remain-
ing 5%.46  Recent voiding will temporarily eliminate
a discharge in more than one half of patients and
will reduce it to cloudy or white in another one
third.46
Signs and symptoms of untreated gonococcal
urethritis in men peak within 2 weeks, with sponta-
neous resolution occurring in more than 95% of
patients within 6 months.45
Asymptomatic Infections in Men
Of infected men, 15% will have only mild symp-
tomatic urethritis, and a minority (1%–2%) will be
asymptomatic.28,47  The actual figures cited in the
literature vary due to the types of populations stud-
ied and how carefully the individuals were ques-
tioned and examined regarding the presence of
symptoms.  The existence of the asymptomatic man
was considered but was not verified until 1974,
when researchers demonstrated that male carriers
of the organism could be identified.48  Two groups
of U.S. Army personnel were surveyed to assess the
incidence of asymptomatic urethral carriage of gono-
cocci.  From a group of 2,628 asymptomatic men
who had sexual intercourse either in Vietnam or in
the Fort Lewis, Washington, area, the investigators
recovered gonococci from the urethras of 59 (2.2%
of the total), of whom 40 (68%) were asymptomatic.
Additionally, 28 asymptomatic men were followed
without treatment for periods ranging from 7 to 165
days and were found to be culture positive for
gonococci until the time of treatment, indicating
that asymptomatic infections in men may be
chronic.48
Acute Endocervicitis in Women
The cervix is the most common site of infection in
women, although the urethral canal, periurethral
glands, or Bartholin’s gland may be primarily or
secondarily involved.  Within about 10 days follow-
ing a single exposure to an infected partner, about
one half of women will become infected with N
gonorrhoeae, and most become infected after mul-
tiple exposures.49  Symptoms include purulent cer-
vical discharge, dysuria, lower abdominal discom-
fort, menstrual irregularities, and uterine bleeding
that varies from minimal to severe.  Although 60%
to 70% of women will have these nonspecific symp-
toms, only 10% to 20% of infected women will have
an obvious purulent cervical discharge or a puru-
lent vaginal discharge that clearly originates from
the cervix.  Women may remain asymptomatic and
infectious for many months before a spontaneous
cure occurs.50  Female prostitutes constitute an im-
portant reservoir of the disease.  The reported preva-
lence of gonorrhea in this group varies from one
study to another—from 5.2% to 11.2%—with the
higher rates seen in developing countries.51  In a
1991 study of 757 female prostitutes in Madrid,
Spain, 89 were infected with N gonorrhoeae.  Of
these, 48 (54%) were asymptomatic.51
OK to put on the Web
OK to put on the Web
Fig. 19-10. (a) This thick, purulent, urethral discharge is typical of primary gonorrhea. (b) In nongonococcal urethritis,
in contrast, the discharge is clear and mucoid. Photograph: Courtesy of C. Kalter, MD, Bethesda, Md.
a
b

Military Dermatology
510
Rectal Infection
The rectal mucosa may be the primary site of
infection in 40% of homosexual men and in 5% of
women.  Of women with gonococcal infections of
the cervix, one third to one half will also have
infection of the rectum, which is mainly due to
contamination of the anus by infected cervical se-
cretions but may also result from anal intercourse.42
In most women, rectal infection is asymptomatic.
However, as a result of receptive anal intercourse, a
syndrome of acute proctitis occurs in homosexual
men with pain, tenesmus, purulent rectal discharge,
and constipation.  Physical examination reveals
perianal erythema and discharge.  Anoscopy shows
inflammatory mucosal changes consisting of a pu-
rulent exudate, erythema, friability, and bleeding.45
Pharyngeal Infection
Infection of the pharynx most commonly occurs
as a result of orogenital intercourse, although occa-
sional cases develop as a result of autoinoculation
from infections at other sites.  More than 90% of
pharyngeal infections are asymptomatic.  In the
remaining 10%, however, an acute pharyngitis or
tonsillitis develops associated with cervical
lymphadenopathy and fever.  The significance of
pharyngeal infection is uncertain and epidemio-
logical studies have shown that without treatment,
spontaneous cure occurs in 100% of affected indi-
viduals within 3 months.45  The prevalence of pha-
ryngeal infection is highest among homosexual
men.42  Transmission of pharyngeal infection to
sexual partners appears to be rare.
Complicated Infections
Local complications of gonococcal disease in-
clude acute salpingitis (ie, pelvic inflammatory dis-
ease) and Bartholin’s gland abscess in women and
epididymitis, penile lymphangitis, prostatitis, semi-
nal vesiculitis and urethral strictures in men.42
Of women with gonococcal infection of the cer-
vix, approximately 15% will develop acute pelvic
inflammatory disease with pelvic and abdominal
pain, cervical discharge, dyspareunia, abnormal
bleeding, and constitutional signs and symptoms
including fever, leukocytosis, and elevated sedi-
mentation rate.49  In the United States, about one
half the cases of pelvic inflammatory disease are
caused by N gonorrhoeae, with chlamydia and other
non-STD organisms responsible for the remaining
cases.  Long-term complications of pelvic inflam-
matory disease include sterility and the risk of ec-
topic tubal pregnancy.
Bartholin’s gland abscess is also common, and
patients present with enlargement of the gland and
tenderness.  Gonococci may be isolated from the
Bartholin’s glands in a significant number of women
who have no symptoms of bartholinitis.45
In men, infection of the urethra may uncom-
monly progress to involve the epididymis, prostate,
testicle, preputial glands (Tyson’s glands),
bulbourethral glands (Cowper’s glands), the me-
dian raphe of the penis, and the glans penis.10
Epididymitis is uncommon, probably because (a)
gonococci have difficulty traversing a long urethra
and vas deferens and (b) men often seek early treat-
ment for symptomatic urethritis.50  Infection is usu-
ally unilateral, with patients complaining of a pain-
ful and swollen testicle.  Physical examination
reveals scrotal erythema and an enlarged and ten-
der epididymis; the testicle is usually normal.  A
secondary hydrocele is frequently found.
Gonococcal prostatitis and seminal vesiculitis
are rare complications.  Signs and symptoms in-
clude urinary urgency, vague pelvic discomfort,
hematuria, fever, and painful erections.  Infection
of the median raphe of the penis is also rare; pa-
tients present with a small papule from which pus
may be expressed (Figure 19-11).10  As a result of
early and effective treatment, urethral strictures are
now an uncommon complication in the United
States.  However, in parts of the world with inad-
equate medical facilities, urethral strictures and
fistula formation are frequent.42
Disseminated Gonococcal Infection
Disseminated gonococcal infection occurs with
6-fold greater frequency in women than men.  There
is a definite relationship to menstruation: the dis-
ease occurs within 1 week of the onset of menses in
more than half the cases.  Disseminated gonococcal
infection is also more common in women during the
third trimester of pregnancy and in homosexual
men.  This complication occurs in 1 in 300 to 1 in 600
patients with genital gonorrhea.47
Patients present with the dermatitis-arthritis syn-
drome, which consists of fever, chills, acute arthri-
tis, tenosynovitis, and tender, erythematous pus-
tules located on the distal extremities.  Any joint
may be involved but most frequently the wrist,
metacarpophalangeal, ankle, or knee joints are af-
fected.  Frank pyogenic arthritis may cause joint
destruction if not recognized and promptly treated.45
The characteristic skin lesions usually number fewer

Sexually Transmitted Diseases
511
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Fig. 19-11. Uncommonly, patients with gonococcal infec-
tion may present with a painful abscess of the median
raphe of the penis. Gram’s stain of the expressed pus
would show typical intracellular gonococci. Photograph:
Courtesy of the Walter Reed Army Medical Center Der-
matology Service slide file, Washington, DC.
than 12 and are concentrated on the extremities,
around the joints.  They are typically tender
vesiculopustules on an erythematous base, which
may become hemorrhagic (Figure 19-12).44
Infections in Infants and Children
Gonococcal infections in infants and children are
the result of sexual abuse, with the exception of
gonococcal conjunctivitis (ophthalmia neonatorum),
which is acquired from an infected birth canal.  This
subject is not discussed in this chapter; readers are
referred to excellent reviews52,53 in the literature.
Laboratory Diagnosis
The present approach to the evaluation of a pa-
tient with suspected gonococcal infection consists
of (a) obtaining Gram-stained smears of exudate, (b)
culture on gonococcal media, and (c) determination
of antibiotic susceptibility (Table 19-3).  Newer
methods, such as monoclonal or polyclonal anti-
OK to put on the Web
Fig. 19-12. This hemorrhagic pustule, when seen in a
sexually active individual in association with acute ar-
thritis and tenosynovitis, should elicit a high degree of
suspicion of disseminated gonorrhea. The patients, usu-
ally women, may have mild preceding symptoms and are
usually unaware that they have gonorrhea prior to the
onset of their illness.
body tests to detect gonococcal antigens in cultures
or exudate, gonococcal complement fixation tests,
and gonococcal deoxyribonucleic acid (DNA) hy-
bridization probes, are available to diagnose the
infection rapidly.  Whenever possible, culture and
sensitivity testing should be obtained.
Gram’s Stain
Staining the genital secretions with Gram’s stain
is the most widely accepted procedure for the im-
mediate diagnosis of gonococcal infection.  In men
with urethral symptoms, the test is both highly
specific and highly sensitive; approximately 90% to
98% of culture-positive men with a purulent dis-
charge have a positive smear.  On urethral smears
from men, the Gram’s stain is considered positive
when Gram-negative diplococci of typical morphol-
ogy are found within or closely associated with
neutrophils.  It is equivocal if only extracellular or-
ganisms or atypical, intracellular, Gram-negative
diplococci are seen.  Nonpathogenic Neisseria organ-
isms are usually not cell-associated (Figure 19-13).9
In women, Gram-stained smears from the
endocervix are relatively insensitive (30% to 60%)50
and interpretation is difficult and time-consuming.
However, the test may permit rapid diagnosis and
treatment in the presence of pelvic inflammatory
disease, acute endocervicitis with a purulent dis-
charge, or a history of exposure to gonorrhea.50  It is
important to avoid mistaking morphologically simi-
lar saprophytes of the normal flora for N gonorrhoeae,

Military Dermatology
512
TABLE 19-3
SENSITIVITY OF GRAM’S STAIN AND CULTURE IN DIAGNOSING GONORRHEA
*These specimens are often contaminated with local flora
Reprinted with permission from Judson FN. Gonorrhea. Med Clin N Am. 1990;74(6):1358.
OK to put on the Web
and only those smears that contain several
polymorphonucleocytes with multiple, intracellu-
lar, Gram-negative diplococci with typical mor-
phology should be considered positive.9
Gram-stained smears of pharyngeal and rectal
exudate are not helpful and the diagnosis rests
principally with a culture.
Culture
In men, culture of exudates adds little (2%) to the
yield and considerable cost but is often employed
when the Gram-stained specimen is negative for N
gonorrhoeae.  However, the CDC currently recom-
mends that all cases of gonorrhea be diagnosed or
confirmed or both by culture.25  The susceptibility of
N gonorrhoeae to antibiotics changes over time in a
locality, and routine culture facilitates antimicro-
bial susceptibility testing.
In women, cultures obtained from multiple sites
provide better yields and a greater chance for isolat-
ing the organism than does a single endocervical
culture.  Ideally, specimens for culture should be
obtained from the endocervix, urethra, rectum, and
pharynx.42
Blood cultures are often positive both early in the
course of disseminated disease and when taken
from synovial fluid of patients with acute purulent
gonococcal arthritis.  In disseminated gonococcal
infection, culture of skin lesions is usually negative,
although Gram’s staining and fluorescent-antibody
testing of smears from pustules often demonstrates
organisms.  Culture requires viable organisms, where-
as stains and fluorescent antibody testing do not.44,54
Immediately after the specimen is collected, it
should be plated on an enriched, selective medium
Fig. 19-13. Gram-negative intracellular diplococci are the
hallmark of gonococcal infection. Photograph: Courtesy
of M. Mulvaney, MD, Albany, NY.
Table 19-3 is not shown because the copyright permission granted to the Borden Institute, TMM, does not
allow the Borden Institute to grant permission to other users and/or does not include usage in electronic
media. The current user must apply to the publisher named in the figure legend  for permission to use this
illustration in any type of publication media.

Sexually Transmitted Diseases
513
and incubated in an atmosphere containing 5% car-
bon dioxide (eg, a candle-extinction jar) at 37°C.55
Treatment
Treatment guidelines for the management of
gonococcal infections have changed dramatically
during the last decade.  Several factors, including
resistance to penicillin, coinfection with gonococci
and chlamydia, and the anatomical site of infection,
are responsible for the shift in therapeutic ap-
proaches.
Resistance to penicillin was first noted in the
1950s, with increasing doses required to cure infec-
tion.56  Penicillinase-producing N gonorrhoeae
(PPNG) were first reported from Southeast Asia
and West Africa during the mid-1970s.  Infected
military personnel returning from Southeast Asia
introduced PPNG to the United States.49  Resistance
is conferred by plasmid-mediated transfer of the
genes responsible for production of β-lactamase.57
During the next several years, only isolated out-
breaks associated with prostitution in urban areas
were reported.58  Since 1980, however, the incidence
of PPNG has risen significantly, and infection with
PPNG is now firmly established in the United
States.58  Additionally, plasmid-mediated, high-level
resistance to tetracycline was first reported in the
mid-1980s, resulting in outbreaks of tetracycline-
resistant strains of N gonorrhoeae (TRNG).59
There is a high incidence of coinfection with
gonococci and chlamydia.  Experimental data have
demonstrated that simultaneous infection with N
gonorrhoeae and chlamydia results in a 100-fold in-
crease in the replication of chlamydia in cervical
epithelium, and current recommendations encour-
age the use of single or multiple agents that are
effective against both organisms.60
The anatomical site of infection has a significant
bearing on the choice and efficacy of antibiotics.
When caused by susceptible strains of N gonorrhoeae,
uncomplicated gonococcal infections of the urethra
and cervix will respond to single-dose therapy.  On
the other hand, not all cases of gonococcal
pharyngitis or proctitis in a homosexual man will
respond to single-agent therapy regimens.  Patients
whose symptoms persist after treatment should be
recultured for N gonorrhoeae, and the gonococci
should be tested for antibiotic susceptibility.
Invasive gonococcal disease (eg, pelvic inflamma-
tory disease, disseminated gonococcal infection)
usually requires multiple-dose parenteral therapy.61
Other factors to consider in the selection of ap-
propriate antibiotic regimens for gonococcal dis-
ease include safety of the drug, incidence of adverse
reactions, patient compliance, ease of administra-
tion, and cost (Exhibit 19-4).
Uncomplicated Gonococcal Infections
In 1993, the CDC recommended the following
regimen for treating uncomplicated gonococcal in-
fections25:
• ceftriaxone 125 mg, administered intramus-
cularly in a single dose, or
• cefixime 400 mg, administered orally in a
single dose, or
• ciprofloxacin 500 mg, administered orally in
a single dose, or
• oflaxicin 400 mg, administered orally in a
single dose;
EXHIBIT 19-4
ANTIBIOTIC SELECTION CRITERIA
FOR GONORRHEA
Adapted with permission from Moran JS, Zeligman JM.
Therapy for gonococcal infections: Options in 1989. Rev
Infect Dis. 1990;12(Suppl 6):S633.
Exhibit 19-4is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does not
include usage in electronic media. The current
user must apply to the publisher named in the
figure legend  for permission to use this illustra-
tion in any type of publication media.

Military Dermatology
514
Patients whose symptoms persist after treatment
should be evaluated by culture for N gonorrhoeae,
and any gonococci isolated should be tested for
antimicrobial susceptibility.  Persistent urethritis,
cervicitis, or proctitis also can be caused by Chlamy-
dia trachomatis and other organisms.
Management of Sexual Partners.  Patients should
be instructed to refer their sexual partners for evalu-
ation and treatment.  Sexual partners of symptomatic
patients who have gonorrhea should be evaluated
and treated for both Neisseria gonorrhoeae and
Chlamydia trachomatis infections if their last sexual
contact with the patient was within 30 days of onset
of the patient’s symptoms.  If the index patient is
asymptomatic, sexual partners whose last sexual
contact with the patient was within 60 days of
diagnosis should be evaluated and treated.
Disseminated Gonococcal Infection
The 1993 CDC recommendations also specify the
following treatment for patients with disseminated
gonococcal infection25:
• Recommended initial regimen:
° ceftriaxone 1 g, administered intramuscu-
larly or intravenously every 24 hours.
• Alternative initial regimens:
° cefotaxime 1 g, administered intravenously
every 8 hours, or
° ceftizoxime 1 g, administered intrave-
nously every 8 hours, or,
° for persons allergic to β-lactam drugs,
spectinomycin 2 g, administered intramus-
cularly every 12 hours.
All regimens should be continued for 24 to 48 hours
after improvement begins; then therapy can be
switched to one of the following regimens to com-
plete one full week of antimicrobial therapy25:
• cefixime 400 mg, administered orally twice
daily, or
• ciprofloxacin 500 mg, administered orally
twice daily.
Ciprofloxacin is contraindicated for children, ado-
lescents younger than 17 years of age, and pregnant
and lactating women.
Hospitalization is recommended for initial
therapy, especially for patients who cannot be re-
lied on to comply with treatment, for those whose
• plus a regimen that is effective against pos-
sible coinfection with Chlamydia trachomatis,
such as doxycycline 100 mg, administered
orally twice daily for 7 days.
In clinical trials, these recommended regimens
cured more than 95% of anal and genital infections;
any of the regimens may be used for uncomplicated
anal and genital infection.  Published studies indi-
cate that ceftriaxone 125 mg and ciprofloxacin 500
mg can cure more than 90% of pharyngeal infec-
tions.  If pharyngeal infection is a concern, one of
these two regimens should be used.25
No ceftriaxone-resistant strains of Neisseria
gonorrhoeae have been reported.  The drawbacks of
ceftriaxone are (1) it is expensive, (2) it is currently
unavailable in vials smaller than 250 mg, and (3) it
must be administered by injection.  Some healthcare
providers believe that the discomfort of the injec-
tion may be reduced by using 1% lidocaine as a
diluent.  Ceftriaxone also may abort incubating
syphilis, a concern when gonorrhea treatment is not
accompanied by a 7-day course of doxycycline or
erythromycin for the presumptive treatment of
chlamydia.25
Cefixime has an antimicrobial spectrum similar
to that of ceftriaxone.  Cefixime appears to be effec-
tive against pharyngeal gonococcal infection, but
few patients with pharyngeal infection have been
included in studies.  No gonococcal strains resistant
to cefixime have been reported.  The advantage of
cefixime is that it can be administered orally.
Whether the 400-mg dose can cure incubating syphi-
lis is not yet known.25
Ciprofloxacin, at a dose of 500 mg, provides
sustained bactericidal levels in the blood.  Cipro-
floxacin can be administered orally and is less
expensive than ceftriaxone.  No resistance has
been reported in the United States, but strains
with decreased susceptibility to some quinolones
are becoming common in Asia.  Quinolones are
contraindicated for pregnant or nursing women
and for persons younger than 17 years of age, on the
basis of information from studies with animals.
Quinolones are not active against Treponema
pallidum.25
Many other antimicrobials are active against
Neisseria gonorrhoeae.  These guidelines are not in-
tended to be a comprehensive list of all effective
treatment regimens.
Follow-Up.  Patients with uncomplicated gonor-
rhea who are treated with any of the regimens in
these guidelines need not return for a test of cure.

Sexually Transmitted Diseases
515
diagnosis is uncertain, and for those who have
purulent synovial effusions or other complications.
Patients should be examined for clinical evidence of
endocarditis and meningitis.  Patients treated for
disseminated gonococcal infection should be treated
presumptively for concurrent Chlamydia trachomatis
infection.25
Pregnant Women
Pregnant women should not be treated with
quinolones or tetracyclines.  They should be treated
with a recommended or alternative cephalosporin,
following the regimen for disseminated gonococcal
infection, above.25
Chancroid is an STD caused by the Gram-nega-
tive coccobacillus Haemophilus ducreyi.  Worldwide,
chancroid is a more important cause of genital ul-
cers than syphilis, and there is a clear association
between chancroid, poverty, and poor hygiene.  This
association is reflected in the incidence of the dis-
ease, which is highest in underdeveloped tropical
and subtropical countries.
Chancroid was well known during the Civil War,
as Surgeon J. G. Bradt of the 26th Massachusetts
Volunteers, New Orleans, Louisiana, reported on 1
January 1863:
Of the various forms of venereal disease, chancre of
the non-indurated variety is the most common.  It
is accompanied in a majority of cases with bubo.
The sores yield readily to cauterization with acid
nitrate of mercury and applications of black wash,
the bowels meanwhile being regulated and the
patient kept on a low diet.40(p892)
There is ample epidemiological evidence that the
incidence of chancroid increases dramatically dur-
ing wartime.10  Among U.S. troops in the Korean
conflict, chancroid was 14- to 21-fold more common
than gonorrhea.62  A study conducted in 1969 found
that among troops in Vietnam, chancroid was sec-
ond only to gonorrhea in the total reported cases of
venereal disease (Figure 19-14).63
Chancroid is more common in uncircumcised
men, and the disease is more often reported in men,
as well.  However, women may have inapparent or
mildly symptomatic infections for which they do
not seek medical care.  In addition, female prosti-
tutes constitute an important reservoir of infec-
tion.64  Of prostitutes who were implicated as sources
of chancroid infection, only 10% had genital ulcers,
and 4% were either transient or persistent
asymptomatic genital carriers.10
Recent epidemiological studies have noted an
association between the presence of genital ulcer
disease and a significant risk of acquiring HIV in-
fection.  In both men and women who are exposed
to partners who are infected with HIV-1, those who
develop genital ulcer disease are at increased risk of
HIV-1 seroconversion.18  In developing countries,
from 10% to 30% of patients presenting with STDs
may have genital ulcer disease, of which chancroid
is the most commonly reported.65  In a study of
female prostitutes in Nairobi with genital ulcer
disease, HIV-1 could be isolated from the ulcer
exudate in 11% of these patients.66  In another study
of 19 men presenting with confirmed chancroid,
HIV-1 could be isolated by viral culture from the
ulcers of two of seven HIV-1–positive patients.67
Polymerase chain reaction confirmed the presence
of the virus in genital exudate in six of the same
seven men.  The fact that it was possible to culture
virus from these chancroidal ulcers suggests that a
concentration of virus sufficient to result in trans-
mission from such lesions is possible.67  Not surpris-
ingly, uncircumcised men are at greater risk of
acquiring both chancroid and HIV-1 infection.68
CHANCROID
Fig. 19-14. A painful, ragged, necrotic, undermined ulcer
of chancroid in the coronal sulcus of the penis. The
yellowish pseudomembrane is characteristic of chancroid,
but can be confused with herpes simplex or other second-
arily infected penile ulcerations.
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Military Dermatology
516
Clinical Manifestations
Following an incubation period that varies from
2 to 35 days (average 7 d), a small papule develops
at the site of initial infection.69  This rapidly becomes
pustular and then ulcerates as a result of thrombotic
occlusion of the underlying dermal vessels.  The
ulcer enlarges, rapidly forming a crater with ragged,
undermined borders surrounded by a thin rim of
erythema.  The ulcer floor is covered by a grayish
membrane; removal of this membrane reveals a
glistening base of granulation tissue.  Unlike the
chancre of primary syphilis, the chancroidal ulcer is
painful and the border is not indurated.  Auto-
inoculation of surrounding areas results in multiple
ulcers in various stages of evolution, which is a
more common finding than a solitary lesion (Figure
19-15).  Ulcers may range from a few millimeters to
more than 2 cm in diameter.  There are no constitu-
tional symptoms.10
In men, the foreskin is the region most commonly
affected, with lesions found less frequently on the
glans or penile shaft.  In women, the labia majora,
introitus, vagina, and perianal areas are involved.
Homosexual men may present with chancroidal
lesions in the perianal area, as well.  Extragenital
lesions are rare, and disseminated infection with H
ducreyi has not been reported.10
In about 50% of cases, unilateral, occasionally
bilateral, tender, inguinal lymphadenitis (ie, a bubo)
develops and is characteristic of chancroid.  The
overlying skin may vary from erythematous to a
dusky violaceous color.  If untreated, buboes
Fig. 19-15. Multiple, small, vulvar erosions of chancroid
can easily be confused with lesions of genital herpes
infection. Smears and culture are required to distinguish
the two. Compare with the lesions shown in in Fig. 19-26.
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progress to form soft, fluctuant abscesses that often
rupture spontaneously, leaving large, nonhealing,
serpiginous ulcers.70  Aspiration of fluctuant buboes
before they rupture will promptly relieve discom-
fort and prevent this complication (Figure 19-16).
There is no permanent immunity following
chancroid infection.
There are several clinical variants of the
chancroidal ulcer:
• Patients with transient chancroid present
with a small, evanescent ulcer that remains
for less than 1 week.  Rapid healing is fol-
lowed by painful inguinal lymphadenitis
that must be differentiated from lympho-
granuloma venereum.
• Patients with follicular chancroid present
with small, follicular ulcerations in the
perineum, which resemble bacterial follic-
ulitis.71
• Patients with phagedenic chancroid present
with large, rapidly spreading, necrotic ul-
cerations, which may result in extensive de-
struction or formation of a urethral fistula.
Superinfection with anaerobic bacteria such
as Treponema vincentii, Fusobacterium nucle-
atum, and Leptotrichia buccalis are respon-
sible for the massive ulceration.10
• Other uncommonly reported clinical vari-
ants include dwarf chancroid, papular
chancroid, and giant chancroid.71
Laboratory Diagnosis
Gram’s Stain
A Gram-stained smear of a specimen taken from
a penile ulcer or bubo aspirate may allow a prelimi-
nary diagnosis of chancroid in approximately half
the patients.  To properly obtain a specimen, the
ulcer should first be cleaned with physiological
saline and then dried.  The specimen is obtained
with a cotton-tipped applicator from the under-
mined edge of the ulcer, and then carefully rolled
across a glass microscope slide in one direction only
(this is important, as it will preserve the morphologic
appearance of the organism).  The Gram-negative
coccobacilli are found in small clusters or parallel
chains of organisms described as “school-of-fish”
or “railroad-track” patterns (Figure 19-17).  Routine
light microscopy lacks both sensitivity and specific-
ity because Gram-negative coccobacilli that are
morphologically similar to Haemophilus ducreyi are
present.  As a result, Gram-stained smears from

Sexually Transmitted Diseases
517
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Fig. 19-16. (a) This patient has inguinal lymphadenitis (buboes,
arrow) with lesions of chancroid on the penile shaft. (b) To
provide symptomatic relief, the bubo should be aspirated (not
surgically incised and drained) from the superior aspect of the
infected node. The thick, brown pus is characteristic but not
diagnostic of chancroid. Surgical incision and drainage are
inappropriate: the incision leaves a chronic ulceration that
heals poorly (see Fig. 19-24), and aspiration from the inferior
pole of the bubo frequently leads to a draining sinus tract.
Photograph (a): Courtesy of M. Mulvaney, MD, Albany, N.Y.
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Fig. 19-17. (a) This biopsy specimen from a vulvar lesion shows Gram-negative rods, some in chains (Brown and Hopf
stain, original magnification 290X). (b) The same biopsy specimen is stained with Warthin-Starry silver stain to
demonstrate numerous organisms (Warthin-Starry stain, original magnification 290X). Photographs: Courtesy of R. C.
Neafie, Armed Forces Institute of Pathology, Washington, DC.
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a
b
a
b
genital ulcers or bubo aspirates are often inconclu-
sive.  When available, culture confirmation is pref-
erable to Gram-stained smears.72
Culture and Serology
Epidemiological studies and laboratory isolation
of H ducreyi from suspected cases of chancroid have
been hampered by (a) the lack of reliable, inexpen-
sive culture media and (b) the absence of a typing
system to assist in contact tracing.  Additionally, H
ducreyi is nearly biochemically inert (ie, nonreact-
ive) on a variety of standard in vitro bacteriological
tests, a characteristic that has hindered the develop-
ment of serologic tests.  Recent improvements in
culture media have replaced the liquid- or clotted-
blood–based media of the past.  Currently, gono-
coccal agar base and Mueller-Hinton agar base are

Military Dermatology
518
two selective media that are used to culture H ducreyi.
Unfortunately, these media, which consist of gono-
coccal chocolate agar, supplemented with blood or
serum and vitamins, amino acids, and antibiotics
(vancomycin), are expensive and difficult to pro-
duce commercially.  Consequently, their availabil-
ity in developing countries, where most chancroid
is reported, is limited.73
Material from the base of the ulcer should
promptly be inoculated on suitable media and incu-
bated at a reduced temperature (33°C–35°C) in a
moist, carbon dioxide–rich (5%–10%) chamber.
Small, yellow-gray, semiopaque or translucent colo-
nies develop in 2 to 4 days, but may require up to 7
days after inoculation for growth.  The colonies
have a characteristic adherence and can be moved
as an entire colony across the culture plate with an
inoculating loop.10  Confirmatory identification uti-
lizes the porphyrin test, which demonstrates a re-
quirement for hemin (the X factor) for growth, and
the oxidase test demonstrates the absence of a re-
quirement for nicotinamide adenine dinucleotide
(NAD, the V factor).70
Serologic tests and specific monoclonal antibod-
ies based on mouse and rabbit systems are still
experimental and are currently unavailable.  Sev-
eral promising antisera without cross-reactivity with
other Haemophilus species may be available in the
future.  Monoclonal antibodies specific for H ducreyi
have been produced74 and used to detect the antigen
in lesional material from experimental animals
and from material in patients with chancroid.  Sero-
logic tests such as complement fixation, precipitin,
and agglutination tests may be positive in some
patients with H ducreyi infections.  A recently
described enzyme-linked immunosorbent assay
(ELISA) using whole, lysed H ducreyi as the source
of antigen is promising.70,75  The nature and dura-
tion of the antibody response to H ducreyi is un-
known.
Treatment
As with other STDs caused by bacteria, strains
are emerging worldwide that are resistant to mul-
tiple antibiotics.  The 1993 CDC recommendations
for treatment of chancroid in the United States are
listed below.  Susceptibility of H ducreyi to the
recommended and alternative antimicrobials var-
ies throughout the world.  Clinical efficacy, re-
lapses, and treatment failures should be carefully
monitored—with laboratory determination of anti-
biotic susceptibility patterns, if available.
Recommended Regimens
The following are the CDC’s 1993 recommended
regimens for the treatment of chancroid25:
• azithromycin 1 g, administered orally in a
single dose, or
• ceftriaxone 250 mg, administered intramus-
cularly in a single dose, or
• erythromycin base 500 mg, administered
orally four times daily for 7 days.
All three recommended regimens are effective for
the treatment of chancroid in patients without HIV
infection.  Azithromycin and ceftriaxone offer the
advantage of single-dose therapy.  Antimicrobial
resistance to ceftriaxone and azithromycin has not
been reported.  Although two isolates resistant to
erythromycin were reported from Asia during the
1980s, similar isolates have not been reported.
Alternative Regimens
The following are the CDC’s alternative regi-
mens for the treatment of chancroid25:
• amoxicillin 500 mg and clavulanic acid 125
mg, administered orally three times daily
for 7 days, or
• ciprofloxacin 500 mg, administered twice
daily for 3 days.
Ciprofloxacin is contraindicated for pregnant and
lactating women, children, and adolescents younger
than 17 years of age.
These alternative regimens have not been evalu-
ated as extensively as the recommended regimens.
Neither regimen has been studied in the United
States.
Follow-Up
Patients should be reexamined 3 to 7 days after
initiation of therapy.  If treatment is successful,
ulcers improve symptomatically within 3 days and
improve objectively within 7 days after therapy is
initiated.  If no clinical improvement is evident,
the medical officer must consider whether (a)
the diagnosis is correct, (b) coinfection with
another STD agent exists, (c) the patient is also
infected with HIV, (d) the treatment was not taken
as instructed, or (e) the strain of H ducreyi causing
the infection is resistant to the prescribed antimi-

Sexually Transmitted Diseases
519
crobial drug.  The time required for complete heal-
ing is related to the size of the ulcer; large ulcers
may require more than 2 weeks.  Clinical resolution
of fluctuant lymphadenopathy is slower than that
of ulcers and may require needle aspiration through
adjacent intact skin—even during successful
therapy.
Management of Sexual Partners
Persons who have had sexual contact with a
patient who has chancroid within the 10 days before
the onset of the patient’s symptoms should be exam-
ined and treated.  The examination and treatment
should be done even in the absence of symptoms.
GRANULOMA INGUINALE
known although it has been estimated to range from
weeks to months.  The primary lesion is an intensely
pruritic papule that occurs in the anogenital area in
more than 90% of cases.  Less commonly, the initial
lesion may be a firm, subcutaneous nodule that
later suppurates, rupturing through the skin to
produce an ulcer.  In women, the primary lesion is
frequently overlooked by the patient.10  The ulcers
are clean, sharply defined, granulomatous, usually
painless lesions (Figure 19-18).  Secondary infection
may, however, result in painful lesions or large,
mutilating, necrotic ulcerations.80  Autoinoculation
may cause multiple primary lesions.  These often
coalesce into a large, irregular ulcer that enlarges
slowly and bleeds easily on contact; the base is
covered by abundant, beefy-red, granulation tis-
sue.81  Over time, the edge of the ulcer becomes
elevated, thickened, and grayish in color.  There are
no constitutional symptoms in the absence of sec-
ondary infection.
Granuloma inguinale (also called Donovanosis)
is a sexually transmitted disease caused by the
Gram-negative encapsulated bacillus Calymmato-
bacterium granulomatis.  In 1905, C. Donovan de-
scribed intracellular organisms with peculiar clump-
ing of chromatin at either end that produce a
“closed–safety pin” morphology on Giemsa stain.76
The disease is rare in the United States, although
sporadic cases are reported from southern states.  In
certain parts of the world, especially New Guinea,
central Australia, India, the Caribbean countries,
and Africa, the disease is endemic and may be
among the most prevalent STDs.  The disease is
reported more often among groups with lower so-
cioeconomic status, and poor hygiene may play a
role in transmission and susceptibility to infection.77
Significant controversy exists regarding the mode
of transmission of the organism.  The primary mode
appears to be through sexual contact.  The disease is
considered to be only mildly contagious and re-
peated exposure is necessary for clinical infection to
occur.  However, the disease is only rarely reported
in prostitutes and is uncommon in sexual partners
of clinically infected individuals.78  The frequent
occurrence of perianal and penile lesions in homo-
sexual men who practice anal intercourse has focused
attention on colonization of the intestinal tract by
organisms resembling C granulomatis.  Auto-inocula-
tion of fecal material onto traumatized or diseased
skin may result in clinical infection.  It is possible
that transmission occurs by both sexual and non-
sexual modes: perineal contamination with fecal
organisms may precede transfer by sexual inter-
course.10,79  The disease has been reproduced only
by introducing infected material from the granu-
loma inguinale lesion into an uninfected human.
Transfers of organisms grown on tissue or bacterial
cultures have not produced clinical disease.80
Clinical Manifestations
The incubation period following exposure is un-
Fig. 19-18. This ulcer of granuloma inguinale is covered
by exuberant, beefy-red, granulation tissue The disease
is asymptomatic and rare, and patients may have mul-
tiple lesions as a result of autoinoculation. The diagnosis is
difficult to make clinically; a biopsy is usually necessary.
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Military Dermatology
520
Bacterial spread through subcutaneous tissues in
the inguinal region may lead to large subcutaneous
granulomas known as pseudobuboes, which can
mimic lymphogranuloma venereum or metastatic
squamous cell carcinoma.  These granulomas
can rupture, leading to typical granulomatous ul-
cers of the overlying skin.  True inguinal lymphad-
enopathy in granuloma inguinale is rare, except
when extensive secondary infection77 or coexistent
involvement of the lymph nodes with syphilis,
lympho-granuloma venereum, or malignancy are
present.10
In addition to the classic large, exuberant, beefy-
red ulcer with rolled borders (ie, the ulcerovegetative
type), other clinical variants occur, albeit less fre-
quently (Figure 19-19):
• In 1975, a case of extensive necrosis of the
penis and perineum with production of a
large, mutilating lesion and destruction of
most of the penile tissue was reported.80
This patient had no systemic involvement.
• Patients with a rare hypertrophic form
present with two types of ulcers: (1) the
large, vegetative masses and (2) the cicatri-
cial type, which produces extensive, spread-
ing scar formation as the primary disease
process, rather than healing.82
Lesions often continue to expand for years
and spontaneous healing is slow to occur.  Heal-
ing generally occurs with extensive fibrosis and
significant deformity, and functional disability can
occur.
Complications
Complications of extensive or untreated granu-
loma inguinale include
• scarring and strictures of the anus, urethra,
and vagina, with deformity of the external
genitalia;
• elephantiasis of the penis, scrotum, or vulva
secondary to destruction of the lymphatics;
and
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Fig. 19-19. Granuloma ingunale often causes large, ulcerative lesions. (a) This patient has a destructive lesion of the
penile shaft and a large, exophytic lesion of the lower abdomen. (b) Undiagnosed, untreated granuloma inguinale may
lead to massive scrotal and inguinal lymphedema.  Photographs: Courtesy of Walter Reed Army Medical Center
Dermatology Service slide file, Washington, DC.
a
b

Sexually Transmitted Diseases
521
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Fig. 19-20. (a) This Wright-Giemsa stain of a crush preparation of tissue shows intracellular bacilli (Donovan bodies)
(arrow). (b) The organisms (arrow) appear black in the Warthin-Starry stain.  Photographs: Courtesy of Walter Reed
Army Medical Center Dermatology Service slide file, Washington, DC.
b
a
• systemic spread of the disease to visceral
organs, resulting in death.83
Malignancy, either basal cell or squamous cell car-
cinoma, has been reported to arise in long-standing
lesions of granuloma inguinale.  Extragenital le-
sions have been reported in a small number of
patients, with occasional involvement of the intes-
tinal tract, bone, orbit, liver, spleen, and oral
mucosa.82
Laboratory Diagnosis
The diagnosis of granuloma inguinale is based
primarily on stained smears of crushed tissue ob-
tained from the ulcer.  The bacterium is an intracel-
lular parasite of macrophages; therefore, swabs or
superficial scrapings from the lesion are apt to be
nondiagnostic.  The lesion is first cleaned with nor-
mal saline on a cotton gauze pad and then wiped
dry.  Under local anesthesia, a punch biopsy,
curettage, or thin wedge of the ulcer base or margin
is obtained.  The tissue is placed between two glass
slides and crushed; the slides are separated and
then air-dried.  Wright-Giemsa stain is used to
demonstrate clusters of blue-to-black organisms that
resemble safety pins within the vacuoles of en-
larged macrophages.77,84  Additionally, the Warthin-
Starry stain has been used to demonstrate the
intracytoplasmic organisms (Figure 19-20).80
Donovan bodies may be difficult to find in for-
malin-fixed, hematoxylin-eosin–stained sections.
However, thin, plastic-embedded sections permit
easy identification of the rod-shaped encapsulated
organisms within macrophages.80
Culture of the organism is beyond the capabili-
ties of most laboratories,81 as the organism fails to
grow on conventional solid media.  Only 14 isolates
have been reported—the latest in 1962.  Isolation is
hampered by the need to eliminate the contami-
nants frequently present in genital ulcers.85
Complement-fixation serologic tests and skin
testing are not routinely available because the  dis-
ease is rare and a suitable source of antigen is
lacking.
Treatment
Numerous antibiotic regimens have been pro-
posed for the treatment of granuloma inguinale.
Tetracycline is the most effective, administered
orally as a dose of 500 mg every 6 hours for 21 days.
Treatment should be continued until all lesions
have completely resolved.77  Other tetracyclines
(eg, doxycycline and minocycline) have also been
used successfully.86
Alternative regimens include erythromycin 500
mg, administered orally every 6 hours for 12 weeks,
or, in cases of treatment failure with tetracycline
and erythromycin, ampicillin 500 mg, administered
orally every 6 hours for the same duration.
Lincomycin, chloramphenicol, and gentamicin are
also effective.77  In 1991, successful treatment was
reported in India with norfloxacin.85
Inguinal pseudobuboes may require surgical ex-
cision if they fail to resolve with antibiotic therapy.80

Military Dermatology
522
TABLE 19-4
SEROTYPES OF CHLAMYDIA TRACHOMATIS AND HUMAN DISEASE
Adapted with permission from from Schachter J. Chlamydial infections. Part 1. N Engl J Med. 1978;298(8):429.
LYMPHOGRANULOMA VENEREUM
The various serotypes of the bacterium Chlamy-
dia trachomatis cause a wide spectrum of serious
diseases (Table 19-4).87  Infections caused by chlamy-
dia, which includes pelvic inflammatory disease
and nongonococcal urethritis, are the most com-
mon STDs; they account for millions of cases per
year and a significant incidence of sterility in women.
This chapter focuses on the serotypes of chlamydia
that cause lymphogranuloma venereum, a condi-
tion characterized by painful inguinal lymphadenitis
or proctocolitis which, if untreated, may result in
scarring and chronic lymphatic obstruction.
Cases of lymphogranuloma venereum are un-
common in the United States and Europe, with only
a few hundred cases reported annually; but the
disease is endemic in Africa, India, parts of South-
east Asia, South America, and the Caribbean re-
gion.88  In the United States, a number of outbreaks
have been reported among sailors, soldiers, and
travelers returning from endemic areas.  In a study
conducted in 1968 of 20 military patients with
lymphogranuloma venereum, 19 were either re-
turning from Vietnam or were sexual partners of a
person returning from Southeast Asia.89  Clusters of
cases in the United States occur in Washington, D. C.,
and the southeastern states, particularly affecting
the poor, urban, black population.90  This parallels
epidemiological data gathered from overseas, where
lymphogranuloma venereum is found to be
more common in urban areas, in particular among
the sexually promiscuous and the lower socioeco-
nomic classes.
Clinical Manifestations
Lymphogranuloma venereum demonstrates
three typical stages, although not every patient will
manifest signs and symptoms of each stage88:
1.
the primary stage, consisting of a small,
inconspicuous, transient papule or ulcer;
2.
the secondary stage, consisting of acute in-
guinal lymphadenitis with bubo formation
(ie, the inguinal syndrome), associated with
fever and other constitutional symptoms;
and
3.
the uncommon third stage (ie, the anogenito-
rectal syndrome), consisting of subacute
to chronic infection leading, in any
combination, to (a) chronic ulceration, (b)
fistulae and strictures of the rectum,
vagina, or urethra, and (c) lymphatic ob-
struction.
Following an incubation estimated to be between
3 and 12 days, a primary lesion develops at the site
of inoculation.  The primary lesion, found in fewer
than one half of patients,91 is most often a herpetiform
ulcer, although a small papule, a shallow ulcer or
erosion, or symptoms of nonspecific urethritis can
also occur.  The primary lesion often goes unnoticed
by the patient, particularly in women.  In men, it is
most commonly found in the coronal sulcus and, in
a minority of patients, elsewhere on the external
genitalia (Figure 19-21).88
After a latent period of 1 to 4 weeks following the
primary lesion, regional lymph node involvement
develops (ie, the inguinal syndrome).  The site of the
primary lesion determines which group of lymph
nodes will be affected, which, in turn, affects the
clinical presentation (Table 19-5).  In men, painful,
regional lymphadenopathy—usually unilateral—
develops, with enlargement of nodes above and
below the inguinal ligament.  This produces the
Table 19-4 is not shown because the copyright permission granted to the Borden Institute, TMM, does not
allow the Borden Institute to grant permission to other users and/or does not include usage in electronic
media. The current user must apply to the publisher named in the figure legend  for permission to use this
illustration in any type of publication media.

Sexually Transmitted Diseases
523
TABLE 19-5
SITE OF PRIMARY INFECTION AND
LYMPHATIC INVOLVEMENT IN
LYMPHOGRANULOMA VENEREUM
Reprinted with permission from Perine PL, Osoba AO. Lym-
phogranuloma venereum. In: Holmes II, Mårdh P-A, Sparling
PF, et al, eds. Sexually Transmitted Diseases. New York, NY:
McGraw-Hill; 1990:197.
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Fig. 19-21. A rarely seen primary lesion of lympho-
granuloma venereum on the penile frenulum. This
small, shallow erosion is easily confused with a trau-
matic injury, genital herpes infection, or syphilis. The
penis was rotated upward and to the right to show the
lesion.
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Fig. 19-22. Massive, bilateral, inguinal lymphadenopathy
of lymphogranuloma venereum with large, fluctuant
nodes. Spontaneous rupture, which is imminent, may
lead to chronic ulcers that heal poorly. Photograph: Cour-
tesy of Walter Reed Army Medical Center Dermatology
Service slide file, Washington, DC.
nal, or low back pain.88
Hematogenous dissemination of the organism
results in clinical signs and symptoms of malaise,
fever, hepatitis, pneumonitis, arthritis, conjunc-
tivitis, and even encephalitis.  Erythema multiforme,
erythema nodosum, photosensitivity, and scarlat-
iniform eruptions may be seen in association with
acute infection.77,86
Long-standing, untreated disease leads to the
development of deep ulcerations, secondary infec-
tion with purulent discharge from the anorectal
area (proctocolitis) or vagina, and, ultimately,
fistulae and scarring.  In the anorectal region, stric-
tures and fibrosis of the bowel wall cause fever,
constipation, diminished caliber of stools, cramp-
ing abdominal pain, and weight loss.  Bowel perfo-
ration and peritonitis leading to death have been
reported.77
Following an outbreak of lymphogranuloma
venereum in a university, a 1976 report92 estimated
that significant penile deformity in chronic
lymphogranuloma venereum occurred in fewer than
5% of infected men.  Elephantiasis of the penis and
scrotum and chronic penile ulcerations were also
reported.  However, serious genitourinary defor-
mity occurs in nearly 25% of all untreated women.
Anal and rectovaginal fistula formation with fibro-
sis are reported complications.  Esthiomene is a de-
forming vulvar elephantiasis characterized by
edema, fibrosis, chronic ulceration, and scarring of
the external female genitalia.92
“groove” sign, which is virtually pathognomonic of
lymphogranuloma venereum.  The nodes enlarge
and become fluctuant, developing a striking bluish
red hue (ie, the characteristic “blue balls”) in the
overlying skin (Figure 19-22).  They subsequently
rupture through the skin to form deep ulcerations
with draining sinus tracts.10  Only 20% to 30% of
women will present with acute inguinal lymph-
adenitis.  Patients complain of deep pelvic, abdomi-
Table 19-5 is not shown because the copyright
permission granted to the Borden Institute,
TMM, does not allow the Borden Institute to
grant permission to other users and/or does
not include usage in electronic media. The
current user must apply to the publisher
named in the figure legend  for permission to
use this illustration in any type of publication
media.

Military Dermatology
524
Laboratory Diagnosis
The diagnosis of lymphogranuloma venereum
rests principally on (a) the exclusion of other STDs
in which patients present with lymphadenopathy
(primarily syphilis, chancroid, and genital herpes
infections) and (b) the lymphogranuloma venereum
complement-fixation test.  Complement-fixation ti-
ters of 1:64 or greater are considered positive for the
disease.  There is cross-reactivity with other chlamy-
dial infections, and high complement-fixation titers
have been found in asymptomatic individuals and
in those with other chlamydial infections.  Titers of
less than 1:64 are equivocal and should be inter-
preted with care.88
Several newer tests have been developed,
but these are not widely available.  The micro-
immunofluorescent test detects type-specific anti-
body (L-1, L-2, or L-3) in the serum of infected
individuals.93  IgG antibody titers greater than
1:1,000 or IgM titers greater than 1:32 on the
microimmunofluorescent test are seen in most pa-
tients with lymphogranuloma venereum.94  A direct
fluorescent antibody technique has been introduced
to detect the presence of antigen in biopsy speci-
mens or, in a recent case, of smears prepared from
lymph node aspirate.95
Culture of the organism on mouse brain, yolk
sac, or tissue culture (ie, McCoy cells) is the defini-
tive diagnostic test but is generally unavailable.77
The Frei test, which involved the intradermal injec-
tion of sterilized bubo aspirate, is no longer
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Fig. 19-23. This histological section through an excised
lymph node shows triangular stellate abscesses of
lymphogranuloma venereum (hematoxylin-eosin stain,
medium-power magnification).
performed and is mentioned only for historical
interest.
Histological sections of involved lymph nodes
show characteristic stellate abscesses surrounded
by a palisading arrangement of epithelioid cells.
No organisms can be seen in histological sections
(Figure 19-23).54
Treatment
The CDC’s 1993 recommended regimen for treat-
ment of lymphogranuloma venereum is doxy-
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b
a
Fig. 19-24. (a) Surgical incision and drainage, as were inap-
propriately done in this patient with lympho-granuloma
venereum, cause chronic, nonhealing, inguinal ulcers. (b)
As seen in a different patient, the proper treatment is
aspiration from the superior aspect of the node, which
reduces pain and the risk of spontaneous rupture, and
allows the lymphadenitis to resolve (also see Fig. 19-16).

Sexually Transmitted Diseases
525
cycline 100 mg, administered orally twice daily
for 21 days.25  The alternative regimens are the
following25:
• erythromycin 500 mg, administered orally
four times daily for 21 days; or
• sulfisoxazole 500 mg, administered orally
four times daily for 21 days; or
• an equivalent course of sulfonamide.
Response to therapy is usually better in acute
cases.  Many cases require two or more 21-day
courses of antibiotic before a clinical response is
observed.  Aspiration of fluctuant inguinal lymph
nodes may speed recovery when rupture of those
nodes is imminent.  Incision and drainage is
contraindicated, as complications such as scarring
and delayed healing may occur (Figure 19-24).96
Follow-Up
Patients with lymphogranuloma venereum
should be followed clinically until signs and symp-
toms have resolved.25
Management of Sexual Partners
Persons who have had sexual contact with a
patient who has lymphogranuloma venereum
within the 30 days before the onset of the patient’s
symptoms should be examined, tested for urethral
or cervical chlamydial infection, and treated.25
Pregnant Women
Pregnant and lactating women should be treated
with the erythromycin regimen.25
GENITAL HERPES INFECTION
Although public awareness of genital herpes in-
fection (caused by herpes simplex viruses [HSVs])
has been eclipsed by the AIDS epidemic, infections
caused by HSVs continue to be an enormous public
health problem (Figure 19-25).  Although genital
herpes infection is not a reportable disease and
therefore exact figures are not available, various
estimates of its incidence in the United States sug-
gest that (a) 5 to 20 million persons are infected,
with 260,000 to 500,000 new cases per year; and (b)
the incidence appears to be increasing.97  This makes
genital herpes infection the most common cause of
genital ulceration in the industrialized nations.98
The increase in this disease may be attributable to
an increase in the number of sexual partners; earlier
sexual activity among adolescents; and the intro-
duction of oral contraceptives and other forms of
contraception, which has led to earlier and more
frequent casual sexual encounters.99  Additionally,
genital ulcer diseases, including genital herpes in-
fection, have been linked to transmission of HIV to
sexual partners.100
Clinical Manifestations
Primary Genital Herpes Infection
Following contact with an infected sexual part-
ner, an incubation period of 3 to 7 days, rarely up to
3 weeks, ensues before clinical signs and symptoms
appear.101  Grouped vesicles on an erythematous,
edematous base quickly develop and may cover
extensive areas of perineal skin.  Pain and itching,
severe in some individuals, are reported by almost
all patients with primary infection.  First-episode
infections are more severe in women.  This may be
due to cervical involvement as well as a greater total
surface area of infection.102  The vesicles rupture
and coalesce into areas of extensive erosions associ-
ated with pain and tenderness.  In women, lesions
are found on the vulva (the most common location),
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Fig. 19-25. Genital herpes infection was the “social dis-
ease” of the 1970s and 1980s. Drawing: Courtesy of B. E.
Benson, Silver Spring, Md.

Military Dermatology
526
labia majora, labia minora, and the perianal skin
(Figure 19-26).  Women with involvement of the
cervix or vagina present with erosions and a pro-
fuse, watery vaginal discharge.  In men, vesicles are
found most frequently on the glans, foreskin, and
penile shaft.  Autoinoculation may lead to extensive
erosions and vesiculation of the penis and the pubic
area.  In homosexual men, primary herpetic lesions
may be seen in the anus or the perianal area.101  Signs
and symptoms of herpes proctitis include rectal
pain and discharge, tenesmus, constipation, fever,
and malaise.  A study published in 1983103 reported
that about one half of patients experience sacral
paresthesias, impotence, urinary retention, and
perianal vesicles; these findings are absent in pa-
tients with proctitis caused by Neisseria gonorrhoeae
or chlamydia.
Tender inguinal lymphadenopathy develops
during the second or third week of primary infec-
tion.  Nodes are enlarged, firm, and nonfluctuant.
HSV has been isolated from inguinal aspirates of
affected nodes.102
Complications of primary infections are most
common in women and include local extension of
the lesions, extragenital involvement secondary to
autoinoculation, and various neurological manifes-
tations.  Up to one third of patients develop com-
plaints consistent with aseptic meningitis: stiff neck,
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c
a
b
Fig. 19-26. A cluster of small herpetic blisters on (a) the
penile shaft and (b) near the coronal sulcus (in a closer
view of the blisters on a different patient).  The patient in
(c) has small blisters and shallow erosions at multiple
sites on the right labial mucosal surface. In both males
and females, clusters of small, painful erosions—which
are actually ruptured vesicles—are often seen instead of
intact vesicles. Compare with the erosions of chancroid
in Fig. 19-16. Photograph (b): Courtesy of Colonel Will-
iam D. James, Medical Corps, US Army, Walter Reed
Army Medical Center, Washington, DC.

Sexually Transmitted Diseases
527
headache, and photophobia.102  Encephalitis is a
rare complication of genital herpes infection and is
more often reported with HSV type 1 (HSV-1), al-
though a fatal case of meningoencephalitis caused
by HSV-2 in an individual infected with HIV was
reported in 1990.  (HSV-1 is more frequently associ-
ated with mucocutaneous infections, and HSV-2
with genital lesions; however, either type can be
isolated from either location.)  Notable findings in
this case were (a) the development of an acyclovir-
resistant strain of virus during therapy and (b)
isolation of the same viral isolate from both a herpetic
perirectal abscess and brain tissue.104
Other reported complications include temporary
sacral anesthesia, urinary incontinence, and impo-
tence.  Cutaneous or visceral dissemination or
thrombocytopenia may also occur.105
In both men and women, lesions persist for 2 to 6
weeks and then resolve, usually without scarring.
Nonprimary Genital Herpes Infection
In 1984, when evaluating patients with clinical
primary genital herpes infection for the presence of
antibody to HSV-2, researchers found that more
than 50% of patients with primary genital herpes
had antibodies to HSV-2 by Western blot analysis.
This unexpected finding suggests that a significant
number of patients have had asymptomatic or
subclinical infections at an earlier time; therefore,
this category of clinical infection is called nonprimary.
The existence of this nonprimary genital herpes
infection is important to remember when counsel-
ing patients or attempting contact tracing to iden-
tify the source of the virus.106
Recurrent Genital Herpes Infection
Within a year after the first episode, about two
thirds of patients will have recurrent episodes of
genital herpes infection.  In one study, approxi-
mately 50% of these patients had monthly recur-
rences, 33% had recurrences every to 2 to 4 months,
and 15% had recurrences fewer than 3 times in the
first year.107  Recurrent lesions are frequently incon-
spicuous, especially those localized to the cervix.  In
men, asymptomatic urethral infections are thought
to occur at an incidence of approximately 1%.101
The clinical manifestations of recurrent disease
are usually less severe and of shorter duration than
primary infections.  The risk of recurrence is influ-
enced by (a) the type of herpes virus and (b) the host
immune response to the viral infection.  There is a
lower rate of recurrence with HSV-1 compared to
HSV-2.  Researchers have hypothesized that the
frequency of sacral ganglionic latency is lower in
HSV-1 infections than in HSV-2, resulting in lower
rates.  Their evaluation of host cellular-immune
factors demonstrated that high titers of neutraliz-
ing antibody after primary infection correlates with
an increased risk of recurrent disease.102
The clinical presentation of recurrent disease dif-
fers considerably from that of primary infection.
Approximately 50% of patients experience pro-
dromal symptoms—tingling, itching, or pain—for
a few hours to 1 to 2 days preceding the attack.  The
lesions tend to be unilateral and fewer in number,
and are grouped vesicles on an erythematous base.
Viral shedding averages only 4 days and healing is
complete in about 10 days.99  There is usually no
lymphadenopathy or systemic symptoms associ-
ated with recurrent disease.
Two theories attempt to explain the reactivation
of HSV from sacral ganglia101:
1.
The ganglionic trigger theory proposes that
a triggering stimulus (eg, menstruation, fe-
ver, or stress) reactivates the virus, which
then travels down the peripheral nerve to
epidermal cells, causing a skin lesion.
2.
The skin trigger theory proposes that within
epithelial cells there is a low level of viral
replication that is eliminated by the host
immune response.  Injury to the skin (eg,
trauma, sunburn) results in clinical disease
by either suppressing local defenses or
stimulating viral replication.
Complications of recurrent genital herpes infec-
tion are few.  Erythema multiforme may develop in
young patients 10 to 14 days following recurrent
disease.  The erythema multiforme may present as
typical target lesions on the extremities or may
develop into severe mucocutaneous involvement.
Spontaneous improvement is the rule, although pa-
tients often have recurrent episodes for 5 to 6 years.108
Genital Herpes Infections in Immunocompromised
Patients
Genital herpes infections in immunocompro-
mised patients (eg, patients who are receiving che-
motherapy, have received bone marrow transplants,
or are infected with HIV) are more severe and more
prolonged than in immunocompetent patients (Fig-
ure 19-27).  Lesions are deep, necrotic, and painful;
viral shedding persists for months in some patients
with AIDS.  In patients infected with HIV, lesions

Military Dermatology
528
are most commonly located in the perianal area,
followed by the buttocks, scrotum, penis, and the
orolabial area.  Although there is an increased risk
of dissemination in these patients, most untreated
infections do not disseminate.99
Laboratory Diagnosis
Numerous laboratory techniques are currently
available for the diagnosis of genital herpes infec-
tions, although only a few are in routine clinical use.
These include viral culture, Tzanck and Papa-
nicolaou smears, direct immunofluorescence stain-
ing, and viral serology.  Other less frequently
employed or research methods include immuno-
peroxidase staining, ELISA, electron microscopy,
and tests to type and subtype virus isolates.
Viral Culture
Isolation by tissue culture is the most sensitive
method for the detection of HSV.  The success of
viral isolation depends on the type of lesion cul-
tured (ie, intact vesicle or erosion), the age of the
lesion, the size of the inoculum, the immune status
of the patient, and the sensitivity of the cell culture
(human foreskin fibroblast, monkey kidney, or pri-
mary rabbit kidney).109  Viral cultures obtained from
intact vesicles or pustules in patients with primary
genital herpes infections are positive in almost 90%
of patients, compared to less than 30% if crusted
lesions are cultured.99  In one large series, HSV was
cultured from 94% of vesicles, 87% of pustules, 70%
of ulcers, and only 27% of crusted lesions.98
The ideal lesion for culture is an intact vesicle or
pustule.  The lesion should be unroofed and the
base swabbed with a synthetic polyester– or cotton-
tipped applicator.  The material is then placed into
a suitable viral transport medium (ie, Hank’s bal-
anced salt solution with antibiotics or veal infusion
broth).  Under refrigeration, the virus can survive in
transport material without loss of infectivity for 72
hours at 4°C.98  The average replication time of HSV
is 12 to 18 hours; typical cytopathic effects of the
virus in culture are seen in 1 to 3 days, although it
may take 6 or 7 days for smaller inocula.  Confirma-
tion that HSV is responsible for the cytopathic effect
is done using type-specific antisera, direct immun-
ofluorescence, or nucleic acid hybridization.110
Cytologic Diagnosis
Cytologic diagnosis can be made using the Tzanck
(Wright-Giemsa) or Papanicolaou stains of smears
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b
a
Fig. 19-27. Immunosuppressed patients (ie, those in-
fected with the human immunodeficiency virus, under-
going chemotherapy, or with advanced malignancy) may
present with chronic ulcerations that in no way resemble
the typical lesions of genital herpes. A high index of
suspicion and a history of previous episodes of genital
herpes are often helpful in making the diagnosis. The
patient shown in (a) has an ulcerated herpetic lesion in
the suprapubic area. The patient shown in (b), who has
advanced acquired immunodeficiency syndrome, pre-
sented with multiple, painful, deep perinanal ulcerations.

Sexually Transmitted Diseases
529
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Fig. 19-28. This Tzanck preparation of a herpetic lesion
shows several multinucleated giant cells. Photograph:
Courtesy of Colonel Purnima Sau, Medical Corps, US Army,
Walter Reed Army Medical Center, Washington, DC.
TABLE 19-6
SENSITIVITY OF DIAGNOSTIC TESTS TO HERPES SIMPLEX VIRUS
Adapted with permission from Moseley RC, Corey L, Benjamin D, Winter C, Remington ML. Comparison of viral isolation, direct
immunofluorescence, and indirect immunoperoxidase techniques for detection of genital herpes simplex virus infection. J Clin
Microbiol. 1981;13:915.
of material taken from the base of lesions.  These are
rapid, bedside, diagnostic tests that provide infor-
mation quickly, especially when the test is positive.
Cells infected in vivo with HSV show intranuclear
inclusions, balloon giant cells, and multinucleated
giant cells similar to those seen in tissue culture.
Both tests are less sensitive than viral culture and
neither differentiates among HSV-1, HSV-2, or
herpes zoster infections.  With either test, greater
sensitivity is seen when intact vesicles or pustules
are present than when erosions or ulcers are
sampled.101
The Tzanck smear is performed by scraping the
base and margins of an unroofed vesicle or pustule,
or the base of an erosion or ulcer, and spreading the
material on a glass slide.  After fixation in absolute
alcohol, the material is stained with Wright-Giemsa
stain and examined for typical balloon and multi-
nucleated giant cells (Figure 19-28).  The Papa-
nicolaou smear is especially useful for asymptomatic
herpes infections of the cervix.  On staining, both
multinucleated giant cells and intranuclear viral
inclusions are visible, making this test more sensi-
tive than the Tzanck smear.
Antigen Detection Using Direct Immunofluorescence
One of the tests most commonly used to detect
the presence of HSV antigen is the fluorescein-
conjugated anti-HSV monoclonal antibody test (also
called the direct immunofluorescence antibody test).
The sensitivity of the test is approximately 70% to
95% compared to viral culture.  The accuracy of the
test depends on the presence of sufficient numbers
of cells to be studied (Table 19-6).111
To prepare a specimen for the direct immunof-
luorescence antibody test, the base of the lesion
is either scraped with a scalpel blade or swabbed
with an applicator.  The scrapings are placed on
a glass slide and transported to the laboratory,
where the specimen is fixed and stained.  If a
swab is used, it is placed in transport medium
and sent to the laboratory.  There, the cells are
Table 19-6 is not shown because the copyright permission granted to the Borden Institute, TMM, does
not allow the Borden Institute to grant permission to other users and/or does not include usage in
electronic media. The current user must apply to the publisher named in the figure legend  for permis-
sion to use this illustration in any type of publication media.

Military Dermatology
530
concentrated and spotted onto glass slides; the
stained slides are then examined under a fluores-
cence microscope (Figure 19-29).  Using monoclonal,
fluorescein-tagged antibodies, the determination
can be made quickly whether the virus is HSV-1
or HSV-2, which provides important prognostic
information.110
Two other diagnostic methods are available for
antigen detection: the ELISA and the immuno-per-
oxidase tests.  These have similar sensitivities as the
immunofluorescence stain; they will not be dis-
cussed further here.
Serologic Tests
Serologic testing for the presence of antibodies to
herpes viruses has limited clinical value except in
primary infections.  Once an individual becomes
seropositive, antibody titers persist for life, and the
titers do not correlate with the timing or severity of
recurrent disease.  Currently available tests do not
differentiate between HSV-1 and HSV-2, and pa-
tients should not be told they have had prior HSV-
2 infections based on the results of routine antibody
screening.99
When primary genital herpes infection is sus-
pected, blood samples for antibody testing should
be taken on the first visit, and then 10 to 14 days
later, for a complement-fixation test.  Anti-HSV
antibody of the IgM class is produced during a
primary infection, but is generally not detected in
recurrent cases.10
Treatment
Over the last decades, many therapies have been
attempted for the management of genital herpes
infections.  The introduction of acyclovir in oral,
topical, and intravenous formulations has revolu-
tionized the management of patients with primary
and recurrent disease.  However, chronic use of the
drug, especially in patients with HIV infections, has
led to the emergence of acyclovir-resistant strains.
Primary Genital Herpes Infections
Primary genital herpes infections are often quite
severe, prolonged, and associated with constitu-
tional symptoms in many patients, especially
women.  Acyclovir, administered orally in a dose of
200 mg five times daily for 7 to 10 days, is consid-
ered the treatment of choice for first-episode pri-
mary genital herpes infections in immunocompe-
tent individuals.  Treatment with oral acyclovir in
this population significantly reduces viral shed-
ding, shortens the time to healing, and often re-
duces the duration of pain and new lesion forma-
tion.112
In patients with complications (eg, dehydration,
severe dysuria, inability to tolerate oral medica-
tions) intravenous acyclovir (5 mg/kg infused over
1 h, administered every 8 h) may be initiated.  When
pain and discomfort have subsided, the patient can
be discharged to complete the 10-day course of
therapy as an outpatient.99
Side effects associated with acyclovir therapy,
although uncommon, include the following113:
• nausea, vomiting, diarrhea, and headache
with oral and intravenous acyclovir;
• agitation, altered mental status, and obtund-
ation with more-serious central nervous
system toxicity; and
• reversible renal dysfunction with intrave-
nous administration (which may be pre-
vented by increasing the infusion time to 1 h
and adequately hydrating the patient).
Unfortunately, regardless of the route of adminis-
tration, acyclovir treatment of primary genital
herpes infection does not prevent the development
of recurrent disease.112,114
Recurrent Disease
Treatment guidelines for recurrent genital herpes
infection vary depending on the frequency of recur-
Fig. 19-29. Direct immunofluorescence test showing posi-
tive fluorescence in a herpes simplex–infected cell. Pho-
tograph: Courtesy of Burroughs Wellcome, Research Tri-
angle Park, NC.
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Sexually Transmitted Diseases
531
rent episodes, duration and severity of the epi-
sodes, and the presence of complications, especially
herpes-associated erythema multiforme.  Treatment
is divided into episodic and long-term suppressive
modes.
Episodic Treatment.  Oral acyclovir, in a dose of
200 mg administered five times daily for 5 days, is
the most consistently effective therapy for episodic
treatment of recurrent genital herpes infection in
immunocompetent individuals.  Studies have fo-
cused on patient-initiated and physician-initiated
therapy, and its impact on duration and severity of
recurrences.  Patient-initiated therapy, in which the
patient begins treatment at the onset of prodromal
symptoms, tends to offer greater benefit than phy-
sician-initiated regimens.  Studies have demon-
strated a statistically significant reduction in viral
shedding and healing times with episodic treat-
ment but less-than-convincing reduction in local
pain and discomfort.115  In recurrent herpes labialis,
higher doses of patient-initiated acyclovir (400 mg
administered five times daily for 5 d) have been
suggested to improve response and decrease symp-
toms.  Likewise, refractory cases of recurrent geni-
tal herpes infection may respond to higher doses.116
The CDC suggests that acyclovir 400 mg,
administered three times daily for 5 days or 800 mg,
administered twice daily for 5 days; might be effec-
tive.25
Long-Term Suppressive Therapy.  Rates of recur-
rent genital herpes infection vary considerably—
from 1 or 2 to more than 12 recurrences per year.
Most patients who seek therapy for recurrent dis-
ease have 5 to 8 recurrences per year.115  Suppressive
therapy is also indicated for the treatment of pa-
tients with recurrent herpes-associated erythema
multiforme.99
Numerous dosing regimens have been proposed;
however, the two most effective are 400 mg, admin-
istered twice daily, and 200 mg, administered three
to five times daily.  Once-daily therapy in any dose
is less effective than twice-daily regimens but should
be considered in poorly compliant patients.  There
appears to be little, if any, long-term toxicity and no
reason that long periods of use are not safe.  How-
ever, patients should be encouraged to interrupt
therapy after 1 year of continuous therapy to deter-
mine if the frequency of recurrences still justifies
the continued use of the drug.25,117
Treatment of Immunocompromised Patients
Treatment of recurrent genital herpes infections
in compromised hosts, particularly patients with
HIV infection, is complicated by persistent viral
shedding, the necessity in some patients for indefi-
nite suppressive therapy, and the emerging prob-
lem of acyclovir-resistant strains of HSV.  In outpa-
tient immunocompromised patients (eg, those with
HIV infection, bone marrow–transplant recipients)
with recurrent mucocutaneous disease, higher doses
of oral acyclovir (400 mg administered five times
daily for 10 d) have been shown to be effective.118
Enthusiasm for topical acyclovir ointment has di-
minished.  However, the topical preparation ap-
plied 6 times daily for 10 days significantly reduces
viral shedding, pain, and healing times.113  The
treatment of hospitalized, immunocompromised
patients with genital herpes infections is beyond
the scope of this discussion.
GENITAL WARTS
Anogenital warts (also called condylomata
acuminata and venereal warts) are an ancient dis-
ease, with the earliest references to them in litera-
ture as condylomata (figs).  It was well known during
the Roman Empire that promiscuous sexual behav-
ior and anal intercourse were implicated in the
spread of this disease.  An early reference to
condyloma acuminata is found in this satirical poem
written in the first century AD by Martial in his
Epigrammata Medicae Philosophicae (XII:3), as trans-
lated by J. D. Oriel:
In order to buy some slave boys
Labienius sold his gardens,
But now the poor man has
Only an orchard of figs.119(p99)
Genital warts result from infection by a group of
DNA-containing human papillomaviruses (HPVs).
Recent investigations of the epidemiology and natu-
ral history of human papillomavirus infections have
shed light on the transmission, infectivity, and prob-
able oncogenic potential of these agents.  Advances in
molecular biology have clearly demonstrated the role
of certain HPV subtypes in Bowenoid papulosis, cer-
vical dysplasia, and cervical carcinoma.  In particular,
subtypes 16, 18, 31, and 33 are most often implicated
in these conditions; many other HPV subtypes have
been found in genital wart tissue and in premalig-
nant and malignant lesions of the genitalia.
The HPV organism consists of circular, double-
stranded DNA enclosed in a protein shell (ie, a

Military Dermatology
532
capsid) (Figure 19-30).  The absence of a lipid enve-
lope renders the virus resistant to drying, freezing,
and inactivation by ether.  HPVs have never been
propagated successfully in tissue culture, which
has hindered laboratory studies and vaccine devel-
opment.  By DNA hybridization techniques, at least
55 subtypes of HPV are currently known, with more
certain to be discovered (Table 19-7).120
TABLE 19-7
TYPES AND CLINICAL ASSOCIATION OF HUMAN PAPILLOMAVIRUS (HPV)
Reprinted with permission from Cobb MW. Human papillomavirus infection. J Am Acad Dermatol. 1990;22(4):548.
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Fig. 19-30. This electron micrograph shows clusters of
human papillomavirus. Photograph: Courtesy of Walter
Reed Army Medical Center Dermatology Service slide
file, Washington, DC.
Table 19-7 is not shown because the copyright permission granted to the Borden Institute, TMM,
does not allow the Borden Institute to grant permission to other users and/or does not include usage
in electronic media. The current user must apply to the publisher named in the figure legend  for
permission to use this illustration in any type of publication media.

Sexually Transmitted Diseases
533
Clinical Manifestations
Clinical signs of genital human papillomavirus
infection vary from latent infection, to extensive
cauliflower-like vegetations, to frank neoplasia such
as cervical carcinoma.  The typical lesions are soft,
grouped, skin-colored-to-pink papules with a
smooth or filiform surface; they occur on moist
surfaces of the external genitalia, cervix, or perianal
area (Figure 19-31).  Although lesions usually are
asymptomatic, some patients complain of itching,
local irritation, or bleeding, especially in the perianal
area.121  Applying 3% to 5% acetic acid to clinically
normal penile or vulvar skin and then examining
with magnification may demonstrate areas of flat,
whitish epithelium or punctate, fine-caliber, vascu-
lar patterns that are subclinical foci of infection
with HPV.122
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Fig. 19-31. (a) Filiform condylomata in the coronal sul-
cus. (b) Grouped and confluent sessile genital warts on
the penis.  These are different expressions of the same
viral infections, (a) being filiform warts, and (b) less-
obvious sessile genital warts on the penile shaft.
a
b
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Fig. 19-32. Exophytic mass protruding from the urethral
meatus. The lesions may extend proximally to involve
the urethral mucosal surface. Intraurethral condylomata
may be better seen with urethroscopy.
Most genital warts are seen in young men and
women between the ages of 16 and 25.  The virus
spreads primarily via sexual transmission, with a
high rate of infectivity.  Nearly two thirds of indi-
viduals with infected sexual partners developed
genital warts within 2 to 3 months.123
In men, condyloma acuminata are most com-
monly found on the glans, coronal sulcus, and fore-
skin—moist areas that are prone to trauma and
therefore vulnerable to the subsequent entry of the
virus during sexual intercourse.  The urethral me-
atus and the urethra itself may be involved with
exophytic condylomata, producing dysuria and
urethral discharge (Figure 19-32).  Papular or flat
warts may involve the penile shaft, scrotum, or
inguinal folds.123  Large, exophytic, perianal
condyloma may also occur.
Women with genital human papillomavirus in-
fection may present with multiple papular sessile
lesions, filiform growths, or vulvar papillomatosis
(ie, numerous, small, coalescing papules over the
entire vulvar vestibule, giving the area a “cobble-
stone” appearance) (Figure 19-33).  Lesions of the
vagina occur in about one third of patients.
Subclinical involvement of the cervix is more com-
mon than is frank condyloma acuminata.  Up to 3%
of routine Papanicolaou smears show changes typi-
cal human papillomavirus infection: koilocytosis,
atypia, and multinucleation.  Application of dilute
acetic acid to the cervix followed by colposcopy
may show flat-topped papules or plaques repre-
senting inconspicuous disease.  These lesions most
commonly contain HPV-6 and HPV-11.  Lesions

Military Dermatology
534
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Fig. 19-35. Perianal condyloma acuminata. These lesions,
which may involve the anal mucosa as well as the perianal
skin, are difficult to eradicate and frequently recur.
Fig. 19-33. Diffuse, confluent lesions of condyloma
acuminata give this patient’s vulva a distinctive “cobble-
stone” appearance.
Fig. 19-34. These are the reddish brown lesions of
Bowenoid papulosis, which were confirmed by shave
biopsy.
that histologically show atypia are more often asso-
ciated with HPV-16.121
Bowenoid papulosis refers to human papillo-
mavirus infection that is characterized by small,
pigmented, smooth-to-verrucous papules that show
histological changes suggestive of carcinoma in situ
(Figure 19-34).  Although previously thought to be
benign, recent studies have shown that female part-
ners of men with Bowenoid papulosis have a higher
incidence of cervical neoplasia, supporting a caus-
ative role of HPV and the subtypes, especially HPV-
16, in these conditions.124
Anal warts may be found in heterosexual,
homosexual, and bisexual men, with HPV-6 and
HPV-11 found in the majority of cases (Figure
19-35).  In renal transplant recipients and men who
are infected with HIV, anal condylomata may
become large, exophytic growths.  These may
be difficult to eradicate with any modality, and
invasive squamous cell carcinomas may develop from
these lesions.121
Giant condyloma of Buschke and Löwenstein is
classified by some54 as a low-grade verrucous carci-
noma, although others125 consider it a benign lesion.

Sexually Transmitted Diseases
535
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Fig. 19-36. (a) Giant condyloma of the inguinal fold. (b)
This closer view of the previous lesion shows the cauli-
flower-like masses of tumor tissue. Photographs: Cour-
tesy of Lieutenant Colonel L. C. Sperling, Medical Corps,
US Army, Walter Reed Army Medical Center, Washing-
ton, DC.
It most commonly occurs on the glans penis and
foreskin of uncircumcised men.  Less often, these
lesions occur on the vulva or in the perianal area.54
Patients with giant condyloma present with large
cauliflower-like growths (Figures 19-36 and 19-37),
which may penetrate into underlying structures
such as the urethra or corpora cavernosa.  Local
compression and destruction of normal structures
result.  The lack of nerve, blood vessel, and lym-
Fig. 19-37. Massive Buschke-Loewenstein tumor of the
vulva. Photograph: Courtesy of Walter Reed Army Medical
Center Dermatology Service slide file, Washington, DC.
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phatic invasion probably accounts for the rarity of
metastases.  DNA sequences of HPV-6 and HPV-11
have been isolated from giant condyloma, support-
ing the contention that HPV is involved in the
genesis, and possible malignant transformation, of
these lesions.123,126,127
When seen in children, condyloma acuminata is
considered a risk factor for sexual abuse, with esti-
mates varying from 30% to 80% of cases (Figure 19-
38).128  Pregnancy has a profound influence on the
condylomata, with lesions increasing dramatically
in size and number.  There is a concomitant increase
in the amount of viral DNA material from pregnant
women compared to nonpregnant women.  There is
a risk of laryngeal papillomatosis and anogenital
condyloma in infants born to mothers with cervical
or vulvar condylomata.122  Condyloma acuminata
in children and during pregnancy will not be dis-
cussed further in this chapter.
Clinical Diagnosis
Clinical examination remains the principal means
of diagnosing genital warts.  In a sexually active
patient with typical condylomata, biopsy with his-
tological examination offers little except reassur-
ance to the patient that the diagnosis is correct.  In
the following instances though, additional studies

Military Dermatology
536
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Fig. 19-38. Extensive condyloma acuminata in a prepu-
bertal female child. This patient was also evaluated for
sexual abuse. Photograph: Courtesy of Major J. Rowe,
Medical Corps, US Army, Fort Bragg, N.C.
• Pediatric presentation.  When lesions are
present in pediatric patients, and when abuse
or other medicolegal issues are at issue, tis-
sue can be submitted for histology and, if
available, HPV typing.
Immunoperoxidase staining, using antibody
against disrupted bovine papillomavirus as the
antigen, has been useful for detecting HPV in tissue
sections.  Methods of DNA hybridization or ribo-
nucleic acid (RNA) hybridization permit typing of
HPV samples; utilizing the polymerase chain reac-
tion to amplify the DNA of the HPV that is present
greatly improves the sensitivity of the tests.120
The virus cannot be cultivated in vitro, and type-
specific viral antigens are currently unavailable for
the development of serologic tests.122
Treatment
Locally destructive methods (eg, cryosurgery,
electrodesiccation, curettage, carbon dioxide–laser
vaporization) and application of chemical agents
(eg, podophyllin, 5-fluorouracil) are reasonably ef-
fective and convenient methods to treat condyloma
acuminata.  Unfortunately, all suffer from the same
shortcomings: frequent recurrence of the lesions
and persistence of the virus in otherwise normal-
appearing tissue.
Cryosurgery with liquid nitrogen remains a time-
honored and effective treatment for smaller lesions.
Liquid nitrogen is applied to the wart until the ice
ball extends 1 to 2 mm beyond the visible edge of the
lesion.  The procedure is somewhat uncomfortable
for the patient, and blistering and erosions may
result.  Local anesthesia during the procedure and
oral analgesics following cryosurgery may be nec-
essary if extensive treatment is performed.
Retreatment may be necessary every week or two
until the lesions have completely resolved.119  Care
should be taken not to treat large areas of the glans
penis or foreskin at one visit: the resulting edema
may cause the patient to be unable to retract the
foreskin, which can lead to acute urinary retention.
Electrosurgery and carbon dioxide–laser vapor-
ization are locally destructive procedures that usu-
ally require the administration of local anesthesia
prior to performing them.  Small localized warts
(eg, on the penile shaft) are treatable with
electrodesiccation.  Undertreatment frequently re-
sults in recurrence and overtreatment may lead to
scarring.  Genital warts in other locations and large
exophytic lesions are not generally suitable for treat-
ment with this modality.119  With the carbon dioxide
or histological confirmation should be considered:
• Atypical lesions.  The condylomata lata of
secondary syphilis may clinically resemble
genital warts.  Condylomata lata (lata means
“broad” or “flat”) tend to be broad, flat, and
more rounded lesions that are covered with
a mucoid exudate.  Dark-field microscopy,
serologic tests, and the presence of other
findings of secondary syphilis are helpful in
making the proper diagnosis.  In some atypi-
cal lesions, biopsy may be necessary for con-
firmation.123
• Lesions that may actually be Bowenoid
papulosis.  Because of the risk of cervical
neoplasia in female sexual partners, histo-
logical findings consistent with Bowenoid
papulosis mandates careful follow-up in this
population.
• Unresponsive lesions.  Lesions that are unre-
sponsive to treatment may not be condyloma
acuminata.  For example, melanocytic nevi,
seborrheic keratoses, and epidermal nevi
have all been mistaken for condylomata.  A
scissor biopsy performed under local anes-
thesia quickly resolves the issue.

Sexually Transmitted Diseases
537
laser, low-wattage treatment in the vaporization
mode is an excellent method of rapidly treating
genital warts with minimal risk of scarring.  The
laser beam destroys infected tissue by evaporation
of water.  However, recent concerns regarding the
presence of viable HPV and other viruses (ie, HIV)
in the electrosurgical and laser smoke plumes have
dampened enthusiasm for these two modalities.129
Isolated lesions can be removed with a sharp curette
or by scissor excision under local anesthesia.123
Application of 20% podophyllin in benzoin
to condylomata results in arrest of cell mitosis
and subsequent cell death.  Podophyllin is an
unstable, crude, plant extract with significant
local reactions including irritation, necrosis, scar-
ring, anal fistulae, and phimosis among the re-
ported complications.121,123
Early in treatment, the medication is washed off
in 3 to 4 hours.  With subsequent applications, the
time may be extended up to 12 hours as tolerated by
the patient.121  Care should be taken to avoid adja-
cent normal skin.  Severe inflammation and necro-
sis can occur when podophyllin is applied to
condylomata on the coronal rim or sulcus, or on the
periurethral area.  Other modalities should be used
when treating genital warts in these areas, espe-
cially in uncircumcised men.
Systemic reactions caused by overzealous or ex-
tensive application are rare but have been reported.
Under no circumstances should podophyllin be used
in pregnant women because of the potential for
maternal and fetal toxicity.121
Podophyllotoxin 0.5% in ethanol has been ap-
proved for home use by patients.  The compound is
applied twice daily for 3 days each week for up to 6
weeks.  A cure rate of 82% was achieved with this
regimen.  The advantage is that patients can apply
the medication at home, reducing the need for fre-
quent office visits and assuring prompt treatment
of recurrent lesions.130
The drug 5-fluorouracil has been used as a 5%
cream in the treatment of warts in the intrameatal
portion of the urethra in men.  The cream is applied
four times daily using an applicator stick, after the
bladder has been emptied.  A severe inflammatory
reaction may develop and this treatment should be
undertaken only by medical officers who are expe-
rienced in this method.  Follow-up urethroscopy is
important.10
Interferons, both intralesional and parenteral,
and systemic retinoids have been used for human
papillomavirus infections that are resistant to other
forms of therapy.  The doses and indications for
these drugs can be found elsewhere.131,132
Although molluscum contagiosum is not a re-
portable disease, there is epidemiological evidence
that a substantial increase in the number of cases
has occurred since the 1970s.  The current estimate
is that from 2% to 8% of the population is affected by
this condition at any time.  However, because it is
not currently possible to cultivate the molluscum
contagiosum virus (MCV) in vitro, estimates are
based on examination of populations of affected
individuals.133–135  Because MCV is a poxvirus, some
researchers135 have speculated that the cessation of
routine vaccinia virus vaccination in the general
population in the 1970s may be responsible for the
increasing incidence.
MCV is a brick-shaped, DNA-containing poxvi-
rus that morphologically and biochemically re-
sembles other members of the Poxviridae (eg,
variola, vaccinia, and cowpox).  By analysis of viral
DNA sequences, two subtypes have been identified
and are designated MCV-1 and MCV-2.  However,
clinical lesions caused by both subtypes are identi-
cal.  Studies of virus–host interaction, development
of serologic tests, and vaccine production are cur-
MOLLUSCUM CONTAGIOSUM
rently not possible because researchers have been
unable to cultivate the virus in vitro.135  There have
been isolated reports of successful propagation of
the virus in cell culture.136,137
The lesions of molluscum contagiosum occur in
two, and perhaps in three, groups.  In adults,
molluscum contagiosum is usually an STD, with
lesions occurring predominately in the genital area
(Figure 19-39).  In children, lesions are often on
exposed surfaces and the face, consistent with trans-
mission by person-to-person contact or possibly by
fomites.  Recently, a third group of individuals,
those with progressive HIV-1 infection, have been
described with extensive cutaneous involvement
(Figure 19-40).138  These lesions are particularly
refractory to therapy.  Additionally, the number of
lesions of molluscum contagiosum increase dra-
matically in these patients with deterioration of
their immune status.
Clinical Manifestations
Adolescents and adults with molluscum contagi-

Military Dermatology
538
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Fig. 19-39. (a) The umbilicated skin-colored-to-reddish
papules of molluscum contagiosum. (b) Grouped um-
bilicated papules on the penile shaft. These papules are
often confused with the lesions of genital herpes infec-
tion unless the contents of the lesions are expressed and
examined.
osum present with multiple, firm, 2- to 5-mm, dome-
shaped, skin-colored papules that have a central
umbilication or “dimple.”  Lesions occur most com-
monly in the inguinal area, buttocks, and inner
thighs in both sexes (Figure 19-41).139  Although most
lesions are only a few millimeters in diameter, “giant”
molluscum may develop, with lesions approaching 1
cm in diameter (Figure 19-42).  In children, lesions are
located on exposed surfaces subject to minor
trauma—especially the face, trunk, and extremities.
Lesions are often grouped, and a linear pattern may
develop as a result of scratching.  Most cases are
asymptomatic; however, a few patients complain of
mild pruritus.  Lesions may rarely be found on the
palms, soles and mucous membranes.140
Two groups of patients are at risk to develop
extensive molluscum contagiosum: those with atopic
dermatitis and those with HIV-1 infection.  Patients
OK to put on the Web
Fig. 19-41. Extensive involvement with molluscum
contagiosum over the buttocks and thighs in an adult.
Patients who present with molluscum in this distribution
should be carefully examined for other sexually trans-
mitted diseases.
Fig. 19-40. This patient, who was infected with the hu-
man immunodeficiency virus, also had hundreds of pap-
ules of molluscum contagiosum on his face. Death oc-
curred within months after the photograph was taken.
Photograph: Courtesy of Colonel William D. James, Medi-
cal Corps, US Army, Walter Reed Army Medical Center,
Washington, DC.

Sexually Transmitted Diseases
539
OK to put on the Web
Fig. 19-42. Solitary “giant” molluscum on the penile
shaft. Biopsy confirmed the diagnosis. Lesions of this
size are often mistaken for cysts or tumors.
with atopic dermatitis often develop numerous le-
sions in areas of active eczematous dermatitis,
especially the flexural folds.  The reasons given for
the widespread lesions include autoinoculation
from scratching, use of topical steroids, and im-
paired cellular immune response.141,142  Patients with
HIV-1 infection can have dozens or even hundreds
of lesions, primarily on the face and trunk instead
of the inguinal area.  As noted previously, a dra-
matic increase in the number of lesions corre-
sponds to the progressive deterioration of immune
function.143  Patients with sarcoidosis and those
receiving chemotherapy or corticosteroids have also
been reported to develop extensive molluscum
contagiosum.138
Complications
Surprisingly few complications arise from infec-
tions with molluscum contagiosum.  Two will be
considered here—molluscum dermatitis and second-
ary bacterial infection—as well as the occurrence of
molluscum lesions in the genital area of children,
which raises the suspicion of child abuse.  In about
10% of patients, a sharply demarcated, annular,
eczematous dermatitis develops around individual
lesions of molluscum contagiosum (Figure 19-43).
A few, some, or all of the lesions may be involved,
and the dermatitis resolves with disappearance of
the molluscum contagiosum papule.144  Lesions lo-
cated on the eyelid or conjunctivae are also occasion-
ally involved in molluscum dermatitis, and conjunc-
tivitis or keratitis may develop.145  Secondary bacterial
infection with cellulitis may also occur.
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Fig. 19-43. This peripheral erythema and crusting is typi-
cal of a lesion of molluscum dermatitis.
Regarding genital molluscum contagiosum in
infants and children, there is considerable contro-
versy over (a) how often the lesions are transmitted
by sexual abuse and (b) when to refer families
to social services for investigation.  More than
90% of lesions of molluscum contagiosum in chil-
dren are found on the trunk, axillae, and extremi-
ties.  Therefore, lesions in the genital area are un-
common and should raise the suspicion of sexual
abuse.  On the other hand, the CDC opinion25 is
that molluscum contagiosum in infants and chil-
dren is most frequently caused by nonsexual means
of transmission.  Several authorities recommend
that a child who has genital molluscum alone should
be viewed with increased suspicion of sexual
abuse.140,146
Diagnosis
Diagnosis is principally on clinical grounds alone,
as the appearance of the smooth, dome-shaped,
umbilicated papules is characteristic.  When doubt
exists, a lesion may be curetted or incised and the
whitish central core crushed between two glass
microscope slides.  It can then be stained with
methylene blue or Wright-Giemsa stain and exam-
ined microscopically.  The large, oval, dense, stain-
ing bodies known as molluscum bodies are
keratinocytes filled with viral particles.54  With atypi-
cal lesions, or in individuals who are infected with
HIV, a shave or punch biopsy of a papule may be
necessary to confirm the diagnosis.  (Recent reports
of the lesions of disseminated cryptococcal infec-
tion mimicking molluscum contagiosum in patients

Military Dermatology
540
infected with HIV lends support to the recommen-
dation for biopsy confirmation in this population.147)
Sections of hematoxylin-eosin–stained tissue show
numerous intracytoplasmic inclusion bodies, which
form in the lower epidermis; these large, basophilic
molluscum bodies measure up to 35 µm in diameter
(Figure 19-44).  Disintegration of the stratum
corneum in the center of the lesion leads to the
development of the central crater.54
As noted above, serologic tests or viral cultures
are not available.
Treatment
Numerous modalities have been successful in
the treatment of molluscum contagiosum.  The dis-
ease is self-limited and asymptomatic, and in some
instances, such as with very young children, it may
be appropriate simply to observe the lesions.  How-
ever, since autoinoculation and spread to other
persons is frequent, it is advisable to initiate treat-
ment.  Curettage with a sharp curette, light
electrodesiccation, light liquid nitrogen spray, or
topical application of 50% trichloroacetic acid are
all simple to perform and are nonscarring.  Slight
OK to put on the Web
Fig. 19-44. This histological section (medium-power view)
shows large keratinocytes filled with molluscum virus.
incision of the lesion with expression of the central
core is also curative.  Other suggested modalities
have included topical retinoic acid or griseofulvin.86
In the case of adolescents and adults with lesions in
the genital area, it is important to look for other
STDs, as they may also be present.
STDs present formidable diagnostic and thera-
peutic challenges for the field medical officer.  The
classic STDs discussed in this chapter can, with
reasonable care and a well-equipped laboratory
and pharmacy, be properly diagnosed and treated.
It is imperative, however, that the clinician be fa-
miliar with the subtle variations in clinical presen-
tation, subclinical disease, and the ever-changing
patterns of antibiotic sensitivity.  Likewise, a par-
ticular STD is not acquired in a vacuum.  The
general medical officer evaluating a soldier with
molluscum contagiosum or genital warts must re-
member that the patient may also be incubating
syphilis or may be an asymptomatic carrier of gon-
orrhea, chlamydia, or HIV infection.  A careful and
thoughtful approach to the evaluation of the pa-
tient with an STD will ensure that both the patient
and his or her sexual contacts will be well served.
SUMMARY
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78.
Goldberg J. Studies on granuloma inguinale. Part 7. Some epidemiologic considerations of the disease. Br J Vener
Dis. 1964;40:140–145.
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80.
Fritz GS, Dodson RF, Rudolph A. Mutilating granuloma inguinale. Arch Dermatol. 1975;111:1464–1465.
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Rothenberg RB. Granuloma inguinale. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, eds.
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Remigio PA. Granuloma inguinale. In: Sun T, ed. Sexually Related Infectious Diseases: Clinical and Laboratory
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Sehgal VN, Shyamprasad AL, Beohar PC. The histopathological diagnosis of donovanosis. Br J Vener Dis.
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Richens J. The diagnosis and treatment of donovanosis (granuloma inguinale). Genitourin Med. 1991;67:441–452.
86.
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Pa: WB Saunders; 1990: 293–294, 312–314, 409–410.

Sexually Transmitted Diseases
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87.
Schachter J. Chlamydial infections. Part 1. N Engl J Med. 1978;298:428–434.
88.
Perine PL, Osoba AO. Lymphogranuloma venereum. In: Holmes II, Mårdh P-A, Sparling PF, et al, eds. Sexually
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Abrams AJ. Lymphogranuloma venereum. JAMA. 1968;205(4):199–202.
90.
Becker L. Lymphogranuloma venereum. Int J Derm. 1976;15:26–33.
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Meheus A, Van Dyck E, Ursi JP, Ballard RC, Piot P. Etiology of genital ulcers in Swaziland. Sex Transm Dis.
1983;10:33–35.
92.
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1976;235:56–57.
93.
Wang S, Grayston JT. Immunologic relationship between genital TRIC, lymphogranuloma venereum, and
related organisms in a new microtiter indirect immunofluorescence test. Am J Ophthal. 1970;70:367–374.
94.
Fiumara NJ. Lymphogranuloma venereum. In: Demis DJ, ed. Clinical Dermatology. Vol 3. Philadelphia, Pa: JB
Lippincott; 1990: Unit 16-20: 6–8.
95.
Heaton S, Hammerschlag MR, Roblin PM, DiPasquale RC. Lymphogranuloma venereum in a pregnant woman.
Sex Transm Dis. 1988;15:148–149.
96.
Schachter J. Chlamydial infections. Part 2. N Engl J Med. 1978;298:490–495.
97.
Marlowe SI. Medical management of genital herpes. Editorial. Arch Dermatol. 1985;121:467–470.
98.
Corey L, Holmes KK. Genital herpes simplex infections: Current concepts in diagnosis, therapy and prevention.
Ann Int Med. 1983;98:973–983.
99.
Mertz GJ. Genital herpes simplex virus infections. Med Clin N Am. 1990;74(6):1433–1454.
100.
Holmberg SD, Stewart JA, Gerber LAR, et al. Prior herpes simplex type 2 as a risk factor for HIV infection. JAMA.
1988;259:1048–1050.
101.
Raab B, Lorincz AL. Genital herpes simplex—concepts and treatment. J Am Acad Dermatol. 1981;5:249–263.
102.
Corey L, Adams HG, Brown ZA, Holmes KK. Genital herpes simplex virus infections: Clinical manifestations,
course and complications. Ann Int Med. 1983;98:958–972.
103.
Quinn TC, Stamm WE, Goodell SE, et al. The polymicrobial origin of intestinal infections in homosexual men.
N Engl J Med. 1983;309:576–582.
104.
Gateley A, Gander RM, Johnson PC, Kit S, Otsuka H, Kohl S. Herpes simplex virus type 2 meningoencephalitis
resistant to acyclovir in a patient with AIDS. J Infect Dis. 1990;161:711–715.
105.
Joseph TJ, Vogt PJ. Disseminated herpes with hepatoadrenal necrosis in an adult. Am J Med. 1974;56:735–739.
106.
Bernstein DI, Lovett MA, Bryson YJ. Serologic analysis of first-episode nonprimary genital herpes simplex
infection: Presence of type 2 antibody in acute serum samples. Am J Med. 1984;77:1055–1060.
107.
Brown ZA, Kern ER, Spruance SL, Overall JC. Clinical and virologic course of herpes simplex genitalis. West J
Med. 1979;130:414–421.
108.
Leigh IM. Management of non-genital herpes simplex virus infections in immunocompetent patients. Am J Med.
1988;85(Suppl 2A):34–38.

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109.
Smith I W, Peutherer JF. Immunological diagnosis of herpes simplex virus. In: Young H, McMillan A, eds.
Immunological Diagnosis of Sexually Transmitted Diseases. New York, NY: Marcel Dekker; 1988: 371–401.
110.
Fife KH, Corey L. Herpes simplex virus. In: Holmes II, Mårdh P-A, Sparling PF, et al, eds. Sexually Transmitted
Diseases. New York: McGraw-Hill; 1990: 941–952.
111.
Moseley RC, Corey L, Benjamin D, Winter C, Remington ML. Comparison of viral isolation, direct immunofluo-
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Clin Microbiol. 1981;13:913–918.
112.
Stone KM, Whittington W. Treatment of genital herpes. Rev Infect Dis. 1990;12(Suppl 6):S610–S619.
113.
Saral R. Management of mucocutaneous herpes simplex virus infections in immunocompromised patients. Am
J Med. 1988;85(Suppl 2A):57–60.
114.
Mertz GL, Critchlow CW, Benedetti J, et al. Double-blind placebo-controlled trial of oral acyclovir in first-
episode genital herpes simplex virus infection. JAMA. 1984;252(9):1147–1151.
115.
Corey L. Genital herpes. In: Holmes II, Mårdh P-A, Sparling PF, et al, eds. Sexually Transmitted Diseases. New
York: McGraw-Hill; 1990: 391–413.
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Spruance SL, Stewart JCB, Rowe NH, McKeough MB, Wenerstrom G, Freeman DJ. Treatment of recurrent herpes
simplex labialis with oral acyclovir. J Infect Dis. 1990;161:185–190.
117.
Landy JL, Grossman JH. Herpes simplex virus. Ob Gyn Clin N Am. 1989;16(3):495–515.
118.
Shepp DH, Newton BA, Dandliker PS, Flournoy N, Meyers JD. Oral acyclovir therapy for mucocutaneous herpes
simplex virus infections in immunocompromised marrow transplant recipients. Ann Int Med. 1985;102:783–785.
119.
Oriel, JD. Genital warts. In: Adler MW. Diseases in the Homosexual Male. London, England: Springer-Verlag; 1988:
99–109.
120.
Cobb MW. Human papillomavirus infection. J Am Acad Dermatol. 1990;22(4)547–563.
121.
Brown DR, Fife KH. Human papillomavirus infections of the genital tract. Med Clin N Am. 1990;74(6)1455–1485.
122.
Koutsky LA, Wolner-Hanssen P. Genital papillomavirus infections: Current knowledge and future prospects.
Ob Gyn Clin N Am. 1989;16(3):541–564.
123.
Oriel JD. Genital human papillomavirus infection. In: Holmes II, Mårdh P-A, Sparling PF, et al, eds. Sexually
Transmitted Diseases. New York: McGraw-Hill; 1990: 433–441.
124.
Devillez RL, Stevens CS. Bowenoid papules of the genitalia. J Am Acad Dermatol. 1980;3:149–152.
125.
Ananthakrishnan N, Ravindran R, Veliath AJ, Parkash S. Loewenstein-Buschke tumour of penis—A carcinomimic.
Br J Urol. 1981;53:460–465.
126.
Gissman L, DeVilliers E-M, Zur Hausen H. Analysis of human genital warts (condylomata acuminata) and other
genital tumours for human papillomavirus type 6 DNA. Int J Cancer. 1982;29:143–146.
127.
South LM, O’Sullivan JP, Gazet JC. Giant condyloma of Buschke and Loewenstein. Clin Oncol. 1977;3:107–115.
128.
DeJong AR, Emmett GA, Hervada AR. Sexual abuse of children: Sex-, race-, and age-dependent variations. Am
J Dis Child. 1982;136(2):129–134.
129.
Sawchuk WS, Weber PJ, Lowy DR, Dzubow LM. Infectious papillomavirus in the vapor of warts treated with
carbon dioxide laser or electrocoagulation: Detection and protection. J Am Acad Dermatol. 1989;21(1)41–49.

Sexually Transmitted Diseases
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130.
Beutner KR, Conant MA, Friedman-Kien AE, Illeman M, Thisted RA, King DH. Patient-applied podofilox for
treatment of genital warts. Lancet. 1989;1:831–834.
131.
Gross G, Roussaki A, Schopf E, De Villiers EM, Papendick U. Successful treatment of condylomata acuminata
and Bowenoid papulosis with subcutaneous injections of low-dose recombinant interferon-alpha. Arch Dermatol.
1986;122(7):749–750.
132.
Lutzner MA, Blanchet-Bardon C. Oral retinoid treatment of human papillomavirus type 5-induced
epidermodysplasia verruciformis. Correspondence. N Engl J Med. 1980;302:1091–1092.
133.
Becker TM, Blount JH, Douglas J, Judson FN. Trends in molluscum contagiosum in the United States, 1966–1983.
Sex Transm Dis. 1986;13:88–92.
134.
Oriel JD. The increase in molluscum contagiosum. Br Med J. 1987;294:74.
135.
Billstein SA, Mattaliano VJ. The “nuisance” sexually transmitted diseases: Molluscum contagiosum, scabies,
and crab lice. Med Clin N Am. 1990;74(6):1487–1515.
136.
Francis RD, Bradford HB. Some biological and physical properties of molluscum contagiosum virus propagated
in cell culture. J Virol. 1976;19:382–388.
137.
McFadden G, Pace WE, Purres J, Dales S. Biogenesis of poxviruses: Transitory expression of molluscum
contagiosum early functions. Virol. 1979;94:297–313.
138.
Katzman M, Carey JT, Elmets CA, Jacobs GH, Lederman MM. Molluscum contagiosum and the acquired
immunodeficiency syndrome: Clinical and immunological details of two cases. Br J Dermatol. 1987;116:131–138.
139.
Lynch PJ, Minkin W. Molluscum contagiosum of the adult. Arch Dermatol. 1969;98:141–143.
140.
Brown ST, Nalley JF, Kraus SJ. Molluscum contagiosum. Sex Transm Dis. 1981;8:227–234.
141.
Solomon LM, Telner P. Eruptive molluscum contagiosum in atopic dermatitis. Can Med Assoc J. 1966;95:978–979.
142.
Pauly CR, Artis WM, Jones HE. Atopic dermatitis, impaired cellular immunity and molluscum contagiosum.
Arch Dermatol. 1978;114:391–393.
143.
Redfield RR, James WD, Wright DC, et al. Severe molluscum contagiosum infection in a patient with human T-
cell lymphotrophic (HTLV-III) disease. J Am Acad Dermatol. 1985;13:821–823.
144.
Douglas JM. Molluscum contagiosum. In: Holmes II, Mårdh P-A, Sparling PF, et al, eds. Sexually Transmitted
Diseases. New York: McGraw-Hill; 1990: 443–447.
145.
Kipping HF. Molluscum dermatitis. Correspondence. Arch Dermatol. 1971;103:106–107.
146.
Schachner L, Hankin D. Is genital molluscum contagiosum a cutaneous manifestation of sexual abuse in
children? Correspondence. J Am Acad Dermatol. 1986;14(5):848–849.
147.
Rico MJ, Penneys NS. Cutaneous cryptococcosis resembling molluscum contagiosum in a patient with AIDS.
Arch Dermatol. 1985;121:901–902.

Common Skin Diseases
549
Chapter 20
COMMON SKIN DISEASES
PETER E. O’NEILL, M.D.*
*3 Claydon Road, Garden City, New York 11530; Assistant Clinical Professor, State University of New York at Stony Brook, Stony Brook,
New York; formerly, Major, Medical Corps, U.S. Air Force; Dermatology Service, Wilford Hall U.S. Air Force. Medical Center, Lackland
Air Force Base, Texas 78236
INTRODUCTION
PSORIASIS
Clinical Features
Types of Psoriasis
Diagnosis
Treatment
Military Considerations
LICHEN PLANUS
Clinical Features
Pathogenesis
Diagnosis
Treatment
Military Considerations
ATOPIC DERMATITIS
Clinical Features
Natural Course
Complications
Diagnosis
Treatment
Military Considerations
URTICARIA
Clinical Features
Types of Urticaria
Diagnosis
Treatment
Military Considerations
PSEUDOFOLLICULITIS BARBAE
Clinical Features
Pathogenesis
Diagnosis
Treatment
Military Considerations
CUTANEOUS VIRAL INFECTIONS
Herpes Simplex Labialis
Herpes Zoster
Molluscum Contagiosum
Warts
Military Considerations
SUMMARY

Military Dermatology
550
TABLE 20-2
PROPORTIONATE DISTRIBUTION OF SKIN
DISEASES SEEN IN U.S. DERMATOLOGY
CLINIC, 95TH EVACUATION HOSPITAL, DA
NANG, VIETNAM, 15 MAY 1970 TO 31 JULY
1971 (14.5 MONTHS) (% of total shown)
Disease
No. of Cases (%)
Verrucae, all types
729
(15.83)
Acne, all types
466
(10.12)
Dermatophytosis, all types
371
(8.06)
Pseudofolliculitis barbae
289
(6.28)
Penile ulcer [? chancroid]
221
(4.80)
Miliaria
199
(4.32)
Pyoderma, all types
178
(3.87)
Contact dermatitis
167
(3.63)
Urticaria
126
(2.74)
Tinea versicolor
123
(2.67)
Psoriasis
106
(2.30)
Atopic dermatitis
95
(2.06)
Dyshidrosis
95
(2.06)
Alopecia areata
82
(1.78)
Monilia
71
(1.54)
Lichen planus
70
(1.52)
Herpes progenitalis
68
(1.48)
Seborrheic dermatitis
56
(1.22)
Miscellaneous dermatoses and
dermatitides
51
(1.11)
Insect bites
48
(1.04)
Molluscum contagiosum
41
(0.89)
Sebaceous cyst
40
(0.87)
Pityriasis rosea
39
(0.85)
Hand and foot eczema
37
(0.80)
Lichen simplex chronicus
35
(0.76)
Syphilis infection, late and early
33
(0.72)
Erythema multiforme
32
(0.69)
Nevi
32
(0.69)
Balanitis
31
(0.67)
Basal cell epithelioma
25
(0.54)
Keloids
24
(0.52)
Corns and calluses
24
(0.52)
Drug eruptions
21
(0.45)
Vitiligo
20
(0.43)
Photoallergy
15
(0.33)
Nummular eczema
14
(0.30)
Pruritus
14
(0.30)
No diagnosis
56
(1.22)
Others
461
(10.02)
Total
4,605
(100.00)
Adapted from Allen AM. Skin Diseases in Vietnam, 1965–72. In:
Ognibene AJ, ed. Internal Medicine in Vietnam. Vol 1. Washing-
ton, DC: Medical Department, US Army, Office of The Surgeon
General and Center of Military History; 1977: 39.
Although common dermatoses are not generally
considered to pose a significant threat to the
health of an individual, they can become a major
problem for an entire armed force.  In harsh
environments, such as one would encounter
on a field of battle, these minor afflictions can be-
come incapacitating, thus rendering an individual
unfit for duty.  In a large unit, this collective loss
of fighting force could seriously impair the
effectiveness of the unit as a whole.  During the
Vietnam conflict, dermatoses were the third-high-
est cause of hospital admissions for disease, and
outpatient dermatology visits were double the
number required for any other condition.1,2  Clearly,
skin diseases can have a staggering impact on mili-
tary operations.
INTRODUCTION
Diagnosis
No. of Cases (%)
Pyoderma
47
(10.0)
Miliaria
43
(9.2)
Tinea
43
(9.2)
Verrucae
37
(7.9)
Eczematous dermatitis
26
(5.6)
Candidiasis
22
(4.7)
Infected eczematous dermatitis
20
(4.3)
Acne
18
(3.8)
Tinea versicolor
15
(3.2)
Urticaria
13
(2.8)
Contact dermatitis
11
(2.3)
Plantar warts
11
(2.3)
Alopecia areata
10
(2.1)
Pseudofolliculitis barbae
9
(1.9)
Psoriasis
7
(1.5)
Others
137
(29.2)
Total
469
(100.0)
Adapted from Allen AM. Skin Diseases in Vietnam, 1965–72. In:
Ognibene AJ, ed. Internal Medicine in Vietnam. Vol 1. Washing-
ton, DC: Medical Department, US Army, Office of The Surgeon
General and Center of Military History; 1977: 38.
TABLE 20-1
MOST COMMON DIAGNOSES IN NEW
PATIENTS SEEN AT DERMATOLOGY
CLINIC, 17TH FIELD HOSPITAL, SAIGON,
VIETNAM, JULY 1967 (% of total shown)

Common Skin Diseases
551
TABLE 20-3
DERMATOLOGY ADMISSIONS TO A BRITISH GENERAL HOSPITAL DURING WORLD WAR I
1915
1916
Nov
Dec
Jan
Feb
Mar
Apr
May
Jun
Total
Impetigo
122
172
151
161
220
170
147
116
1,259
Scabies
95
770
170
8
25
5
9
23
1,105
Boils
24
59
50
51
42
36
65
48
375
Pediculosis
–
17
62
69
36
3
5
6
198
Psoriasis
11
24
17
17
29
21
36
29
184
Eczema
7
22
18
11
37
22
33
31
181
Seborrhoea
8
12
13
11
40
18
18
11
131
Acne
6
22
19
12
8
6
10
7
90
Dermatitis
7
10
10
11
11
8
8
7
72
Syphilis
8
13
4
3
6
4
17
16
71
Folliculitis
1
11
13
9
8
2
5
1
50
Urticaria
2
4
3
3
2
11
8
1
34
Sycosis
4
2
4
1
3
2
5
7
28
Pityriasis rosea
3
2
2
5
3
2
2
3
22
Erythema
3
7
5
–
4
1
–
1
21
Carbuncle
2
4
3
1
4
2
1
2
19
Herpes zoster
2
2
2
–
3
3
1
–
13
Lupus
–
–
2
–
–
3
2
2
9
Erysipelas
–
–
–
–
1
–
1
2
4
Ecthyma
–
–
1
2
–
–
–
–
3
Lichen planus
–
–
1
1
–
–
1
–
3
Erythema nodosum
–
–
–
–
–
–
–
2
2
Ichthyosis
–
–
1
–
–
–
–
1
2
Sudamina
–
–
–
–
–
–
–
2
2
Adapted from Macpherson WG, Herringham WP, Elliott TR, Balfour A, eds. Medical services. Diseases of the war. In: History of the
Great War. Vol 2. London, England: His Majesty’s Stationery Office; 1923: 68.
One might expect the largest category of derma-
tologic casualties to be composed of exotic tropical
diseases; however, the greatest number of casual-
ties has been related to common skin maladies.
Experience from previous battles clearly indicates
that common dermatoses are a major source of
ineffectiveness and temporary disability among
battlefield personnel.  Pillsbury and Livingood3 re-
ported that the entire group of rare dermatoses was
of no significance in the total disability from skin
diseases in World War II.  Statistics available from
Vietnam and World War I (Tables 20-1 through 20-
3) support a similar conclusion.3,4  It is apparent
from these experiences that many casualties can be
averted in the future if more military medical per-
sonnel are trained in the recognition and manage-
ment of some common skin diseases.
Tables 20-1 through 20-3 list a number of skin
diseases that were discussed in previous chapters,
such as impetigo (Chapter 13, Bacterial Skin Dis-
eases), scabies (Chapter 8, Arthropod and Other
Animal Bites), and miliaria (Chapter 3, Skin Dis-
eases Associated with Excessive Heat, Humidity,
and Sunlight).  This chapter will address common
dermatoses that did not fit in the previous chapters
of this textbook.

Military Dermatology
552
PSORIASIS
Psoriasis is a common, genetically determined,
inflammatory skin disease characterized by distinc-
tive lesional morphology and distribution.  It af-
fects men and women equally5 and typically runs a
chronic course that is marked by frequent relapses.
It occurs worldwide and affects approximately 1%
of the population in the United States.6  Psoriasis
can have its onset at any age, but is most likely to
appear in early adulthood.7  Although its exact
etiology is unknown, it is clear that psoriatic skin is
in a hyperproliferative state with a marked increase
in the rate of keratinocyte replication.8–10
Fig. 20-1. Psoriasis. (a) Large, geographic plaques. Note how lesions suggest the coastline of a map. (b) Note symmetry and
extensive involvement of lesions. (c) Lichenified geographic plaques in obese individual. (d) Characteristic silvery scale.
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b
c
d
a
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Common Skin Diseases
553
Clinical Features
Psoriasis is a classic example of a papulosquam-
ous disease, characterized by erythematous pap-
ules and plaques with a silvery scale.  The disorder
can vary from a focal disease consisting of localized
lesions to a widespread eruption and even a gener-
alized erythroderma with exfoliation.11,12
The characteristic early lesion of psoriasis is an
erythematous papule with a scale that can be subtle
but is usually obvious.  Typically, the papules gradu-
ally expand and coalesce to form sharply demar-
cated, symmetrically distributed plaques (Figure
20-1).  Frequently, the plaques become surrounded
by a thin zone of perilesional blanching, known as
a Woronoff ring.  This ring is most frequently seen
in the early stages of resolution in ultraviolet (UV)
light therapy (Figure 20-2).  Although some au-
thorities13 have shown evidence of prostaglandin
inhibition to explain this phenomenon, the precise
mechanisms involved are likely to be more com-
plex.14
Psoriasis can occur at any cutaneous site, al-
though it has a predilection for the scalp, elbows,
knees, extensor aspects of the extremities, and the
nails.  It also frequently involves the penis (Figure
20-3).  Oral lesions are unusual in psoriasis; how-
ever, some authorities15–17 believe that the condition
known as geographic tongue (Figure 20-4) may
actually be a manifestation of psoriasis, because the
histological features are identical.  Occasionally,
only intertriginous areas are involved (inverse pso-
riasis).  When one suspects a diagnosis of psoriasis,
it is often helpful to inspect the intergluteal cleft for
Fig. 20-3. Psoriasis on the penis. Note the paucity of scale.
involvement (Figure 20-5).  A typical feature of
psoriasis is Köebner’s phenomenon, the appear-
ance of lesions in scars or other sites of trauma.18
The lesions may appear in sites of old, major trauma
such as surgical scars or in areas of recent or mini-
mal injury such as an abrasion.  The cause of this
phenomenon is not known, although recently, specu-
lation has focused on microbial factors.19
The scale in psoriasis is typically silvery white
and stacked in layers.  In this way, the scale is said
to be micaceous (slatelike).  When the scale is re-
moved with curettage or scraping, pinpoint bleed-
ing may be noted.  This is known as the Auspitz
sign.  It is more common, however, to observe a
loose scale that easily flakes off in patients with
long-standing lesions.  Although traditionally con-
Fig. 20-2. Woronoff’s rings. Note the zones of hypopig-
mentation outlining the resolving psoriatic plaques in
this patient undergoing ultraviolet-B phototherapy.
Fig. 20-4. Annular and arcuate pustular lesions of geo-
graphic tongue.
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Military Dermatology
554
sidered a hallmark of psoriasis, the Auspitz sign’s
sensitivity and specificity have been questioned by
Bernhard, who elicited the sign in several
nonpsoriatic, scaling disorders.20
When examining a patient with presumed pso-
riasis, one should always examine the fingernails
and toenails, which frequently reveal diagnostic
clues (Figure 20-6).  Onycholysis—separation of the
distal free edge of the nail plate from the nail bed—
is a frequent finding.  Less common, but more
specific, is nail pitting—actual punctate depres-
sions on the surface of the plate.  The most specific
nail finding, often said to be pathognomonic, is the
so-called “oil spot,” which describes a yellowish
brown, irregular macule beneath the nail plate and
represents involvement of the nail bed with psoria-
Fig. 20-5. Annular erythematous plaque with fine surface
scale in the intergluteal cleft.  This is a common site for
psoriasis.
a
c
b
d
Fig. 20-6. Psoriatic nails. (a) Pitting, thickening, and discoloration. (b) Pitting, distal onycholysis, and “oil spot.” (c)
Distal onycholysis and “oil spots” in patient with large psoriatic plaques. (d) Onycholysis, discoloration, and
crumbling of nail plate.  Photograph c: Courtesy of Dr. Charles Trapp, MacDill Air Force Base, Fla.
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Common Skin Diseases
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sis.  When the nail matrix is involved, severe
onychodystrophy can result, with diffuse crum-
bling and yellowing of the plate.  In pustular psoria-
sis and acrodermatitis continua of Hallopeau, one
commonly observes subungual pustules.
Types of Psoriasis
Psoriasis Vulgaris
Psoriasis Vulgaris  is the most frequent presenta-
tion of psoriasis, consisting of chronic, stable, well-
defined plaques that may persist for years.  While
the plaques can occur on any cutaneous surface,
they are most likely to appear in the areas of predi-
lection described above.
Guttate Psoriasis
Guttate psoriasis most commonly occurs in young
adults and is usually eruptive in onset.  It consists of
multiple, small, guttate (raindroplike) lesions over
the trunk and proximal extremities (Figure 20-7).
Frequently, careful history-taking will reveal an
antecedent streptococcal pharyngitis or viral respi-
ratory infection.21
Localized Pustular Psoriasis
Localized pustular psoriasis consists of two types:
pustular psoriasis of the palms and soles, known as
pustulosis palmoplantaris (Figure 20-8), and
acrodermatitis continua of Hallopeau.  Both forms
present with pustules, the former involving the
palms and soles, and the latter involving the distal
fingers and toes with severe nail dystrophy (Figure
20-9).  Both conditions are noted for chronicity and
refractoriness to treatment.  When severe, either can
be disabling.  Pustulosis palmoplantaris has been
associated with arthritis of the anterior chest wall,22
cigarette smoking, and thyroid disease.23
Generalized Pustular Psoriasis
Generalized pustular (von Zambusch) psoriasis
is one of the rarer presentations of psoriasis,24,25
marked by acute attacks of generalized pustules on
erythematous skin and associated with fever,
leukocytosis, and systemic toxicity.  This disease
can be fatal, so hospitalization is mandatory.  Sev-
eral provocative factors are claimed to precipitate
attacks, but the most important to consider is the
association with steroid withdrawal (ie, systemic
and potent topical steroids).25,26
Fig. 20-7. Guttate psoriasis. Note scattered distribution
of discrete, small, erythematous papules and plaques
with scale.
Psoriatic Arthritis
Psoriatic arthritis is an inflammatory, sero-nega-
tive arthritis clearly associated with psoriasis (Fig-
ure 20-10).27  It has been neatly classified into five
general categories (Table 20-4).28
Diagnosis
When chronic, scaling plaques are present on
extensor surfaces or on the penis or scalp, the diag-
nosis is usually obvious.  Occasionally, however,
psoriasis can mimic other papulosquamous disor-
ders: seborrheic dermatitis, lichen planus, pityriasis
rosea, pityriasis rubra pilaris, drug eruptions, or
even syphilis.  Isolated lesions may be confused
with lichen simplex chronicus, nummular derm-
atitis, cutaneous lupus erythematosus, or mycosis
fungoides.  When one suspects the diagnosis of
psoriasis, it is essential to perform a thorough cuta-
neous exam looking for clues such as nail involve-
ment, evidence of Köebner’s phenomenon,
or pinking of the intergluteal cleft.  Obtaining a
family history can also provide useful information.
If doubt still exists, biopsy should be obtained
because the histopathological features are fairly
distinctive.
Treatment
Numerous modalities are available for the treat-
ment of psoriasis.  This fact speaks for the complex-
ity of the disease, the mystery of its pathogenesis,
and the limitations of all of the available treatments.
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Military Dermatology
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Fig. 20-8. (a) Psoriasis of the palms. (b) Psoriasis of the soles. (c) Pustulosis plantaris. (d) Close-up view of (c) to reveal
characteristic yellow-brown pustules.
a
c
b
d
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Common Skin Diseases
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Fig. 20-10. Psoriatic arthritis. (a) Proximal interphalangeal
joint of finger. (b) Toe involvement—”sausage digit.” (c)
Severe involvement of fingers and hand.
Fig. 20-9. Scaling and crusted lesions with border of
peripheral pustules on the distal digits, characteristic of
acrodermatitis continua of Hallopeau.
c
a
b
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Military Dermatology
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TABLE 20-4
ARTHRITIS IN PSORIASIS
Type of Arthritis
Characteristics
Asymmetric involvement of a few joints
Affects 70% of patients with psoriatic arthritis; “sausage digit”
 of the fingers
Symmetric polyarthritis
Affects 15% of patients with psoriatic arthritis; resembles rheumatoid
arthritis (seronegative)
Distal interphalangeal joint involvement
Affects 5% of patients with psoriatic arthritis; “classic” psoriatic
arthritis
Arthritis mutilans
Affects 5% of patients with psoriatic arthritis; deforming arthritis
with bony destruction, telescoping of digits, and ankylosis
Ankylosing spondylitis
Affects 5% of patients with psoriatic arthritis; may also have
peripheral joints involved
Data source: Moll JMH, Wright V. Familial occurrence of psoriatic arthritis. Ann Rheum Dis. 1973;22:181.
There clearly is no treatment of choice in the man-
agement of psoriasis.  Many new modalities have
been described recently, such as vitamin D,29 fish
oil,30 and cyclosporine.31  At this point, these thera-
pies should be considered investigational.  Medical
officers are advised to consider first the more tradi-
tional, time-honored modalities available.
No treatment is without side effects.  The risks
for adverse side effects can often be reduced by
combination therapy, such as retinoids combined
with psoralen and UV-A (PUVA).  The advantage of
combination therapy is that the cumulative dose of
each agent is diminished.  Thus, while the beneficial
effects may be additive, the adverse effects are
usually decreased.  Furthermore, when approach-
ing the treatment of psoriasis, one must realize that
the aim of treatment should not be to obtain com-
plete clearing.  That is often an unrealistic approach
in the management of psoriasis.  Complete clearing
is often unattainable without experiencing signifi-
cant toxicity.  Realistic expectations by the physi-
cian as well as the patient are perhaps the most
important aspects of therapy.
Topical Corticosteroids
Topical corticosteroids are frequently employed
in the management of psoriasis and can be quite
beneficial.  Due to a potent antiinflammatory effect
and inhibition of deoxyribonucleic acid (DNA) syn-
thesis (with a subsequent antiproliferative effect),
topical steroids are a logical and effective modality
in this disease.  Intralesional steroids may be con-
sidered for isolated or resistant plaques.  The limit-
ing factor for topical corticosteroids is epidermal
and dermal atrophy, which can result in marked
thinning of the skin and striae formation (Figure
20-11).  More importantly, sustained use of potent
topical steroids can lead to suppression of the
hypothalamic-pituitary-adrenal axis.32,33  Pulse
dosing may permit extended maintenance with
potent topical steroids while limiting adverse ef-
fects.34  Another drawback to consider regarding
steroid therapy is the development of tachyphy-
laxis.  For these reasons, one is encouraged to con-
sider alternative topical agents for the treatment of
psoriasis.
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Fig. 20-11. Linear atrophic striae on the back of this
patient, who is taking oral steroids.

Common Skin Diseases
559
Anthralin
Anthralin is a synthetic anthrone derivative that
reduces mitotic activity and suppresses free radi-
cals.  It is widely used in Europe as an integral
component of the Ingram regimen, which consists
of a daily coal tar bath followed by subery-
themogenic UV-B exposure, then the application of
dithranol paste of gradually increasing concentra-
tion.5  Although this method is quite effective and
safe, it is cumbersome.  For this reason, short-con-
tact anthralin treatment plans have been devised,35
frequently with the addition of coal tar36,37 to dimin-
ish the irritancy of anthralin, which can limit its use.
Due to its lack of systemic toxicity, carefully super-
vised anthralin therapy combined with thorough
patient explanation and education is an ideal
modality for the treatment of chronic plaque-type
psoriasis.
Coal Tar
Coal tar has been widely employed in the treat-
ment of psoriasis for more than a century.  It is a
complex mixture of over 10,000 substances,38 which
may possess antimitotic activity.39  Coal tar gained
popularity after introduction of a simple method
described by Goeckerman in 1925,40 which consists
of continued application of 2% crude coal tar, which
is removed with mineral oil once daily for UV-B
exposure.  The tar is reapplied after bathing.
Coal tar is an extremely safe agent.  The most
frequent side effect is a tar-induced folliculitis.  There
have been reports of skin cancers associated with
coal tar application41,42; however, this is an uncom-
mon event, and such case reports usually involve
patients who have been exposed to multiple other
skin cancer–inducing agents.
Systemic Methotrexate
Methotrexate, given in weekly oral doses of 5 to
25 mg, is an extremely valuable agent for treating
severe psoriasis and psoriatic arthritis that are not
adequately controlled by more conventional thera-
pies.  It is a folate antagonist that exerts its
antiproliferative effect on psoriatic epidermal cells
by directly inhibiting DNA synthesis.43
Methotrexate is absolutely contraindicated in
pregnant or lactating females.  Relative contrain-
dications are many, including liver or renal abnor-
malities, excessive alcohol consumption, and ane-
mia, leukopenia, and thrombocytopenia.  Guidelines
for appropriate use of methotrexate in psoriasis are
published periodically by the Psoriasis Task Force
of the American Academy of Dermatology.44  Medi-
cal officers should be thoroughly knowledge-
able with these guidelines before considering
methotrexate for the treatment of psoriasis.  The
greatest limitation of methotrexate is its hepato-
toxicity.  For this reason, newer folate antagonists
with perhaps fewer effects on the liver are being
investigated.45
Systemic Retinoids
The retinoids are synthetic derivatives of vita-
min A and vitamin A acid.  The effects of vitamin A
and vitamin A analogs on the growth and terminal
differentiation of epidermal cells and the vitamin’s
beneficial effect on disorders of keratinization have
long been known.  Retinoids have been shown to
affect growth of epidermal cells by altering keratin
synthesis and formation of the cell envelope.46
Etretinate (0.5–1.0 mg/kg/d) is the retinoid ap-
proved for use in the treatment of psoriasis.  It
should be considered for initial treatment in the
management of pustular psoriasis or erythrodermic
psoriasis.47  It is also beneficial for the patient with
extensive plaques and severe involvement recalci-
trant to more conventional modalities and has been
successful in clearing acrodermatitis continua of
Hallopeau.48
Etretinate has significant risk for adverse effects
including teratogenicity, elevation of serum lipids,
liver toxicity, and numerous mucocutaneous side
effects.  In addition, cases of skeletal hyperostoses
have been documented with long-term use.49  Fur-
thermore, it is known to be stored in adipose tissue
for long periods, thus leading to a prolonged half-
life (> 100 d).50  In fact, blood levels are detectable
for more than 2 years after discontinuation of
therapy.  For these reasons, in addition to its potent
teratogenicity, etretinate is best avoided in women
of child-bearing potential.  Alternatives include
isotretinoin and, once available, acitretin—the main
metabolite of etretinate—which has been shown to
be effective in treating psoriasis and has a much
shorter half-life (50 h for acitretin vs 120 d for
etretinate).51  Because the side effects of acitretin are
similar to those of etretinate, including potent ter-
atogenicity, effective contraception is essential for
women and long-term use is discouraged.  Because
risks are greatly increased with long-term use of
retinoids, they are probably best used in combina-
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Military Dermatology
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Ultraviolet-B Phototherapy
Natural sunlight has long been known to im-
prove psoriasis.  An excellent (and more reliable)
substitute is an artificial light source that produces
light primarily in the ultraviolet-B (UV-B) range
(290–320 nm).  This allows for continuous monitor-
ing and metered delivery of UV radiation, thus
diminishing the potential for accidental overexpo-
sure and burning.  Although the mechanism of the
therapeutic effect is unknown, UV-B alone or with
coal tar is an excellent method for clearing psoriasis
and maintaining remission.  Its use should be con-
sidered early in the course of management.
Psoralen and Ultraviolet-A Phototherapy
Introduced in 1974 by Parrish and Fitzpatrick,52
PUVA phototherapy has gained worldwide accep-
tance in the treatment of psoriasis.  Patients ingest
a specific dose of methoxsalen (consult chart in
package insert for precise dosage based on weight),
followed in approximately 90 minutes by a care-
fully metered UV-A (320–400 nm) exposure, which
is increased with progressive treatments.  Initially,
Oxsoralen was the drug employed.  This has now
been replaced by Oxsoralen-Ultra (methoxsalen,
manufactured by ICN Pharmaceuticals, Inc., Costa
Mesa, Calif.), a liquid form in a gel capsule that
provides more uniform serum drug levels.53  Pa-
tients are treated two to three times per week, and
generally respond within 20 to 25 treatments.  PUVA
can then be continued and gradually tapered to
maintain prolonged remission.
PUVA exerts its effect through the production of
bifunctional DNA adducts and subsequent inhibi-
tion of DNA synthesis and epidermal cell replica-
tion.54  It is an excellent modality for managing
severe psoriasis on an outpatient basis.  However, it
is not without risk.  Patients must wear protective
eyewear (wraparound UV-A filtering glasses) for
24 hours after ingestion of the drug to prevent
cataracts.  It has been well documented that PUVA
is clearly associated with an increased risk for
nonmelanoma skin cancer, particularly squamous
cell carcinoma.55,56  The study by Fitzpatrick and
Parrish55 reveals that the risk of developing squa-
mous cell carcinoma increases with cumulative
PUVA exposure.  The higher exposure group (> 260
treatments) has a risk that is 12-fold that of the
lower exposure group (< 160 treatments) and 100-
fold that of the general population.55  This fact
emphasizes the point made previously: the goal of
therapy when managing psoriasis should not be
100% clearing.  Ninety percent clearing is, gener-
ally, much easier to attain and maintain at far less
risk, and this is usually quite acceptable to the
patient.  Clearly, PUVA should not be used unless
the patient’s psoriasis is severe.  While PUVA-in-
duced squamous cell carcinoma has little potential
for metastatic spread, all patients receiving PUVA
must be carefully monitored to ensure early detec-
tion and prevention of disfigurement.  All men
should shield the genital region during therapy, as
this area has proven to be at particular risk for
developing PUVA-induced tumors.57
PUVA-associated carcinogenesis may possibly
be avoided by employing PUVA bath treatments
using a trioxsalen solution.  This technique has been
used extensively in Europe and has been shown to
be of equal efficacy58 to and probably safer than
standard PUVA.58–60  This author has found a simi-
lar technique using a solution of Oxsoralen, as de-
scribed by Coleman et al,61 to be extremely effective
in the management of pustulosis palmoplantaris.
All forms of PUVA may be combined with other
treatments such as retinoids to obtain superior re-
sults while diminishing adverse effects.
Military Considerations
The main point to emphasize to the military
physician regarding psoriasis is its tendency to-
wards chronicity and its sometimes unpredictable
course.  Consider the individual with mild plaque-
type psoriasis who is easily controlled with anthralin
and intermittent UV-B therapy.  That same indi-
vidual deployed to a northern climate or hostile
environment may experience a significant flare-up
requiring medical evacuation and preventing mis-
sion completion.  This author has observed this
scenario repeatedly.  In World War II, dermatolo-
gists found that approximately 20% of psoriatic
patients became liabilities and questioned whether
troops with significant psoriasis should ever be sent
overseas.62  In U.S. Army medical clinics in Viet-
nam, psoriasis accounted for up to 6% of outpatient
visits.2  Individuals with psoriasis of even mild
severity should be considered for presentation to a
medical evaluation board for determination of
worldwide qualification.
Another point to consider about psoriasis in the
military is a controversial one: the role of
antimalarial chemoprophylaxis in inducing exacer-
bations of psoriasis.63  This author witnessed one
case of a young sailor who experienced a pustular
flare-up of his psoriasis while on chloroquin pro-
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Common Skin Diseases
561
bers with psoriasis.  Kuflik reported on 48 U.S.
Army patients with psoriasis on prophylactic
chloroquin in Vietnam: 42% of the cases worsened,
but only 6% had significant flare-ups.64
ship and a prolonged hospital course, including an
initial stay in the intensive care unit.  While this is
anecdotal, it illustrates the argument for reconsid-
ering worldwide eligibility for all military mem-
Lichen planus (LP) is an inflammatory skin
disease that is often pruritic, with distinctive
mucocutaneous findings.  In 1969, Erasmus Wilson
published a series of 50 cases describing the
classic features of LP.65  The prevalence of LP in the
general population is estimated to be 0.13% to 0.34%
for cutaneous involvement and 0.19% to 1.5%
for oral involvement.66  In a study of over 670,000
patients in the United States, LP was seen in
0.44%.67  In a general dentistry clinic, oral LP was
seen in 0.6%.68
LP predominantly afflicts people in their middle
ages, with approximately two thirds of those af-
fected between the ages of 30 and 60.67  It is world-
wide in its distribution with no racial predisposi-
tion.  Both sexes are affected approximately equally.
Familial cases have been reported.69,70
Clinical Features
The characteristic lesion of LP is a flat-topped,
shiny, polygonal papule that is most often described
as violaceous in color.  Individual papules range in
size from pinpoint to greater than 1 cm and may
remain discrete or become confluent.  Frequently,
one can observe fine, reticulate white streaks on the
surface.  These streaks, known as Wickham’s striae,
are most easily seen with the use of mineral oil and
LICHEN PLANUS
Fig. 20-12. Lichen planus. (a) Ankle. Note violaceous, flat papules with reticulated white scale. (b) Flexor surface of
the wrist, a common location. (c) Dorsum of hand. (d) Close-up of (a) to demonstrate Wickham’s striae.
b
a
d
c
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Military Dermatology
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the aid of a hand-held lens.  Köebner’s phenomenon
is sometimes observed.18,71
LP may remain a localized process or have a
generalized distribution.  When LP becomes gener-
alized it usually does so within the first month of
onset and is typically symmetric in its distribution.
The majority of cases begin on the extremities, espe-
cially the ankles72 and the flexor aspects of the
wrists (Figure 20-12).73  The ankles and shins are the
most common sites for hypertrophic lesions.74  Other
cutaneous sites commonly involved include the
lumbar region and the penis; the latter site may
have annular or ulcerative lesions (Figure 20-13).
Erosive and ulcerative forms of LP can also be
found on other mucous membranes as well as on the
palms, soles, and arms (Figure 20-14).75,76
The natural course of LP is usually spontaneous
resolution—93% within 2 years in Samman’s study.77
Among this same series of patients, the rate of
relapse was 20%.  Typically, marked postin-
flammatory hyperpigmentation, hypopigmentation,
or both will occur as lesions regress.78
Nail involvement is seen in 10% of cases.77  This
is most commonly manifested as surface roughness
or flaking with longitudinal ridging.  Other changes
include brownish discoloration, pitting, and thin-
ning of the nail plate with splitting of the free edge.
Chronic nail involvement can result in pterygium
formation as a result of the growth of the cuticle and
subsequent adherence to the nail bed, resulting in
permanent loss of the nail plate.  Occasionally, the
nails may be the only site of involvement.79,80  These
cases normally require histological confirmation
for diagnosis.  Twenty-nail dystrophy, a disorder of
Fig. 20-14. Annular lichen planus on the arm. Note the
central hyperpigmentation and characteristic violaceous
border with slight scale.
acquired dystrophic nail changes in children, may
be a manifestation of LP.81,82  Several other variants
of cutaneous LP exist (Exhibit 20-1).
Involvement of oral mucosa is very common in
LP.  In Altman and Perry’s series of 197 patients,
40% had cutaneous and mucosal involvement, and
25% had oral alone.83  Oral lesions can be found
in up to 71% of LP patients seen in dermatology
clinics.77,83
Oral LP typically involves buccal mucosa, al-
though other sites can be involved.  These include
Fig. 20-13. Annular lichen planus on the penis—a com-
mon location. Note violaceous border and central hyper-
pigmentation.
EXHIBIT 20-1
VARIANTS OF CUTANEOUS LICHEN
PLANUS
Hypertrophic lichen planus
Linear lichen planus
Annular lichen planus
Atrophic lichen planus
Lichen planus subtropicus (actinicus)
Bullous lichen planus
Lichen planopilaris
Lichen planus pemphigoides
Lichen planus–lupus erythematosus overlap
Ulcerative lichen planus
Hepatitis-associated lichen planus
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Common Skin Diseases
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a
b
Fig. 20-15. Oral lichen planus. (a) Characteristic reticulate, white plaque on the buccal mucosa—the most commonly
involved site. (b) Involvement of the lower lip.
the tongue, gingiva, and vermilion border of the lip
(Figure 20-15).84  Involvement of the palate and
sublingual region is rare.  Almost always, oral LP
occurs bilaterally.  The appearance of LP in the oral
mucosa can be quite varied.  The most common
morphology is that of a plaque consisting of slightly
elevated, very fine white lines in a reticulate pat-
tern, similar to Wickham’s striae.  This has been
referred to as “Honniton lace.”  Other forms include
a papular variant or a plaquelike form (resembling
leukoplakia), an atrophic form (resembling
erythroplakia), bullae (rare), and an erosive form.84
Erosions are often extensive and can result in
desquamative gingivitis.85
The natural course of oral LP is one of chronicity,
with a mean duration of almost 5 years.72  Oral LP
has been shown to persist for more than 25 years.85
Persistent, erosive, oral LP may have a potential for
the development of squamous cell carcinoma, al-
though this is controversial.86–89  Some authorities88
consider oral LP to be a premalignant condition.
Pathogenesis
The precise etiology of LP remains unknown
despite intensive investigation.  Multiple hypoth-
eses support numerous etiologies, including infec-
tious agents, tobacco, betel nuts, psychogenic stress,
chemicals, and numerous drugs.  Some cases of LP
have occurred in patients with diabetes, hepati-
tis,89,90 hepatic biliary cirrhosis,91 hypertension, and
urolithiasis.  While the exact triggering mechanism
for LP remains unknown, recent work strongly im-
plicates T-cell–mediated cytotoxicity as the final
common pathway leading to the development of
the lesion of LP.92,93  Norris94 recently demonstrated
marked staining for ICAM-1 (intercellular adhe-
sion molecule-1) of basal cells in skin from lesions of
lichen planus.  One could propose that this would
lead to binding between the basal keratinocytes and
T lymphocytes within the dense dermal infiltrate,
resulting in the cytotoxic destruction of the
keratinocytes.
Diagnosis
Lichen planus has a rather distinctive clinical
presentation.  Other entities to consider in the dif-
ferential diagnosis are lichenoid drug eruptions,
psoriasis, syphilis, and LP-like keratoses.  When the
skin lesions suggest a diagnosis of LP, always ex-
amine the mouth, which will frequently reveal the
characteristic white, reticulate plaques typical of
LP.  Oral lesions, in the absence of cutaneous find-
ings, may be confused with candida, traumatic ero-
sions, aphthae, leukoplakia, or bullous diseases such
as pemphigus vulgaris or erythema multiforme.
Biopsy will usually confirm the diagnosis of LP,
which has specific histological features.  History is
the most important feature to distinguish a lichenoid
drug eruption from LP.
Treatment
The mainstay of therapy for LP is corticosteroids.
In localized forms, potent topical steroids or
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Military Dermatology
564
steroids applied under occlusion may be bene-
ficial.  Large plaques generally respond to
intralesional triamcinolone (3–5 mg/mL).  General-
ized or eruptive LP usually requires systemic
steroid therapy.  Alternatives to consider are
PUVA95,96; retinoids97,98; and griseofulvin (125–250
mg twice daily), which has been reported to have
a cure rate as high as 90%,99,100 although other re-
ports show it to be completely ineffective.101  Oral
lesions may respond to topical steroids in Orabase
(gelatin, pectin; manufactured by Colgate-Hoyt,
Canton, Mass.) or aerosolized betamethasone val-
erate.  Recently, two groups102,103 have reported sig-
nificant improvement of oral LP using a topical
cyclosporine rinse with no systemic adverse effects
and little systemic absorption over a 2-month pe-
riod.  However, the cost of cyclosporine may prove
prohibitive.
In addition, antihistamines and antipruritic lo-
tions may be useful and should be employed for
relief of pruritus.
Military Considerations
Although LP is generally considered to be a
benign, self-limited disease, the pruritus that usu-
ally accompanies it may interfere with perform-
ance of duty.  It is important, then, to treat
symptomatic patients aggressively to keep them
functional.
Of historical significance is the widely reported
relationship of atypical LP with the administration
of quinacrine for antimalarial prophylaxis in World
War II.104–107  The study by Bazemore et al104 of 400
patients reveals that long-term therapy with
antimalarials is necessary to induce atypical LP, as
only 20% of patients developed the disease within 3
months, while 80% developed the disease within 7
months.  Many cases were complicated by a second-
ary pyoderma—usually caused by Streptococcus
pyogenes and Staphylococcus aureus.  This most likely
was a result of inadequate hygiene in a tropical
environment.  The eczematous process frequently
involved the hands, thus disqualifying many indi-
viduals from full military duty.  On return to duty,
relapse was almost certain, so prompt evacuation
became the treatment of choice.62
A variant of LP rarely seen in the United States
that could potentially be of significance for de-
ployed military personnel is LP subtropicus
(actinicus).  This is common in the Middle East and
consists of annular lesions on sun-exposed sur-
faces, particularly the face.108–110  The course is chronic
and the condition worsens with sun exposure.  Treat-
ment consists of using sun blockers and limiting
sun exposure.
Atopic dermatitis is an environmentally induced
disorder occurring in genetically predisposed indi-
viduals.  It is characterized by acute episodes of
eczematous cutaneous eruptions with characteris-
tic distribution, usually accompanied by xerosis.
The disorder may be considered part of the atopic
diathesis that also includes allergic rhinitis,
conjunctivitis, and asthma.  It is prevalent world-
wide and is more common among children, particu-
larly of industrialized countries.  Its incidence in
England is 1.1% to 3.1%.111,112  In the United States it
is 0.7 to 2.4%.113
Clinical Features
The clinical features of atopic dermatitis can be
classified into major features that are seen in most
atopic patients and minor, nonspecific features that
are frequently seen in atopic patients (Exhibit
20-2).114  There is no primary lesion of atopic
dermatitis.  The lesions are eczematous and marked
by erythema, weeping, scaling, crusting, and
lichenification (thickening of skin in response to
continual rubbing).  Often, the lesions may be
excoriated or secondarily infected.  Atopic dermatitis
is recognized by observing these findings in a
typical pattern of distribution.  In infants and chil-
dren under 2 years of age, the lesions typically
occur on the face (Figure 20-16) and extensor sur-
faces.  Paradoxically, in older children and adults,
the characteristic pattern is that of predominantly
flexural involvement with sparing of the face
(Figure 20-17).
History is extremely helpful in establishing
the diagnosis of atopic dermatitis.  The age of on-
set is usually in childhood—60% within the
first year of life.115  Seventy percent of patients
will have a history of asthma, hay fever, or
both.114  A family history of atopy is almost always
present.
ATOPIC DERMATITIS

Common Skin Diseases
565
EXHIBIT 20-2
CLINICAL FEATURES OF ATOPIC
DERMATITIS
Major Features
Pruritus
Flexural lichenification in adults
Facial and extensor involvement in infants and
children
Chronic or chronically relapsing dermatitis
Personal or family history of atopy (asthma,
allergic rhinitis, atopic dermatitis)
Minor Features
Xerosis
Ichthyosis, palmar hyperlinearity, keratosis
pilaris
Immediate (type 1) skin test reactivity
Elevated serum immunoglobulin E
Early age of onset
Tendency toward cutaneous infections (espe-
cially with Staphylococcus aureus and herpes
simplex virus), impaired cell-mediated
immunity
Tendency toward nonspecific hand or foot
dermatitis
Nipple eczema
Cheilitis
Recurrent conjunctivitis
Dennie-Morgan infraorbital fold
Keratoconus
Anterior subcapsular cataracts
Orbital darkening
Facial pallor, facial dermatitis
Pityriasis alba
Anterior neck folds
Pruritus when sweating
Intolerance to wool
Perifollicular accentuation
Food intolerance
Course influenced by environment or emo-
tional factors
White dermographism, delayed blanch
Data source: Hanifin JM. Clinical and basic aspects of
atopic dermatitis. In: Seminars in Dermatology. New York,
NY: Thoieme-Stratton, Inc; 1983: 25–29.
Natural Course
The natural course of atopic dermatitis is one of
repeated episodes of acute flare-ups, followed by a
subacute phase of slow resolution.116  Acute episodes
tend to occur in response to psychic or emotional
stress.  In a study in which more than 500 patients
were interviewed, stress was considered the primary
precipitating factor.117  Between flare-ups, patients
will often be bothered by generalized xerosis, which
often is quite pruritic and creates an intolerance of the
skin for exposure to solvents, soaps and other cleans-
ers, and water (in excessive amounts).
Fig. 20-16. Atopic dermatitis in an infant most commonly
involves the face, with perioral sparing.
Fig. 20-17. Atopic dermatitis in a young adult, with
typical involvement of antecubital fossae and marked
symmetry.
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Hand dermatitis is frequently seen in patients
with atopic dermatitis, particularly adults.  Ap-
proximately 70% will experience it.118  Careful
questioning of adult patients with hand derma-
titis will often reveal a prior history of atopic
dermatitis.
Complications
Staphylococcal pyoderma is a frequent compli-
cation of atopic dermatitis.  The skin of nearly all
patients with atopic dermatitis is heavily colonized
with S aureus. 
119,120  This is partially explained by the
observation that S aureus may have specific binding
sites for tissue fibronectin and laminin.121,122  In
general, these infections remain superficial, but cases
of osteomyelitis have been reported in children
with severe atopic dermatitis.123
As a result of impaired cellular immune re-
sponses,124 patients with atopic dermatitis some-
times are unable to adequately handle viral or
fungal infections of the skin.  This increased suscep-
tibility has resulted in widespread cutaneous viral
infections such as eczema vaccinatum (vaccinia vi-
rus from smallpox vaccine) and Kaposi’s vari-
celliform eruption, which is usually caused by herpes
simplex virus (HSV) (Figure 20-18), but has also
been seen with coxsackievirus A16.  Both produce a
similar clinical picture of an acute, widespread,
vesiculopustular eruption marked by fever,
adenopathy, and prostration.  The patients may
appear quite ill and some have died.125,126  Treatment
is with intravenous acyclovir (750 mg/m2/d) and
antibiotics for secondary bacterial infection.  Other
Fig. 20-18. Kaposi’s varicelliform eruption from herpes
simplex virus in a young adult female with a history of
eczema in childhood.
EXHIBIT 20-3
COMMON PRECIPITATING FACTORS
IN ATOPIC DERMATITIS
Excessive exposure to soap, hot water, or chemicals
Psychic stress
Overheating (by physical exertion or hot climate)
Cutaneous infection or infestation (eg, scabies)
Extremes of temperature (hot or cold)
Prickly clothes
Allergic exposure (when relevant)
viruses that can cause problems for atopic patients
include molluscum contagiosum and human
papillomavirus (HPV).
Diagnosis
Atopic dermatitis is most often confused with
contact dermatitis (irritant or allergic), but other
dermatoses in the differential diagnosis include
seborrheic dermatitis, psoriasis, scabies, nummular
dermatitis, and lichen simplex chronicus.  Atopic
dermatitis is a clinical diagnosis based on the find-
ings of at least three major and three minor criteria
(see Exhibit 20-2).
Treatment
When approaching the management of atopic
dermatitis, it is useful to keep in mind that this is a
disease that is precipitated in genetically predis-
posed individuals by an environmental stress.  The
first goal of treatment, therefore, is the elimination
of known precipitating factors (Exhibit 20-3).
Topical steroids are a mainstay of therapy in
relieving the inflammation of acute episodes and
the associated pruritus.  Their use should be care-
fully supervised by the treating physician.  Patients
must be aware of the risks for dermal atrophy,
adrenal suppression, and tachyphylaxis.  Because
flexural areas are commonly involved, one must be
especially alert for possible steroid-induced atro-
phy.  Topical steroids should be applied sparingly
and only on inflamed areas.  Highly potent topical
steroids such as clobetasol propionate applied twice
daily may be useful in short courses (less than 2 wk)
for treating areas of lichenification, but are best
avoided in children.  Systemic steroids, while effec-
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Common Skin Diseases
567
tive, are not recommended as patients are likely to
become dependent on them.
Because xerosis is so often a precipitating factor,
hydration of the skin is an essential component of
therapy.  Emollients such as Eucerin (water, min-
eral oil; manufactured by Beiersdorf, Norwalk,
Conn.), Lac-Hydrin (ammonium lactate, manufac-
tured by Westwood Pharmaceuticals, Buffalo, N.Y.),
Moisturel (petrolatum, glycerin; manufactured by
Westwood Pharmaceuticals, Buffalo, N.Y.), and 10%
urea cream are effective agents that are best applied
after bathing.  They can be applied to the entire
cutaneous surface; topical steroid is applied only to
inflamed areas.
Antihistamines such as hydroxyzine (25 mg three
times daily), cyproheptadine hydrochloride (4 mg
three times daily), and doxepin (75–150 mg/d) can
be useful for relieving pruritus.  They may be as
useful for their associated antiserotonin, anticho-
linergic, anxiolytic, and sedative effects as for their
antihistaminic effect.  Topical antipruritic lotions
such as Sarna lotion (camphor, menthol, phenol;
manufactured by Stiefel, Coral Gables, Fla.) may
also be helpful.
Antibiotics are often useful in the management
of acute episodes as secondary impetiginization is
very common.  Erythromycin and dicloxacillin (for
both drugs, 250–500 mg twice daily for 10 d) are
useful agents and topical mupirocin (applied topi-
cally twice daily for 10 d) has been shown to be
effective.19
Coal tar may be a useful adjunct to therapy.
Liquor Carbonis Detergens (coal tar, nonpropri-
etary) can be compounded with a topical steroid
such as triamcinolone acetonide.  This particular
combination can be quite effective.
Phototherapy can be very beneficial in the man-
agement of atopic dermatitis.  Successful results
have been reported with PUVA,127 UV-B,128 and a
combination of UV-A and UV-B.129  As these mo-
dalities command significant patient cooperation
and sophistication, and have long-term risks, they
are not recommended for preadolescents.  Because
PUVA has the greatest long-term risks, it should be
reserved for severe, refractory cases.
A time-honored treatment for atopic dermatitis
is the Scholtz method developed over 25 years ago.130
In a modified and simplified form, it consists essen-
tially of
• reducing bathing to a 1-minute shower,
• avoiding soaps (use Cetaphil lotion [manu-
factured by Owen/Galderma Laboratories,
Fort Worth, Tex.] as soap substitute),
• avoiding greasy preparations, and
• applying mild topical steroid solutions (eg,
Synalar [fluocinolone acetonide, manufac-
tured by Syntex Laboratories, Palo Alto,
Calif.])
In addition, erythromycin (250 mg four times
daily) is advocated for any secondary bacterial in-
fections.  Vitamin A and desiccated thyroid, al-
though part of Scholtz’ original regimen, are not
recommended by this author.  However, several
clinicians have reported excellent results employ-
ing the Scholtz method.131,132
Usually, however, in managing atopic dermatitis,
no one regimen is effective for all patients.  Manage-
ment must be individualized, with particular atten-
tion focused on each patient’s specific precipitating
factors.  In most cases, control will be maintained
with basic therapy emollients, mild-to-midpotency
topical steroids or coal tar products, and antihista-
mines.  Other modalities discussed should be re-
served for severe, refractory cases.
Military Considerations
One need only glance at the common precipitat-
ing factors (see Exhibit 20-3) to realize that life in the
military can be hostile for the individual with atopic
dermatitis.  It is difficult, if not impossible, to elimi-
nate all of these factors from the military environ-
ment.  It is not surprising, then, that Sulzberger
estimated that atopic dermatitis accounted for 3%
to 5% of all disease-related military discharges dur-
ing World War II.133  It was the opinion of most
dermatologists who served in World War II that it
was not prudent to send overseas any man with a
history of atopic dermatitis, as these men frequently
required prolonged and repeated hospitalization.62
Frequently, an individual will appear to have
“outgrown” his or her atopic dermatitis and, in-
deed, will not have experienced an outbreak for
several years.  It is important to remember, how-
ever, two features of the atopic diathesis: a propen-
sity for hand dermatitis, and an impaired cellular
immune response.  Both factors are negative con-
siderations for a military career.
Hand dermatitis is most likely to result from
exposure to chemical irritants.  Often, the exposure
is occupationally related.  Studies have determined
that of patients with an occupational dermatitis,
85% have a personal or family history of atopic
disease.134,135  An individual with a history of atopic
dermatitis and a propensity for developing hand
dermatitis would be disqualified from many mili-

Military Dermatology
568
tary occupations in order to avoid duty-related
exposure to irritant chemicals.
Impaired cellular immunity renders the atopic
patient susceptible to disseminated vaccinia infec-
tion (eczema vaccinatum).  For this reason, small-
pox vaccination becomes dangerous, even if the
atopic dermatitis is in remission.  Although small-
pox vaccination is no longer recommended, the
military could require it under special circum-
stances.
Urticaria is a common pruritic eruption, marked
by characteristic evanescent lesions known as
wheals.  It affects approximately 15% to 20% of the
population at some point during their lifetime.136
Wheals are, by definition, superficial in nature.
When the edematous process spreads to involve the
deep dermis and subcutaneous tissue, then it is
termed angioedema (Figure 20-19).  The edema can
involve other organ systems, particularly the car-
diopulmonary system and the gastrointestinal tract.
Patients can present with urticaria alone (40%),
angioedema alone (10%), or urticaria and angio-
edema combined (50%).137
Clinical Features
The clinical hallmark of urticaria is the wheal
or hive.  It is an elevated, sharply demarcated, pale
red or white, dermal flat-topped plaque with no
associated epidermal change.  Wheals may be
bordered by a thin, pale, or red halo (Figure
20-20).  Their size varies from a few millimeters to
several centimeters and they may be round or oval
or coalesce into large, bizarre polycyclic or
serpiginous forms.  The most characteristic feature
of the wheal is its evanescent nature.  Although the
process can last weeks or even months, individual
lesions usually resolve in a matter of hours and
rarely persist beyond 24 hours.  Wheals are typi-
cally quite pruritic and can occur anywhere on the
integument.
The occurrence of systemic symptoms is not un-
usual in urticaria or angioedema.  For this reason, a
thorough history—including an extensive review
of systems—and a physical examination are re-
quired.  Associated symptoms include arthralgias,
headache, hypotension, hoarseness, dyspnea, ab-
dominal pain, nausea, and diarrhea.  Because
angioedema is a deeper process that more com-
monly involves mucosal surfaces, it is more likely
URTICARIA
Fig. 20-19. Angioedema. Note marked hand swelling in
this man who is taking captopril.
Fig. 20-20. Hives. (a) Close-up view of typical pale, edema-
tous wheal with no epidermal change. (b) Note periph-
eral erythematous halo.
b
a
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Common Skin Diseases
569
to cause these systemic symptoms, which can be
life-threatening.
Urticaria has an unpredictable course.  The ma-
jority of cases are acute and self-limited with spon-
taneous resolution after a few hours to several days.
Many of these patients do not seek medical atten-
tion.  Urticaria that persists beyond 8 to 12 weeks is
arbitrarily classified as chronic urticaria.  Approxi-
mately 50% of patients are lesion-free in less than 1
year, while 20% may experience recurrent episodes
beyond 20 years.138
Types of Urticaria
The urticarias can be grouped in a variety of
clinical entities.  Champion has described some 50
separate classifications.139,140  Some of the more im-
portant types of urticaria are discussed below.
Physical Urticarias
The physical urticarias account for approximately
16% of all urticarias seen in specialty clinics.139  Over
20 types have been described.  Understanding physi-
cal urticaria will permit the identification and pos-
sible elimination of the etiologic mechanism, thus
preventing recurrent episodes.
Dermatographism is the most common of the
physical urticarias (Figure 20-21).  It is easily repro-
ducible by the firm, brisk stroking of the skin with
a blunt-tipped object.  The resultant wheal occurs in
minutes in the exact location that the pressure was
applied.  It can be elicited in approximately 1.5% to
Fig. 20-21. Wheal and flare appeared after firm stroking
of the back.  Such physically induced urticarial response
(dermatographism) may be seen in otherwise normal
individuals.
Fig. 20-22. Pressure urticaria. Wheals occurred when the
patient lay on his back for prolonged periods. The circled
wheals occurred at the exact location where pressure had
been previously applied with a ballpoint pen.
4% of healthy individuals.141
Pressure urticaria is a much less common form,
characterized by deep, sometimes painful, wheals
that occur at sites exposed to deep pressure for
prolonged periods (Figure 20-22)—usually the but-
tocks or feet.  The timing of these wheals is unique
in that they occur hours after pressure has been
applied and often persist for more than 24 hours.  In
a study of 44 patients with pressure urticaria, Daves
et al142 determined that the mean onset of whealing
was 3.5 hours with a peak at 10 hours, and a mean
lesion duration of 36 hours.  In their experience,
systemic corticosteroids were the only effective treat-
ment.  Fifty percent of the patients also exhibited
delayed dermatographism.  Delayed dermato-
graphism has also been described143 as an indepen-
dent entity, distinct from pressure urticaria.  In
general, however, dermatographism is easily dis-
tinguished from pressure urticaria by its immediate
onset (minutes versus hours).
Cold urticaria represents from 1% to 7% of all
forms of the physical urticarias.144,145  It occurs in an
acquired and a familial form with autosomal domi-
nant inheritance.  The primary acquired form is the
most common (96%),146 and the familial form is
quite rare.147  Cold urticaria has been associated
with cryoglobulins, cryofibrinogens, cold aggluti-
nins, and paroxysmal hemoglobinuria.146  Such cases
are referred to as secondary acquired cold urticaria.
In response to cold stimuli, localized symptoms are
produced (erythema, pruritus, wheals), as well as
systemic manifestations including respiratory dis-
tress, hypotension, and even anaphylaxis.  The di-
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Military Dermatology
570
agnosis is easily confirmed by applying an ice cube
to the skin.  A wheal will occur several minutes later
during the rewarming phase.  The ice cube test is
negative in the familial type.147  The duration of cold
urticaria is from 3 weeks to over 37 years.146  Patients
are advised to avoid cold climates and rapid de-
creases in temperature, as may occur in ocean swim-
ming.148
Solar urticaria is a rare condition characterized
by wheal formation within minutes of sun expo-
sure, sometimes with associated systemic symp-
toms.  Lesions can be induced by light of varying
wavelengths from the UV-B range (290–320 nm)
to the visible light spectrum (> 400 nm).149  Al-
though the precise mechanisms of lesion induction
are not entirely clear, Leiferman et al150 have pro-
vided convincing evidence for the role of eosino-
phil degranulation in the pathogenesis.  In addition,
a circulating photoallergen has been described151 that
is generated by absorption of light energy.  Re-
moval of this factor by plasmapheresis has been
shown152 to result in prolonged remission.  Toler-
ance may be induced by PUVA153 or UV-A alone.154,155
Aquagenic urticaria is precipitated by contact
with water, regardless of temperature.  It is a rare
condition that resembles cholinergic urticaria (de-
scribed below).  Shelly and Rawasley156 reported
successful control with ChlorTrimeton (chlor-
pheneramine maleate, manufactured by Schering
Corp., Kenilworth, N.J.), 4 mg four times daily.
Aquagenic urticaria is a separate clinical entity from
aquagenic pruritus.157
Vibratory angioedema is also a rare condition in
which localized erythema and edema occur in re-
sponse to vibration.  Autosomal dominance has
been described,158 as well as an acquired form that
can be occupationally related.159  A good therapeu-
tic response to terfenadine (60 mg twice daily) has
been reported in at least one case.160
Localized heat urticaria, another rare physical
urticaria, occurs in response to skin exposure to
heat above 43°C.  Successful induction of tolerance
through graduated incremental exposure under
medical supervision has been reported.161
Cholinergic Urticaria
In cholinergic urticaria, which accounts for 4% of
urticarias,137 wheals are provoked by heat, emotion,
or gustatory stimuli.  The lesions produced are
characteristically tiny (1–3 mm), markedly pruritic,
and persist for roughly 45 minutes to 1 hour.  The
cutaneous response is felt to be produced by the
action of acetylcholine on the mast cell.136  A new
entity of exercise-induced anaphylaxis that is dis-
tinguishable from cholinergic urticaria has been
described.162  Cholinergic urticaria is usually easily
treated with antihistamines.
Contact Urticaria
Contact urticaria is an uncommon condition that
consists of a wheal-and-flare response to a variety
of substances applied to the skin, and occurs within
20 to 30 minutes after application.  Anaphylaxis can
result; it has been described in 12 individuals dur-
ing surgery, and was caused by their hypersensitiv-
ity to natural latex in the surgical glove.163
Urticarial Vasculitis
Leukocytoclastic vasculitis presenting as urticaria
or angioedema was first recognized at the Mayo
Clinic.164  The cutaneous findings may be identical
to common urticaria except that the wheals may be
somewhat purpuric, tend to persist for 3 to 5 days,
and often heal with residual hyperpigmentation.  It
is an important entity to recognize because of its
frequent association with systemic diseases such as
serum sickness, systemic lupus erythematosus,
Sjögren’s syndrome, and infections such as viral
hepatitis type B.165
Hereditary Angioedema
Hereditary angioedema is a rare cause of
angioedema with its onset in childhood and auto-
somal dominant inheritance.  The episodes of swell-
ing usually recur frequently, are often painful and
persistent, and are aggravated by trauma.140  This
form of angioedema occurs without urticaria, so the
presence of wheals should exclude the diagnosis.
The angioedema is due to a lack of functional C1
esterase inhibitor, an enzyme that controls comple-
ment activation.  The inhibitor may be diminished
in quantity, or may be present but dysfunctional.166
Daily administration of danazol, an anabolic ste-
roid, may prevent attacks.
Urticaria due to Histamine-Releasing Agents
Many substances (Exhibit 20-4) are capable of
causing direct mast cell degranulation with subse-
quent histamine release.  This is not an immune-
modulated mechanism.  The resultant wheals occur
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Common Skin Diseases
571
that have an obvious cause will be self-evident, so
those patients will often not seek medical attention.
The process may be multifactorial, so careful his-
tory taking is mandatory to try to uncover possible
precipitating factors (Exhibit 20-5).
Diagnosis
It is tempting to order multiple screening labora-
tory tests to rule out the rarer causes of urticaria.
Although it may be reasonable to order a few tests,
such as a complete blood count or an erythrocyte
sedimentation rate, extensive laboratory investiga-
tion is often pointless and expensive, and should
not be routine.  What is important and should be
routine is a thorough history and physical examina-
tion.  The history should be directed at determining
whether or not a definable type of urticaria exists
that may be related to a physical stimulus, an inhal-
ant, an ingested substance, a systemic disease, an
infection, or emotional stress.  The information ob-
tained from both the history and the physical will
guide any laboratory evaluation.  If no specific
cause is found, and the symptoms warrant, the
patient should be treated empirically.
Treatment
The majority of patients with idiopathic urticaria
will respond to antihistamine therapy.  Hl-receptor
antagonists are the major class of therapeutic agents
employed in the management of urticaria.  Atarax
(hydroxyzine, manufactured by Roerig, New York,
N.Y.), 25 mg three times daily, is an excellent first-
line therapy and dose may be increased to toler-
ance, with sedation being its primary dose-limiting
effect.  It is often useful to add a second H1 blocker
from a different chemical class.  Combination with
an H2-receptor blocker such as cimetidine (300 mg
four times daily) may also be helpful.167  Similarly,
good results have been obtained with doxepin (75–
150 mg/d), an antidepressant with known anti-H1
and anti-H2 activity, in the management of chronic
idiopathic urticaria.168
Because of the problems with sedation from the
traditional antihistamines available, much effort
went into the development of newer agents with
fewer central nervous system (CNS) side effects.  Of
these second-generation antihistamines, Hismanal
(astemizole, manufactured by Janssen Pharmaceu-
ticals, Piscataway, N.J.), 10 mg daily, is the only one
currently approved for the treatment of urticaria,
but Seldane (terfenadine, manufactured by Marion
Adapted with permission from Burrell BA, Halpean
GM, Huntley AC. Chronic urticaria. West J Med.
1990;152:269.
EXHIBIT 20-4
AGENTS CAPABLE OF DIRECT
HISTAMINE RELEASE
urticaria by altering the production of prostaglan-
dins and leukotrienes, but not by direct histamine
release.140  Contact urticaria can occur via exposure
to direct histamine-releasing agents.  When evalu-
ating angioedema of the oral mucosa, one should
consider the possibility of contact urticaria from
cinnamic acid or cinnamaldehyde, which are com-
mon ingredients in toothpaste.
Immunoglobulin E–Mediated Urticaria
Although many patients as well as physicians
assume that most cases of urticaria are immunoglob-
ulin (Ig) E-mediated, in fact only 3% to 4% actually
are.140  This type of urticaria requires exposure to an
allergen, which can occur via inhalation (pollen,
spores, animal dander), ingestion (food, food addi-
tives, drugs), or injection (Hymenoptera stings,
drugs).  Of the drugs, penicillin is the most common
cause of IgE-mediated urticaria.
Idiopathic Urticaria
Idiopathic urticaria is, by far, the most common
category that the physician will see.  Many cases
Exhibit 20-4 is not shown because the copyright
permission granted to the Borden Institute, TMM,
does not allow the Borden Institute to grant
permission to other users and/or does not include
usage in electronic media. The current user must
apply to the publisher named in the figure legend
for permission to use this illustration in any type
of publication media.

Military Dermatology
572
EXHIBIT 20-5
CAUSES OF URTICARIA
Systemic Diseases
Thyroid disease
Systemic lupus erythematosus
Malignancies
Serum sickness
Other
Candida sensitivity
Worms/infestations
Psychological
Drugs
Aspirin
Penicillins
Cephalosporins
Aminoglycosides
Sulfonamides
Barbiturates
Hydralazine
Phenylbutazone
Tranquilizers
Hydantoins
Quinine
Angiotensin-converting enzyme
inhibitors
Infections
Chronic bacterial (sinus, dental,
urinary tract, etc.)
Viral (hepatitis, Epstein-Barr,
coxsackie)
Foods
Shellfish
Eggs
Milk
Cheese
Nuts
Berries
Tomatoes
Chocolate
Food Additives or Contaminants
Salicylates
Tartrazine
Tyramine
Benzoates
Hydroxybenzoates
Sulphites
Azo dyes
Penicillin
Yeasts
Citric acid
Data sources: (1) Burrell BA, Halpean GM, Huntley AC. Chronic urticaria. West J Med. 1990;152:268–276. (2) Champion RH.
Urticaria: Then and now. Br J Dermatol. 1988;119:427–436.
World War II, hospital admission statistics do re-
veal that there were almost 30,000 admissions for
urticaria and more than 7,000 for angioedema be-
tween 1942 and 1945.62  In dermatology clinics in
Vietnam, urticaria was seen in 1.75% to 2.74% of
patients examined.2
Another aspect of urticaria that the military phy-
sician must consider is the potential harm from the
side effects of therapy.  As discussed, antihista-
mines, the mainstay of therapy for urticaria, can
have profound CNS side effects—particularly seda-
tion.  Again, this could jeopardize individual safety
and mission accomplishment.  Thus, the physician
must address each patient’s military occupation
and consider imposing temporary duty restrictions.
The newer antihistamines, by virtue of their dimin-
ished permeability of the blood–brain barrier, will
lessen the hazards.
Merrell Dow, Kansas City, Mo.), 60 mg twice daily,
can also be beneficial.l69
Military Considerations
Because most cases of urticaria resolve spontane-
ously in a short period of time, they usually do not
become a problem of any special significance in the
military.  Patients with a physical urticaria could
have military occupational exposures that would
exacerbate the disease.  This obviously poses a
potential threat to their health and safety, or to the
safety of others, as well as to mission accomplish-
ment.  It is hard to imagine a career in the military,
particularly in time of war, protected from physical
stresses such as heat, cold, pressure, or vibration.
Although comprehensive etiologic studies of
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Common Skin Diseases
573
PSEUDOFOLLICULITIS BARBAE
Pseudofolliculitis barbae (PFB) is a condition that
occurs in black men in response to shaving.  It is
common in the military services, where shaving is
mandatory, with the prevalence estimated to be
45%170 to greater than 80%.171
Clinical Features
PFB typically manifests as perifollicular, inflam-
matory papules and papulopustules of the beard
area, particularly the anterior portion of the neck
and the submandibular region.  On close inspec-
tion, ingrown hairs are almost always visible (Fig-
ure 20-23).  In long-standing cases, hyperpigmenta-
tion is typical.  Severe cases can result in scarring
and disfigurement from keloid formation (Figure
20-24).
Acne keloidalis nuchae is a similar condition that
b
a
occurs on the nape of the neck.  It also presents with
multiple smooth, flesh-colored papules that are quite
firm and may coalesce to form keloids (Figure 20-
25).  Pustules, cysts, and sinus tracts occasionally
form.  The condition is aggravated by cutting the
hair too close to the skin.
Pathogenesis
The pathophysiological mechanism responsible
for PFB has been clearly elucidated.  Essentially, it
represents a foreign body reaction172 that is the
result of beard hair penetrating the dermis.  The
tightly curled and undulating surface of hair in
black people has several features that facilitate this
process.  It is elliptical in shape,173 so it develops a
pointed tip when shaved.  Furthermore, the hair
initially grows parallel to the skin surface,174 so that
when cut obliquely by shaving, the point is even
sharper.  Finally, because of its tight curl, the hair
has a tendency to grow back toward the epidermis,
which is easily penetrated by the pointed hair.  The
actual penetration of the skin can occur via one of
two pathways: through the stratum corneum after
growing out from the follicle and arching back
toward the skin,174 or by piercing the follicular wall
directly.175  The latter results from applying tension
to the skin during shaving, thus allowing the sharp-
ened tip to retract under the skin when tension is
released.
Fig. 20-24. Keloid in an individual with severe
pseudofolliculitis barbae.
Fig. 20-23. Pseudofolliculitis barbae. (a) Typical location
on anterior neck. (b) Close-up view to show characteris-
tic papules with ingrown hairs.
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Military Dermatology
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Fig. 20-25. Acne keloidalis nuchae, recurrent after carbon
dioxide laser ablation.
ingrown hairs will have been pulled free by the
growth of the hair shaft in a direction away from the
skin surface.
The next step is to resume shaving.  However,
the individual should never attempt a close shave:
this will facilitate retraction of the sharpened hairs
below the skin surface with subsequent penetration
of the follicular wall and renewal of the entire
process.  The simplest mechanism that avoids this
problem is shaving with electric clippers, which
produces a stubble shave appearance.  Excellent
results have been reported with this technique,176,177
and it is this author’s treatment of choice.  Patients
must also be taught to inspect the beard hair closely
and to attempt to free any ingrown hairs with a
pick.  Use of a coarse facial sponge, such as Buf-Puf
(manufactured by 3M Products, St. Paul, Minn.), is
also helpful for accomplishing this.176,178  At the
shaving clinic at Lackland Air Force Base, Texas,
this method has been successfully initiated at the
time of initial patient presentation, without having
to wait the customary 30 days.  This allows the
patient (usually a basic trainee) to maintain a mili-
tary appearance and control the problem at the
same time.
Shaving can also be accomplished with a manual
razor, provided that the proper guidelines are fol-
lowed (Exhibit 20-6).  Careful following of these
guidelines is time consuming.  With practice, it
usually requires about 15 minutes.  There are no
shortcuts.  If an individual is usually rushed in the
morning, we often recommend shaving in the
evening when he can devote the proper amount of
attention that is required.
Successful results have also been reported using
electric razors179 and a foil-guarded manual razor
specifically designed for patients with PFB (PFB
Diagnosis
The clinical presentation of PFB is quite charac-
teristic, so the diagnosis is not a difficult one.  It is
most often confused with acne vulgaris.  The ab-
sence of comedones (the primary lesions of acne
vulgaris), the restriction of disease activity to the
beard area, and the history of onset after close
shaving all support the diagnosis.  Careful visual
inspection with magnification will almost always
reveal ingrown hairs in some of the perifollicular
papules, confirming the diagnosis of PFB.
Treatment
Usually, the first phase treatment should be to
discontinue shaving and allow beard growth for up
to 30 days.  By this period of time, most of the
EXHIBIT 20-6
SHAVING GUIDELINES FOR PATIENTS WITH PSEUDOFOLLICULITIS BARBAE
1. The beard must be thoroughly hydrated and lubricated; liberal application of shaving cream (foam or gel)
will hydrate and soften the beard. Warm, moist heat (hot towel) is also useful.
2. Never pull the skin taut.
3. Never shave over the same area twice; one need shave an area only once, provided the blades are kept
sharp by frequent changing (after two shaves).
4. Always shave with the grain of the beard.
5. Carefully inspect the beard area before and after shaving; gently extract the ingrown hairs; avoid plucking.
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Common Skin Diseases
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Shaving System, manufactured by American Safety
Razor Co., Staunton, Va.).180
Chemical depilatories are also an effective treat-
ment modality.181,182  Many patients, however, find
them irritating.  In addition, they are time consum-
ing and they produce a characteristic odor that
many patients find bothersome.  A minority of
patients seem to prefer this mode of treatment.
Keloids may respond to intralesional steroid
therapy, which should be instituted early and ag-
gressively to prevent disfigurement.  Severe cases
have required excision and grafting.183  The results
of surgical therapy are usually disappointing.
Systemic antibiotic therapy is rarely required in
the management of PFB, except in those few cases
that become secondarily infected.  Some authorities
claim efficacy for various topical medications such
as tretinoin184 (applied nightly) and clindamycin
(applied twice daily).185  Occasional use of mild
topical steroids may also be useful, particularly for
relieving any irritation from depilatories.
Patients must be instructed to avoid plucking of
hairs as this may cause breakage of the hair shaft
within the follicle with subsequent transfollicular
dermal penetration and foreign body response.
Military Considerations
To prevent PFB, one need only grow a beard.
Unfortunately, this is contrary to military regula-
tions.  This simple fact has created much strife.  In
the past, the lack of a consistent policy regarding
shaving requirements and the management of PFB
from an administrative as well as medical view-
point turned a relatively minor medical problem
into a major social issue.  Racial tension over this led
to public demonstrations and even frank mutiny by
disgruntled black enlisted members in the 1970s.171
In 1979, one investigator wrote that “pseudofollic-
ulitis barbae has now become the most significant
dermatologic disease in the U.S. Army”171(p62)  and
some military dermatologists called for “the pan-
service acceptance of the voluntary growth of a
beard by any service member”.170(p459)
Fortunately, the lack of a consistent policy was
recognized and rectified so that today, PFB clinics
are functioning smoothly throughout the military.
Administrative guidelines are clearer, commanders
are better informed, and medical providers are bet-
ter educated on the unique problems regarding
PFB.
The importance of keeping PFB under control
without growing a beard is not simply to maintain
a uniform, clean shaven appearance.  It is also
important for the safety of the individual in a com-
bat environment, where the threat of chemical weap-
ons is ever present.  Although tests on the efficacy of
gas masks reveal that beard growth of as much as 1⁄8
in. (up to 3 d) did not significantly alter the seal to
the mask,186 it seems obvious that excessive beard
growth would have an adverse effect on the seal.
An individual whose PFB was poorly controlled
and who required a 30-day profile to allow for
beard growth, would likely require evacuation to
the rear.  Thus, proper management of a common
condition like PFB is essential for avoiding unnec-
essary loss of manpower.  The key to the successful
management of PFB will always be education and
communication among soldiers, healthcare provid-
ers, and supervisors.
CUTANEOUS VIRAL INFECTIONS
Herpes Simplex Labialis
Herpes simplex labialis is the condition com-
monly referred to as “fever blisters.”  It is caused by
herpes simplex virus (HSV), a double-stranded DNA
virus, of which two types exist.  Most infections
involving the oral mucosa are of type 1, while type
2 is responsible for most HSV infections involving
the genitalia (genital herpes is discussed in Chapter
19, Sexually Transmitted Diseases).  Like all herpes
viruses, HSV-1 is able to persist in a latent form in
its host, causing recurrent outbreaks.187  It occurs
worldwide, and by the fourth decade of life more
than 90% of the population have developed anti-
bodies to HSV.188  Thus, recurrent HSV labial infec-
tion is an extremely common condition; it affects
20% to 40% of the adult population.189
Clinical Features
Pharyngitis and gingivostomatitis are the usual
manifestations of primary infection with HSV-1, seen
most commonly in children and young adults.190
Vesicles or erosions may be seen on the palate, gingiva,
tongue, lip, or perioral region of the face.191  Primary
infection usually is associated with fever and cervical
adenopathy as well, and is most severe in adults.
Recurrent infection manifests as vesicles or ero-
sions on the vermilion border of the lip (Figure
20-26) that usually crust over within 48 hours.  Of-

Military Dermatology
576
Fig. 20-26. Herpes simplex labialis. Note intact vesicle.
Fig. 20-27. Targetlike lesions in erythema multiforme.
Note vesiculation.
ten, the patient experiences burning and itching at
the site prior to vesicle formation.  The rate of
recurrence varies between 16% and 45%.192  Recur-
rent outbreaks represent reactivation of the virus
from its latent form in the trigeminal ganglion.192
Although the exact mechanism of reactivation is not
known, it is assumed that the virus travels down the
axon of the nerve to infect keratinocytes on the
adjacent location on the lip.  Many precipitating
factors have been identified including trauma, UV
light exposure, fever, immunosuppression, psycho-
logical stress, and exposure to excessive amounts of
alcohol, tobacco, or spicy foods.193,194
Recurrent HSV-1 outbreaks can precipitate a re-
action known as erythema multiforme, an acute,
widespread eruption with characteristic targetlike
lesions (Figure 20-27).  Antiviral therapy with
acyclovir has been shown to prevent relapses of
recurrent erythema multiforme.195
Diagnosis
Grouped vesicles or crusted erosions on the lip
are strongly suggestive of HSV infection.  Lesions
that are secondarily infected with bacteria may
be difficult to distinguish from primary impetigo,
which is characterized by honey-colored crusts.
A history of recurrence in the exact location of
episodes of minor trauma or stress or UV light
exposure support the diagnosis of herpes
simplex.  Primary gingivostomatitis may resemble
aphthae, hand-foot-and-mouth disease (coxsackie
virus), Behçet’s syndrome, or Stevens-Johnson
syndrome.
The diagnosis of HSV infection is facilitated by
performing a Tzanck smear.  Material is obtained
by scraping the base of a vesicle or erosion.  The
specimen is then smeared on a glass slide, stained
with Wright’s stain, and examined under the micro-
scope.  In HSV-infected tissue, multinucleated gi-
ant cells and/or keratinocytes with large, pale nu-
clei with peripheral clumping of chromatin will be
seen (Figure 20-28).  In addition, culture confirma-
tion of HSV is available through most laboratories.
Confirmation of HSV infection through detection of
the virus’s DNA by polymerase chain reaction, an
exquisitely sensitive technique, has been described196
but is expensive and impractical for ordinary use.
Fig. 20-28. Tzanck smear (original magnification 100X).
Note the large multinucleated keratinocyte in the center.
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Common Skin Diseases
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Treatment
In most instances, systemic treatment of herpes
simplex labialis is not required.  Cool compresses
and topical application of an antibiotic oint-
ment may promote healing and prevent bacterial
superinfection.  Topical acyclovir is ineffective in
immunocompetent individuals.197  Patients may
benefit from oral acyclovir (200 mg five times daily)
if initiated immediately after symptom onset.198
Recurrences of herpes simplex labialis can be
decreased by prophylactic administration of oral
acyclovir (200 mg three times daily).199  In most
cases, the expense of this method of treatment pre-
cludes its use.  It is indicated, however, for patients
with recurrent erythema multiforme due to
HSV.195,200  It has also been shown to be of practical
value in individuals with a history of UV radiation–
induced herpes simplex labialis who are going to be
exposed to periods of intense UV exposure such as
snow skiing (or desert deployment).199,201  Zinc ox-
ide, a complete sun blocker, should also be consid-
ered for these individuals.
Herpes Zoster
Herpes zoster, also called shingles, is a common
neurocutaneous disease caused by the varicella-
zoster virus (VZV), a member of the herpesviridae
group, which is also the etiologic agent for
chickenpox.  It occurs in 1.3 to 4.8 persons per 1,000
per year,202–204 and is characterized by a vesicular
eruption in a dermatomal distribution.  Often, it is
associated with varying degrees of pain, which may
persist beyond the point of healing of the rash.
Clinical Features
Herpes zoster occurs in individuals with a previ-
ous history of varicella.  Patients typically present
Fig. 20-29. Herpes zoster. (a) Thoracic dermatome. Note sharp cutoff at the midline. (b) Close-up view of (a) to reveal
characteristic grouped vesicles on an erythematous base. (c) Lumbar distribution. (d) Sacral distribution with sharp
cutoff at midline; note vesicles coalescing and becoming purpuric.
d
b
c
a
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Military Dermatology
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Fig. 20-30. Herpes zoster. Vesicles have coalesced into
larger bullae, which have become (a) purpuric or (b)
pustular.
elderly or immunocompromised patients.  The ar-
eas involved may heal with residual postinflam-
matory hyperpigmentation and can result in
significant scarring (Figure 20-31).
Types of Herpes Zoster
Herpes Zoster Ophthalmicus.  Involvement of
any branch of the trigeminal nerve is called herpes
zoster ophthalmicus (Figure 20-32).  Although ocu-
lar involvement may occur in association with max-
illary or mandibular nerve involvement, this is un-
common.  Most frequently, the supraorbital and
supratrochlear divisions of the frontal nerve are
involved.  Hutchinson’s sign consists of lesions on
the nasal tip, which indicate involvement of the
nasociliary branch of the ophthalmic nerve and a
high likelihood of ocular complications.  When
Hutchinson’s sign is present, immediate ophthal-
mological consultation is warranted.  Eye complica-
tions include lid ulceration and scarring; conjunc-
a
b
with grouped vesicles on an erythematous base
in a dermatomal distribution (Figure 20-29).  A
generalized eruption may occur in 2% to 5% of
patients, particularly in elderly or immuno-com-
promised patients.205  The eruption is almost always
unilateral and rarely extends across the midline.
The vesicles may coalesce into larger bullae and
may become hemorrhagic or even pustular (Figure
20-30).  The patients may or may not experience the
prodrome of fever, malaise, and headache.  Often,
the rash is preceded by radicular pain, a burning
sensation, or hyperesthesia in the region of the
same dermatome.  The most common dermatomes
involved are the thoracic, followed by the cranial,
cervical, lumbar, and sacral.  The most common
single nerve involved is the trigeminal nerve—usu-
ally a single branch.206
New lesions can develop for up to approximately
8 days, but usually do not occur after 4 days from
the onset of the rash.207  Crusting occurs in 10 to 14
days, but lesions may persist for longer periods in
Fig. 20-31. Midline and unilateral forehead and eyelid
atrophic scars that resulted after healing of herpes zoster
infection.
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Common Skin Diseases
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Fig. 20-32. Herpes zoster ophthalmicus with marked
periorbital and lid edema. Immediate ophthalmological
consultation is required.
Diagnosis
The presence of grouped vesicles on an erythem-
atous base in a dermatomal distribution, with asso-
ciated pain in a similar location, creates little ques-
tion about the diagnosis of shingles.  Disseminated
cases may resemble primary varicella infection or
disseminated HSV.  The Tzanck smear will not
differentiate the three.  Viral cultures are available,
but can take up to 2 weeks to grow.  Fluorescein-
tagged VZV antibody applied to a Tzanck smear
may help to differentiate VSV from HSV but re-
quires a fluorescent microscope.
Treatment
In most cases involving immunocompetent pa-
tients, symptomatic treatment will suffice.  Cool
compresses with Burow’s solution will hasten dry-
ing and crusting of the vesicles.  For analgesia,
narcotics may be required.
Acyclovir has been shown to be effective in short-
ening the duration of disease and reducing the
acute and postzoster pain.209–211  VZV is up to 8-fold
less susceptible to acyclovir than HSV,212 so higher
doses are required.  The recommended dose is 800
mg orally five times daily for 10 days.
The role of systemic corticosteroid therapy in the
treatment of VZV infection is somewhat controver-
sial.213  A short course (60 mg/d orally for 5 d
tapered over 2 wk) combined with a 10-day course
of acyclovir may be useful for the prevention of
tivitis; proptosis; keratitis; corneal ulceration, vas-
cularization, or perforation; uveitis; and vascular
ischemic injuries.206
Ramsay Hunt’s Syndrome.  Ramsay Hunt’s syn-
drome includes facial nerve palsy as a result of
involvement of the geniculate ganglion with VZV
(Figure 20-33).  Vesicles are usually present on the
external ear or tympanic membrane, and auditory
symptoms may be present such as tinnitus, vertigo,
or diminished auditory acuity.  Early intervention
with systemic steroids may be beneficial.  The facial
nerve palsy usually resolves, but can be permanent.
Postherpetic Neuralgia.  The acute pain of herpes
zoster is usually of a transitory nature.  In some
individuals, however, particularly the elderly, se-
vere pain may persist for months and become dis-
abling.  The frequency of postherpetic neuralgia
varies between 15% and 70%.205  It is particularly
frequent and severe in patients with herpes zoster
ophthalmicus.  The neuralgia resolves spontane-
ously in 50% of patients within 3 months and in 75%
within 1 year.208
Fig. 20-33. Ramsay Hunt’s syndrome: inability to raise
eyebrow with ipsilateral drooping of the corner of the
mouth.
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postherpetic neuralgia in patients at high risk, such
as those greater than 60 years old with VSV involv-
ing the trigeminal nerve.
Molluscum Contagiosum
Molluscum contagiosum is a benign cutaneous
infection caused by a poxvirus.214  It occurs in
children and young adults and is worldwide in
distribution.  It is spread by fomites as well
as by direct contact,215 including venereal trans-
mission.216  (Molluscum contagiosum is also
discussed in Chapter 19, Sexually Transmitted
Diseases.)
Clinical Features
The pathognomonic lesion of molluscum
contagiosum is a small (2–5 mm), firm, smooth,
dome-shaped, translucent papule with a central
umbilication.  Rapid freezing may accentuate this
central depression, thus aiding in the diagnosis
(Figure 20-34).  With pressure, a white, curdlike
substance can be expressed from the center of fully
developed lesions.  Microscopical examination of a
Fig. 20-34. Molluscum contagiosum. (a) Flesh-colored
papules in periorbital location. Note central umbilication
of some lesions. (b) Slightly erythematous papules on the
trunk. (c) Use of cryotherapy to accentuate the central
umbilication, facilitating diagnosis.
smear of this substance after staining will reveal the
characteristic cytoplasmic inclusions known as
Henderson-Patterson bodies.
Patients may have few or numerous lesions.  They
can occur on any cutaneous site, but have a predi-
lection for the pubic region and adjacent locations
in adults; in children, the trunk, face, and proximal
extremities are most often involved.  In general, the
lesions are asymptomatic.  Without treatment, the
disease will last an average of 6 months to 3 years;
individual lesions persist for approximately 2
months.217
Diagnosis
The appearance of typical, small, umbilicated
papules on the exposed areas of children or the area
of the genitalia of adults usually leaves little doubt
as to the diagnosis of molluscum contagiosum.  In
acquired immunodeficiency syndrome (AIDS) pa-
tients, lesions may appear with atypical features.218
Recently, there have been reports of cutaneous
cryptococcosis in AIDS patients resembling
molluscum contagiosum,219,220 and a case of
molluscum contagiosum mimicking a basal cell car-
a
b
c
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Common Skin Diseases
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cinoma in a patient with AIDS.221  If any doubt
exists, demonstration of the pathognomonic
Henderson-Patterson intracytoplasmic inclusions
by cytological or histological examination will con-
firm the diagnosis.
Treatment
When approaching the management of mollus-
cum contagiosum, it is important to consider that it
is a benign disease in which the lesions eventually
resolve spontaneously.  Therefore, one should avoid
aggressive treatment that may be painful or result
in scarring.  Some argue that the disease should not
be treated at all, particularly in children.222  Treat-
ment may be justified, however, as an attempt to
shorten the course of the disease, thus preventing
viral transmission and autoinoculation.
Treatment involves destruction of the lesions by
mechanical means such as curettage, cryotherapy,
or electrosurgery or by chemical irritants such as
retinoic acid, cantharidin, phenol, podophyllin, or
trichloroacetic acid.  The most effective of these
modalities is probably removal by curettage.  The
treatment may be facilitated in children by use of
newly developed topical anesthetic agents such as
eutectic mixture of local anesthetic (EMLA).223
Warts
Warts are benign cutaneous tumors that will
affect up to 10% of the population.224  They are
caused by the human papillomavirus (HPV), a vi-
rus that has gained a considerable degree of atten-
tion due to its ubiquitous nature, tenacity, and
oncogenic potential.  (Genital warts caused by HPV
are discussed in Chapter 19, Sexually Transmitted
Diseases.)
The papillomavirus (PV) of the papova group of
viruses consists of multiple species that are host-
specific such as bovine PV, sheep PV, cottontail
rabbit PV (Shope fibroma virus), and HPV.225  Natu-
ral infection by PV is limited to the skin and mucous
membranes of the host species.  HPV is an ether-
resistant virus with icosahedral symmetry and a
double-stranded circular DNA.226  It is the pre-
sumed etiologic agent of human warts, based on the
facts that DNA and viral particles of HPV have been
found in human warts, and filtered extracts of warts
will produce papillomas if injected into the skin of
human.227
At least 55 types of HPV have been recognized
based on DNA homology, and each type appears to
have some degree of anatomic specificity.  For in-
stance, HPV type 4 is associated with common warts,
while types 6 and 11 are associated with condyloma
acuminata of the genital region.228  Some types ap-
parently have significant oncogenic potential, par-
ticularly types 16, 18, and 31, which are commonly
identified in cervical carcinoma.228
Clinical Manifestations
Like all papillomaviruses, HPV can infect the
skin and mucous membranes including the genita-
lia, conjunctiva, oral cavity, and larynx.  This dis-
cussion is limited to HPV infection of the skin.
Common Warts.  The common wart (verruca
vulgaris) is an exophytic, rough-textured, hyper-
keratotic papule that is usually painless.  Although
typically smaller than 1 cm, warts can form larger
plaques.  Warts can occur almost anywhere on the
skin, but are most common on the dorsum of the
hands and fingers, particularly in young children
(Figure 20-35).  Patients may present with single
lesions, but multiple lesions are more common since
autoinoculation is a frequent process.  Common
warts will frequently resolve spontaneously after
several months, but they may persist or recur after
many years.  Warts that resolve spontaneously do
not scar.  When they occur in the periungual region,
they may cause nail plate deformities (Figure 20-36).
Flat Warts.  Flat warts (verruca plana) are small
(1–3 mm), slightly elevated, flesh colored, flat pap-
ules that are almost always multiple.  They occur
mainly on the face, neck, hands, or knees of young
adults and adolescents (Figure 20-37), and are resis-
tant to treatment.
Filiform Warts.  Filiform warts (verruca
filiformis) occur most commonly on the face.  Mul-
tiple lesions may be seen, but they are usually
single.  These are elongated, thin, pointed projec-
tions that, although cornified, remain relatively soft.
Plantar Warts.  Plantar warts (verruca plantaris)
are of two types: mosaic and myrmecia (Figure 20-
38).  The most commonly seen are the mosaic types,
which appear as multiple flat, slightly elevated,
hyperkeratotic papules that are usually coalescent.
They are most frequently seen in adolescents over-
lying the metatarsal heads, and are frequently ten-
der and can cause pain on walking.  Close inspec-
tion of these warts will reveal the typical coarse
surface that is sharply demarcated from the sur-
rounding skin.  The normal skin markings are inter-
rupted on the surface of the warts.  Paring of the
keratotic surface will reveal dark, punctate areas
that represent thrombosed capillaries.  Continued
paring will produce pinpoint bleeding.

Military Dermatology
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a
b
c
d
Fig. 20-35. Common verrucae. (a) Typical grouped warts in a periungual location. (b) Isolated wart on dorsum of hand.
(c) Larger wart on thumb; note thrombosed capillaries visible on the surface. (d) Large wart on arm.
Fig. 20-36. Periungual wart causing lifting of distal free edge of the nail plate.
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Common Skin Diseases
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a
b
Fig. 20-37. Flat warts. (a) Facial involvement. (b) Lesions on the knee.
Fig. 20-38. Plantar warts. Mosaic types predominate sur-
rounding a myrmecia type. Location over metatarsal
heads is common.
The second type of plantar wart is the myrmecia
(“ant hill”) type.  These are deeper, dome-shaped
papules that frequently become inflamed.
Other Cutaneous Manifestations.  Epidermo-
dysplasia verruciformis is a rare, inherited disease
characterized by widespread verruciform plaques
that occur in childhood and persist into adulthood.
These plaques represent extensive infection with
HPV in individuals with impaired immunity.  Squa-
mous cell carcinoma will develop in a large number
of these patients, particularly on sun-exposed ar-
eas.229
The DNA of HPV has been demonstrated in some
keratoacanthomas230 and lesions of Bowen’s disease
(squamous cell carcinoma in situ).231
Diagnosis
The morphology of warts usually is distinctive
enough to allow diagnosis by visual inspection.  At
times they may resemble seborrheic keratoses, ac-
tinic keratoses, molluscum contagiosum, cutane-
ous horns, or acrokeratosis verruciformis of Hopf.
Plantar warts may mimic corns (clavi) or calluses.
Squeezing a plantar wart usually elicits pain, unlike
a callus.  In contradistinction to warts, the normal
skin markings are accentuated in clavi and calluses.
Paring of the warts with a scalpel blade will reveal
the characteristic dark, punctate, thrombosed capil-
laries.
Treatment
Like molluscum contagiosum, cutaneous warts
are generally a benign infectious process that will
frequently resolve spontaneously.  Spontaneous
remission is seen in 40% of patients within 6 months,
and 66% in 2 years.232  Therefore, the physician
should avoid overly aggressive treatment that may
result in scarring, and be particularly careful to
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Military Dermatology
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avoid scarring on the plantar surface as this could
cause pain on walking.  The modalities available for
treating warts are numerous, which speaks for the
tenacity of HPV.  Recalcitrance is common with
warts, and the physician should explain to patients
at the initial visit that multiple treatments are some-
times required and recurrences are frequent.
Effective topical keratolytic agents are available.
These include salicylic acid, which is available in
40% concentration in a self-adhesive tape (Mediplast,
manufactured by Beiersdorf, Norwalk, Conn.) and
combined with lactic acid in flexible collodion
(Duofilm, manufactured by Stiefel, Coral Gables, Fla.).
Both work well under occlusion, if applied daily for
several weeks.  These may be helpful for treating
plantar warts, particularly in children, but can re-
quire a fair amount of patience and compliance.
One of the easiest and most effective treatments
for warts is curettage with or without electrodesic-
cation or cryotherapy to the base.  Mahrle and
Alexander233 report good results in the treatment of
periungual and plantar warts with light focal
electrocoagulation, followed by curettage.
Cryotherapy with liquid nitrogen can also be an
effective means of eradication.  Again, multiple treat-
ments may be required.  Bunney et al234 reported a cure
rate of 80% when treating warts on the hands with
cryotherapy every 3 weeks for up to 12 weeks.
For warts recalcitrant to the methods already
described, particularly periungual or plantar, one
might consider intralesional bleomycin235 or vapor-
ization with the carbon dioxide laser.236  Facial ver-
ruca plana can be most refractory to treatment.
Daily application with Retin-A (tretinoin, manufac-
tured by Ortho, Raritan, N.J.) may be helpful, as can
twice-daily application of Efudex (5-fluorouracil,
manufactured by Roche Laboratories, Nutley, N.J.).237
Military Considerations
An important consideration for the military phy-
sician regarding cutaneous viral infections concerns
the role played by stress in triggering outbreaks.
The battlefield certainly provides a degree of stress,
both emotional and physical, that most people will
never experience elsewhere.  For this reason, the
incidence of infections such as herpes simplex
labialis or herpes zoster is likely to be increased.  It
is extremely important, then, for the military physi-
cian to have some useful knowledge regarding their
treatment and possible prevention.  Some degree of
protection may be granted to the individual with a
history of UV radiation–induced herpes labialis
with the prophylactic use of acyclovir and sun
blockers such as zinc oxide.  There are no measures
available to prevent an episode of shingles.  How-
ever, the physician can intervene to prevent second-
ary bacterial infection, which is certainly more likely
to occur during wartime, when standards of hy-
giene are unavoidably lowered.  This can be achieved
through temporary isolation or hospitalization and
the use of topical or systemic antibiotics.
In the treatment of warts, early medical inter-
vention is encouraged to avoid the possible impair-
ment of performance that may occur as the result of
widespread involvement of the fingers or the pres-
ence of painful plantar lesions.  However, overly
aggressive treatment should be avoided, because
scars or large, iatrogenic bullae could negatively
affect performance, permanently or temporarily.
SUMMARY
It is imperative for the medical officer to have
some basic understanding of the common derm-
atoses.  Historically, these skin diseases have had a
substantial impact on the number of casualties suf-
fered during armed conflicts.  While usually not
considered significant threats to an individual’s
health, these maladies will frequently be exacer-
bated under battlefield conditions, resulting in sig-
nificant morbidity with a subsequent negative im-
pact on performance of combat duty.
The common dermatoses are usually not difficult
to manage.  Prompt recognition and intervention by
the medical officer may prevent a simple problem
from rapidly escalating into an incapacitating con-
dition.
Medical officers with a firm grasp on the recogni-
tion and management of common skin diseases
will be able to intervene easily to maintain the
health of individual troops as well as the collective
fighting effectiveness of their units.  During armed
conflict, given the harsh environmental conditions
that exist, intervention may be required frequently.
Understanding the information contained in
this chapter will enable the medical officer to man-
age these common dermatoses appropriately and
skillfully.

Common Skin Diseases
585
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174.
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175.
Craig G. Shaving. Arch Dermatol. 1955;71:11.
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184.
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Mahrle G, Alexander W. Surgical treatment of recalcitrant warts. J Dermatol Surg Oncol. 1983;9:445–450.
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Bunney MH, Nolan MW, Williams DA. An assessment of methods of treating viral warts by comparative
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Lockshin N. Flat facial warts treated with fluorouracil. Arch Dermatol. 1979;115:929–930.

T
2,4,5-T:   2,4,5-trichlorophenoxyacetic acid
TCDD:   2,3,7,8-tetrachlorodibenzo-p-dioxin
TOE:   Table of Organization and Equipment
TRNG:   tetracycline-resistant strains of Neisseria gonorrhoeae
TRUST:   toluidine red unheated serum test
TTp:   tuberculoid tuberculoid polar leprosy
TTs:   tuberculoid tuberculoid subpolar leprosy
U
USR:   unheated serum reagin
UV:   ultraviolet
UV-A:   ultraviolet A
UV-B:   ultraviolet B
V
VDRL:   Venereal Disease Research Laboratory test
VZV:   varicella-zoster virus
W
WHO:   World Health Organization
WRAIR:   Walter Reed Army Institute of Research

Index
599
INDEX
A
Abdomen
and contact dermatitis, 136
Achiya, Michihiko, 70, 71
Acids
See Alkalis and acids
Acquired immunodeficiency syndrome (AIDS)
and atypical mycobacterial infections, 404, 417
and cryptococcosis, 481
and genital herpes infection, 531
and leprosy, 352
and molluscum contagiosum, 580-581
and secondary syphilis, 503
and tuberculosis, 376, 377, 379
See also Immunocompromised patients
Acrocyanosis, 33
clinical manifestations, 33
etiology, 33
treatment, 33
Acrodermatitis chronica atrophicans, 311
Actinomycosis, 483-485
Africa
and dracunculiasis, 279
and filariasis, 274
and histoplasmosis, 457
and loiasis, 276
and lymphogranuloma venereum, 522
and mycetoma, 476
and onchocerciasis, 277, 278
and schistosomiasis, 281
and streptocerciasis, 279
African trypanosomiasis, 266-268
clinical manifestations, 267
diagnosis, 267
treatment, 267-268
Afzelius, A., 309
Age differences
and plague, 298
and Rocky Mountain spotted fever, 220
AIDS
See Acquired immunodeficiency syndrome (AIDS)
Albrecht, 305
Alexander the Great, 321
Alexander, W., 584
Algorithms
for diagnosing blisters, 14
for diagnosing changing growths, 15
for diagnosing deep fungal diseases, 455
for diagnosing genital ulcer disease, 496
for diagnosing and isolating atypical mycobacteria, 402
for diagnosing macular erythema, 17
for diagnosing new growths, 15
for diagnosing pruritic, inflamed papules, 18
for diagnosing pustular lesions, 13
for diagnosing scaling papules, plaques, and patches, 16
for diagnosing and treating Rocky Mountain spotted fever,
225
for diagnosing vesicles and bullae, 14
for treating dermatophyte infections, 436
for treating reactional states in leprosy, 349
Alimentary toxic aleukia, 87
Alkalis and acids
and irritant contact dermatitis, 132
Allen, Alfred M., 5, 112, 396, 425
Allergic contact dermatitis, 113-131
and cashew, 118-119
and clothing, 129-130
and fragrances, 131
and ginkgo, 119-120
and Gluta, 120
and India marking nut tree, 117
and Japanese lacquer tree, 117-118
and mango, 118
and metals, 125-128
and miscellaneous sensitizers, 131
and plants, 113-114
geographical distribution, 120-123
and poison ivy and poison oak, 114-117
and poison sumac, 117
and preservatives, 130-131
and rubber compounds, 129
and shoes, 128-129
and sunscreens, 125
and topical drugs, 123-125
See also Atopic dermatitis; Contact dermatitis; Irritant
contact dermatitis
Almeida, Louis, 323
Altman, J., 562
Amebiasis, 268-269
clinical manifestations, 269-269
diagnosis, 269
treatment, 269
Amenhotep II, 321
American Dermatologic Association, 464
American Revolution
and cold injuries, 22
and shoes, 56
Americas
and allergenic, indigenous plants, 120-122
and filariasis, 274
and onchocerciasis, 277
and schistosomiasis, 281
and tularemia, 300
Amherst, 71
Anacardiaceae, 113-114, 117
Anesthesia
for surgery on cutaneous trauma, 150
Angioedema, hereditary, 570
Animal bites
arachnids, 170-178
arthropods, 159
and bacterial contamination, 149
cats and dogs, 180
centipedes and millipedes, 160
insects, 160-170
reptiles, 179-180
Animal hookworm, 272
Annelids, 269
See also Helminthic infections
Annular lesion, 12
Ansamycins
and leprosy, 346

Military Dermatology
600
See also Drugs
Anthralin
in treatment of psoriasis, 559
Anthrax in biological warfare, 82-84
clinical findings, 83
cutaneous findings, 83
diagnosis, 83-84
military significance, 84
prophylaxis, 84
treatment, 84
Antibiotics
and contact dermatitis, 138
Antigen detection
of genital herpes, 529-530
Arabian peninsula
and schistosomiasis, 281
See also Middle East
Arachnids, 170-178
mites and ticks, 185-190
nonscabietic mites, 173-174
scabietic mites, 172-173
scorpions, 174-175
spiders, 175-178
ticks, 170-171
Arenaviridae-caused hemorrhagic fevers, 205-207
Aretaeus, 322, 357
Argentine hemorrhagic fever, 206-207
laboratory findings and treatment, 207
signs and symptoms, 206-207
Aristotle, 22, 322, 357
Aronson, 394
Arsenic
and contact dermatitis, 128
Arsenical vesicants in chemical warfare, 101
Arthritis, psoriatic, 555, 558
Arthritis-dermatitis syndrome, 307
Arthropods, 184
and bites, 159
as vectors of disease, 184
See also Arachnids; Centipedes and millipedes; Insects;
Vectors of disease
Atopic dermatitis, 564-568
clinical features, 564, 565
complications, 566
course, 565-566
diagnosis, 566
military considerations, 567-568
precipitants, 566
treatment, 566-567
Ashworth, 480
Asia
and allergenic, indigenous plants, 122-123
and filariasis, 274
and lymphogranuloma venereum, 522
and tularemia, 300
Asklepiades, 322
Asteatotic eczema, 27
clinical manifestations, 27
etiology, 27
treatment, 27
Atrophy, 10
Aufrecht, 358
Aurelianus, Caelius, 322
Australia
and allergenic, indigenous plants, 123
and atypical mycobacterial infections, 412
and histoplasmosis, 457
and murine typhus, 234
and tick paralysis, 189
Avicenna, 324
Azithromycin
for chancroid, 518
B
Bacille bilié de Calmette-Guérin (BCG), 351, 363
Bacillus anthracis, 82
Bacterial index
and leprosy, 332
Bacterial skin infections
and heat and humidity, 46
Baillie, 357
Baldwin, E.R., 356
“Balkan grippe,” 238
Balsam of Peru
and allergic contact dermatitis, 131
Bamboo Book, 322
Bancroft, J., 189, 198
Bancroftian filariasis, 274-275
clinical manifestations, 274-275
diagnosis, 275
treatment, 275
Barrett, O., Jr., 356
Baumgarten, 358, 359
Bayle, Gaspard Laurent, 357
Bazemore, J.M., 564
Beaman, J.H., 114
Bedbugs, 193-194
Bees, wasps, and hornets, 168
Beetles, 167
Belly
See Abdomen
Benzocaine
and allergic contact dermatitis, 123-124
Bernhard, J.D., 554
Bible
and leprosy, 321
and swarm of flies, 184-185
Bikini BRAVO shot, 76
Biological and Toxin Weapons Convention, 73
Biological warfare, 82-90
anthrax, 82-84
botulism, 87
hemorrhagic fevers, 84-87
history, 71-73
mycotoxins, 87-90
plague, 84
tularemia, 84
Biting flies, 194
See also Mosquitoes and flies
Black Death, 295
See also Plague
Black piedra, 448
Black widow spider, 177-178
Blackhead, 11
Blastomycosis, 464-467
clinical manifestations, 465-466
diagnosis, 466
distribution, 464-465
epidemiology, 464
history, 464
military implications, 467
primary cutaneous inoculation, 466
primary pulmonary, 465

Index
601
systemic, 465-466
treatment, 466-467
Bloch, Iwan, 321
Blood agents, 105
Body lice, 164
Bojalil, 394
Bolivian hemorrhagic fever, 207
Borovsky, 257
Borrelia burgdorferi, 187, 309
Bosch, Hieronymus, 71, 72
Botulism in biological warfare, 87
cutaneous and other clinical findings, 87
diagnosis, 87
military significance, 87
prophylaxis, 87
treatment, 87
Boutonneuse fever, 215, 225-228
clinical findings, 226-227
diagnosis, 228
differential diagnosis, 227
epidemiology, vectors, and hosts, 226
laboratory findings, 227
microbiology, 225-226
prevention, 228
treatment, 228
Bowenoid papulosis, 534
Boxer Rebellion
and leprosy, 325
Bradt, J.G., 515
Brazil
and lobomycosis, 479
and sporotrichosis, 470
Bretonneau, 301-302
Brill-Zinsser disease, 215, 233
See also Recrudescent typhus (Brill-Zinsser disease)
B’rit milah, 365
Brown recluse spider, 176-177
Brugia malayi, 275
See also Malayan filariasis
Brugia timori, 275
See also Timorian filariasis
Brugsch, 321
Bubo, 295
Bubonic plague, 297-298
Buhl, 358
Bulla, 8
Bunney, M.H., 584
Bunyaviridae-caused hemorrhagic fevers, 202-205
Burgdorfer, W., 309
Burkina Faso
and yellow fever, 201
Burrow, 11
Byogenkorosenkin-ho, 323
C
Calomys callosus, 207
Candidosis, 437-443
clinical features, 438-441
diagnosis, 441-442
intertrigo, 438-439
onychomycosis, 439-441
paronychia, 439-441
treatment, 442-443
Caribbean region
and allergenic, indigenous plants, 120-122
and filariasis, 274
and lymphogranuloma venereum, 522
and schistosomiasis, 281
Carter, Vandyke, 476
Case histories
of tuberculous gumma, 374
Cashew
and contact dermatitis, 118-119
Cat and dog bites, 180
Caterpillars and moths, 160-161
Catherine the Great, 295
Ceftriaxone
for chancroid, 518
Cell wall
and leprosy, 328, 329
Cellulitis, 293
Celsus, 357
Celsus, Aulus Cornelius, 322
Centers for Disease Control and Prevention
diagnostic criteria for Rocky Mountain spotted fever, 221
Plague Branch, 298
Centipedes and millipedes, 160
Cercariae, 281
Chagas’ disease, 193
Chagoma, 264-265
Champion, R.H., 569
Chancroid, 515-519
clinical manifestations, 516
laboratory diagnosis, 516-518
treatment, 518-519
Chang Chung-ching, 323
Chemical warfare, 90-105
and arsenical vesicants, 101
and cyanides, 105
doctrine and weaponry, 90
history, 73-76
and nerve agents, 105
and oximes, halogenated, 104-105
and sulfur mustard and nitrogen mustard, 90-101, 101-104
Chemoprophylaxis
of meningococcal infections, 308
Chernobyl (U.S.S.R.), 82
Chien Chen, 323
Chilblain, 31
Children
and condyloma acuminata, 535
and gonorrhea, 511
and leprosy, 346
and tetracycline, 301
and tick paralysis, 189
and treating Lyme disease, 313
China, ancient
and leprosy, 322-323
and plague, 295
and schistosomiasis, 281
and syphilis, 498
Chiracanthium, 178
Chloracne
and irritant contact dermatitis, 132-133
Chlorovinyldichloroarsine, 101
Cholinergic urticaria
and heat and humidity, 45
Christ, Jesus, 321, 322
Chromates
and contact dermatitis, 127
Chromoblastomycosis, 473-475
clinical manifestations, 473
diagnosis, 473-475

Military Dermatology
602
epidemiology and distribution, 473
history, 473
treatment, 475
Chrysops deerflies
vectors for loiasis, 276
Civil War
and chancroid, 515
and shoes, 56
Cleland, 198
Clinics of Dermatology, 120
Clofazimine
and leprosy, 345
See also Drugs
Clostridium botulinum, 87
Clothing
and contact dermatitis, 129-130
and heat loss, 26
and mite control, 237
and preventing Rocky Mountain spotted fever, 224
See also Shoes
Clovis, 357
Coal tar
in treatment of psoriasis, 559
Coccidioidomycosis, 459-464
clinical manifestations, 461
diagnosis, 461-463
distribution, 460-461
epidemiology, 460
history, 459-460
prevention, 463-464
treatment, 463
Cold-induced injury, 21-37
direct, 27-30
history, 22-24
indirect, 31-36
influential factors, 25-26
mechanisms, 24-25
pathogenesis, 27
prevention, 24
Cold panniculitis, 34
clinical manifestations, 34
etiology, 34
treatment, 34
Coleman, W.R., 560
Colophony
and allergic contact dermatitis, 131
Columbus, Christopher, 192, 498
Combat type
and heat loss, 26
Comedo, 11
Commentary of Taiho-rei, 323
Conder, 321
Conduction, 24
Confucius, 322
Contact dermatitis, 112
allergic, 113-131
by anatomical site, 135-137
irritant, 131-133
and mechanical injury, 133
patch and use testing, 137-138
and pharmacological reactions, 133-134
treatment, 138-139
urticaria, 134
See also Allergic contact dermatitis; Atopic dermatitis;
Irritant contact dermatitis
Contact urticaria, 134
See also Urticaria, contact
Convection, 24
Cook, Albert, 392
Corticosteroids, topical
in treatment of psoriasis, 558
Corynebacterium diphtheriae, 301
Creosote
and contact dermatitis, 132
Crimean-Congo hemorrhagic fever, 203
laboratory findings and treatment, 203
signs and symptoms, 203
Crimean War
and frostbite, 224
Crust, 10
Cryptococcosis, 481-482
clinical manifestations, 481-482
diagnosis, 482
epidemiology and distribution, 481
treatment, 482
Culicoides grahami
and streptocerciasis, 279
Culture
for diagnosing gonorrhea, 512-513
Culture, viral
to diagnose genital herpes, 528
Culture and serology
for chancroid, 517-518
Cunningham, D.D., 256-257
Cuprozinc-superoxide dismutase (CSD), 81
Cutaneous manifestations
of amebiasis, 269
of human hookworm disease, 270-271
of strongyloidiasis, 273
Cutaneous nerve biopsy
and leprosy, 333
Cutaneous trauma, 143-156
anatomy, 146-148
evaluation and first aid, 148-149
friction blisters, 144-146
microbiology, 149
pathogenesis, 144-145
prevention and treatment, 145-146
risk factors, 145
surgical intervention, 149-154
Cutaneous viral infections
See Viral infections, cutaneous
Cutis marmorata, 31
Cyanides in chemical warfare, 105
Cytologic diagnosis
of genital herpes, 528-529
D
da Costa Cruz, 393, 415
da Rocha-Lima, Henrique, 456
Dally, Clarence, 70
Damsch, 358
Dante, 324
Dapsone
and leprosy, 343
See also Drugs
Darier, Jean, 380
Darius I, 321
Darling, Samuel Taylor, 456
Daves, J.S., 569
Debridement, 151

Index
603
Dengue hemorrhagic fever, 198-200
laboratory findings and treatment, 200
signs and symptoms, 200
Deoxyfructo-5-hydroxytryptamine (DF5-HT)
and leprosy, 346
See also Drugs
Dermatitis
See Allergic contact dermatitis; Atopic dermatitis; Contact
dermatitis; Irritant contact dermatitis
Dermatology
See Military dermatology
Dermatophytes, 424
Dermatophytosis, 425-437
clinical features, 425-426
diagnosis, 433-434
tinea barbae, 428
tinea capitis, 426-428
tinea corporis, 428-430
Majocchi granuloma, 429
tinea faciei, 429
tinea imbricata, 429-430
tinea cruris, 430
tinea manuum, 431
tinea pedis, 430-431
tinea unguium, 432-433
treatment, 434-437
Deutschmann, 358
Dhobie itch, 117
Dhobie mark dermatitis, 117
Diadochen, 321
Diagnosis, principles, 6-19
anatomy, 6
differential diagnostic considerations, 8, 13-18
patient history, 7
physical examination, 7, 8-12
Diethyltoluamide dermatitis, 132
Diphtheria, 301-305
clinical manifestations, 303-304
diagnosis, 304
epidemiology, 302-303
etiology, 302
immunization, 305
treatment, 304-305
Direct cold injury, 27-30
asteatotic eczema, 27
frostbite, 28-30
Dog bites, 180
Donovan, C., 257, 519
Donovanosis, 519
See also Granuloma inguinale
Dopter, 305
Doughty, John W., 73, 74, 75
Downgrading reaction, in leprosy, 347, 351
Dracunculiasis, 279-280
clinical manifestations, 279
diagnosis, 279-280
treatment, 280
Dracunculus medinensis
and dracunculiasis, 279
Drugs
antimycotic, 435
against leprosy, 343-346
Drugs, topical
and contact dermatitis, 123-125
Duncan, T., 4
Dyshidrosis, 45
Dyshidrotic eczema
and heat and humidity, 45-46
E
Ebola hemorrhagic fever, 208-209
laboratory findings and treatment, 208-209
signs and symptoms, 208
Ebstein, 358
Ecthyma, 293
Ecumenical Council to the Lateran, 73
Edison, Thomas, 70
Edward the Confessor, 357
Egypt, ancient
and leprosy, 321
Ehrlich, 358, 359
Ehrlichiae, 240
See also Ehrlichiosis; Sennetsu fever
Ehrlichiosis, 215, 241-244
clinical findings, 243
diagnosis, 243-244
differential diagnosis, 243
epidemiology, 242
laboratory findings, 243
microbiology, 241
treatment, 244
vectors and reservoirs, 241-242
Emergency War Surgery NATO Handbook, 6
Emperor Gwyo, 323
Empress Komyo, 323
Endemic (murine) typhus, 215, 233-235
clinical manifestations, 234
control, 235
diagnosis, 234
differential diagnosis, 234
epidemiology, vectors, and hosts, 233-234
laboratory findings, 234
microbiology, 233
treatment, 234
Endocervicitis, 509
Entomophthoramycosis, 482-483
Epidemic typhus, 215, 229-233
and Brill-Zinsser disease, 233
clinical findings, 231-232
control, 232-233
diagnosis, 232
differential diagnosis, 232
epidemiology, hosts, and vectors, 230-231
laboratory findings, 232
microbiology, 230
military significance, 229-230
treatment, 232
Epidermization
in wound healing, 152-153
Epidermodysplasia verruciformis, 583
Epigrammata Medicae Philosophicae, 531
Erosion, 10
Erythema chronicum migrans, localized, 310
Erythema induratum, 380-382
clinical features, 381
course, 382
differential diagnosis, 382
epidemiology, 380-381
etiology and pathogenesis, 381
histopathology, 381
laboratory features, 381

Military Dermatology
604
treatment, 382
Erythema nodosum leprosum, 347
histological findings, 350
treatment, 350-351
Erythermalgia
and heat and humidity, 47
Erythrocyanosis, 34
clinical manifestations, 34
etiology, 34
treatment, 34
Erythromycin
for chancroid, 518
Erythropoietic protoporphyria, 52
Espundia, 261
Esthiomene, 523
Ethionamide
and leprosy, 345
See also Drugs
Ethiopia
and murine typhus, 234
Euphorbin, 133
Europe
and histoplasmosis, 457
and leprosy in the Middle Ages, 323-324
and leprosy in the Renaissance, 324
and Lyme disease, 311
and plague, 295
and syphilis, 498
and tularemia, 300
Evaporation, 25
Exposure duration
and heat loss, 26
Eye findings
and Rocky Mountain spotted fever, 219
See also Herpes zoster ophthalmicus
Eyedrops
See Topical drugs
Eyelids
and contact dermatitis, 135
F
Face
and contact dermatitis, 135-136
and cutaneous trauma, 146-147
Faget, Guy, 325
Feasby, W.R., 4
Feet
and contact dermatitis, 137
Fibroplasia
in wound healing, 152
Filariae
of medical significance, 274
Filariasis, 274-279
Bancroftian, 274-275
loiasis, 276-277
Malayan, 275
onchocerciasis, 277-279
streptocerciasis, 279
Timorian, 275
Filiform warts, 581
Filoviridae-caused hemorrhagic fevers, 208-209
Finlay, Charles, 200-201
Fire ants, 169
Fissure, 10
Fitzpatrick, T.B., 560
Flat warts, 581, 583
Flaviviridae-caused hemorrhagic fevers, 198-202
Fleas, 169-170, 190-193
and bites, 192
and papular urticaria, 192
and plague, 192
and tungiasis, 192-193
as vectors of diseases, 191
Flexner, 305
Foot injuries, 55-68
immersion foot, 63
management, 63
trench foot, 57-62
tropical immersion foot, 64-66
warm water immersion foot, 66
Fort Chaffee, Arkansas, 241
Fracastorius, 324
Fragrances
and contact dermatitis, 131
Franciscella tularensis, 84, 299
Franco-Prussian War
and frostbite, 22
Frederick the Great, 295
Frei test, 524
Friction blisters, 144-146
and heat and humidity, 47
pathogenesis, 144-145
prevention and treatment, 145-146
risk factors, 145
Friede, H., 190
Friedländer, 358
Friedman, 415
Frostbite, 28-30
clinical manifestations, 28-29
etiology, 28
prognostic signs, 29
treatment, 30
Frostnip, 28
Fuller, J.F.C., 76
Fungal skin diseases, deep, 453-492
actinomycosis, 483-485
blastomycosis, 464-467
chromoblastomycosis, 473-475
coccidioidomycosis, 459-464
cryptococcosis, 481-482
entomophthoramycosis, 482-483
histoplasmosis and histoplasmosis duboisii, 456-459
introduction, 454-456
lobomycosis, 478-479
mycetoma, 475-478
nocardiosis, 485
paracoccidioidomycosis, 467-469
rhinosporidiosis, 480-481
sporotrichosis, 470-473
Fungal skin diseases, superficial, 423-451
candidosis, 437-443
clinical features, 438-441
diagnosis, 441-442
treatment, 442-443
causative fungi, 424
dermatophytosis, 425-437
clinical features, 425-426, 426-433
diagnosis, 433-434
Majocchi granuloma, 429
tinea barbae, 428
tinea capitis, 426-428
tinea corporis, 428-430
tinea cruris, 430
tinea faciei, 429
tinea imbricata, 429-430

Index
605
tinea manuum, 431
tinea pedis, 430-431
tinea unguium, 432-433
treatment, 434-437
epidemiology and military history, 424-425
miscellaneous infections, 447-449
black piedra, 448
tinea nigra, 447-448
white piedra, 448-449
pityrosporum infections, 443-447
clinical features, 443-445
diagnosis, 445-447
treatment, 447
Fungal skin infections
and heat and humidity, 46
Fungi, 424
Funk, E.H., 356
Furunculosis, 293
G
Galen, 22, 322, 324, 357
Gambia
and yellow fever, 201
Gastrointestinal manifestations
of human hookworm disease, 271-272
of strongyloidiasis, 273
See also Intestinal manifestations
Genetics
and leprosy, 328-329
Geneva Gas Protocol, 73
Genital herpes, 525-531
clinical manifestations, 525-528
in immunocompromised patients, 527-528
nonprimary infection, 527
primary infection, 525-527
recurrent infection, 527
laboratory diagnosis, 528-530
antigen detection, 529-530
cytologic diagnosis, 528-529
serologic testing, 530
viral culture, 528
treatment, 530-531
Genital warts, 531-537
clinical manifestations, 533-535
diagnosis, 535-536
treatment, 536-537
Germany
and chemical warfare, 75
research to inactive mustard compounds, 103-104
Ghon, 305
Gila monsters, 179-180
Gilchrist, Thomas Caspar, 464
Ginkgo
and contact dermatitis, 119-120
Gluta
and contact dermatitis, 120
Goeckerman, W.H., 559
Gold
and contact dermatitis, 128
Goldberg, 360
Gonococcal infection, disseminated
diagnosis, 510-511
treatment, 514-515
Gonococcal infection, uncomplicated
treatment, 513-514
Gonorrhea, 508-515
clinical manifestations, 508-511
asymptomatic infection in men, 509
complicated infections, 510
disseminated gonococcal infection, 510-511
endocervicitis in women, 509
infections in infants and children, 511
pharyngeal infection, 510
rectal infection, 510
urethritis in men, 508-509
laboratory diagnosis, 511-513
treatment, 513-515
Gorgas, William, 456
Granulation
in wound healing, 152
Granuloma inguinale, 519-521
clinical manifestations, 519-520
complications, 520-521
laboratory diagnosis, 521
treatment, 521
Great Dying, 295
Great Fire of 1666, 295
Great Pestilence, 295
“Great Pox,” 498
Greece, ancient
and leprosy, 321-322
Groin
and contact dermatitis, 136
Ground itch, 270
Guatemala
and onchocerciasis, 278
Guiton, C.R., 356
Gummata, 503
Guttate psoriasis, 555
H
Haber, L.F., 73
Haffkine, 296
Hammurabi, 320
Handbook of Diseases of the Skin, 356
Hands
and contact dermatitis, 137
“Hanging groin,” 278, 279
Hansen, G. Armave, 324, 392
Hansen’s disease
See Leprosy
Hantaan virus, 204
Harwood, R.F., 184
Hawaii
and allergenic, indigenous plants, 120
Hazleton Research Products, 208
Head
and cutaneous trauma, 146-147
Head lice, 162-164
Heat cramps, 41
Heat exhaustion, 41
Heat injury, 40-41
cramps, 41
exhaustion, 41
heatstroke, 41
Heat loss mechanisms, 24-25
conduction, 24
convection, 24
evaporation, 25
radiation, 24-25
respiration, 25
Heatstroke, 41
Hebra, 32
Hellerström, 393

Military Dermatology
606
Helminthic infections, 269-282
animal hookworm, 272
dracunculiasis, 279-280
filariasis, 274-279
human hookworm disease, 270-272
schistosomiasis, 280-283
strongyloidiasis, 272-273
trichinosis, 280
Helminths, 269
and cutaneous disease, 270
Hematologic manifestations
of strongyloidiasis, 273
Hemorrhagic fevers, viral, 197-212
Argentine, 206-207
associated viruses, 199
Bolivian, 207
Crimean-Congo, 203
dengue, 198-200
Ebola, 208-209
introduction, 198
Kyasanur Forest disease, 202
Lassa fever, 205-206
Marburg, 209
Omsk, 202
prevention, 210
with renal syndrome, 203-205
Rift Valley fever, 202-203
supportive treatment, 210
yellow fever, 200-202
Hemorrhagic fevers in biological warfare, 84-87
cutaneous and other clinical findings, 84-85
diagnosis, 85
military significance, 86-87
prophylaxis, 86
treatment, 85-86
Henry IV, 357
Henry of Navarre, 357
Herodotus, 321
Herpes simplex labialis, 575-577
clinical features, 575-576
diagnosis, 576
treatment, 577
Herpes zoster, 577-580
clinical features, 577-578
diagnosis, 579
treatment, 579-580
types, 578-579
Herpes zoster ophthalmicus, 578-579
Herxheimer, 132
Hippocrates, 22, 321, 322, 357
Histamine
agents, and urticaria, 570-571
Histoplasmosis and histoplasmosis duboisii, 456-459
clinical manifestations, 457-458
diagnosis, 458-459
epidemiology and distribution, 457
history, 456-457
military implications, 459
treatment, 459
Histoplasmosis duboisii
See Histoplasmosis and histoplasmosis duboisii
History of the First Gas Regiment, 75
Hitler, Adolf, 75
Hollstrom, E., 309
Hookworm
animal, 272
human, 270-272
Hornets
See Bees, wasps, and hornets
Hugar, D.W., 62
Human hookworm disease, 270-272
clinical manifestations, 270-272
diagnosis and treatment, 272
Human papillomavirus (HPV)
types, 532
Hunter, John, 498
Hutchinson, Jonathan, 34, 360
Hydrocarbons
and irritant contact dermatitis, 132
Hypohidrosis syndrome
and heat and humidity, 44
Hyskos, 321
I
Iatrogenic immunization tuberculosis, 375
Immersion foot, 63
Immersion foot syndromes, 57
comparison, 60-61
Immunity, cell-mediated
and leprosy, 330
Immunity, humoral
and leprosy, 329-330
Immunization
against diphtheria, 305
against meningococcal infections, 308
See also Vaccines
Immunocompromised patients
and genital herpes, 527-528, 531
See also Acquired immunodeficiency syndrome (AIDS)
Immunoglobulin E
and mediation of urticaria, 571
Impetigo, 293
India
and allergenic, indigenous plant, 117
ancient, and leprosy, 322
and dracunculiasis, 279
and histoplasmosis, 457
and Kyasanur Forest disease, 202
and lymphogranuloma venereum, 522
and murine typhus, 234
and mycetoma, 476
and plague, 295-296
and rhinosporidiosis, 480
India marking nut tree
and contact dermatitis, 117
Indirect cold injury, 31-36
acrocyanosis, 33
cold panniculitis, 34
erythrocyanosis, 34
livedo reticularis, 31-33
pernio, 31
Raynaud’s disease and phenomenon, 34-36
trench foot, 34
Indonesia
and histoplasmosis, 457
and schistosomiasis, 281
Infants
and gonorrhea, 511
Inflammation
in wound healing, 152
Insect repellents
See Diethyltoluamide dermatitis
Insects, 160-170
bedbugs, 193-194
beetles, 167

Index
607
biting flies, 194
caterpillars and moths, 160-161
fleas, 169-170, 190-193
lice, 162-164, 193
mosquitoes and flies, 164-167
stinging insects, 168-169
true bugs, 161-162
See also Arachnids; Arthropods; Centipedes and millipedes
Intertrigo, 438-439
Intestinal manifestations
of amebiasis, 268-269
See also Gastrointestinal manifestations
Iran
and sulfur mustard victims, 95-97
Irritant contact dermatitis, 131-133
and alkalis and acids, 132
chloracne, 132-133
diethyltoluamide dermatitis, 132
and hydrocarbons, 132
from plants, 133
Irving, Laurence, 57
Isocrates, 357
Isolation
of rickettsiae, 221-222
Italy
and chemical warfare, 75
J
James, M.T., 184
Japan
and allergenic, indigenous plant, 117-118
ancient, and leprosy, 323
and chemical warfare, 75
and Sennetsu fever, 244
and sporotrichosis, 470
Japanese lacquer tree
and contact dermatitis, 117-118
John of Gaddesden, 324
K
Kanjin, 323
Katayama fever
See Schistosomiasis
Kerandel’s sign, 267
Kerion, 427
Kiefer, 305
Kirchheimer, Waldemar, 325
Kissing bugs, 162, 263
Kitasato, 296
Klebs, E., 302, 358
Klingmüeller, V., 320
Koch, Robert, 356, 358-361, 381, 392
Köebner’s phenomenon, 553
Korean conflict
and chancroid, 515
and cold injuries, 23-24
and heat injuries, 40
and jump boots, 56
and meningococcal disease, 306
and sexually transmitted diseases, 497
and tuberculosis, 361
Kortum, 357
Koster, 358
Ktesias, 321
Kuflik, E.G., 561
Kwo-Hon, 323
Kyasanur Forest disease, 202
L
Laennec, Réné, 357
Lai-ping, 323
Lamb, B.H., 300
Lamberg, S.I., 132
Langhans, 358
Lanolin
and allergic contact dermatitis, 131
Larrey, Baron, 22
Lassa fever, 205-206
laboratory findings and treatment, 206
signs and symptoms, 206
Last Judgment, 71, 72
Leakey virus, 204
Leather
See Shoes
Leiferman, K.M., 570
Leishman, W.B., 257
Leishmaniasis, 256-263
cutaneous manifestations, 258-260
diagnosis, 262
mucocutaneous manifestations, 260-261
treatment, 262-263
visceral manifestations, 261-262
Lennhoff, C., 309
Lepromin test
and leprosy, 330-331
Leprosy, 319-354
and acquired immunodeficiency syndrome, 352
clinical and histological diagnostic criteria, 333-342
complications, 346-351
epidemiology, 326-328
history, 320-326
immunology, 329-331
introduction, 320
laboratory diagnosis, 331-333
microbiology, 328-329
pathogenesis, 335
treatment, 343-346
vaccination, 351
Lewisite (L), 101
compared with mustard, 102
Lice, 162-164, 193
body, 164
head, 162-164
pubic, 164
Lichen planus, 561-564
clinical features, 561-563
diagnosis, 563
military considerations, 564
pathogenesis, 563
treatment, 563-564
variants, 562
Lichen scrofulosorum, 383-384
clinical features, 384
course, 384
differential diagnosis, 384
laboratory and histopathological features, 384
prognosis, 384
treatment, 384
Lichenification, 10
Linear lesions, 12
Linell, 394
Liston, 296
Livedo reticularis, 31-33
clinical manifestations, 33
etiology, 32-33

Military Dermatology
608
treatment, 33
Livingood, C.S., 4, 56, 551
Loa loa, 276
See also Loiasis
Lobo, Jorge, 478
Lobomycosis, 478-479
clinical manifestations, 479
diagnosis, 479
epidemiology and distribution, 478-479
treatment, 479
Loeffler, 302
Loiasis, 276-277
clinical manifestations, 276
diagnosis, 276
treatment, 276-277
Long, E., 356
LOST, 90
Lovell, Joseph, 56
Lucio’s phenomenon, 347, 351
Lucretius, 322
Lupus vulgaris, 371-374
clinical features, 372-373
course and prognosis, 374
differential diagnosis, 374
epidemiology, 371
histological features, 373
laboratory features, 373
pathogenesis, 371-372
Lutz, Adolpho, 467
Lyme disease, 309-313
clinical manifestations, 309-312
diagnosis, 312
epidemiology, 309
and mites and ticks, 187-188
treatment, 312-313
Lymphogranuloma venereum, 522-525
clinical manifestations, 522-523
laboratory diagnosis, 524
treatment, 524-525
M
M258 kit, 89, 102
M-1944 Shoepac, 56
MacKenna, R.M.B., 5
Macule, 8
Magee, James C., 3
Maggots, 165-167
Admiral Mahan, 73
Mahrle, G., 584
Majocchi granuloma, 429
Malassezia furfur, 443
Malaya
and murine typhus, 234
Malayan filariasis, 275
Malaysia
and filariasis, 275
and Sennetsu fever, 244
Management
of vesicant injury, 101
Manetho, 321
Mango
and contact dermatitis, 118
Manson, Patrick, 324
Mansonella streptocerca, 279
See also Streptocerciasis
Mantoux, Charles, 360
Marburg hemorrhagic fever, 209
Maturation
in wound healing, 153
McCoy, G.W., 299
McCrae, T., 356
Mein Kampf, 75
Mellanby, K., 159
Men
and gonorrhea, 508-509
and nickel dermatitis, 127
See also Sex differences; Women
Meningitis, 307
Meningococcal infections, 305-308
chemoprophylaxis in carriers, 308
clinical manifestations, 307-308
diagnosis, 308
epidemiology, 306
etiology, 306
treatment, 308
vaccines, 308
Meningococcal pneumonia, 307-308
Meningococcemia, fulminant, 307
Mercurialis, 184
Mercury
and contact dermatitis, 127-128
Metals
and contact dermatitis, 125-128
Methotrexate, systemic
in treatment of psoriasis, 559
Mexico
and murine typhus, 234
and mycetoma, 476
and onchocerciasis, 278
and sporotrichosis, 470
Microbiology and Virology Institute, 84
Microscopy, dark-field
for syphilis, 504
Microscopy, direct fluorescence
for syphilis, 504
Middle East
and schistosomiasis, 281
Miliaria, 41-44
crystallina, 42
and heat and humidity, 41-44
pathogenesis and treatment, 42-44
profunda, 42
pustulosa, 42
rubra, 42
Miliary tuberculosis of the skin, 369
clinical features, 369
course and prognosis, 369
differential diagnosis, 369
laboratory and histological features, 369
Military dermatology
recommendations, 5-6
unlearned lessons, 4-5
in Vietnam conflict, 3-4
in World War I, 2
in World War II, 3
Millipedes
See Centipedes and millipedes
Minocycline
and leprosy, 346
See also Drugs
Miracidium, 281
Mites and ticks, 170-171, 185-190
characteristics, 185-187
as disease vectors, 186
and handling, 187

Index
609
and Lyme disease, 187-188
nonscabietic mites, 173-174
and relapsing fever, 188
and Rickettsial diseases, 188-189
scabietic mites, 172-173
and tick paralysis, 189-190
and tick-bite alopecia, 190
and tick-bite reactions, 190
Molluscum contagiosum, 537-540, 580-581
clinical features, 537-539, 580
complications, 539
diagnosis, 539-540, 580-581
treatment, 540, 581
Modern Medicine: Its Theory and Practice, 356
Modern times
and advances against leprosy, 324-325
Móller-Christensen, 324
“Moon-boot syndrome,” 66
Morgagni, 357
Morphologic index
and leprosy, 333
Morton, Samuel, 357
Moses, 321
Mosquitoes and flies, 164-167
as vectors of diseases, 165
See also Biting flies
Moths
See Caterpillars and moths
Mulrennan, J.A., 132
Multibacillary leprosy
treatment, 343
Multidrug-resistant tuberculosis, 376
Murine typhus, 233-235
See also Rickettsial diseases
Musculoskeletal manifestations
of Lyme disease, 311
Mustard
compared with Lewisite, 102
Mustard toxicity
skin manifestations, 98
Mycetoma, 475-478
clinical manifestations, 476-477
diagnosis, 477-478
epidemiology and distribution, 476
history, 475
treatment, 478
Mycobacterial diseases, atypical, 391-422
and acquired immunodeficiency syndrome, 404, 417
atypical infections, 404-417
classification systems, 398-400
colony growth
and temperature, 403
diagnosis and isolation, algorithm, 402
epidemiology, 397-398
distribution, 398
incidence, 397
organism sources, 397-398
histopathology, 400
history, 392-396
general, 392-395
military, 395-396
mycobacteriology, 401-404
Mycobacterium, 401
Mycobacterium avium-intracellulare disease, 411-412
clinical presentation, citations, 408
course, treatment, prognosis, prevention, 412
diagnostic features, 411-412
histopathology, 412
laboratory features, 412
epidemiology, 411
Mycobacterium chelonae disease
clinical presentation, citations, 408
Mycobacterium fortuitum-chelonae complex disease, 415-416
course, treatment, prognosis, prevention, 416
diagnostic features, 415-416
histopathology, 416
laboratory features, 416
epidemiology, 415
Mycobacterium gordonae disease, 410-411
clinical presentation, citations, 408
course, treatment, prognosis, prevention, 411
diagnostic features, 410-411
histopathology, 410-411
laboratory features, 411
epidemiology, 410
Mycobacterium haemophilum disease, 413-414
course, treatment, prognosis, prevention, 414
diagnostic features, 414
histopathology, 414
laboratory features, 414
epidemiology, 413-414
Mycobacterium kansasii disease, 407
clinical presentation, citations, 408
course, treatment, prognosis, prevention, 407
diagnostic features, 407
histopathology, 407
laboratory features, 407
epidemiology, 407
Mycobacterium leprae
and drug resistance, 345-346
persistence, 346
See also Leprosy
Mycobacterium malmöense disease, 414-415
course, treatment, prognosis, prevention, 414-415
diagnostic features, 414
histopathology, 414
laboratory features, 414
epidemiology, 414
Mycobacterium marinum disease, 404-407
clinical presentation, citations, 408
course, treatment, prognosis, prevention, 406-407
diagnostic features, 405-406
differential diagnosis, 405-406
histopathology, 406
laboratory features, 406
epidemiology, 404-405
Mycobacterium scrofulaceum disease, 409
clinical presentation, citations, 408
course, treatment, prognosis, prevention, 409
diagnostic features, 409
histopathology, 409
laboratory features, 409
epidemiology, 409
Mycobacterium smegmatis disease, 416-417
course, treatment, prognosis, prevention, 416-417
diagnostic features, 416
histopathology, 416
laboratory features, 416
epidemiology, 416
Mycobacterium szulgai disease, 408-409
course, treatment, prognosis, prevention, 408-409
diagnostic features, 408
histopathology, 408
laboratory features, 408
epidemiology, 408
Mycobacterium ulcerans disease, 412-413

Military Dermatology
610
course, treatment, prognosis, prevention, 413
diagnostic features, 412-413
histopathology, 413
laboratory features, 413
epidemiology, 412
Mycobacterium xenopi disease, 409-410
course, treatment, prognosis, prevention, 410
diagnostic features, 410
histopathology, 410
laboratory features, 410
epidemiology, 409-410
Mycoses, opportunistic, 481-485
Mycoses, subcutaneous, 470-481
Mycoses, systemic, 456-469
Mycotoxins in biological warfare, 87-90
clinical findings, 88
cutaneous findings, 88
diagnosis, 88-89
military significance, 89-90
prophylaxis, 89
treatment, 89
Myocardial manifestations
of Lyme disease, 311
Myocarditis
and diphtheria, 303
N
Napoleon, 230, 295
Napoleonic Wars
and cold injuries, 22
Native Americans
and biological warfare, 71
and mosquitoes, 184
and polymorphous light eruption, 50
and syphilis, 498
Neck
and contact dermatitis, 136
Neisser, Albert L.S., 356, 358
Nematodes, 269
See also Helminthic infections
Neomycin
and allergic contact dermatitis, 123
Nernst, Walther, 73
Nerve agents in chemical warfare, 105
Nerve biopsy, cutaneous
and leprosy, 333
Neuralgia, postherpetic, 579
Neurological manifestations
of Lyme disease, 311
and Rocky Mountain spotted fever, 219
New Guinea
and atypical mycobacterial infections, 412
New York City
and Rickettsialpox, 228
Nickel
and contact dermatitis, 126-127, 136
Nigeria
and yellow fever, 201
Nitrogen mustard
See Sulfur mustard and nitrogen mustard in chemical
warfare
Nocardiosis, 485
clinical presentation, citations, 408
Nodule, 9
Nonscabietic mites, 173-174
Nonsteroidal antiinflammatory drugs (NSAIDs), 103
Nontreponemal tests
and false-positive reactions, 507
for syphilis, 505
See also Treponemal tests
Norden, 394
Norris, D.A., 563
North Africa
and mustard poisoning, 101
Nuclear warfare, 76-82
history, 70-71
radiation and thermal effects, 76-79
cutaneous, treatment, 79-81
sequelae, late, 81-82
O
Ofloxacin
and leprosy, 346
See also Drugs
Oklahoma
and sporotrichosis, 470
Oleoresin, 114
Omsk hemorrhagic fever, 202
Onchocerca volvulus, 277
See also Onchocerciasis
Onchocerciasis, 277-279
clinical manifestations, 277-278
diagnosis, 278-279
treatment, 279
Onychomycosis, 432, 439-441
Oozing, 10
Operations Desert Shield/Desert Storm
and heat injuries, 40
Organization
and military dermatology, 4, 5-6
Oriel, J.D., 531
Orr, K., 24
Osler, W., 356
Oximes, halogenated
in chemical warfare, 104-105
P
Pacific
and filariasis, 274
“Paddy foot,” 64
Pakistan
and dracunculiasis, 279
and murine typhus, 234
Papular urticaria
and fleas, 192
Papule, 9
Papulonecrotic tuberculid, 382-383
clinical findings, 383
course, 383
differential diagnosis, 383
epidemiology, 382-383
laboratory and histopathological findings, 383
pathogenesis, 382
treatment, 383
Paracoccidioidomycosis, 467-469
clinical manifestations, 468-469
diagnosis, 469
epidemiology and distribution, 467
history, 467
treatment, 469
Parasitic infections, tropical, 255-290
African trypanosomiasis, 266-268

Index
611
amebiasis, 268-269
animal hookworm, 272
dracunculiasis, 279-280
filariasis, 274-279
human hookworm disease, 270-272
introduction, 256
leishmaniasis, 256-263
schistosomiasis, 280-283
South American trypanosomiasis, 263-265
strongyloidiasis, 272-273
trichinosis, 280
Paronychia, 439-441
Parrish, J.A., 560
Pasteur, Louis, 184, 358
Paucibacillary leprosy
treatment, 343
Pefloxacin
and leprosy, 346
See also Drugs
Pellagra, 52
Peloponnesian War
and chemical warfare, 73
Perfumes
and contact dermatitis, 131
Pernio, 31
clinical manifestations, 31
etiology, 31
treatment, 31
Perry, H.O., 562
Persia, ancient
and leprosy, 321
Peru
balsam of, and dermatitis, 131
Peterson, G., 62
Pharaoh Sapti 5th, 321
Pharynx
and gonorrhea, 510
Philippine Insurrection
and leprosy, 325
Philippines
and filariasis, 275
and schistosomiasis, 281
Philon, 322
Philumenus, 322
Phosgene oxime (CX), 104-105
Phototoxicity and photoallergy, 48, 49-50
Piatt, A.D., 361
Piedra, black, 448
Piedra, white, 448-449
Pillsbury, D.M., 4, 56, 551
Pin-yüan-hou-lun, 323
Pityriasis versicolor, 443-444
Pityrosporum folliculitis, 444-445
Pityrosporum infections, 443-447
clinical features, 443-445
diagnosis, 445-447
treatment, 447
Plague, 295-299
in biological warfare, 84
clinical features, 297-298
diagnosis, 298
epidemiology, 296-297
etiology, 296
and fleas, 192
laboratory findings, 298
transmission, 296-297
treatment, 298-299
Plantar warts, 581-583
Plants
and contact dermatitis, 113-114
geographical distribution, 120-123
and irritant contact dermatitis, 133
See also individual plants
Plaque, 9
Platinum
and contact dermatitis, 128
Platyhelminths, 269
See also Helminthic infections
Pliny, 324, 357
Pliny the Elder, 322
Plutarch, 322
Pneumonia, meningococcal, 307-308
Pneumonic plague, 298
Poison ivy and poison oak
and contact dermatitis, 114-117
field identification, 117
signs and symptoms, 114-117
Poison sumac
and contact dermatitis, 117
Polymorphous light eruption, 50-51
Pompey, 322
Pompholyx, 45
Pope Damasius II, 324
Pope Innocent III, 73
Porphyria cutanea tarda, 52
Posadas, Alejandro, 459
Pregnancy
and condyloma acuminata, 535
and gonorrhea, 515
and lymphogranuloma venereum, 525
and plague treatment, 299
and tetracycline, 301
and treating genital warts, 537
and treating Lyme disease, 313
Preservatives
and contact dermatitis, 130-131
Prevention, Treatment and Control of Heat Injury, 40
Prickly heat, 42
Primary inoculation tuberculosis, 365-368
clinical features, 367
course and prognosis, 367
differential diagnosis, 367-368
epidemiology, 365
laboratory and histological features, 367
Primary lesions, 8
Promin, 326
Properdin deficiency, 306
Prospect Hill virus, 204
Prothionamide
and leprosy, 345
See also Drugs
Protozoal infections, 256-269
African trypanosomiasis, 266-268
amebiasis, 268-269
leishmaniasis, 256-263
South American trypanosomiasis, 263-265
Pseudofolliculitis barbae, 573-575
clinical features, 573
diagnosis, 574
military considerations, 575
pathogenesis, 573
and shaving guidelines, 574
treatment, 574-575
Psoralen and ultraviolet-A phototherapy (PUVA)

Military Dermatology
612
in treatment of psoriasis, 560
Psoriasis, 552-561
clinical features, 553-555
diagnosis, 555
guttate, 555
military considerations, 560-561
psoriatic arthritis, 555, 558
pustular, generalized, 555
pustular, localized, 555
treatment, 555-560
vulgaris, 555
Psoriasis vulgaris, 555
Psoriatic arthritis, 555
Pubic lice, 164
Pulex irritans, 190
Pulmonary findings
of human hookworm disease, 271-272
and Rocky Mountain spotted fever, 219
of strongyloidiasis, 273
Pustular psoriasis, generalized, 555
Pustular psoriasis, localized, 555
Pustule, 8
PUVA (psoralen and ultraviolet-A phototherapy)
in treatment of psoriasis, 560
Puumala virus, 204
Pyodermas, 292-295
clinical features, 293-295
etiology, 292-293
prognosis, 295
treatment, 295
Q
Q fever, 215, 238-240
clinical findings, 239-240
diagnosis, 240
epidemiology, 239
microbiology, 238-239
prevention, 240
rare presentations, 239
treatment, 240
R
Racial differences
and coccidioidomycosis, 461
and pseudofolliculitis, barbae, 573
and pyodermas, 292
and Rocky Mountain spotted fever, 220
and sunburn, 47
Radiation, 24-25
Ramon, 302
Ramsay Hunt’s syndrome, 579
Rawasley, H.M., 570
Raynaud, 34-35
Raynaud’s disease and phenomenon, 34-36
causes, 34
clinical manifestations, 35
etiology, 35
treatment, 35-36
Recrudescent typhus (Brill-Zinsser disease), 215, 233
Rectum
and gonorrhea, 510
Reed, Walter, 184, 200, 201, 210
Rees, 324
Refugees
and tuberculosis control, 379-380
Reid, 357
Relapsing fever
and mites and ticks, 188
Renal syndrome, and hemorrhagic fever, 203-205
laboratory findings and treatment, 205
signs and symptoms, 204-205
Renault, 32
Reptiles, 179-180
gila monsters, 179-180
snakes, 179
Research
and military dermatology, 6
Respiration, 25
Reston, Virginia
and Ebola virus, 208
Retinoids, systemic
in treatment of psoriasis, 559
Reversal reaction, in leprosy, 346-349
histological findings, 348
treatment, 348, 349
Rhamses II, 321
Rhinosporidiosis, 480-481
clinical manifestations, 480-481
diagnosis, 481
epidemiology and distribution, 480
history, 480
treatment, 481
Richter, 321
Ricketts, Howard T., 229
Rickettsiae
identifying, 222
isolating, 221-222
of spotted fever group diseases, 226
Rickettsial diseases, 213-254
boutonneuse fever, 225-228
ehrlichiosis, 241-244
endemic (murine) typhus, 233-235
epidemic typhus, 229-233
introduction, 214
and mites and ticks, 188-189
Q fever, 238-240
recrudescent typhus (Brill-Zinsser disease), 233
rickettsialpox, 228-229
Rocky Mountain spotted fever, 214-225
scrub typhus, 235-237
Sennetsu fever, 244
trench fever, 237-238
Rickettsialpox, 215, 228-229
clinical findings, 228-229
differential diagnosis, 229
epidemiology, vectors, and hosts, 228
laboratory findings, 229
microbiology, 228
treatment, 229
Ridley Logarithmic Scale, 332
Rifampin
and leprosy, 343
See also Drugs
Rift Valley fever, 202-203
laboratory findings and treatment, 203
signs and symptoms, 202-203
Rig veda sanhita, 322
Rocky Mountain spotted fever, 214-225
clinical manifestations, 217-219
diagnosis, 220-222
differential diagnosis, 222-223
epidemiology and vectors, 216-217
laboratory findings, 219-220

Index
613
microbiology, 215-216
pathological findings, 222
prevention, 224-225
prognosis, 220
treatment, 223-224
vectors, 217
Roentgen, W.C., 70
Roman Empire
and leprosy, 322
Rosin
and allergic contact dermatitis, 131
Ross, M.S., 190
Roux, 302
Rubber compounds
and contact dermatitis, 129
Runyon, E.H., 392, 394, 396, 398-399
Rush, Benjamin, 22, 357
S
Samman, P.D., 562
Sarin, 105
Satyriasis, 322
Scabietic mites, 172-173
Scale, 9
Scar, 11
Schenck, Benjamin Robinson, 470
Schick, 302
Schistosoma haematobium, 280
Schistosoma japonicum, 280
Schistosoma mansoni, 280
Schistosoma mekongi, 280
Schistosoma intercalatum, 280
Schistosomiasis, 280-283
clinical manifestations, 281-282
diagnosis, 282
treatment, 282-283
Schistosomulum, 281
Scholtz, J.R., 567
Schüller, 358
Scopulariopsis (blochi)
clinical presentation, citations, 408
Scorpions, 174-175
Scrofuloderma, 369-371
clinical features, 369-370
course and prognosis, 371
differential diagnosis, 371
epidemiology, 369
laboratory and histopathological features, 370-371
Scrub typhus, 215, 235-237
clinical findings, 236
control, 237
diagnosis, 237
differential diagnosis, 236
epidemiology and vectors, 236
laboratory findings, 236
microbiology, 235-236
military significance, 235
treatment, 237
Scutt, R.W.B., 128
Scutula, 428
Secondary lesions, 8
Secundus, Cajus Plinius, 322
Seeber, Guillermo, 480
Sennetsu fever, 215, 244
Septicemic plague, 298
Septuigent, 321
Serologic testing, 504-506
of genital herpes, 530
and leprosy, 333
nontreponemal tests, 505
sensitivity of, in untreated syphilis, 506
treponemal tests, 505-506
Sex differences
and chancroid, 515
and erythermalgia, 47
and papulonecrotic tuberculid, 382-383
and Raynaud’s disease, 35
and Rocky Mountain spotted fever, 220
See also Men; Women
Sex partners
and chancroid, 519
and gonorrhea, 514
and lymphogranuloma venereum, 525
Sexually transmitted diseases (STDs)
chancroid, 515-519
clinical manifestations, 516
laboratory diagnosis, 516-518
treatment, 518-519
genital herpes, 525-531
clinical manifestations, 525-528
laboratory diagnosis, 528-530
treatment, 530-531
genital warts, 531-537
clinical manifestations, 533-535
diagnosis, 535-536
treatment, 536-537
gonorrhea, 508-515
clinical manifestations, 508-511
laboratory diagnosis, 511-513
treatment, 513-515
granuloma inguinale, 519-521
clinical manifestations, 519-520
complications, 520-521
laboratory diagnosis, 521
treatment, 521
introduction, 494-497
lymphogranuloma venereum, 522-525
clinical manifestations, 522-523
laboratory diagnosis, 524
treatment, 524-525
and military impact, 497-498
molluscum contagiosum, 537-540
clinical manifestations, 537-539
complications, 539
diagnosis, 539-540
treatment, 540
syphilis, 498-508
clinical manifestations, 500-503
incidence, 499-500
laboratory diagnosis, 504-506
treatment, 506-508
Shaving guidelines
for pseudofolliculitis barbae, 574
Shelly, W.B., 570
Shepard, Charles, 325
Shingles
See Herpes zoster
Shoes
and American Revolution, 56
and Civil War, 56
and contact dermatitis, 128-129
and risk of friction blister, 145
See also Clothing

Military Dermatology
614
Prince Shotokautaifa, 323
Siegler, 361
Simulium blackflies
and onchocerciasis, 277
Skin anatomy, 6-7, 144
Skin diseases, bacterial, 291-317
diphtheria, 301-305
introduction, 292
Lyme disease, 309-313
meningococcal infections, 305-308
plague, 295-299
pyodermas, 292-295
tularemia, 299-301
Skin diseases, common, 549-595
dermatitis, atopic, 564-568
introduction, 550-551
lichen planus, 561-564
pseudofolliculitis barbae, 573-575
psoriasis, 552-561
urticaria, 568-572
viral infections, cutaneous, 575-584
Skin diseases associated with heat and humidity
bacterial skin infections, 46
cholinergic urticaria, 45
dyshidrotic eczema, 45-46
erythermalgia, 47
friction blisters, 47
fungal skin infections, 46
hypohidrosis syndrome, 44
miliaria, 41-44
tropical acne, 44-45
Skin diseases associated with sunlight
erythropoietic protoporphyria, 52
phototoxicity and photoallergy, 48, 49-50
polymorphous light eruption, 50-51
porphyria cutanea tarda, 52
solar urticaria, 51-52
sunburn, 47-49
Skin Diseases in Vietnam, 1965-72, 292, 396
Slit-skin examination technique
and leprosy, 331
Smadel, Joseph E., 235
Smith, J.L., 63
Snakes, 179
Socks, 145
Solar urticaria, 51-52
Soman, 105
South Africa
and histoplasmosis, 457
South America
and histoplasmosis, 457
and lymphogranuloma venereum, 522
and murine typhus, 234
South American trypanosomiasis, 263-265
clinical manifestations, 264-265
diagnosis and treatment, 265
Soviet Union
and biological warfare, 71, 73
and chemical warfare doctrine, 90
and Lyme disease, 311
Spalteholz, 32
Spanish-American War
and leprosy, 325
Spiders, 175-178
black widow, 177-178
brown recluse, 176-177
Chiracanthium, 178
tarantulas, 178
Sporotrichosis, 470-473
clinical manifestations, 470-472
clinical presentation, citations, 408
diagnosis, 472
epidemiology and distribution, 470
history, 470
treatment, 472-473
Sri Lanka
and rhinosporidiosis, 480
Stark, 357
STDs
See Sexually transmitted diseases (STDs)
Steere, A.C., 309
Steroids
and contact dermatitis, 138-139
Stinging insects, 168-169
bees, wasps, and hornets, 168
fire ants, 169
Storrs, Eleanor, 325
Stout, M., 4
Streptocerciasis, 279
Streptomycin
and leprosy, 346
See also Drugs
Strongyloidiasis, 272-273
clinical manifestations, 273
diagnosis and treatment, 273
Su-wen, 322
Sulfur mustard and nitrogen mustard in chemical warfare,
90-91, 90-101, 101-104
complications, 104
decontamination, 101-102
pathophysiology of poisoning, 93-95
properties, 92-93
signs and symptoms, 95-101
structure, 90-92
treatment, traditional, 102-103, 104
treatment, unconventional, 103-104
Sulzberger, M.B., 567
Sunburn, 47-49
Sunscreens
and contact dermatitis, 125
Surgery, for cutaneous trauma, 149-154
anesthesia, 150
complications, 153-154
technique, 150-151
wound dressings, 153
wound healing, 152-153
Sverdlovsk (former U.S.S.R.)
and anthrax, 71, 84
Sylvius, 357
Synanthropy, 184
Syphilis, 498-508
incidence, 499-500
clinical manifestations, 500-503
clinical presentation, citations, 408
laboratory diagnosis, 504-506
treatment, 506-508
latent syphilis of unknown duration, late latent
syphilis, and tertiary syphilis, 508
primary, secondary, and early latent syphilis, 506-508
Systemic lupus erythematosus, 52
T
Dr. Tabuchi, 70
Tabun, 105

Index
615
Tarantulas, 178
Tartars
and biological warfare, 71
Tasker, A.N., 2
Telangiectasia, 11
Thailand
and murine typhus, 233, 234
Thalidomide
and leprosy, 345
See also Drugs; Management
Thatcher, James, 22
Theodoric of Cervia, 324
Thothmes IV, 321
Threadworm, 272
Tiberius, 322
Tick paralysis
and mites and ticks, 189-190
Tick-bite alopecia
and mites and ticks, 190
Tick-bite reactions
and mites and ticks, 190
Ticks
See Mites and ticks
Timorian filariasis, 275
Timpe, A., 392, 394, 398
Tinea barbae, 428
Tinea capitis, 426-428
Tinea corporis, 428-430
Tinea cruris, 117, 430
Tinea faciei, 429
Tinea imbricata, 429-430
Tinea manuum, 431
Tinea nigra, 447-448
Tinea pedis, 430-431
Tinea unguium, 432-433
Tompkins, E.A., 506
Topical drugs
and contact dermatitis, 123-125
Training
and military dermatology, 4-5, 6
Travis, Richard T., 75-76
Trematodes, 269
See also Helminthic infections
Trench fever, 215, 237-238
clinical findings, 238
diagnosis and treatment, 238
epidemiology, vectors, and host, 237-238
microbiology, 237
prevention and control, 238
Trench foot, 22, 34, 57-62
Treponemal tests
and false-positive reactions, 507
for syphilis, 505-506
See also Nontreponemal tests
Trichinella spiralis
and trichinosis, 280
Trichinosis, 280
clinical manifestations, 280
diagnosis, 280
treatment, 280
Trichothecene toxicosis, stages, 88
Tropical acne
and heat and humidity, 44-45
Tropical diseases
See Parasitic infections, tropical
Tropical immersion foot, 64-66
True bugs, 161-162
Trunk
and contact dermatitis, 136
Trypanosomiasis
African, 266-268
South American, 263-265
Tsui Yen, 323
Tuberculids, 380-384
erythema induratum, 380-382
lichen scrofulosorum, 383-384
papulonecrotic, 382-383
Tuberculosis
and acquired immunodeficiency syndrome (AIDS), 376,
377, 379
clinical presentation, citations, 408
See also Tuberculosis, cutaneous
Tuberculosis, cutaneous, 355-389
bacteriology, 363
classification, 364-375
control, among refugees, 379-380
diagnosis, 375-376
epidemiology, 361-363
histopathology, 363-364
history, 356-361
introduction, 356
pathogenesis, 366
prevention, 378-379
treatment, 376-378
and tuberculids, 380-384
See also Tuberculosis
Tuberculosis cutis orificialis, 371
clinical and diagnostic features, 371
epidemiology, 371
Tuberculosis fungosa serpiginosa, 375
Tuberculosis verrucosa cutis, 368-369
clinical features, 368
course and prognosis, 368
differential diagnosis, 368-369
epidemiology, 368
laboratory and histological features, 368
Tuberculous gumma, 374-375
Tuberculous mastitis, 375
Tularemia, 299-301
in biological warfare, 84
clinical manifestations, 300-301
clinical presentation, citations, 408
diagnosis, 301
epidemiology, 300
etiology, 300
treatment, 301
Tumor, 9
Tunga penetrans, 192
Tungiasis
and fleas, 192-193
Typhus
See Endemic typhus; Epidemic typhus; Recrudescent
typhus; Scrub typhus
U
U.S. military
and leprosy, 325-326
USS John Harvey, 75
Uganda
and atypical mycobacterial infections, 412
Ulcer, 10
Ultraviolet-B phototherapy
in treatment of psoriasis, 560

Military Dermatology
616
United States
and murine typhus, 234
Unna, Paul Gerson, 32, 321, 324, 360
Urethritis
and gonorrhea, 508-509
Urticaria, 568-572
causes, 572
cholinergic, 570
clinical features, 568-569
contact, 134, 570
diagnosis, 571
hereditary angioedema, 570
from histamine-releasing agents, 570-571
idiopathic, 571
immunoglobulin E-mediated, 571
military considerations, 572
physical, 569-570
treatment, 571-572
vasculitis, 570
V
Vaccine
against leprosy, 351
against meningococcal infections, 308
against plague, 296
See also Immunization
Valentine, 324
Valsalva, 357
Vasculitis, urticarial, 570
Vectors of disease, 183-196
bedbugs, 193-194
biting flies, 194
fleas, 190-193
lice, 193
mites and ticks, 185-190
Vesicant Workshop, 75
Vesicants, arsenical
in chemical warfare, 101
Vesicle, 8
grouped, 12
Vietnam conflict
and atypical mycobacterial infections, 396
and candidosis, 438
and chancroid, 515
and dermatologic disease, 158
and dyshidrotic eczema, 45-46
and heat injuries, 40
and immersion foot, 57, 63
and leprosy, 326
and meningococcal disease, 306
and military dermatology, 3-4
and murine typhus, 233
and pyodermas, 292
and schistosomiasis, 281
and sexually transmitted diseases, 497-498
and skin diseases, 3, 396
and tuberculosis, 361
Vieusseaux, 305
Villemin, Jean Antoine, 358
Viral culture
of genital herpes, 528
Viral hemorrhagic fevers
See Hemorrhagic fevers, viral
Viral infections, cutaneous, 575-584
herpes simplex labialis, 575-577
herpes zoster, 577-580
military considerations, 584
molluscum contagiosum, 580-581
warts, 581-584
Virchow, 357
Viruses
associated with hemorrhagic fevers, 199
von Aue, Hartmann, 324
Von Behring, 302
von Hebra, Ferdinand, 383
von Pirquet, Clemens, 360
von Prowazek, Stanislaus, 229
W
Wade, 324
Warm water immersion foot, 66
Warts, 581-584
clinical features, 581-583
diagnosis, 583
military considerations, 584
treatment, 583-584
Warts, common, 581
Wasps
See Bees, wasps, and hornets
Waterhouse-Friderichsen syndrome, 307
Weather
and heat loss, 26
Weichselbaum, 305
Weigert, 358
West Africa
and yellow fever, 201
Wheal, 9
Wherry, W.B., 299-300
White piedra, 448-449
Whitehead, 11
Willis, I., 65
Wilson, Erasmus, 561
Women
and coccidioidomycosis, 461
and disseminated gonococcal infection, 510
and gonorrhea, 509
and nickel dermatitis, 126-127
and solar urticaria
See also Men; Sex differences
Woodward, T.E., 309
Woolhandler, H.W., 112
World Health Organization (WHO)
estimates on leprosy prevalence, 326
guidelines for treating leprosy, 344
World War I
and biological warfare, 71
and cold injuries, 22
and dermatologic disease, 158
and footware, 56
and leprosy, 325
and meningococcal disease, 306
and military dermatology, 2
and mustard exposure, 95
and pyodermas, 292
and sexually transmitted diseases, 497
and trench foot, 23
and tuberculosis, 360
and typhus, 230
World War II
and biological warfare, 71
and combat boots, 56
and dermatologic disease, 158
and diphtheria, 302
and heat injuries, 40

Index
617
and hypohidrosis syndrome, 44
and immersion foot, 63
and leprosy, 325-326
and meningococcal disease, 306
and miliaria, 41-42
and military dermatology, 3
and murine typhus, 233
and mycotoxins, 87
and pyodermas, 292
and relapsing fever, 188
and rickettsial diseases, 230
and schistosomiasis, 281
and sexually transmitted diseases, 497
and topical drug overtreatment, 123
and tuberculosis, 360-361
and trench foot, 23
Wound contraction
in healing, 152
Wound dressings, for cutaneous trauma, 153
Wound healing, 152-153
epidermization, 152-153
fibroplasia and wound contraction, 152
granulation, 152
inflammation, 152
maturation, 153
Wright, 257
Wuchereria bancrofti, 274
See also Bancroftian filariasis
X
Xerxes I, 321
Y
Yaws
clinical presentation, citations, 408
Yellow fever, 200-202
laboratory findings and treatment, 201-202
signs and symptoms, 201
Yemen
and onchocerciasis, 277, 278
Yersin, 296, 302
Yersinia pestis, 84, 192, 296
Yperite, 90
Z
Zaire
and atypical mycobacterial infections, 412
Ziehl, 358
Ziemssen, v.H., 356

