Manual of Tropical Dermatology

John H. S. Pettit
Lawrence Charles Parish

Manual of
Tropical DerIllatology

With 119 Figures and 12 Color Plates

Springer-Verlag
New York Berlin Heidelberg Tokyo
John H.S. Pettit, M.D., F.R.C.P. (London), Department of Tropical Medicine, Liv-
erpool School of Tropical Medicine, Liverpool, England; and Department of Medi-
cine, Universiti Kebangsaan, Kuala Lumpur, Malaysia.
Lawrence Charles Parish, M.D., F.A.C.P., Department of Dermatology, Jefferson
University, Philadelphia, Pennsylvania 19107; and Division of Dermatology, Univer-
sity of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania,
19104, U.S.A.

Library of Congress Cataloging in Publication Data

Pettit, John H. S.
Manual of tropical dermatology.
Bibliography: p.
Includes index.
I. Dermatology-Handbooks, manuals, etc. 2. Tropical
medicine-Handbooks, manuals, etc. I. Parish, Lawrence
Charles. II. Title.
RL74.P48 1984 616.5'00913 94-5323

© 1984 by Springer-Verlag New York, Inc.

Softcover reprint of the hardcover I st edition 1984
All rights reserved. No part of this book may be translated or reproduced in any form without
written permission from Springer-Verlag, 175 Fifth Avenue, New York, New York 10010,
U.S.A.
The use of general descriptive names, trade names, trademarks, etc., in this publication, even if
the former are not especially identified, is not to be taken as a sign that such names, as under-
stood by the Trade Marks and Merchandise Marks Act, may accordingly be used freely by
anyone.
While the advice and information of this book is believed to be true and accurate at the date of
going to press, neither the authors nor the editors nor the publisher can accept any legal
responsibility for any errors or omissions that may be made. The publisher makes no warranty,
express or implied, with respect to material contained herein.
Typeset by University Graphics, Incorporated, Atlantic Highlands, New Jersey.

9 8 7 6 5 4 3 2 1
ISBN-13 :978-1-4613-8294-2 e-ISBN-13: 978-1-4613-8292-8
DOl: 10.1 007/978-1-4613-8292-8
Dedicated to two of our favorite teachers and colleagues:
Geoffrey B. Dowling, M.D., F.R.C.P., (London) (deceased), Dermatologist, St.
Thomas Hospital, London, and St. John's Hospital Diseases of the Skin,
London
and
Herman Beerman, M.D., Sc.D., F.A.C.P., Emeritus Professor of Dermatol-
ogy, University of Pennsylvania School of Medicine and Emeritus Professor
and Chairman, Department of Dermatology, University of Pennsylvania
Graduate School of Medicine, Philadelphia, Pennsylvania.
Contents

Foreword
Francisco Kerdel-Vegas ix
Preface Xl
Acknowledgments xiii

I Introduction
Introduction to Tropical Dermatology 3
2 Clinical Index 6

II Bacterial Diseases
3 Anthrax 21
4 Yaws 27
5 Tuberculosis of the Skin 36
6 Leprosy 47
7 Buruli Ulcer (Mycobacterium Ulcerans) 78
8 Tropical Ulcers 88

III Fungal Diseases

9 Tropical Tineas 95
10 Chromomycosis 106
11 Madura Foot and Other Mycetomas 112
12 Sporotrichosis 118
13 Actinomycosis 124
14 Botryomycosis 129
15 Rhinosporidiosis 133
16 Rhinoscleroma 137
17 North American Blastomycosis 141
18 Paracoccidioidomycosis 146
19 Lobo's Disease 152
viii Contents

IV Parasitic Diseases
20 Leishmaniasis 159
21 Amebiasis 178
22 Toxoplasmosis 183
23 Onchocerciasis 187
24 Filariasis 195
25 Dracunculosis 200
26 Schistosomiasis 205

V Other Dermatoses
27 Lichen Planus Tropicus 215
28 Dietary Deficiencies 221
29 Phrynoderma 228
30 Brazilian Pemphigus Foliaceous 232
31 Chronic Arsenical Poisoning 238

Appendix One Useful Techniques 243

Appendix Two Useful Addresses 250

Index 253
Foreword

We live today in a world densely populated by human beings living in close commu-
nication with one another all over the surface of the planet. Viewed from a certain
distance it has the look of a single society, a community, the swarming of an intensely
social species trying to figure out ways to become successfully independent. We obvi-
ously need, at this stage, to begin the construction of some sort of world civilization.
The final worst-case for all of us has now become the destruction, by ourselves, of our
species. I

Although this warning is often repeated, we must not forget its paramount
importance and the commitment that each sector of society has to make a
world civilization possible.
Tropical dermatology is a good example of an important area of our spe-
cialty that has never caught the proper attention of the leading centers of
research in the developed countries, even though it comprehends major infec-
tious, parasitic, and nutritional problems of one-half of the world's land area
and three-quarters of the world's population.
The relevance of tropical dermatology in this extensive and overpopulated
area of the globe has public health connotations that emphasize its importance.
The sheer size of the problem makes it an urgent and outright need to recruit
and train adequate personnel to do a proper job, and that includes not only
dermatologists but paramedical personnel, nurses, and laboratory technicians.
This book written by John H. S. Pettit and Lawrence Charles Parish is pre-
cisely the type of guidance needed by the uninitiated, presented in a logical and
intelligent manner so it can be used throughout the world as a training manual.
Such initiative is welcome and needed, and complements very well other efforts
in the same direction.
Even in tropical countries, tropical dermatology does not occur everywhere,
and the ordinary tourist, staying in a metropolitan hotel, rarely becomes
exposed to what were once called exotic diseases. The moment the pleasures of

ILewis Thomas: Late Night Thoughts on Listening to Mahler's Ninth Symphony. New York,
Viking Press, 1983.
x Foreword

a big city are left behind, however, it seems that, in the rural areas of many
developing countries and in this century of unprecedented scientific and tech-
nologic advances, most people remain living under conditions that have not
changed for centuries and suffering from a host of infecious and contagious
diseases that are the main obstacle to any program designed to improve their
lives.
It is the duty of the medical profession, and in this case the dermatologists,
to study these problem with the greatest attention and coherence and to pro-
duce a strategy to overcome this burden in a short period of time. What has
been done until now is not sufficient and the problem remains unsolved.

Francisco Kerdel-Vegas, M.D.

Caracas, Venezuela and
Department of Dermatology
Jefferson Medical College
Thomas Jefferson University
Philadelphia, Pennsylvania
U.S.A.
Preface

When the world was young and transport was difficult, most people lived their
lifetime without venturing far from home. Migrants were few, whether they
traveled on foot, on horseback, or by boat, but those who did travel carried
their diseases with them as well as other more accepable examples of their
culture. The unacceptable ones often led to war, an additional method of
spreading disease.
As travel has become easier, diseases have become increasingly widespread,
but unfortunately knowledge of such illnesses has not extended as rapidly as
the diseases themselves. This book has been so conceived that it will aid in the
recognition and treatment of some of the more exotic of the world's diseases.

September, 1984 John H. S. Pettit, M.D.

Lawrence Charles Parish, M.D.
Acknowledgments

We want to acknowledge the magnificent resource material available at the

Library of the College of Physicians of Philadelphia (Anthony Aguirre, librar-
ian) and the Scott Medical Library of the Jefferson Medical College, Thomas
Jefferson University (John Timour, librarian).
Although many of the illustrations are of our own patients, we have called
upon a number of colleagues throughout the world for their assistance. Our
most heartfelt thanks to all of them; all such collaborators are acknowledged
under the appropriate pictures. We hope we have not missed any.
Dr. Florante C. Bocobo, Princeton, New Jersey reviewed the chapters on
actinomycosis and North American blastomycosis. Dr. Joseph Scrafani, Scher-
ing-Plough Corporation, Kenilworth, New Jersey provided a grant-in-aid for
the production of the color plates.
Lastly, we wish to thank Carmela Ciferni and Margaret DiFrancesco of
Philadlephia for working through this project and typing the manuscript.
Color Plates
Plate 1 Ulcer, lepromatous-Note the granulation tissue in the ulcer on the sole and
the lack of surrounding erythema. This Malaysian patient had lepromatous leprosy.
Plate 2 Ulcer, phagedenic-Note the extending margins of this patient with a pha-
gedenic ulcer of the foot. The diagnosis was tropical ulcer.
Plate 3 Verrucous formation-Note the warty heaped-up lesions, reddish, and
slightly scaling on the buttocks of a Chinese man. The diagnosis was tuberculosis ver-
rucosa cutis.
Plate 4 Sun sensitivity-Note the symmetrical reddish-brown pigmentation with
sharp borders indicating the photosensitive areas. This Egyptian woman had pellagra.
(Courtesy of Mohsen Soliman, M.D., Cairo, Egypt.)
Plate 5 Erosion, ear-Note the destruction, ulceration, and surrounding erythema
on the upper aspects of the outer ear. This Philadelphia anthropology student had
contracted chic1ero ulcer on a dig.
Plate 6 Papules, coalescent-Note the coalescent papules with purplish color. This
Italian man was sun sensitive and developed lichen planus tropicus. (Courtesy of F.
Ayala, M.D., Naples, Italy.)
Plate 7 Ulcer, Buruli-Note the destruction with shaggy borders on the ankle. This
Malaysian aborigine first developed swelling seven months before the ulcer appeared.
Plate 8 Nodules, heaped-up-Note the heaped-up, shiny lesions in this patient with
lepromatous leprosy which was sulfone resistant.
Plate 9 Ulcer, penile-Note the granulomatous formation at the edge of the ulcer,
which is somewhat shaggy. This North Carolina man had North Americn blastomy-
cosis. (Courtesy of David M. Warshauer, M.D., Chapel Hill, North Carolina.)
Plate 10 Verrucous formation-Note the warty papules that have coalesced and
have become covered with thick scale and the sharp borders of the lesions on the foot
of this 58 year old Indian man who worked barefoot on a farm. The diagnosis was
chromomycosis.
Plate 11 Keratoses-Note the crusting, scaling, and hyperkeratoses characteristic
of arsencial keratoses. This Malay youth had used a Thai folk remedy containing
21.5% arsenic.
Plate 12 Scarring-Note the destructive atrophic scars in this Iranian patient with
lupoid leishmaniasis.
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Plate 1 Ulcer, lepromatous Plate 2 Ulcer, phagedenic

Plate 3 Verrucous formation Plate 4 Sun sensitivity

Plate 5 Erosion, ear Plate 6 Papules, coalescent

Plate 7 Ulcer, Buruli Plate 8 Nodules, heaped-up

Plate 9 Ulcer, penile Plate 10 Verrucous formation

Plate 11 Keratoses Plate 12 Scarring

PART ONE

Introduction
CHAPTER 1

Introduction to Tropical Dermatology

The reader may well ask why we have written another book on tropical der-
matology, when at least two good ones currently exist i ,2 and two others could
be useful to dermatologists. 3,4 Are there not already too many books on various
subjects related to dermatology? Why should two dermatologists working on
opposite sides of the world undertake this apparently unnecessary task?
We have felt for some time that practical advice on the diagnosis and han-
dling of tropical dermatoses in a book telling the reader what to do and how to
do it in a simple, straightforward way may be more useful than a detailed
account of the more highly sophisticated diagnostic procedures that are avail-
able in centers of excellence throughout the Western world. Such details are
of little practical value to physicians who are seeing patients in the jungles of
Mrica, in a small mission hospital in South America, in the countryside of
Asia, or, for that matter, in any of those areas, where the poverty of the people
and of their governments makes it unlikely that they will be able to afford the
luxury of recently devised and probably expensive investigations.
In addition, we hope this book will assist not only doctors working in the
less sophisticated parts of the world but also those physicians living in the West
who find immigrants, refugees, students, and tourists arriving on their door-
steps, bringing with them diseases from elsewhere. Such health care personnel
do not need a detailed account of the etiologic or immunologic features of these
diseases.
It is not the purpose of this book to be encyclopedic. Out of the innumerable
references in the medical literature we have selected and appended to the end
of each chapter a small selection of recommended readings for those who wish
to expand their knowledge.
In choosing the subjects for this book, we first had to ask ourselves, What
is tropical dermatology? Sir Patrick Manson gave an answer many years ago:
 4 1. Introduction to Tropical Dermatology

"I employ the term 'tropical' in a meteorologic rather than a geographic sense,
meaning by it a sustained high atmospheric temperature; and by the term
'tropical diseases,' I wish to indicate diseases occurring only, or which from one
circumstance or another are especially prevalent, in warm climates.,,5 We are
not completely convinced by this definition and believe that on some occasions
the word tropical is indeed interchangeable with geographical-some diseases
are limited to certain parts of the world for overt or covert reasons, while others
take on different manifestations depending on humidity, sanitation, or the local
flora and fauna.
If we were to limit ourselves to the discussion of those problems seen only
between the tropics of Cancer and Capricorn, we would have had to exclude
almost all of the Middle East (including Iran, Iraq, and most of Saudi Arabia),
all of Pakistan and Bangladesh, and most of northern India, and the whole of
the north African littoral would also be outside our scope. We have, however,
included such diseases as anthrax, favus, and those tropical ulcers whose inci-
dence is highest in the dryer desert areas.
We have not forgotten that such conditions as Gilchrist's disease (originally
recognized in Baltimore) and the Mycobacterium ulcerans infections (first seen
not far from Melbourne), although predominantly found in tropical countries,
are not excluded from cooler areas; indeed, many of the diseases common in
the jungles of South America and Africa may be found in New York, where,
for example, amebiasis is a major problem. Because we are convinced that
tropical dermatoses may be seen in aflluent as well as in developing countries
and in major cities as well as in isolated hamlets, we believe that this book may
help not only those doctors working near the equator but also those in subtrop-
ical and temperate zones.
We have arranged the chapters in four categories that follow the introduc-
tory section. Most of part two (bacterial diseases) is devoted to mycobacterial
diseases of the skin, leprosy, tuberculosis, and the Buruli ulcer, but we have
also included yaws, anthrax, and the other bacterial ulcers seen in warmer
climates.
Part three (fungus diseases) starts with discussions of a few dermatophyte
infections that are mainly found in the tropics; however, most of this part cov-
ers the deeper mycotic infections. Some of these are almost never seen outside
the Americas, while others have a wider distribution. In this part, we have also
included actinomycosis, the nocardioses, and botryomycosis, all of which were
originally thought to be of fungal origin but are now known to be caused by
various bacteria. We have bowed to the tradition that permits inclusion of these
diseases in the section on mycology.
Part four consists of a number of parasitic diseases that are most frequently
seen in Africa, and part five gives an account of some of the noninfective der-
matoses found in the warmer parts of the world.
Realizing as we do that most of our readers will have had little experience
in investigating the diseases mentioned here, we have thought it helpful to
Introduction to Tropical Dermatology 5

describe in appendix one certain techniques that may be useful, and in appen-
dix two we list a number of addresses from which may be obtained supplies of
those drugs, sera, and laboratory aids that can be mOre than usually difficult
to find.

References
1. Caiiizares, 0: Clinical Tropical Dermatology. London, Blackwell Scientific Publi-
cations, 1975.
2. Caiiizares, 0: A Manual of Dermatology for Developing Countries. New York,
Oxford University Press, 1982.
3. Maegraith, B: Adams and Maegraith: Clinical Tropical Diseases. London, Black-
well Scientific Publications, 1980.
4. Peters, W, Gilles, HM: Color Atlas of Tropical Medicine and Parasitology. Chi-
cago, Year Book Medical Publishers, 1977.
5. Manson, P: Tropical Diseases: A Manual of the Diseases of Warm Climates. Lon-
don, Cassell, 1898, p 3.
CHAPTER 2

Clinical Index

Writers and publishers assume that an index is essential, if a medical textbook

is to be of real value to its readers. Unfortunately, this is not always true. A
typical index, such as the one at the end of this book, is only of use if the reader
knows the name of the condition, about which he or she wishes to read. The
majority of doctors who, for the first time, see in their clinical practice a case
of porokeratosis of Mibelli or lichen sclerosus et atrophicus will, if they do not
know its name, be reduced to an aimless leafing through the pages in the hope
that the volume will include a photograph that looks something like the con-
dition they have just seen on their patient. If a photograph is not present, the
reader may be compelled to read the entire text before realizing that the dis-
ease in question is not included.
In a volume such as this, which treats conditions that are rare in many parts
of the world, we suspect that most of our readers will not be able instantly to
recognize the diseases described and so will not know what to look up in the
index.
To help such readers, we have incorporated a clinical index that covers the
major clinical presentations (signs, symptoms, and sites) the condition may
show. It is not an index of all the diseases that show these signs and symptoms
but merely a checklist of the major findings of the diseases described here. It
is necessarily incomplete-most diseases sometimes occur in unusual presen-
tations and in unexpected sites, and such variants are not included. Similarly,
all methods of describing each sign cannot be covered. We believe, however,
that if readers list the major features of the case they are trying to diagnose
and look them up here, they may well be reminded to add one or two of the
more common tropical dermatoses to their list of diagnostic possibilities.
Clinical Index 7

A
Abdomen, abscess Amebiasis, dracunculosis
distension Amebiasis, kala-azar
Abscess, epidermal Botryomycosis, chromomycosis
internal Amebiasis, dracunculosis
micro- North American blastomycosis
Achromia See hypopigmentation
Alopecia Favus, leprosy,
mepacrine eruption
cicatricial Favus
eyebrows Anergic leishmaniasis, lepromatous
leprosy
Anemia Kwashiorkor, marasmus,
schistosomiasis
Anesthesia of lesions Leprosy
Animals, spread from Anthrax, toxoplasmosis
Ankle, papule Dracunculosis
ulcer Buruli ulcer
Annular lesions Borderline leprosy
face Leprosy
Anus Amebiasis, mucocutaneous
leishmaniasis
Arms Anthrax, Lobo's disease,
pellagra, sporotrichosis
Arthritis, painful Scurvy
Ascites Kwashiorkor, leprosy (ENL)
Atrophy of skin Lupoid leishmaniasis
onchocerciasis

B
Bite, insect Leishmaniasis
Bitot's spots Kwashiorkor, vitamin A deficiency
Blindness Onchocerciasis
night Phrynoderma
Boil, blind Acute leishmaniasis, anthrax
Bone swelling See osteomyelitis
pain Yaws
Bowen's disease Arsenism
Bulla, multiple Brazilian pemphigus
single Dracunculosis
Buttock, nodule Onchocerciasis
ulcer Buruli ulcer
verrucous formation Tuberculosis verrucosa cutis
8 2. Clinical Index

C
Carcinoma of skin See epithelioma
Cataract Onchocerciasis
Cheilitis Ariboflavinosis, pellagra
Chest wall, edema Anthrax
sinus Actinomycosis
vesicles Brazilian pemphigus
Chiggers Schistosomiasis
Chorioretinitis Toxoplasmosis
Chyluria Filariasis
Cirrhosis Amebiasis, schistosomiasis
Comedo Phrynoderma
Condyloma lata Rhinosporidiosis, yaws
Conjunctivitis Onchocerciasis
Crusting papules on leg Schistosomiasis
scalp Brazilian pemphigus, favus
Cutis laxa Onchocerciasis

D
Dandruff Brazilian pemphigus, favus
Dementia Pellagra
Depression Pellagra
Dermatitis Onchoceriasis, schistosomiasis
Diarrhea Amebiasis, pellagra, phrynoderma,
schistosomiasis

E
Ear, nodules Leishmaniasis, leprosy
erosion Chiclero ulcer
Earlobe, enlarged Leprosy
Ecchymoses Scurvy
Ectropion Leprosy,
North American blastomycosis
Edema Anthrax, kwashiorkor
of skin Anthrax
pulmonary Anthrax
Elbow, ulcer Buruli ulcer
Elephantiasis Filariasis
leg Filariasis
genitalia Filariasis, schistosomiasis
Encephalitis Toxoplasmosis
Eosinophilia Filariasis, dracunculosis,
onchocerciasis, schistosomiasis
Epistaxis Anergic leishmaniasis,
rhinosporidiosis
Clinical Index 9

Epithelioma, basal cell Arsenism

pseudo epitheliomatous Buruli ulcer, yaws
hyperplasia Arsenism
squamous cell
Erosion See ear, erosion
Erysipelas, bullous Anthrax
pseudo Onchocerciasis
Erythema Brazilian pemphigus
febrile Leprosy (ENL)
morbilliform Toxoplasmosis
nodosum Tuberculosis, North American
blastomycosis
nodular leprosy (ENL)
toxic Toxoplasmosis
Eschar Anthrax
Eyebrows, missing Anergic leishmaniasis, leprosy
Eye changes Leprosy, phrynoderma, vitamin A
deficiency, onchocerciasis

F
Face, annular lesions Leprosy (borderline)
destruction M ucocu taneous, leishmaniasis,
tuberculosis, yaws
leonine Anergic leishmaniasis, lepromatous
leprosy, onchocerciasis

nodules Leishmaniasis, Lobo's disease,

tuberculosis
scarred Leishmaniasis, lupus vulgaris
smoothed Leprosy
ulcerated Anthrax, leishmaniasis
vesicles Brazilian pemphigus
Fever Anthrax, erythema nodosum
leprosum, post-kala-azar
leishmaniasis, schistosomiasis
Fingers, contracted Leprosy, yaws
ulcerated Leprosy
Fistula Actinomycosis, botryomycosis,
mycetoma, schistosomiasis,
tuberculosis
Follicular plugging Phrynoderma
Foot, anesthetic Leprosy
dropped foot Leprosy
infected nodules Botryomycosis, sporotrichosis
10 2. Clinical Index

sinuses Mycetoma, sporotrichosis

mossy See lymphostasis verrucosa
ulcer Buruli ulcer, leprosy
Fungus ray Actinomycosis

G
Gastrointestinal disease Amebiasis, paracoccidioidomycosis,
anthrax
Grains See granules
Granules, grapelike Botryomycosis
hard Mycetoma
in pus Actinomycosis, botryomycosis,
chromomycosis, mycetoma,
nocardiosis
soft Actinomycosis, botryomycosis
yellow Actinomycosis, botryomycosis,
mycetoma
Granuloma Chromomycosis, leprosy, Lobo's
disease, paracoccidioidomycosis,
schistosomiasis, tuberculosis
atrophic Lupoid leishmaniasis, lupus
vulgaris, North American
blastomycosis
infected Chromomycosis, schistosomiasis
midline Mucocutaneous leishmaniasis
mulberry Paracoccidioidomycosis
nasal Mucocutaneous leishmaniasis,
rhinoscleroma, rhinosporidiosis
tuberculoid Chromomycosis, leishmaniasis,
leprosy, tuberculosis
Gumma Yaws
Gums, bleeding Ariboflavinosis, scurvy
erosions Paracoccidioidomycosis

H
Hairs, broken Favus
fluorescent Favus
corkscrew Scurvy
dyschromic Kwashiorkor
Halo, hypopigmented Subtropical lichen planus
Hands, crusting Anthrax, botryomycosis,
sporotrichosis
deformed Leprosy, yaws
Clinical Index 11

Hematuria Schistosomiasis
Hemorrhage, perifollicular Scurvy
Hepatosplenomegaly Kala-azar, schistosomiasis
Hydrocele Filariasis, onchocerciasis
Hydrocephalus Toxoplasmosis
Hyperidrosis, palmar or plantar Arsenism
Hyperkeratosis, plantar Yaws, Brazilian pemphigus,
arsenism
Hyperpigmentation Arsenism, Brazilian pemphigus,
pellagra
palm Tinea nigra
neck Tinea nigra, pellagra
mottled Arsenism, onchocerciasis
sun-precipitated Pellagra
Hyperplasia, pseudoepitheliomatous Buruli ulcer, yaws
Hypertrophy of lower limb Filariasis
genitalia Filariasis
Hypoesthesia See anesthesia
Hypopigmentation Arsenism, leprosy, leishmaniasis,
onchocerciasis, yaws

I
Ichthyosis Leprosy
Iliac crest nodules Onchocerciasis
Induration, inflammatory Filariasis
acute Anthrax, botryomycosis
chronic Actinomycosis, elephantiasis,
mossy foot
Isoniazid therapy, reaction to Pellagra

J
Joints, achromia Yaws
ankle Buruli ulcer, dracunculosis, yaws
painful Scurvy
swollen Scurvy, tuberculosis

K
Kala-azar See leishmaniasis
Keloidal scars Anergic leishmaniasis,
Lobo's disease
Keratitis punctata Leprosy, onchocerciasis
Keratoacanthoma Arsenism
Keratomalacia Kwashiorkor, vitamin A deficiency
 12 2. Clinical Index

Keratoses Arsenism, phrynoderma

Knee, painful Scurvy
swollen Tuberculosis
ulcer Buruli ulcer

L
Langhans' cells Chromomycosis, leprosy
(tuberculoid), leishmaniasis
(lupoid), tuberculosis
Larynx, hypertrophic lesions Rhinoscleroma, rhinosporidiosis
Leonine facies Anergic leishmaniasis, leprosy
(lepromatous) onchocerciasis
Lichenification of skin Onchocerciasis
Lichenoid eruption Chloriquine, p-aminosalicylic acid
(and other drugs), lichen planus
tropicus
Liver, enlarged Kala-azar, paracoccidioidomycosis,
leishmaniasis
Loose skin Onchocerciasis
Lung See pulmonary disease
Lymphadenitis Chromomycosis, filariasis, leprosy
(ENL), paracoccidiodomycosis,
sporotrichosis, tuberculosis
Lymphadenopathy Filariasis, onchocerciasis, pian bois,
sporotrichosis, tuberculosis
Lymphangitis Filariasis
Lymphedema Elephantiasis, filariasis,
onchocerciasis; see also
lymphostasis verrucosa
Lymphostasis verrucosa Chromomycosis, filariasis, leprosy,
yaws

M
Macules, pruritic Schistosomiasis
Madarosis Anergic leishmaniasis, leprosy
Malignancies, internal Arsenism
skin Arsenism, Buruli ulcer, tropical
ulcer, yaws
Melanodermatitis, lichenoid
mottled Arsenism
Melanosis See hyperpigmentation
Meningitis Toxoplasmosis
Clinical Index 13

Migratory lesions Dracunculosis, larva migrans

Mossy foot See lymphostasis verrucosa
Mouth, granuloma Paracoccidioidomycosis,
rhinosporidiosis
strawberry lesions Rhinosporidiosi
ulceration Mucocutaneous leishmaniasis,
paracoccidioidomycosis,
tuberculosis
Mucous, nasal discharge Rhinosporidiosis

N
"Necklace" Pellagra
Nerves, enlarged Leprosy
Neuritis, peripheral Phrynoderma
Nodule, apple jelly Lupoid leishmaniasis, lupus
vulgaris
edematous Filariasis, leprosy reactions
face Leprosy, leishmaniasis
fluctuant Actinomycosis
generalized Anergic leishmaniasis, lepromatous
leprosy
hypertrophic Leishmaniasis, Lobo's disease
inflammatory Botryomycosis, Buruli ulcer,
filariasis
perioral Leishmaniasis
scarring Leishmaniasis, tuberculosis
su bcu taneous Onchocerciasis
ulcerated Anthrax, leishmaniasis, leprosy
North American blastomycosis,
Buruli ulcer, chromomycosis, lichen
planus, Lobo's disease, tuberculosis
Nose, blocked Anergic leishmaniasis, lepromatous
leprosy, rhinoscleroma,
rhinosporidiosis
collapsed Leprosy, leishmaniasis,
tuberculosis, yaws
intranasal nodules Leprosy, paracoccidioidomycosis,
rhinosporidiosis, rhinoscleroma
septal destruction Leprosy, mucocutaneous
leishmaniasis, rhinoscleroma,
tuberculosis, yaws
14 2. Clinical Index

o
Orchitis Filariasis, leprosy (ENL),
Osteomyelitis North American blastomycosis,
Madura foot, mycetoma,
tuberculosis, yaws
p
Pain, in nerves Leprosy reactions
Palate, granuloma Paracoccidioidomycosis,
rhinoscleroma, rhinosporidiosis
Palm, pigmented Tinea nigra
Papilloma, conjunctival Rhinosporidiosis
strawberry Rhinosporidiosis
warty Chromomycosis, rhinosporidiosis
Papule, craw Onchocerciasis
bullous Dracunculosis
erythematous Leprosy (in reaction), yaws
follicular plugged PhI)'hoderma
hemorrhagic Anthrax
hyperpigmented Lichen planus tropicus
hypertrophic Yaws
pruritic Drancunculosis, onchocerciasis
raspberry Yaws
violaceous Lichen planus tropicus
warty Chromomycosis, tuberculosis
verrucosa cutis
Perinel,lm, watering-can Schistosomiasis
Photodermatotis See sun-sensitivity
Photophobia Onchocerciasis
Plaque, anesthetic Leprosy
Pleural effusion Leprosy (ENL)
Polyp, conjunctival Rhinosporidiosis
strawberry Rhinosporidiosis
Pruritus Onchocerciasis, schistosomiasis
Pulmonary disease North American blastomycosis,
paracoccidiodomycosis, tuberculosis
Purpura Scurvy, toxoplasmosis
Pus, granules in See granules
microabscesses North American blastomycosis,
sporotrichosis
R
Reaction (reversal) Anergic leishmaniasis, leprosy
Renal disease Leprosy, North American
blastomycosis
Clinical Index 15

Rhinitis Rhinoscleroma, leprosy, yaws

Ringworm See tinea

S
Scaliness, concentric Tinea imbricata
diffuse Brazilian pemphigus, tinea
imbricata
scalp Brazilian pemphigus, favus
Scalp See alopecia
Scars, atrophic Leishmaniasis, North American
blastomycosis, tuberculosis, yaws
hypertrophic Tuberculosis
Scrotum, swelling Filariasis
Serology See VDRL
Shins, nodules Onchocerciasis
Sinuses Actinomycosis, botryomycosis,
Madura foot, mycetoma, North
American blastomycosis,
tuberculosis
Skin. dyschromic Arsenism, kwashiorkor, pellagra
"flaky paint" Kwashiorkor
hanging Onchocerciasis
hypochromic Yaws
Soil, infection from See vegetation
Sore, crusted Acute leishmaniasis
ear Chiclero's ulcer
facial Anthrax, leishmaniasis
multiple Pian bois
Spirochaetes Yaws
Spleen, enlarged Kala-azar, leprosy (ENL),
paracoccidiodomycosis
Spores, thick-walled Chromomycosis
golden Chromomycosis
multiple budding Paracoccidioidomycosis
in sporangia Rhinosporidiosis
Sunsensitivity Pellagra, tropicus lichen planus

T
Thorax, sinus Actinomycosis
Tibia, bowed Yaws
Tinea, capitis Favus
concentric Tinea imbricata
pigmented Tinea nigra
 16 2. Clinical Index

Trachea, blocked Rhinosporidiosis

Trunk, dyschromic Arsenism

U
Ulcer Actinomycosis, botryomycosis,
Buruli ulcer, anthrax, amebiasis,
diphtheritic ulcer, leprosy, North
American blastomycosis,
paracoccidiodomycosis, tropical,
tropicaloid, tuberculosis
anal Amebiasis, mucocutaneous
leishmaniasis
hemorrhagic Anthrax
mouth Paracoccidiodomycosis
nose Leishmaniasis,
paracoccidiodomycosis
penile North American blastomycosis
phagedenic Tropical ulcer
plantar Leprosy
undermined Buruli ulcer
Umbilicus, granuloma Schistosomiasis
Urticaria Dracunculosis, filariasis,
schistosomiasis

V
VDRL reactive Leprosy (Lepromatous), yaws
Vegetation, infection from Chromomycosis, North American
blastomycosis, sporotrichosis
Verrucous formation Arsenism, chromomycosis,
leishmaniasis, tuberculosis
verrucosa cutis
Vesicles Brazilian pemphigus
hemorrhagic Anthrax
Vincent's organisms Tropical ulcer
Vitiligo Onchocerciasis, yaws
Vulva, hypertrophy Filariasis
ulcer Amebiasis, mucocutaneous
leishmaniasis

W
Weight loss Kwashiorkor, marasmus, scurvy
Wood, infection from See vegetation
Wool, infection from Anthrax
Clinical Index 17

Worm, in deep tissues Dracunculosis, onchocerciasis,

filariasis, schistosomiasis
in eye Onchocerciasis
in skin Dracunculosis
Wrist, achromia Yaws
dropped Beriberi, leprosy
ulcer Buruli ulcer, tuberculosis
PART Two

Bacterial Diseases
CHAPTER 3

Anthrax

Anthrax occurs naturally in herbivorous animals feeding on infected pastures

in the dryer parts of the world. Carnivorous animals acquire the infection indi-
rectly by eating infected carcasses of sheep, goats, cows, or even horses, while
the disease spreads to humans from contaminated animal products, such as
hides, wool or bone meal.
Most commonly seen in the Middle East (especially Iran), not unusual in
North or central Africa, central India, and the more arid parts of South Amer-
ica, the condition most frequently affects slaughterers, tanners, skinners, and
wool-sorters, as well as others whose occupations bring them into direct contact
with animals. In nonendemic areas, infection can be acquired from bone meal,
shaving brushes (infected bristles), skins, or raw wool. It has even been
reported as spreading from person to person following the communal use of an
infected loofah in public baths. The disease may start in any country in the
world, although it is more common in the veldt and savannah.

Etiology
The causative organism, Bacillus anthracis, is a large Gram-positive organism
(2.5/oL X 10-12 /oL) that occurs singly or in pairs in infected living tissue. It is
often difficult to detect these bacilli in the crusted lesions; they can more easily
be found by probing the edge of the lesion with a small dental burr using the
Dutz technique (see Appendix one).
The organisms produce three different toxins: an edema factor, a protective
antigen, and a lethal factor. Different combinations of these three are respon-
sible for the varying pathogenicity of individual strains. When the host animal
dies, sporulation takes place; the dormant spores are some of the most resistant
22 3. Anthrax

living organisms and are known to withstand dry heat at 140· C for more than
two hours.
For more than 100 years, it has been known that meat-fed rats are less
susceptible to infection than their grain-fed littermates. There is no doubt that
human disease is more common in patients with relative protein deficiency, but
the major epidemic of inhalation anthrax that occurred a few years ago in
Russia shows that even well-fed individuals are susceptible to massive
infection.

Clinical Features
Cutaneous Anthrax
The name malignant pustule has nothing to recommend it other than tradition
because the B. anthracis does not stimulate a polymorphonuclear leukocytic
reaction. Instead, it causes various types of necrotic lesions, according to the
toxicity and virulence of the bacillus.
The mildest form of anthrax starts as a small hemorrhagic papule (Figure
3-1) that is raised and pruritic and rapidly dries up producing a thick necrotic
eschar (Figure 3-2), usually on the face or hands, which normally heals without
leaving a scar. This type of disease probably occurs in endemic areas fairly
frequently without the patients seeking medical assistance.
If the organism is one of the more toxic forms, edema soon supervenes and
complicates the ulcer (Figure 3-3). The initial hemorrhagic papule starts to
look like a boil or even bullous erysipelas. The lesion becomes surrounded with

FIGURE 3-1 Hemmorhagic papule with surrounding erythema. (Courtesy Efriede

Kohout-Dutz, M.D. and Werner Dutz, M.D., Richmond, Virginia.)
Clinical Features 23

FIGURE 3-2 Thickening and crusting with some necrosis. (Courtesy Efriede Kohout-
Dutz, M.D. and Werner Dutz, M.D., Richmond, Virginia.)

hemorrhagic vesicles, and the severe edema may produce an extensive subcu-
taneous thickening that can be several centimeters thick. Occasionally, severe
infections spread along the lymphatics and cause large swellings of regional
nodes, but usually the cutaneous lesions remain fairly localized, with a necrotic
and hemorrhagic eschar that is surprisingly painless.

FIGURE 3-3 Edematous thickening of periorbital area with ulceration. (Courtesy

Efriede Kohout-Dutz, M.D. and Werner Dutz, M.D., Richmond, Virginia.)
24 3. Anthrax

Pulmonary Anthrax
The inhalation of spores most commonly occurs in those who work with treated
wool (Osler pointed out nearly a century ago that greasy wool was less dan-
gerous than wool that had been degreased). After they are inhaled, the spores
are phagocytosed in the lung tissue and taken to the pulmonary nodes, where
they often cause such extreme hemorrhagic lymphadenopathy that the nodes
have been described as looking like bags of blood.
Pulmonary edema and septicemia are shortly followed by suffocation and
death due to toxemia.

Gastrointestinal Anthrax
This type of anthrax may be acquired by eating contaminated animals.
Although a number of cases have been reported with ulceration and edema of
the gastrointestinal tract leading to ascites and a profuse watery diarrhea, most
cases probably are relatively mild and pass unnoticed in animals and humans.

Natural History
Itching occurs only a few hours after inoculation has taken place, shortly fol-
lowed by a papulovesicle that crusts to form an eschar. The surrounding tissue
may swell severely. If the edema occurs on the hand or arm, relatively little
trouble is caused; however, if the edema affects the head and neck, vision, swal-
lowing, or breathing can be greatly hindered. Whereas nowadays the majority
of these complications resolve leaving only a scar, some 20 percent of such
patients died, before the advent of antibiotics.
Although untreated pulmonary and gastrointestinal infections are often
fatal, most patients (and animals) affected by the less toxic organisms get bet-
ter without the diagnosis being made.

Differential Diagnosis
The relatively unimportant dry eschars sometimes look like an established case
of dermal leishmaniasis, but the natural history enables differentiation to be
made, as anthrax takes only a few days to develop while leishmaniasis takes
much longer (see Chapter 20).
In severe cases of anthrax, the lesions may look like boils or burns, but the
edema and hemorrhage are so typical that clinical diagnosis is rarely in doubt.
Any suspected case can easily be confirmed by demonstration of organisms in
the fluid of the bullae or in nonnecrotic tissue.
Follow-up 25

Investigations
These large Gram-positive organisms may be confused with Bacillus cereus (a
nonpathogenic organism of much the same appearance), but if the organism is
cultured the characteristic box-car chain of B. anthracis will soon develop, and
if it is stabbed into gelatin, the typical inverted fir tree can soon be
demonstrated.
As most cases of anthrax are easily recognizable, there is little need for
histologic study. Biopsies are rarely taken and infrequently helpful. There are
no diagnostic histopathologic findings-various combinations of edema, hem-
orrhage, and necrosis are all that can be seen.

Treatment
The organism seems to be regularly and reliably susceptible to penicillin: pen-
icillin G 600,000 units intramuscularly twice daily for five days or amoxicillin
500 mg every six hours for one week. For patients who are known to be sen-
sitive to penicillin, tetracycline (500 mg every four hours) is also said to be
curative.
Under successful treatment, the ulcers heal and the eschars dry up and sep-
arate from the underlying skin. Unfortunately, elimination of the B. anthracis
does not alone save the life of the patients in a more toxic condition; the edema
can cause such severe fluid loss that fluid replacement and correction of the
electrolyte imbalance may be needed, while toxemia (which is often exacer-
bated after bacterial death and the subsequent release of further endotoxins)
may require heavy doses of corticosteroids for several days.
A vaccine is available in some countries for people who are regularly
exposed to infection (see appendix two for addresses), and the suppliers will
give recommendations for suitable dosages.

Follow-up
As with all infectious disease, attempts should be made to trace and eliminate
sources of infection. Possibly infected hides, skins, hairs, bristles, meats, and
bonemeal should be destroyed. Because of the resistant spores that develop in
infected carcases, the bodies of animals known to have anthrax should be
burned or buried in quicklime. Regrettably, in endemic areas too much pas-
tureland is infected by the spores to make it possible to eradicate the disease
in the foreseeable future.
26 3. Anthrax

Selected Readings
Amidi, S, Dutz, W, Kohout, E, Ronaghy, HA: Anthrax in Iran. Z Tropenmed Par-
asito/1977; 24:250.
Davies, JCA: A major epidemic of anthrax in Zimbabwe. Cent Afr J Med 1983;
28:291.
Dutz, W: Anthrax, in Braude, AI (ed), Medical Microbiology and Infectious Disease,
Philadelphia, WB Saunders, 1981, P 1806.
Dutz, W, Kohout-Dutz, E: Anthrax. Int J Dermato/1981; 20:203.
Knight, AH, Wynne-Williams, CJE, Willis, AT: Cutaneous anthrax: The non-indus-
trial hazard. Br Med J 1969; 1:416.
Perl, D, Dooley, J: Anthrax, in Binford, CH, Conno, DH (eds), Pathology of Tropical
and Extraordinary Diseases. Washington, DC, Armed Forces Institute of Pathol-
ogy, 1976, pp 118-123.
CHAPTER 4

Yaws

Yaws used to be an extremely common disease in the tropical parts of the

world, with millions of cases spreading from the West Indies to the coastal and
riverine areas of Central and South America, across the whole of central Africa
to Sri Lanka, southern India, Southeast Asia, northern Australia, New Guinea,
and the Pacific islands. At one time, it appeared in Scotland as sibbens or the
Scottish yaws. Widespread eradication campaigns by WHO and UNICEF
during the 1950s were so successful that many authorities believed the disease
to be almost extinct. Throughout the 1970s, however, the condition slowly but
surely returned to its original homelands.
Patients are usually found among scantily clothed, younger members of the
rural population living in high year-round temperatures and humidity, but doc-
tors in temperate zones should not be surprised if an occasional early case (in
a refugee or an immigrant) is found in Europe or North America. Scarring
and bone deformity associated with the later stages of yaws are more likely to
be seen outside endemic areas and can pose diagnostic problems.

Etiology

Yaws is one of the diseases caused by a spirochete. There is considerable debate

about the Treponema pertenue. Scattered throughout the world is a range of
treponematoses: venereal syphilis, bejel, pinta, and yaws are the most extensive.
Although these diseases have such varied clinical presentations, the causative
organisms seem to be undifferentiable, and there is disagreement as to whether
the T. pallidum (syphilis, bejel), the T. carateum (pinta), and the T. pertenue
(yaws) are indeed separate organisms. Clinically, however, there is no doubt
that yaws is a separate disease whose signs and symptoms differ from those of
the other trepanematoses.
28 4. Yaws

It is transmitted by skin-ta-skin nonvenereal contact and usually starts on

uncovered sites in children, where bites, scratches, and grazes facilitate bac-
terial penetration of the epidermis.
The inability of the spirochete to grow in culture has made it impossible to
search for it outside the human body, and it is not known whether T. pertenue
confines itself to humans or whether it can exist elsewhere; its very slow return
from almost complete eradication suggests that there are no major sources of
infection outside humankind and that person-ta-person contact is the only
mode of transmission.

Clinical Features
In the past, it was the custom to divide the clinical features of yaws into pri-
mary, secondary, and tertiary lesions (perhaps encouraged by comparison with
the clinical features of syphilis), but it is simpler to group the primary and
secondary lesions together, as they tend to overlap and are separated by a
period of latency from those forms previously called tertiary.

FIGURE 4-1 Mother yaw:

small crusted papillomatous
lesion. (Courtesy Arturo Tapia,
M.D., Panama City, Panama.)
Clinical Features 29

Early Yaws
The initial lesion, often known as the mother yaw (Figure 4-1), starts as a small
erythematous papule, enlarges to give a proliferating and crusting papilloma,
spreads and ulcerates for two to six months (sometimes even longer), and
finally heals spontaneously, leaving a large depressed scar.
The features that used to be called secondary are manifestations of the
blood-borne spread of infection. Waves of skin lesions erupt, often associated
with severe bone pain caused by periostitis and with swelling of the joints of
the legs, hands, and feet.
The skin conditions are basically of two types, the papular and the hyper-
keratotic. Soft proliferating papules looking like raspberries (hence the name
frambesia) (Figures 4-2, 4-3) start to break out well before the disappearance
of the mother yaw. Called daughter yaws, these differ from the original patch
only in size and not in nature; they erupt in crops all over the body, prolifer-
ating, oozing, healing, and recurring for two or three years. They rarely ulcer-
ate and do not leave scars. If the mucous membranes are affected (the mouth
and perineum in particular), the papillomata take the form of soft, moist con-
dylomata lata.

FIGURE 4-2 Frambesia: soft

proliferating papules. (Cour-
tesy Arturo Tapia, M.D., Pan-
ama City, Panama.)
30 4. Yaws

FIGURE 4-3 Verrucous sec-

ondary lesions. (Courtesy D.
Ngreh, M.D., Penang, Malay-
sia.)

Although the palms and soles may develop typical wet papillomata, more
often hyperkeratotic patches form especially on the soles. Fissuring and sec-
ondary infection make walking painful and cause the typical gait that has
caused these lesions to be known as crab yaws. Early yaws finally subsides; the
miserable patient, relieved of the sores and bone pain, enters into a relatively
symptom-free period of latency interrupted only by occasional attacks of crab
yaws.

Late Yaws
While the early lesions of the disease are rarely destructive, this does not hold
true for the late manifestations. The onset of late yaws is marked by the
appearance of gummata in the bone, skin, and subcutaneous tissues. Fortu-
nately, these never spread to the nervous system or the cardiovascular system.
Clinical Features 31

FIGURE 4-4 Scarring and distortion from late yaws.

Gummatous osteitis and periostitis cause severe bone pain and may result
in hypertrophy or necrosis. A sabre tibia shows anterior bowing and thickening,
nodular swelling of the skull causes frontal bossing and swelling, and necrosis
of the carpal bones may lead to destruction of the wrist (Figure 4-4). Partic-
ularly in Africa, the center of the face may collapse following destruction of
the nasal septum (gangosa) (Figure 4-5). Hypertrophy of the maxillae, known
as goundou, is sometimes attributed to yaws.
In the skin, the gumma starts as a nodule that enlarges and breaks down in
the center to cause a punched-out ulcer that slowly heals, leaving a thin, wrin-
kled, tissue-paper scar. This process may take years, during which neighboring
lesions may coalesce to produce serpiginous ulcers, which, if combined with
 32 4. Yaws

FIGURE 4-5 Gangosa: inactive

late yaws. (Courtesy Liverpool
School of Tropical Medicine.)

underlying bone or joint disease, may cause severe deformity and even produce
elephantiasis in the distal part of the affected limb.
Browne points out that certain areas-the triangular area on the anterior
aspect of the wrist, the shin, and the fronts of elbows and ankles-may show
a depigmentation amounting to complete achromia. If this is present, it is
strong confirmatory evidence that associated chronic ulcerated or scarring
lesions are caused by late yaws rather than syphilis or tuberculosis.
Epitheliomatous change has been known to complicate these ulcers or their
succeeding scars.

Natural History
The mother yaw appears some two to six weeks after initial infection; it is
unlikely that the disease ever undergoes spontaneous cure, although with time,
each individual lesion may resolve. In the early period, the lesions are predom-
inantly soft papillomatous excrescences that, except for the mother yaw, do not
scar (Figure 4-6). This period may last for up to five years, after which a five-
Differential Diagnosis 33

FIGURE 4-6 Active yaws with

multiple soft papillomata and
postinfiammatory pigmentation.
(Courtesy Liverpool School of
Tropical Medicine.)

to ten-year period of latency occurs, followed by the appearance of gummatous

lesions.
The only dermatologic link between these two active periods is seen on the
palms and soles, where patches of hyperkeratosis, nodular or fiat, fissured and
painful, may come and go, causing few symptoms other than a painful hin-
drance to walking.
When the late lesions appear, they will probably continue to cause trouble
until treatment is undertaken. Although individual lesions slowly regress, the
ulceration and bone deformities can be expected to last indefinitely.

Differential Diagnosis
Because of the long period during which yaws seemed almost entirely to have
disappeared, its recent resurgence has often taken the medical profession by
surprise, and the diagnosis, at least in the early stages, has frequently been
missed. The mother yaw can be differentiated from the ulcerative proliferation
of anthrax by the absence of complicating edema, plus the malignant pustule
34 4. Yaws

of anthrax develops much more rapidly than yaws and the geographic indic-
ence of the two diseases does not overlap at all.
In the eruptive phase of daughter yaws, the raspberry-shaped papilloma
should not be mistaken for any other condition, while condylomata around the
mouth and anus almost never appear unless in association with other signs.
The hyperkeratotic lesions of the feet and hands should be easily differen-
tiable from palma-plantar keratoses not only because of the history (such
lesions are usually congenital or familial), but also because these rather local-
ized hyperkeratotic swellings of yaws often ooze a spirochete-containing serum
through the fissures if they are squeezed. It is sometimes difficult to separate
late yaws from a syphilitic lesion, especially a syphilitic plantar keratoderma.
In such cases the previous history is almost the only helpful clinical feature,
since bacteriologic, serologic, and histopathologic investigations are of very lit-
tle help. The patchy achromia over some of the joints may be a useful clue to
yaws.

Investigations
In early yaws, the exuding serum is full of spirochetes. As there is no presently
known method for separating T. pertenue from T. pal/idum or T. carateum (if
indeed they differ in any way other than tissue preference and virulence), find-
ing an organism is rarely the aid to diagnosis that might be expected. The
clinical appearance is more reliable because the mother yaw is larger, softer,
and longer-lasting than a syphilitic chancre. It usually develops on the exposed
parts of the limbs or face.
All the serologic tests used for syphilis are also positive for T. pertenue.
These investigations are of no help in differentiating the two conditions.
If a gumma is biopsied, it is frequently indistinguishable from syphilis-all
cases of syphilis and yaws show heavy plasma-cell infiltrates. It has been
pointed out that the histology of the early lesions may show two helpful fea-
tures. The endarterial proliferation common in syphilis is absent in yaws, and
sometimes in yaws there is a profuse invasion of spirochetes into the epidermis.
This is the only real differentiation from syphilis, in which the organisms are
mesodermotropic and are not found in the epidermis in significant numbers.

Treatment
Twenty-five years ago, it was believed that penicillin was curative and that a
single injection of 1.2 million units of penicillin G was all that was needed to
eradicate the disease in an adult. Newly seen cases are as susceptible as other's
to a single injection, but the disease must have returned either because infec-
tion spread into the treated area from elsewhere or, equally possible and more
Treatment 35

worrisome, treatment did not eradicate all the organisms in every patient. It is
urged that 1.2 million units of penicillin G be injected into each buttock of the
patient and all the immediate contacts: the previously recommended half-dose
for contacts is not recommended.
If a patient is sensitive to penicillin, large doses of tetracycline or erythro-
mycin (2 g daily for two weeks) may be substituted.

Selected Readings
Browne, SJ: Yaws. Br Med J 1980; 281:1090.
Browne, SJ: Yaws. Int J Dermatol1982; 21:220.
Endemic treponematoses in the 1980's. Lancet 1983; 2:552.
Hackett, CJ: Yaws. WHO monograph series No. 36, 1957.
Hackett, CJ, Guthe, T: Yaws. Bull WHO 1956; 15:869.
Lanigan-O'Keefe, FM, Holmes, JG, Hill, D: Infectious and active yaws in a Midland
city. Br J Dermatol1967; 79:325.
Morton, RS: The sibbens of Scotland. Med Hist 1967; 11:374.
Willcox, RR: The treponemal evolution. Trans St. John's Hosp Dermatol Soc 1972;
58:21.
CHAPTER 5

Tuberculosis of the Skin

In the past 40 years, the incidence of tuberculosis has declined steadily

throughout the Western world. It is not known whether this is due to the suc-
cessful use of BCG as an antituberculosis vaccine (a belief widely held in
Europe) or whether it is simply the result of a better standard of living and
more efficacious antituberculosis therapy (more widely believed in the United
States). Tuberculosis is still rife in the less affluent parts of the third world;
however, it is not a tropical disease in the same sense as are onchocerciasis and
rhinoscleroma. Its high persistance in the tropics justifies the consideration of
cutaneous tuberculosis in this book.

Etiology
Three types of Mycobacterium tuberculosis known to produce disease in
humans (human, bovine, and avian) can enter the human body by inhalation,
ingestion or inoculation.
Human tuberculosis (which most commonly affects the skin and the lungs)
is transmitted from person to person by droplet infection from the cough of a
patient with pulmonary disease or by inhalation of dust contaminated by
infected sputum. Bovine tuberculosis is usually acquired from infected milk
and affects the gastrointestinal tract and the cervical and abdominal lymph
nodes. Little is known about avian tuberculosis except that it is less common
and perhaps less sensitive to treatment.
Inoculation is the commonest cause of cutaneous tuberculosis, being found
in butchers and slaughterhouse workers whose cuts and grazes can be contam-
inated by material from infected animals. Surgeons and pathologists may be
similarly infected in their professional work. In the tropics, lightly-dressed indi-
Clinical Features 37

viduals who are in the habit of sitting on the floor of wooden houses may
acquire lesions from an infected splinter. Cutaneous tuberculosis may also
result from extension of the disease from an underlying bone, joint, or lymph
node.
When the organism enters a person for the first time, the body reacts with
a nonspecific inflammation with polymorphonuclear leukocytes and necrosis.
This form of reaction is unsuccessful in handling the infection. Within two or
three weeks the histology changes and a granulomatous reaction slowly takes
over. With the appearance of epithelioid cells, mycobacteria diminish in num-
ber; presumably in many patients, this process satisfactorily cures the infection.
If the T-cells are not fully competent, differing clinical pictures are found,
varying from lupus vulgaris, with high but incomplete immunity via scrofulo-
derma (moderate immunity), to miliary tuberculosis, in which little or no
immunity exists.

Clinical Features
Tuberculous Chancre
This is a rare condition that develops only when intradermal inoculation affects
a previously uninfected patient (Figure 5-1). A small, usually painless, nodule
containing numerous tubercle bacilli breaks down rapidly, producing a ragged

FIGURE 5-1 Tuberculous chan-

cre. (Courtesy Mohsen Soliman,
M.D., Cairo, Egypt.)
38 5. Tuberculosis of the Skin

ulcer covered by a crust. This is followed by enlargement of the regional lymph

nodes, which liquefy and discharge. The diagnosis is often not made until a
painless unilateral adenitis draws attention to a healing scar.

Scrofuloderma
Scrofuloderma is caused by a liquifying, caseating necrosis extending into and
through the skin from underlying disease, usually lymphadenitis or tuberculous
osteitis. In almost all cases, there is clinical evidence of the associated abnor-
mality. First, painless bluish-red nodules enlarge and ulcerate. Later, sinuses
can be found tracking from the soft underlying tissues, and, finally, an irreg-
ularly scarred and fluctuant mass forms that discharges, ulcerates, and heals
at the same time around a group of sinuses and fistulae (Figure 5-2).

Tuberculous Ulcers
When infection spreads to the skin from an underlying tuberculous bone or
joint (usually the sternum, ribs, hands, wrists, feet, and ankles), the skin soon
breaks down, producing an ulcer with a bluish edge. Sometimes an ulcer devel-
ops in mucous membranes after autoinoculation from bacilli in the sputum,
urine, or feces; these ulcers may spread to the adjacent skin. The clinical
appearance is not specific, although the lesion is full of bacilli.

Tuberculosis Verrucosa Cutis

When tuberculosis involves the upper part of the dermis, the epidermis some-
times reacts with a proliferative hyperplasia, and warty nodules develop that
slowly extend centrifugally to produce irregular verrucose plaques, often with
a central atrophic scar in which further nodules may develop. This happens
when bacterial inoculation affects a patient already sensitized to the tubercle
bacillus. It is the most common form of tuberculosis of the skin in India and
southeast Asia and is usually found on the buttocks or ankles, knees, and
elbows. Smaller, warty lesions on the fingers of butchers or postmortem atten-
dants are sometimes called verruca necrogenica. The plaques are often fissured
and sometimes have pustules and superficial discharging abscesses to produce
a lesion that is boggy rather than warty and often only diagnosed on biopsy
(Figure 5-3).

Miliary Tuberculosis
In those deprived areas where pulmonary tuberculosis still poses a major public
health problem, it is not unusual to find patients whose physiologic, dietetic, or
immunologic deficiencies have permitted the establishment of an engulfing
Clinical Features 39

FIGURE 5-2 Scrofuloderma: note

ulcerations and fluctuant masses
around sinus tracts. (Courtesy
Marwali Harahap, M.D., Rumah
Sakit Pirngada, Medan, Indonesia,
with permission of the Interna-
tional Journal of Dermatology and
the International Society of Tropi-
cal Dermatology.)

infection that permeates the whole body before it kills the patient. The skin is
not free from this disaster, and such patients may develop an explosion of papulo-
vesicles. This eruption will usually be recognized only by its association with
severe weight loss and the other signs of generalized disease.

Lupus Vulgaris
The most famous form of cutaneous tuberculosis is today less common than
tuberculosis verrucosa cutis. Patients whose reaction to a primary infection has
protected them for several years will, if reinfected, develop a high immunity
tuberculous granuloma. The reinfecting organism may arrive in the skin by
primary inoculation or by direct extension: lupus vulgaris can be seen beside a
patch of scrofuloderma or breaking out in what was apparently an old tuber-
culous scar.
A slowly extending plaque develops, studded with many small translucent
nodules best demonstrated by diascopy (see appendix one). It has been the
 FIGURE 5-3 Tuberculosis verru-
cosa cutis. Crusting, redness, and
scaling on leg. (Courtesy Ste-
phanie lablonska, M.D., Warsaw,
Poland.)

FIGURE 5-4 Lupus vulgaris. a.

Apple jelly nodules on face.
(Courtesy Stephanie lablonska,
a M.D., Warsaw, Poland.)
Clinical Features 41

FIGURE 5-4 b. More extensive

lesions with central ulcerations.
(Courtesy Stephanie Jablonska,
M.D., Warsaw, Poland.)

habit in the West to call these nodules apple jelly (Figure 5-4a), because they
appear greenish-yellow in Caucasian or oriental skin, but the term is inaccurate
for Africans and Asians, whose nodules are orange-brown. Peripheral expan-
sion will often leave a central scar that can be keloidal but is more often
atrophic with a tendency to ulcerate. It is not unusual for further lupus nodules
to form in the scar (Figures 5-4b, c).
In the past, lupus vulgaris frequently affected the center of the face (hence
the name-the mutilation produced is similar to the damage found in a person
savaged by a wolf). Destruction of the nose and nasal septum can cause the
nose to collapse, producing a parrot beak deformity. Lupus vulgaris produces
a range of clinical changes, from the atrophic and ulcerating to the hyper-
trophic and pseudotumorous, but in all types the active lupus nodule can be
detected.

Other Tuberculous Lesions

Various other lesions were frequently described in early textbooks as being seen
in patients with tuberculosis. It is now believed that some tuberculids' (ery-
thema induratum, lupus miliaris disseminatus faciei, acne agminata, rosaceous
tuberculid, etc.) are not of tuberculous etiology. Two other conditions are
thought to be true tuberculids: lichen scrofulosorum and papulonecrotic tub-
 FIGURE 5-4 c. Ulceration and
atrophy on upper lip. (Cour-
tesy Marwali Harahap, M.D.,
Rumah Sakit Pirngada, Medan,
Indonesia.)

FIGURE 5-4 d. Lupus vulgaris

below the knee spreading pheri-
pherally. (Courtesy 1. Sidney
Rice, M.D. Collection of the
College of Physicians of Phila-
d delphia.)
Differential Diagnosis 43

erculids are both rare. They show outcrops of lichenoid or centrally necrotic
papules and are often difficult to cure.

Natural History
Not every tubercle bacillus that successfully penetrates the human skin will
cause a recognizable infection; most people can satisfactorily eliminate the
invaders. Patients with an inadequate immune status develop diseases that
progress inexorably, with scarring and destruction extending in all directions.
The time between inoculation and the appearance of a tuberculous chancre
is only a matter of weeks, but it may be many years before lupus vulgaris
appears. The patient shown in Figure 5-3 developed lupus vulgaris in the scar
of an operation that had been performed for tuberculous osteitis 47 years
previously.

Differential Diagnosis
The acute onset of a small tuberculous chancre that ulcerates and crusts may
be confused with an early dry case of anthrax (see chapter 3) and can also be
mistaken for the infection caused by Mycobacterium balnei (swimming pool or
fish tank granuloma), but this only rarely spreads to the regional lymph nodes.
Scrofuloderma can usually be recognized fairly easily. Sporotrichosis
involves lymph nodes, where it causes a large discharging inguinal or axillary
mass, but it rarely affects cervical nodes, while on the limbs it is possible to
find a chain of nodules along the lymphatics connecting the primary lesion with
the regional adenopathy. Actinomycosis is easily distinguished by the yellow
granules in the discharge.
Tuberculosis verrucosa cutis is easily differentiated from verruca vulgaris
when the lesion is larger than 1 cm in diameter. The hyperkeratotic lesions of
chromomycosis can have a similar appearance but rarely show atrophy. Syphil-
itic gummata have a much shorter clinical history-what syphilis does in
months, tuberculosis does in years. Hypertrophic lichen planus is usually prur-
itic, multiple, and limited to the lower limbs. If the patient has been unfortu-
nate enough to acquire an infection by one of the rarer mycobacteria, the diag-
nosis will never be confirmed unless a bacteriologist can produce a successful
and diagnostic culture.
Lupus vulgaris is occasionally mimicked by a patch of tuberculoid leprosy
but is of course not anesthetic. In some parts of the world, sarcoidosis, which
affects Africans more than Asians, will sometimes show clinically similar
lesions, but the Mantoux test is negative. It is most difficult to differentiate
between lupus vulgaris and the chronic lupoid form of leishmaniasis (see chap-
ter 20); a careful clinical history may help establish the diagnosis.
44 5. Tuberculosis of the Skin

Investigations

Bacteriology
The detectable presence of acid-fast bacilli is not diagnostic. M. leprae, M.
ulcerans. M. balnei, and other atypical mycobacteria can all invade the skin.
It may be necessary to take a punch biopsy, extract the organisms, and set up
cultures in vitro (Lowenstein-Jensen medium) and in vivo (guinea pig inocu-
lation). It is recognized that the subleties of mouse footpad culture will usually
not be available.
In orificial tuberculosis and scrofuloderma and other types where there is
an underlying active tuberculosis, suitable investigations may demonstrate
mycobacteria in the sputum, gastric washings, or even in the urine or feces.
Discharge from the sinuses of scrofuloderma should also be examined.

Histopathology
When a patient is suspected of having tuberculosis of the skin, the most impor-
tant investigation is a biopsy. Sections should be stained not only with hema-
toxylin and eosin but also with Ziehl-Neelsen stain to demonstrate acid-fast
bacilli.
In a classical tuberculous granuloma, epithelioid cells and some Langhans'
giant cells are surrounded by a mantle of lymphocytes. Numerous acid-fast
bacilli are found in the primary chancre and scrofuloderma, but these are
uncommon in warty tuberculosis and rare or completely absent in lupus vul-
garis and the tuberculids. Caseation occurs to some degree in all forms of
tuberculosis, being proportional to the number of mycobacteria in the lesions,
but unfortunately these granulomata are not diagnostic even in the presence of
caseation, which may also be seen in tuberculoid leprosy, particularly the
neural form. Tuberculoid granulomata are found not only in leprosy but also
in chromomycosis and chronic leishmaniasis. Careful search must be made for
distinguishing features. Destruction of small nerves in the skin by a tuberculoid
granuloma is evidence of leprosy, while the classical golden-brown spores of
chromomycosis are diagnostic. Unfortunately, the Leishman-Donovan body is
no more frequently seen in chronic leishmaniasis than is M. tuberculosis in
lupus vulgaris. Further investigations are needed to determine whether the
granuloma is tuberculous or tuberculoid.

Other Tests
Every case of suspected cutaneous tuberculosis should have an x-ray of the
chest in case of concomitant pulmonary infection, and erythrocyte sedimenta-
tion rate (ESR) should be determined.
The Mantoux test will almost always be positive. If it is negative, further
Follow-up 45

consideration should be given to the possibility that the patient has sarcoidosis,
chromomycosis, or lupoid leishmaniasis.
If the diagnosis remains uncertain, it may be necessary to perform a ther-
apeutic trial as a last resort. Patients who do not show definite improvement
within two months of the onset of effective therapy do not have skin
tuberculosis.

Treatment
When cutaneous tuberculosis is associated with an underlying disease, it is
sometimes difficult to decide who should treat the patient. It is recommended
that treatment be supervised by a team rather than an individual. If this is not
possible, all cases should be treated as if there were active underlying disease.
If suitable laboratory facilities are available, drug sensitivity studies should be
made to determine which medication should be used. In the absence of such
tests the following routine is suggested:

1. Patients should be given 300 mg of isonicotinic acid hydrazide daily in a

single dose and rifampin 600 mg daily. Both treatments should be continued
for one year after the disappearance of all signs of clinical activity.
2. For diseases with a high bacterial content, ethambutol (not more than 20
mg/kg) should supplement therapy for the first two months in an effort to
reduce the bacterial load as quickly as possible. (Ethambutol should not be
given to children under six years of age.) All these drugs can be taken in
single daily doses-there is no advantage in divided dosage.

Before the development of specific antituberculosis drugs, calciferol was used

with success in the treatment of lupus vulgaris. In tropical countries where
pulmonary disease is still rampant, the incidence of cutaneous disease is
smaller than might be expected. This may be due to the prolonged exposure to
sunlight of many of the lightly clad indigenous population, and perhaps this is
why most cases of cutaneous tuberculosis resolve spontaneously on monother-
apy with isoniazid. The possibility is quite high that the infecting organism
may now be resistant to isoniazid, which, combined with the possible coexis-
tence of an underlying infection that has been overlooked, makes it advisable
that all patients be treated with polytherapy.

Follow-up
Patients should be seen every two weeks for the first two months of treatment
and then at monthly intervals until the lesion has disappeared and treatment
has been stopped. It must always be expected that diseases that have healed
46 5. Tuberculosis of the Skin

with atrophy may in the long term undergo malignant degeneration. Patients
should be warned that the appearance in a scar of a nodule or an erosion should
not go unchecked. Such lesions should be biopsied if there is any doubt as to
their nature. It is probably wise for all those with atrophic scars on exposed
areas to be protected by sun barriers for the rest of their lives.

Selected Readings
Brown, FS, Anderson, RH, Burnett, JW: Cutaneous tuberculosis. J Am Acad Der-
mato/1982; 6:101.
Harahap, M: Tuberculosis of the skin. Int J Dermato/1983; 22:542.
Immunological tests for tuberculosis, Lancet 1983; 1:1024.
Morrison, JG, Fourie, ED: The papulonecrotic tuberculide-from arthus reaction to
lupus vulgaris. Br J Dermato/1974; 91:263.
Ut, NV: Cutaneous tuberculosis in Vietnam. Int J Dermato/1973; 21:372.
Walker, AE, Frenk, E, Smith, AJ: Therapeutics XVII-reserve drugs in the treat-
ment of tuberculosis Br J Dermatol 1972; 86:210.
Wardman, AG, Williams, SF, Curzon, PGD, et al: Tuberculosis-who should pre-
scribe? Br Med J 1982; 2:569.
CHAPTER 6

Leprosy

No physician should be surprised if the next patient he or she sees has lep-
rosy-it has been found in every country in the world. Variously described as
starting in China or India, it is reputed to have been carried to the Middle East
and Europe by troops returning from the campaigns of Alexander the Great.
The relative lack of medical sophistication in the first half of the Christian era
resulted in leprosy being called by many names, and similarly many diseases
were called leprosy. Clarification of this confusion has become possible because
the bone changes associated with severe untreated disease are now easily rec-
ognizable, and studies in cemeteries, catacombs, and other burial places have
made it possible to detect whether or not leprosy existed in a certain area at a
certain time. Despite the original diagnostic uncertainty, which probably
caused the incarceration of many patients who did not actually have the dis-
ease, it is now known, for example, that many people buried in the Aebelholt
monastery in Denmark between 1175 and 1544 were definitely infected.
The medieval remains found in northern Europe and the fact that the caus-
ative organism was originally found by Armauer Hansen in Bergen, working
with Norwegian patients, have not prevented the lay public from believing that
the disease is limited to tropical countries. It is true that in the past 100 years
it has disappeared from Scandinavia and England, while patients now being
detected in Japan and the United States have almost always acquired the infec-
tion elsewhere. New cases still originate in Spain, Malta, southern Italy,
Greece, Turkey, and Cyprus, as well as in the Middle East. Mrica, Central
and South America, Asia, and the Pacific islands all have leprosy to a greater
or lesser extent.
It should be emphasized, however, that the increased mobility of the world's
population, traveling voluntarily (tourists, immigrants, and students) or invol-
untarily (refugees and military personnel), has ensured that, at least sporadi-
cally, leprosy can occur everywhere.
48 6. Leprosy

Etiology
When the Mycobacterium leprae attempts to establish itself in the human
body, the clinical picture that develops is not of a unique and diagnostic cluster
of signs and symptoms. An astonishing range of different presentations can be
seen, from a single enlarged painless nerve or a small localized patch of skin
that is anesthetic to a most profuse eruption of shiny nodules covering the
whole body and showing no evidence of sensory loss. It is a matter of wonder
that physicians working in the past without any knowledge of the pathology or
the etiology should have been able to recognize that these widely varying symp-
tom complexes were manifestations of the same disease, more particularly,
since in some forms of leprosy, mycobacteria are so few in number that they
are usually undetectable, and the widely differing presentations show an enor-
mous difference in their histopatholgy.

Immunologic Background
The different types of leprosy are not caused by varying species of M. leprae.
but rather by the varying susceptibilities of different individuals. It is probably
true that, despite various claims to the contrary, the leprosy bacillus has never
been cultured in vitro. We cannot be certain that different varieties of the
organism do not exist, but even if that were the case, there is little reason to
believe that the body would react differently to such variants.
It is not known how the disease is transmitted; the suggestion in the past of
prolonged contact with an infected person is completely untenable. The M.
leprae may occasionally penetrate the skin after trauma, but more likely lep-
rosy is caused by inhalation or ingestion of bacilli sprayed into the atmosphere
from the infected, ulcerated nasal cavities of untreated lepromatous patients.
In certain parts of the world today, some communities still have a high inci-
dence of disease-as much as 1 percent of the population. The popular belief
of the high infectivity of leprosy is obviously misplaced, since in such commu-
nities more than 95 percent never develop any evidence of the disease, even
though every member of the population will regularly encounter infected indi-
viduals. It is suggested that most people have complete immunity to the infec-
tion and are able to obliterate any leprosy bacilli that manage to enter the body
without producing any recognizable signs and symptoms. The wide range of
clinical signs of leprosy occurs in individuals whose personal immunity to infec-
tion is either incomplete or totally absent.

Patients with High but Incomplete Immunity

Patients with a less-than-perfect ability to overcome infection produce a reac-
tion of the cell-mediated type in which epithelioid cells and Langhans' giant
cells are surrounded by a mantle of lymphocytes, producing a classical tuber-
Etiology 49

culoid granuloma. These patients will be dealing with very few mycobacteria.
Even if the infecting load were heavy, multiplication will be prevented by the
relatively high resistance; consequently, recognizable lesions will be few and
almost certainly asymmetrical. Such patients will have the pure neural or
tuberculoid forms of disease.

Anergic Patients (Absent Immunity)

When people are completely unable to combat infection, the organisms, enter-
ing tissues of their choice, multiply almost indefinitely. Until recently, it has
been suggested that the patients had no suitable T-cells, but further knowledge
of these thymus-dependent cells has shown that the T-suppressor cells are
increased and the helper cells diminished in this type of individual. Whether
this is immunologically important or not is immaterial to the mycobacteria,
whose multiplication continues apace without provoking a tuberculoid granu-
loma. As time goes on, the organisms multiply to such a degree that the patient
develops foreign-body granulomata in reaction to the bacillary mass, and
swarms of acid-fast bacilli are enveloped by histiocytes and foam cells. Epithe-
lioid cells and lymphocytes are conspicuous by their absence. This type of dis-
ease is called lepromatous leprosy.

Patients with a Small Amount of Immunity

The existence of tuberculoid and lepromatous leprosy does not mean that there
is an all-or-none classification into which all infected individuals have to be
confined. Many patients whose immunity is lower than that found in tubercu-
loid individuals but higher than that of the lepromatous will, according to their
position in a spectrum ranging between these two poles, show increasing num-
bers of lesions and bacteria, with an intermediate type of pathology that is
neither one thing or the other. In most parts of the world, these patients are
said to have borderline leprosy, but there are still some stalwart traditionalists
who prefer to say these patients have intermediate or dimorphous disease.

The Spectrum of Leprosy

Most research workers classify the disease into five basic types (see Table 6-
1): the pure tuberculoid (IT) and the pure lepromatous (LL) are at opposite
ends of the spectrum, while between them are various forms of borderline dis-
ease known as borderline tuberculoid (BT), borderline (BB), and borderline
lepromatous (BL).
This Ridley-Jopling research classification covers almost all cases that are
seen. The types of disease vary in the number of lesions present, the number
of bacteria in each lesion, and the nature of the histopathology, as well as the
positivity of the lepromin test (see Appendix one). A number of other diagnoses
 VI
o

TABLE 6-1 The Leprosy Spectrum

Polar Borderline Borderline
Tuberculoid Tuberculoid Borderline Lepromatous
(IT) (BT) (BB) (BL) Polar Lepromatous (LL)

Number of One or two Few Some Many Multiple or Total (diffuse

lesions (nodular lepromatosis)
leproma)
Bacterial index in o 1+ 2+ 3+ 4+ 5+ (6 + occasionally seen)
untreated cases
Anesthesia Asymmetrical and early Early occasionally seen Symmetrical and late onset

Pathology Classical tuberculoid Mixture of epithelioid Foreign body granuloma with

granuloma with epithelioid cells and histiocytic cells histiocytes and foam cells
Lepromin test +++ ++ + ± o o o 0
Reactions Probably never Downgrading Downgrading Reversal or ENL ENL only ENL or Lucio
seen most or reversal phenomenon
common

?'
h
"0
(3
~
Clinical Features 51

are sometimes used (neural leprosy, indeterminate leprosy, diffuse leprosy,

etc.). Their places alongside the classical spectrum will be considered later.

Clinical Features
Pure Neural Leprosy
The prediliction of M . /eprae for nervous tissue, particularly the Schwann cell,
ensures that very few cases of leprosy exist in which nerves are not demonstra-
bly involved either clinically or histologically. Sometimes, a patient shows nerve
involvement but absolutely no evidence of dermatologic lesions (Figure 6-1).
Such a condition cannot occur in an anergic patient, whose inability to cope
with infection would be unable to prevent skin involvement to a greater or
lesser degree. A highly resistant patient, putting up a good struggle, sometimes
may not be able to prevent the appearance of a single patch of tuberculoid
leprosy on the skin. (Figure 6-2), and it is not surprising that occasionally this
single lesion occurs in a nerve rather than in the dermis.
The disease usually affects one of the more superficial nerves, most fre-
quently the ulnar, but also the radial, the preauricular, and the lateral poplit-

FIGURE 6-1 Neural leprosy: this

patient had no lesions on his skin.
52 6. Leprosy

FIGURE 6-2 Neural leprosy

with a single early tuberculoid
lesion at the corner of the
mouth.

eal. The nerve becomes thickened, harder, and sometimes more nodular than
normal. Enlargement alone is totally insufficient to suggest the diagnosis, but
very few nerves are both enlarged and hardened, and an enlarged, easily palp-
able, and nodular superficial nerve should always be suspect, especially if asso-
ciated with a patch of anesthesia later followed by a gradual loss of power and
ultimate wasting in a group of muscles. Skin scrapings will be negative for
AFB. The lepromin test should when possible be performed-a mildly positive
reaction is not unusual in residents of endemic areas, but a strongly positive
test is diagnostically helpful.
Ideally, no case should be diagnosed unless a nerve biopsy has been per-
formed. This will show a classical tuberculoid histology that, taking up a fair
amount of space but confined within the fibrous perineurium, explains the
enlargement and hardening of the nerve as well as the associated peripheral
neurologic changes (Figure 6-4).
Similar nerve involvement associated with skin lesions can be found in
tuberculoid and some types of borderline disease, producing asymmetric nerve
involvement among the early clinical signs. In lepromatous patients, intra-
neural foreign-body granulomata slowly produce a stocking-and-glove anes-
thesia that extends up the limbs in association with more or less general wast-
FIGURE 6-3 Neural leprosy:
wasting of the interossei result-
ing from leprosy infection of the
ulnar nerve.

FIGURE 6-4 Facial paralysis in

tuberculoid leprosy-the per-
sistent exposure of the right
cornea needs urgent attention
from an ophthalmic surgeon.
54 6. Leprosy

ing of the muscles of the hands and feet. By the time this occurs, the patients
will have had extensive lepromatous leprosy for many years.

Tuberculoid Leprosy (IT)

The polar type of tuberculoid disease is usually a rather scaly infiltrated single
lesion that may be anything from 1 or 2 to 20 or 30 centimeters in diameter:
such areas are invariably anesthetic. They have raised edges and, if they have
attained a reasonable size, are most often found to be spreading peripherally
and healing centrally. Sometimes, a few smaller lesions are present elsewhere
on the body, but normally such patients do not have more than three or four
plaques. Occasionally, such patches consist of small clusters of papules looking
like a group of cobblestones, which histologically can be shown to have mini-
ature tuberculoid granulomata but are too small for anesthesia to be detected
(Figure 6-5).
Many tuberculoid patches are hypopigmented. If the patient is examined in
direct sunlight (traditionally said to be the proper way to look at a patient
suspected of having leprosy), one or two areas of hypopigmentation may be
seen in the absence of other detectable change. Indeed, now and then a patient
has nothing but a few hypopigmented and hypoesthetic areas.

FIGURE 6-5 Tuberculoid lep-

rosy: the patch is scaly and sur-
rounded by cobblestone pap-
ules. A lesion consisting only of
such papules is on the right.
Clinical Features 55

FIGURE 6-6 Tuberculoid lep-

rosy: the skin is slightly thick-
ened and mildly scaly, and the
well-demarcated patch is anes-
thetic.

Diagnosis of tuberculoid leprosy is easy because no other skin lesion is anes-

thetic. When the diagnosis has been suspected, the next thing to do is to exam-
ine the patient carefully for evidence of affected nerves (Figure 6-6). An abnor-
mal preauricular nerve may be seen crossing the sternomastoids, and by
running the back of a fingernail along each clavicle, the physician may be able
to detect enlargement in one or more of the fine supraclavicular nerves that
course over the clavicle directly beneath the skin. The ulnar should be exam-
ined at the elbow, where it is normally palpable. If it is affected, it will not only
be big and hard, but the pain that normally radiates down the limb when a
normal nerve is squeezed will be diminished or absent. Enlarged superficial
branches of the radial nerve can be felt crossing the end of the radius and, if
one wraps one's fingers around the head of the fibula and then moves them
slightly down and backwards, it is possible to detect an abnormal lateral pop-
liteal nerve running around the neck of the fibula.
Whether or not it is possible to detect large nerves, the whole skin should
be carefully examined for anesthesia. The earliest sensory change is usually a
dulling of temperature appreciation, best demonstrated by asking patients to
close their eyes and recognize the difference between two test-tubes, one full of
crushed ice and the other of boiling water. Later loss of sensation to pin prick
and cotton may be found not only in the visible patches of cutaneous disease
56 6. Leprosy

but in other areas supplied by nerves that have not been recognized clinically
as having an infection.
If more than five lesions are detected (neural or cutaneous), the patient
probably does not have tuberculoid disease of the polar type.

Lepromatous Leprosy (LL)

Patients who are completely unable to combat M. /eprae infection are of two
types. A few (more common in Central America) probably have a congenital
anergy and react to infection by producing a diffuse lepromatosis (see page 74),
while more commonly, and much more widespread, some patients will produce
a nodular lepromatous disease probably due to secondary anergy. They have a
mixture of macules, papules, nodules, and diffusely infiltrated plaques scat-
tered throughout the skin. Occasionally, particularly in the early stage, the
macules are hypopigmented, but later the lesions become raised, red, and
shiny, never showing any signs of epidermal involvement, such as the scaling
seen in IT. They are to be found almost everywhere, but less frequently affect
the palms and soles, axillae, groin, and scalp.
The face is always involved, ultimately producing a leonine facies, while the
lobes of the ears are grossly enlarged and pendulous. Involvement of the fore-
head frequently causes destruction of the outer parts of the eyebrows (mada-

FIGURE 6-7 Early leproma-

tous leprosy. The earlobes and
eyebrows are already involved
as well as the thickening of the
skin of the face. (Courtesy J.
Sidney Rice, M.D. Collection
of the College of Physicians of
Philadelphia. )
Clinical Features 57

FIGURE 6-8 Marked leproma-

tous leprosy affecting the lips as
well as the nose, ears, eyebrows,
and chin.

rosis), and in the later stages the whole of the eyebrow may be permanently
destroyed (Figures 6-7 to 6-9).
It is not only the skin that is affected; the nose is involved early in the course
of disease. Small ulcerated nodules produce a crusting and secretion that will
be full of AFB-some authorities believe that nasal discharge may be the

FIGURE 6-9 Leonine facies of

lepromatous leprosy.
58 6. Leprosy

source of all transmitted infection. Before the advent of satisfactory treatment

the mouth and larynx were involved in the final stages of the disease, but this
is rarely seen today.
Thickened peripheral nerves such as are seen in IT are not found in the
early stages of lepromatous leprosy, unless the patient has a form of disease
that has evolved from a previous borderline phase. As the disease extends,
peripheral nerves slowly degenerate, starting with the hands and feet, where a
stocking-and-glove anesthesia spreads up the limbs. At the same time, neuro-
trophic atrophy, combined with disuse atrophy caused by muscle paralysis,
leads to absorption of the small bones, particularly the phalanges. Repeated
unnoticed trauma and secondary infection allow wounds of the hands and feet
to penetrate deeply into the tissue, where a combination of these effects pro-
duces the gross deformities that are such a feared element of the illness.

Borderline Leprosy
The different types of borderline disease are less clear than might be hoped for,
as their diagnosis relies to some extent on quantity judgments.

Borderline Tuberculoid (BT)

Although they are more numerous in this group, each individual lesion is
almost indistinguishable from those in IT, perhaps showing a little less scaling

FIGURE 6-10 Borderline leprosy-note the numerous annular lesions with well-
defined inner margins.
Clinical Features 59

and sensory loss but still being well demarcated. If BT patients have any annu-
lar lesions (and most of them do) the outer border of the ring is clearly defined
while the inner border is less clear-cut (Figure 6-10).
Lesions are asymmetrical, but hypopigmentation is less marked and ery-
thema more frequent.

Borderline (BB)
This shows a further increase in number of lesions, of which many have a mod-
erate degree of hypoesthesia. The patches are redder and more infiltrated than
those seen in tuberculoid cases and often have annular lesions that differ from
those in BT -the outer border will be diffuse and unclear while the inner bor-
der is so well marked that it has been described as having a punched-out or
Swiss-cheese appearance (Figures 6-10, 6-11).

Borderline Lepromatous (BL)

This has so many nodules, papules, and plaques that at first sight it may be
mistaken for LL (Figure 6-12). The lesions, however, are still somewhat asym-
metrical. Madarosis, nasal ulceration, and other features of true lepromatous
disease are missing. It is not unlikely that the patient will have a few annular
lesions of the BB type.

FIGURE 6-11 The clear zone in

the center of a borderline lesion
is sometimes called the immune
zone. It is unusually extensive
in this patient; elsewhere the
skin has progressed to fully lep-
romatous disease with large
nodules on the arms and de-
formed hands.
60 6. Leprosy

FIGURE 6-12 Borderline lep-

romatous disease. Multiple
nodules that have recently
become edematous and erythe-
matous as a result of a reversal
reaction.

In all cases of borderline leprosy, the immunologic status may vary and so
produce overlapping of symptoms with a neighboring type. It is often possible
to combine the "colors" of the spectrum and to say that a patient has BTJBB
or BLJLL-a refinement that is more elegant than necessary.

Natural History
Incubation Period
Most people who are infected by M. /eprae never develop a recognizable dis-
ease. Even those whose insufficient immunity ensures that signs and symptoms
will ultimately appear have the infection for many years before it becomes vis-
ible. The incubation period is at least five years, since it takes this long to
develop in a child whose parents both have untreated lepromatous disease and
who is therefore immunologically wide open to infection and lives in an area
that must be profusely contaminated with the organisms. Most patients take
many years longer; American soldiers who have never left the continental
United States since their return from military service in the Pacific sometimes
have not developed the disease for 25 years or more. It may be said that they
were infected in their own country, but probability is against this.
Natural History 61

It must be emphasized that a clinical suspicion that someone has leprosy

should not be ruled out because the patient has not visited an endemic area for
a long time.

Progress of Untreated Leprosy

In most parts of the world today, patients usually manage to receive some treat-
ment; it is only in the most undeveloped areas that people are found with a
history of 20 to 30 years of visible infection. Such individuals are covered with
large nodules, ulceration has usually caused the nose to collapse, the palate
may be perforated, the eyes destroyed, and the hands and feet mutilated
beyond all recognition. LL will not get better spontaneously.
At the other pole, 'IT cases rarely give a history of having had the lesion for
many years. Two reasons must be considered: either all cases of 'IT get worse
and progress into borderline disease or many of these cases spontaneously
resolve. The latter suggestion is more likely, and it is probable that individuals
with high but incomplete immunity are sometimes able to enhance such immu-
nity a little and overcome the disease. Doctors working in endemic areas will
have seen many cases with wasting of peripheral muscles associated with an
area of anesthesia and a large hardened nerve that have been present for many
years. It is sometimes possible to obtain a history that a transient skin lesion
was present in the past. Although 'IT may undergo spontaneous resolution, this
possibility should never be invoked as an excuse to withold treatment in case
the patient's history is unreliable and the disease is continuing.
Clinical progress of borderline leprosy may follow a much more variable
course. Sometimes the patient's disease remains more or less stable for many
years, but as the immunity is less fixed than that seen in polar disease abrupt
changes in the clinical and histologic picture are by no means unknown. These
are usually referred to as lepra re,actions.

Reactions in Leprosy
Most skin diseases either get worse steadily, get better steadily, or remain
unchanged. Borderline leprosy does not necessarily follow any of these exam-
ples. For a long time, it has been known that there may be a sudden severe
exacerbation of the preexisting leprosy lesions. This sometimes occurs before
treatment has been initiated (stimulating an urgent search for medical assis-
tance), but may also be seen in patients who are receiving effective antileprosy
therapy. It has taken a long time for leprologists to realize that although such
incidents look the same, two different reactions are involved: one associated
with a diminution of the previously existing immunity and the other accom-
panying an enhancement of immunity. It goes without saying that these two
reactions cannot occur together.
62 6. Leprosy

Downgrading
Patients who have never sought medical advice for their leprosy are often stim-
ulated to do so by the sudden explosive exacerbation of all the lesions on the
skin, which, whether they are few or many, suddenly become much redder and
more swollen than they have ever been before. The dermatologic aggravation
will be associated with severe nerve pain if a similar edematous reaction occurs
in an intra-neural lesion; foot-drop, wrist-drop, or facial palsy can develop rap-
idly, and even urgent treatment may not prevent permanent paralysis (Figure
6-4). This used to be called the downgrading reaction, but the use of the word
reaction is not logical since what has happened is that the patient's immunity
has undergone a sudden collapse and progress toward lepromatous disease has
been speeded up. Downgrading cannot occur if a patient is receiving effective
antibacterial treatment.

Reversal Reaction
Unfortunately, the exacerbation seen in a downgrading patient is not unique.
Patients whose immunity suddenly improves will experience a clinically similar
and equally rapid swelling and erythema of all their preexisting lesions. Occa-
sionally, this stretches the skin to such a degree that the epidermis ruptures,
and ulceration occurs.
If this happens in a leprosarium, where patients are regularly biopsied on
admission, it will be found that such cases starting with a pathology of BB or
BL have developed a pathology much closer to the tuberculoid pole (when the
reaction has subsided). This reversal reaction is associated with a much more
rapid reduction in bacterial number than may be expected under the normal
course of therapy.
Most often reversal reactions occur some three to six months after the start
of effective treatment, probably because treatment has reduced the viable bac-
terial load to such an extent that the T-cells have been able to work more
effectively.

Progress in Treated Cases

When suitable antileprosy therapy is administered to a new case, the lesions
will slowly resolve and the dermatologic changes will begin to disappear. In
tuberculoid patients, usually nothing is visible after three years, and most lep-
romatous patients will be considerably improved after seven years, the infil-
trating granulomata having dissolved. Unfortunately, the existence for so long
of tumors stretching and destroying dermal connective tissue often means that
lepromatous patients are left with a lax, wrinkled skin on the face and softly
pendulous earlobes, as well as the missing eyebrows that are such a common
feature of the disease.
Natural History 63

Neurologic lesions usually do not improve. Sometimes patches of anesthesia

diminish in area, probably because of reinervation from unaffected nerves
spreading in from the periphery, and small lesions 1 to 2 cm in diameter may
regain sensation entirely.
Muscle wasting is unaltered, and the sad fact remains that neurotrophic
changes of the hands, penetrating infection, and repeated ulceration of the feet
cause the orthopedic aspects of leprosy to progress unchanged.
Recurrent attacks of infection of the feet are often associated with lym-
phangitis, which may ultimately obliterate the lymphatics, and in an unfortu-
nate few cause the unpleasant and irremediable complication known as lym-
phostasis verrucosa or mossy foot (Figures 6-13, 6-14).

Erythema Nodosum Leprosum

Perhaps the most serious complication of all and certainly the one that is most
liable to have a fatal outcome is the condition known as erythema nodosum
leprosum (ENL), which was originally described by Murata in Japan in 1912.
It is limited to LL and BL cases and has, along with other reactions, been the
subject of a tremendous amount of confused thinking.
In the section on bacteriology (see page 67) it will be explained in greater
detail that microscopic studies of AFB obtained by skin smear will show two
sorts of organisms, those that take suitable stains in a smooth, uniform way
(called solid-staining mycobacteria and known to be viable) and others whose

FIGURE 6-13 Mossy foot (lymphostasis verrucosa) in a patient with long-standing

lepromatous leprosy and extensive anesthesia.
64 6. Leprosy

FIGURE 6-14 Another example of the mossy foot.

cytoplasm looks beaded and broken, which are known as fragmented organ-
isms, are nonviable, and are in the process of disintegration. Untreated patients
have a fairly high percentage of viable organisms, called the morphologic index
(MI). Within a few months of the start of satisfactory therapy all organisms
become fragmented: the morphologic index falls to zero. ENL begins at this
time.
For reasons that are difficult to explain, dead leprosy bacilli take a very long
time to disintegrate, and the slow release of bacterial toxins from these disin-
tegrating organisms sets up a form of allergic vasculitis that may vary from
mild to exceedingly severe. Some leprologists have claimed the ENL is caused
by dapsone and have even urged that sulfone therapy be stopped. This is com-
pletely illogical, since dapsone given for other diseases in equal or higher dos-
age for a similar or longer period does not produce ENL. The drug is nonethe-
less implicated, however, because without its therapeutic effect M. /eprae
would not have been killed and the subsequent release of high quantities of
bacterial toxin would not have occurred. In the last few years it has been shown
that people with lepromatous disease develop ENL when treated with other
successful antileprosy medications. Patients who get this complication must be
clearly told that it is no more than an unfortunate reaction to the effective
killing of the acid-fast bacilli.
As the name suggests, the basic lesion is a small red papule that is usually
painful. In contrast to downgrading and reversal reactions, these lesions do not
involve the ordinary leprosy nodule but may be seen anywhere on the skin,
including the face. It has become an unfortunate habit of some workers to refer
to this condition as erythema nodosum. Such a practice is to be condemned, as
erythema nodosum is a well-known dermatologic condition of different etiology
Differential Diagnosis 65

that affects different areas (common on the shin and never on the face) and
has a different, purplish, color.
ENL starts some 6 to 12 months after the start of treatment-about half
of all LL cases get it during the course of treatment and about 20 percent of
BL cases are affected.
It starts modestly with a few small, painful nodules not much more than a
centimeter in diameter. Sometimes, with the help of a little therapy, this is all
that happens. Often it becomes more severe. Increasing numbers of lesions are
associated with mildly raised temperature, and later there may be a persistant,
high, swinging fever and recurrent eruption of nodules, each individual lesion
lasting from 10 to 14 days. In the most severe type the nodules will ulcerate,
discharging a mucopurulent necrotic material and finishing with a ragged
irregular scar. This is fortunately rare.
Not only is the skin involved: superficial lymph nodes and peripheral nerves
may become enlarged and painful, and enlargement of the spleen and liver,
swelling of the testes, ascites, and pleural effusion may all be associated with
a fever that can continue for years. Finally, the bacterial index becomes neg-
ative, and at this time, there being no more bacterial toxins available to cause
trouble, the ENL will subside. This persistant disease may lead to secon&uy
amyloidosis, which in the 1920s and 1930s was a common cause of death from
leprosy.

Differential Diagnosis
The multiplicity of signs and symptoms produced by M. /eprae means that in
various patients widely differing disease may cause diagnostic confusion.

Pure Neural Leprosy

An enlarged and hardened nerve is very unusual. The condition known as
familial hypertrophic interstitial neuritis (Dejerine's disease) will show thick-
ening of peripheral nerves with sensory loss and motor change, but the nerves
themselves are not particularly hard, and usually several are involved at the
same time. This will not be the case in pure neural leprosy, while in tuberculoid
disease, if several nerves are affected, there will also be diagnostic skin signs.
Trauma may damage a nerve but not cause it to be enlarged. Syringomyelia,
familial radicular neuropathy, and primary amyloidosis of peripheral nerves
have all at times caused diagnostic confusion.

Tuberculoid Leprosy
An established patch of tuberculoid leprosy should never be mistaken for any-
thing else; whether it is scaly (usual) or smooth (rare), it is invariable anes-
thetic and so unlike any other dermatosis. It is, of course, necessary to test the
66 6. Leprosy

apparently normal skin on the same limb as well as the visible lesion to ensure
that anesthesia is not generalized but limited to the patch.
Despite the histologic similarities between tuberculoid leprosy, lupus vul-
garis, and lupoid leishmaniasis, clinical confusion is unlikely to occur, since
most tuberculoid granulomata show apple-jelly nodules in an extending scar, a
presentation that is never seen in leprosy.

Borderline Disease
All forms of borderline disease may be missed by doctors who, having sus-
pected that the patient had leprosy, rule out the possibility because the lesions
are not anesthetic. It must always be remembered that many types of leprosy
are not anesthetic.
Annular lesions of BT and BB can be confused with annular psoriasis or a
centripetal tinea corporis. In both these conditions, the epidermis is demon-
strably involved. In borderline disease, there is no epidermal change.
Late yaws and certain forms of leishmaniasis may present difficult diagnos-
tic problems. In areas where two of these diseases exist simultaneously, skin
scraping and biopsy may be needed to clarify matters.

Lepromatous Disease
Anergic leishmaniasis, post-kala-azar dermal leishmaniasis, late yaws, and var-
ious lymphomas, including mycosis fungoides, may all be confused with lep-
romatous leprosy, but nodular sarcoidosis is rarely extensive enough to be a
problem. In all these cases, nasal ulceration, madarosis, contractures, and
neural changes will help to confirm the diagnosis.

Downgrading and Reversal Reactions

These frequently occur in patients already diagnosed, in which case problems
should not arise, but if a patient is seen for the first time while in reaction,
sarcoidosis or lymphoma may be suspected. A careful history will reveal the
existence of skin lesions prior to the exacerbation and lead to a careful search
for neurologic signs.

Erythema Nodosum Leprosum

ENL is nothing like erythema nodosum and only occurs in patients with exten-
sive lepromatous disease. Diagnosis should never be in doubt if the patient has
nodular disease, but may be missed if it is associated with diffuse lepromatosis.
Patients with transient painful nodules and a persistent fever may be suspected
to have a severe vasculitis or even polyarteritis nodosa, but diffuse thickening
of the earlobes and madarosis will usually be present. Routine bacterial and
pathologic studies will confirm the presence of diffuse lepromatosis.
Investigations 67

Investigations
Bacteriology
In most bacterial diseases, an unsuccessful search for the causative organism
will raise doubts as to the accuracy of the diagnosis. This is not necessarily true
in leprosy; not only is it impossible to find any organism in many tuberculoid
cases, but even in those patients with a profusion of organisms, in vitro culture
is invariably negative.
A search for M. /eprae must be carried out to confirm that the clinical clas-
sification of the patient has been as accurate as possible. Tissue smears should
always be taken by the skin-slit technique (see Appendix one). If only a few
lesions are present smears should be taken from them all. In lepromatous indi-
viduals six smears should be taken: from the left earlobe, the right earlobe, the
left elbow, the back, the right arm, and one of the legs. In most cases, lesions
should be tested, but it is wise to take one of the smears from apparently nor-
mal skin, as the presence of bacilli in such skin will indicate that the patient
has LL rather than BL.
Unfortunately, this test is not particularly scientific, since an unmeasured
quantity of tissue fluid is spread over an unmeasured area on the glass slide
and the number of AFB in each smear will depend not only on the lesion but
also on the technician. It is recommended that the organisms be counted and
reported on Ridley's logarithmic index (see appendix one), in which the bac-
terial index (BI -total bacterial number in each smear) is graded as 1 + if a
single organism is detected in 100 oil-immersion fields and 5 + if more than
100 bacilli are seen in each field. The use of the logarithmic scale means that
when the BI falls from 5+ to 4+ there has been a 90 percent reduction in
organisms. If the average BI of six smears is taken, a fairly reliable graph can
be drawn of the patient's progress, particularly if the same technique is always
used. In this way, satisfactory coordination will be found with diagnostic clas-
sification. IT patients will show completely negative smears, and the BI will
rise (as is shown in Table 6-1) to an average of 5+ in cases of untreated LL.
Unfortunately, the presence of bacilli is not an indication of the activity of
the disease. M. /eprae has a cell wall that is much less fragile than that found
in other organisms, and instead of disappearing rapidly as happens after treat-
ment with gonorrhea or tuberculosis, the dead organisms disintegrate with such
painful slowness that it may take up to ten years for a heavily infected lepro-
matous patient to become smear negative despite the continuous use of a com-
pletely successful therapy. Fortunately, however, there is another way to assess
progress.
Even when Dr. Hansen first saw the bacilli in 1873, he noticed that some
had a beaded appearance and suggested that they might be dead. In the past
30 years, it has been recognized that, when a skin smear is stained and suitably
decolorized, some of the organisms stain uniformly while others do not. Solid-
68 6. Leprosy

staining bacilli, injected into the footpad of a thymectomized and irradiated

mouse, will multiply, but fragmented organisms will not. It is believed that the
solid-staining bacilli are viable and the fragmented ones are not.
A new method of counting the organisms has therefore been devised that
has the advantage of being more informative. II) each smear, 100 consecutive,
clearly visible organisms are examined, and the number of those staining sol-
idly is recorded. The morphologic index (MI) is the percentage of viable bacilli
present in a smear. If six smears are studied, both the BI and the MI should
be recorded for each site. This must be done at the start of treatment, after six
weeks, three months, six months, and then at yearly intervals. An untreated
patient will have some 20 to 40 percent solid organisms (even mycobacteria are
not immortal), and with satisfactory therapy the MI will fall to zero within six
months. Slowly the BI will follow suit, and Ridley's logarithmic index will be
recognizably lower after a year's therapy.
It is now possible to grow M. /eprae not only in the footpads of mice but in
armadilloes and other animals. The expense of such techniques, however,
makes them unsuitable for any but research purposes.

Histopathology
It should not be necessary to biopsy a tuberculoid lesion; anesthesia of the
plaque is total confirmation of the diagnosis. In other types of disease, the his-
topathology will be helpful.
In the tuberculoid cases a classical tuberculoid histology (epithelioid cells,
Langhans' cells, and lymphocytes) will be found in the dermis and may also
be detected in any peripheral nerve seen in the section. Caseation, which may
occur in neural leprosy, is very rare indeed in the skin, and if seen is much
more suggestive of tuberculosis. Tuberculosis, however, will never affect a
nerve.
As the degree of immunity diminishes, epithelioid cells give way, and the
presence of histiocytes, foreign-body giant cells, foam cells containing large
clusters of mycobacteria known as globi, and an almost total disappearance of
lymphocytes will produce a diagnostic pathology.
In downgrading and reversal reactions, leprosy can still be recognized, but
there is in addition vascular dilation and edema running parallel with the ery-
thematous swelling of the clinical lesions. At the same time, the change in clin-
ical immunity that has been responsible for such exacerbations will cause an
unexpected increase or decrease in bacilli and also a change in the type of
granuloma.
Erythema nodosum leprosum may be seen fortuitously in a routine lepro-
matous section. Larger lesions that have been specifically biopsied show the
same changes only more marked. Numerous polymorphonuclear leukocytes
will be present predominantly in the early stages, and later a vasculitis is seen
in some of the superficial blood vessels, which also show bacterial infiltration
Treatment 69

in their walls. In the most severe cases, necrotizing lesions may develop in the
dermis, associated with subsequent epidermal necrosis.

Lepromin Test
This should be of assistance in confirming the diagnosis; unfortunately, some-
times tuberculoid patients have a false negative reaction, and while false pos-
itives are rare in lepromatous cases, a contaminated needle may produce an
infected papule that can be misread as positive and cause some diagnostic
perturbation.
If lepromin is not easily available, its absence need not be mourned.

Treatment
The treatment of leprosy will always take a long time. Because the clinical
appearance only slowly improves, it may take many months before a physician
can decide clinically whether there has been any improvement. Evidence of
successful therapy must therefore depend on laboratory investigations.

Dapsone
For many years, diamino-diphenylsulfone was the only successful drug and one
that was apparently invariably effective. In the 1960s and 1970s, many dosages
were advocated, but it is now generally agreed that all cases of leprosy should
be given 100 mg dapsone daily and that this dose should neither be increased
or decreased without overriding reason. To follow the patient's progress the BI
and the MI should be taken regularly. The morphologic index usually falls to
zero within six months; in the past few years, however, it has shown that some
leprosy bacilli are sulfone resistant.
The first cases of this type were found in patients in whom, despite pro-
longed therapy, organisms had been able to flourish and whose MI was 20 to
30 percent. Such cases showed hard, shiny nodules, usually darker and less
erythematous than ordinary lepromatous lesions, with an overgrowth of fibro-
blastic histiocytes complicating the histology (Figures 6-15, 6-16). More
recently, it has been found that in some people sulfone resistance is present ab
initio; the disease persists and the MI remains unchanged despite what is
believed to be suitable sulfone therapy. In these cases, the footpad technique
demonstrates that mice receiving sulfone in their diet are unable to combat the
AFB infection.
Before the recognition of sulfone resistance, the search for other antileprosy
drugs was somewhat desultory, because they were only needed if the patient
was sulfone sensitive (a rare occurrence). More recently, it has become
urgently necessary to find other successful medications.
70 6. Leprosy

FIGURE 6-15 Sulfone-resistant

leprosy with hard, dark, and
shiny nodules, returning in the
hypochromic sites of previous
infection.

FIGURE 6-16 Close-up of sulfone-resistant nodules (see Figure 6-15).

Treatment 71

Clofazimine
A riminophenazine dye, clofazimine is equally successful in causing a reduc-
tion of the MI to zero within three to four months. Because this dye stains the
skin red and the leprosy lesions a slate grey color, however, it is less than whole-
heartedly accepted by Caucasians, Chinese, Koreans, and Japanese; Africans
and southern Indians usually find the treatment acceptable. One hundred mil-
ligrams given three times a day indefinitely will be as successful as sulfone, but
some unpleasant side effects (particularly necrosis of abdominal lymph nodes)
make it necessary to reduce treatment to 100 mg daily if it is used for more
than three months.

Rifampin
This expensive drug, when given in doses of 600 mg daily, produces a fall in
the MI to zero in less than six weeks (faster than any other therapy), but if it
is continued for a long time, side effects (nausea, abdominal pain, and even
toxic changes in the liver and kidney) are not infrequent.

Bacterial Resistance
Sporadic reports of bacterial resistance both to clofazimine and to rifampin
make monotherapy no longer to be relied on. Because the newer medications
are very expensive, however, the less affluent countries may well be unable to
afford to use effective polytherapy.

Routine Treatment
The following routine is suggested for lepromatous disease: rifampin 1,800 mg
to be given once a month for a year in addition to the standard dapsone 100
mg daily and clofazimine 100 mg three times a day to be used for three
months. If this polytherapy is successful and the MI falls to zero it may well
be possible after the first year of treatment to maintain the patients on dapsone
alone, provided that a careful three-month check on the MI shows no evidence
of increasing numbers of M. leprae.
In paucibacillary cases of leprosy (TT-BB), treatment with sulfone alone
will be satisfactory.

Reversal and Downgrading

These exacerbations if limited to the skin would not be particularly important,
but when such reactions occur in a nerve urgent treatment is needed to reduce
the intraneural edema as quickly as possible and so present permanent nerve
paralysis. Corticosteroids must be used, as well as prednisone 50 mg daily for
a week, reduced to 40 mg for a further week and then 20 mg indefinitely until
72 6. Leprosy

the reaction has subsided. This is best given by injection, but the dose is the
same for oral or systemic therapy.
Under no circumstances should antileprosy therapy be hindered.

Erythema Nodosum Leprosum

This is the unfortunate side effect of a necessary process (the elimination of M.
leprae), and antileprosy treatment must not be interrupted.
In early, mild cases of ENL chloroquine tablets two or three times a day
have been used to relieve the condition, and the injection of stibophen (fouad-
ine) 1 to 3 ml on alternate days may also be of help.
More severe cases needed, until recently, corticosteroid therapy, often for
many years. These gravely ill patients with recurrent attacks of high fever were
given prednisone, usually not much more than 20 mg daily, in the hope that
steroid side effects would be less serious than the amyloidosis that develops in
long-standing untreated cases.
Pain and swelling of peripheral nerves due to ENL inside the nerve used to
be treated with intraneural injections of hydrocortisone combined with hyalu-
ronidase, but this exquisitely painful treatment is no longer necessary.

Thalidomide
The recognition by Jacob Sheskin that thalidomide is useful in ENL was of
major importance. In 1964, when given as a sedative to patients with severe
ENL, it was found to have a dramatic effect on the reaction. Worldwide expe-
rience has now confirmed that doses ranging from 100 to 500 mg, according
to the severity of the ENL, will completely suppress the signs and symptoms.
It has to be given for a long time, but provided that suitable precautions are
taken in women to ensure that pregnancy is avoided, it is undoubtedly true that
thalidomide is at present the drug of choice for ENL.
It has no effect on the progress of leprosy itself or on downgrading and rever-
sal reactions, and, somewhat surprisingly, it is of no therapeutic help for other
forms of allergic vasculitis.
Thalidomide is not always easy to obtain, so the address of the manufac-
turers is included in Appendix two.

Orthopedic and Plastic Surgery

The deformities produced by leprosy need surgical assistance. Replacement of
eyebrows, repair of ectropion, reduction of enlarged earlobes, correction of
interosseal wasting, and tendon transplants for wrist-drop or foot-drop all chal-
lenge the inventiveness of orthopedic and plastic surgeons, whose enthusiasm
sometimes persuades them to embark on operative procedures while the disease
is still active. It is wiser to wait until one can be sure that the disease will not
continue to progress after surgery.
Some Leprosy Variants 73

Follow-up
It is always necessary to follow up leprosy cases with more than usual care.
Patients should be taught to view any exacerbation of their dermatosis as being
potentially serious and to seek advice at the earliest possible moment. It is not
unknown for individuals to go into a reversal reaction and develop permanent
nerve palsy without referring to their medical adviser.
In the later progress of lepromatous patients, after the lesions have more or
less subsided, an eruption of hard, shiny nodules may mean that sulfone resis-
tance is developing. The MI must be taken from these nodules, as in the early
stages resistance is not widespread and other areas may not yet be involved.

Duration of Treatment
Not all cases need to be treated for the same length of time. Tuberculoid
patients rarely need to continue treatment for more than two years after the
total disappearance of skin lesions. Further medication will not modify the neu-
romuscular changes.
Borderline cases will take longer to resolve; it is wise to treat them for two
to three more years. Lepromatous patients should be treated for life, not
because the disease is incurable, but because patients with lepromatous disease
do not acquire immunity and it is by no means impossible for them to get
leprosy again. This will be particularly true for those who live in leprosaria.
During follow-up, a few nodules of ENL may continue to appear. This
should not be surprising, as even six negative skin smears are not a complete
reflection of the bacillary status of the whole patient, and scattered bacilli that
are disintegrating more slowly than their culleagues may stimulate a few
lesions of ENL after the patient is apparently cured.

Some Leprosy Variants

Indeterminate Leprosy
Many cases of leprosy start with areas of hypopigmentation that in the earliest
stages are not anesthetic. As such lesions are frequently on the face they are
usually not biopsied, but if a section is taken AFB may not be seen and the
pathology may simply show a nonspecific lymphocytic inflammation. Many
doctors call such lesions indeterminate leprosy, but in various parts of the world
leprologists seem to use the term for different things. In Africa thousands of
cases diagnosed as indeterminate leprosy are said to clear up spontaneously
while in India other workers claim that only 50% of such cases get better after
several years of treatment.
It is urged that the diagnosis of leprosy be made only when there is incon-
trovertible evidence: if it is only suspected that an individual will later develop
74 6. Leprosy

the disease, diagnosis and treatment should be withheld until confirmatory evi-
dence is forthcoming. All patients with bacterial or pathologic evidence of lep-
rosy should of course be properly treated, but hypopigmentation and scaliness
alone are not sufficient bases for the diagnosis of any sort of leprosy. It is sus-
pected that at various times pityriasis alba, vitiligo, and other hypopigmented
dermatoses have been misdiagnosed. We would prefer the term indeterminate
leprosy to fall into abeyance. Patients proved to have leprosy should be suitably
classified, and in all other cases the diagnosis of leprosy should not be invoked.

Diffuse Lepromatosis
In 1852, Lucio in Mexico described a special form of lepromatous leprosy that
showed a diffuse general infiltration of the skin without formation of nodules
or tubercles at any time during its evolution. The disease is obviously the result
of a primary and total anergy of the patient and is exceedingly rare outside
Mexico and Central America. It is usually associated with marked madarosis
and destruction of the nasal septum. In young men the beard often fails to
develop. In older patients diffuse infiltration may smooth out the age-lines on
the face, producing an unexpectedly youthful appearance, sometimes called
lepra bonita-the pretty leprosy.
The annals of leprosy are studded with reports of these patients, whose dis-
ease remains undiagnosed for years; by the time it is recognized the patient
usually has a generalized sensory anesthesia most noticeable on the arms and
legs.

The Lucio Phenomenon

Another remarkable feature of this strange variant of lepromatous leprosy is a
complication that has become less common since the advent of sulfone. Usually
called the Lucio phenomenon or erythema necrotisans, it is unique to diffuse
lepromatosis. Starting with small outbreaks, acute eruptions become more and
more numerous, particularly on the forearms and legs. They are variable and
bizarre in shape, often irregular or even triangular. Starting with a well-defined
pinkish, painful patch that is not usually infiltrated, a few days later a darker
area appears in the center of the lesion, soon forming a small, dry scab that
later drops off to leave an insignificant scar. Larger lessions may be bullous,
which on bursting leave ulceration with a jagged edge surrounded by an inflam-
matory zone. Before the advent of sulfone it was said that death occurred
within six months of the outbreak of such ulcerating lesions, which histologi-
cally resemble a severe form of erythema multiforme produced by necrotising
lesions in blood vessels whose walls are packed with M. ieprae. Secondary
infection, pyoderma, and amyloidosis follow rapidly.
The differential diagnosis between this and ENL is easy, as the Lucio phe-
nomenon only occurs as a late complication of untreated diffuse lepromatosis
while ENL follows the initiation of successful therapy. If diffuse lepromatosis
Some Leprosy Variants 75

were regularly diagnosed early in its course, the Lucio phenomen would be
prevented by effective antileprosy treatment. As it is, the outbreak of these
sores and ulcers causes the patient to seek medical assistance. Sometimes anti-
leprosy therapy has to be supplemented with corticosteroids, but it seems that
thalidomide is not helpful.

Ulceration of the Skin

The skin of leprosy patients has many opportunities to ulcerate: it may break
down in severe reversal reaction or downgrading; ENL can sometimes be
necrotic, and the Lucio phenomen almost always ulcerates, healing with ragged
white scars.
Ulceration of the feet may be associated with diffuse or localized nerve
involvement. A dropped foot usually follows downgrading or reversal in a lat-
eral popliteal nerve; contracture of the originally paralyzed muscles will lead
to neurotrophic ulceration on the part of the deformed foot that is most dam-
aged when walking. The symmetrical anesthesia in lepromatous illness ensures
that the patient does not know that the sole has been damaged. As a result,
infection is not associated with normal pain and discomfort, but penetrates
deeply to give swelling of the foot and a plantar ulcer. Probing the lesion will
reveal sinuses leading down to necrotic bony fragments. Such ulcers will never
heal unless widespread curettage of the sinuses and removal of all the necrotic
tissue is followed by immobilization of the foot until fibrosis has replaced necro-
sis. In such cases, orthopedic surgeons and physiotherapists can combine to
produce suitable footwear that, by extending the weight-bearing area of the
foot, will reduce the chance of further ulceration.

Leprosy Alopecia
It is often said that leprosy does not cause hair loss, but there are two excep-
tions to this rule. In diffuse lepromatosis, the scalp, too, is involved-up to 20%
of such patients in Mexico show a diffuse thinning of the scalp hair, especially
over the occiput and nape of the neck.
Many years ago, Mitsuda described an alopecia in Japanese with severe
lepromatous leprosy (not the diffuse type) in which most of the hair falls out,
leaving on each side of the scalp a treelike pattern where the hair grows imme-
diately over the temporal arteries and their branches.
All the usual forms of alopecia may occur in leprosy patients, but these have
no particular etiologic connection.

Ichthyosis
In all forms of leprosy anesthesia the subsequent reduction of perspiration may
not be noticed by patients, but they often complain of increased dryness of the
skin. Patients who originally had ichthyosis will find the condition to be more
76 6. Leprosy

FIGURE 6-17 Ichthyosis of the

shin secondary to lepromatous
leprosy and aggravated by clo-
fazimine therapy.

severe than before, while often in lepromatous patients, a severe secondary

ichthyosis develops on the legs. (Figure 6-17). It has been suggested that clo-
fazimine also causes ichthyosis, but probably the discoloration of the skin sim-
ply makes already established scaliness more visible.
Patients will have to soak the affected areas in water to rehydrate the ker-
atin layer and then apply some form of emollient to reduce evaporation. Ten
percent urea creams are sometimes useful, and bath oils will also be helpful.

Selected Readings
Barnhill, RL, McDougall, AC: Thalidomide-use and possible mode of action in reac-
tionallepromatous leprosy. JAm Acad Dermatol1982; 7:317.
Frenken, JH: Diffuse Leprosy of Lucio and Latapi. Orangestaad, Aruba, DeWit Inc.,
1963.
Harboe, M: Significance of antibody studies in leprosy and experimental models of
the disease. Int J Lepro11982; 50:342.
Jopling, WH, Morgan-Hughes, JP: Pure neural tuberculoid leprosy. Br Med J 1965;
2:799.
Kundo, KK, Ghosh, D: Observations on clinical manifestations of primary polyneu-
ritic types of leprosy. Indian J Dermatol Venereol 1970; 15:45.
Some Leprosy Variants 77

Moller-Christensen, V: Bone Changes in Leprosy. Copenhagen, Munksgaard, 1961.

Pettit, JHS, Rees, RJW, Ridley, DS: Studies on sulfone resistant leprosy. I-detec-
tion of cases. Int J Lepro11966; 29:375.
Pettit, JHS, Waters, MFR: The etiology of erythema nodosum leprosum. Int J Leprol
1967; 35:1.
Rea, TH, Ridley, DS: Lucio's phenomenon: A comparative histological study. Int J
Lepro11979; 47:161.
Ridley, DS, Jopling, WH: A classification of leprosy for research purposes. Int J
Leprol 1960; 28:254.
Sheskin, J: Thalidomide in the treatment of lepra reaction. Clin Pharmacol Therapeut
1965; 6:303.
Skinsnes, OK: Epidemiology and decline of leprosy in Asia. Int J Dermatol 1983;
22:348
CHAPTER 7

Buruli Ulcer
(Mycobacterium Ulcerans)

For many years, this easily recognizable ulcer has had no commonly accepted
dermatologic name. Recently, the tendency to call it Buruli ulcer has become
more widespread, and under this name the condition will be discussed.
Originally recognized in Australia, it was further studied in Uganda (from
an area near Buruli along the Victoria Nile). Since that time cases have been
seen in Papua, New Guinea, Malaysia, Mexico, most of central Africa includ-
ing Nigeria, and the northern parts of South America, including French
Guiana. It is believed that with wider recognition of the condition, other foci
will be found in countries in which the tropical equatorial forest is a feature of
the landscape. Probably no case will occur that is actually acquired in temper-
ate or colder zones.
This does not mean that the ulcers cannot be seen in unexpected places; at
least one worker in the United States Peace Corps has taken his ulcer back to
the United States, and a Buruli ulcer has also been recognized in France in a
patient who had worked in the Congo.

Etiology
A mycobacterium, later named Mycobacterium ulcerans, was originally
detected in association with skin ulceration in a patient living in the vicinity of
Bairnsdale in Victoria, Australia (sometimes the organism is referred to as the
Bairnsdale bacillus.) It is an acid-alcohol-fast organism, ranging from I to 4 I.L
long and 0.4 I.L in diameter, and is strongly Gram positive (thus differentiating
it from M. leprae or M. tuberculosis.) While at 37· C, inocula may occasionally
produce a sparse growth after 12 weeks' incubation, it grows best at 32"C
taking 3 to 4 weeks on Lowenstein-Jensen medium to produce a buff-colored,
hard, flaky colony. If the organism is injected into the footpad of a mouse,
Clinical Features 79

within 3 weeks swelling and ulceration will develop. If it is injected intraperi-

toneally into a mouse, gross generalized edema develops in the subcutaneous
tissue with exudates into the pleural and peritoneal cavities. Both these phe-
nomena are believed to be unique to M. ulcerans.
There is no certain evidence as to the method of transmission of the disease.
It is usually seen in the swampy neighborhood of a sluggish, winding river, and,
as the inhabitants of infected communities are usually sparsely clothed,
patients sometimes suggest that bites (mosquitoes, red ants, or even cock-
roaches) may spread the disease, while cuts from plants and grasses have also
been blamed. As most ulcers occur on the knee, elbow, or ankle, none of these
suggestions is convincing.

Clinical Features
The lesion starts as a small, painless nodule in the dermis that in paler skins
can be seen to be erythematous. Beginning in the deeper parts of the dermis or
the subcutaneous tissue, the nodule enlarges, looking rather like a painless car-
buncle, and becomes fluctuant. After a few weeks the center breaks down to
form a small ulcer, from which a gelatinous serosanguinous material can be
expressed. Even in this early period, a swab inserted into the ulcer to clean
away the necrotic material will demonstrate that the edge of the ulcer is under-
mined to a surprising degree, thus demonstrating that the necrosis in the lower
part of the dermis is much greater in diameter than is the overlying ulcer (Fig-
ure 7-1). From now on, the necrosis and the ulcer steadily extend. The patient

FIGURE 7-1 Mycobacterium ulcerans infection. Note swelling and a punched-out

ulcer that is undermined to a depth of more than a centimeter.
80 7. Buruli Ulcer (Mycobacterium Ulcerans)

b
FIGURE 7-2 a. Mycobacterium ulcerans. A very extensive ulcer of the elbow; this
child had previously had a leg removed for a similar ulcer. b. The same ulcer after
medical treatment and grafting. The arm was saved but the joint was fixed.
Clinical Features 81

FIGURE 7-3 Undermined Buruli ulcer of the arm.

may first appear with an extremely large ulcer 10 cm or more in diameter with
a necrotic base. (Figure 7-2 a, b). The ulcer is suprisingly painless, although
cleaning beneath the undermined edge is rather uncomfortable. Occasionally,
such large areas are undermined that other parts of the skin break down to
form neighboring ulcers separated from each other by skin bridges under which
a probe can be passed (Figures 7-3 to 7-5).

FIGURE 7-4 Buruli ulcer of the outer side of the left leg with extensive undermining
of ulcer edges.
 82 7. Buruli Ulcer (Mycobacterium Ulcerans)

FIGURE 7-5 a. Extensive Buruli ulcer over left lateral malleous. The undermined
edge is rolled in on itself. b. Same patient after treatment. The ulcer has completely
healed, leaving a number of skin tags around the margin.

The patient hardly ever shows systemic symptoms; fever is rare, and lym-
phadenitis and lymphadenopathy are probably unknown except in association
with secondary infection. Multiple lesions, arising in different parts of the body,
are unusual in most countries but seem to be much more frequent in Zaire,
where up to 20 percent of the cases are multiple.
Differential Diagnosis 83

A less common presentation is sometimes seen in African cases, in which

the buttocks or thigh become swollen and indurated and pass through a dra-
matic range of discoloration until massive necrosis intervenes. It is not known
whether this is a manifestation of different susceptibility in the patients or var-
iant toxicity in the organism. In a few cases, the infection spreads along the
tissue planes and even penetrates to the bone and cartilage of the joints. It is
difficult to understand how this spread can be caused by an organism that pre-
fers to grow at less than body temperature. Probably, such extension will only
be seen when massive infection invades an unusually susceptible individual, one
who is malnourished or has poor immunity.

Natural History
The incubation period is unknown, but as inoculation of the M. ulcerans into
the skin of various animals usually produces lesions in four to eight weeks, the
disease probably takes about the same time in humans. The nodule breaks
down about six weeks after it has appeared, and the ulcer spreads steadily,
usually reaching a diameter of three or more centimeters in about four to five
months. It is hard to decide how many patients undergo spontaneous recovery
and so do not present themselves for treatment. Sometimes, individuals are
seen with an active ulcer and a scar elsewhere, which, they claim, was a similar
ulcer that healed by itself. As ulcers are often seen that are spreading actively
in some areas and seem to be epithelializing well in others, it is possible that
spontaneous healing does occur, but patients take such a long time to improve,
even with treatment, that it is thought most cases do not heal naturally. Grisly
stories of amputation are not infrequent in endemic areas, where the diagnosis
has only recently been recognized.

Differential Diagnosis
Any form of ulcer that has started in a tropical area always should be viewed
carefully, as there are other possibilities to be excluded. Staphylococcal furun-
cles and carbuncles are hot and painful and easily differentiated from the cool,
painless early Buruli ulcer, while pyodermatous ulcers are rarely solitary, large,
or undermined. Phagedenic ulcers, which are sometimes blamed on fusospiro-
chetes, heal rapidly when treated with metronidazole. The usually single ulcers
caused by Corynebacterium pyogenes occur in epidemics affiicting school chil-
dren and respond rapidly to a course of penicillin for one week. Ulcers due to
diphtheritic organisms in the skin, so common in North Africa during World
War II, seem to have disappeared almost entirely, while tuberculous ulcers (see
Chapter 5) and vasculitis ulcers differ widely in clinical presentation.
The most similar lesion is probably that of pyoderma gangrenosum, but the
undermining here is less extensive and the rapid improvement that usually fol-
84 7. Buruli Ulcer (Mycobacterium Ulcerans)

lows even a few weeks' treatment with clofazimine (despite the absence of any
mycobacteria) will soon separate these patients.
A rare condition, called Meleney's burrowing ulcer, also called synergistic
bacterial gangrene, is a bacterial infection complicating surgical proceedings;
it has a totally different clinical history.
Other ulcers that contain mycobacteria (Lucio's phenomenon and erythema
nodosum leprosum) occur in lepromatous leprosy, but they are multiple, small,
and associated with general symptoms, fever, leprosy adenitis, etc. (see Chap-
ter 6.) Scorpion and snake bites could cause similar morphologic destruction.

Investigations
It must always be borne in mind that a chronic spreading ulcer with deeply
undermined edges in a patient who either lives in or has visited the tropics is
probably a Buruli ulcer. The clinical appearance is so typical that laboratory
confirmation of the diagnosis is frequently an unnecessary luxury.

Bacteriology
A swab taken from the depths of the undermined pocketing may produce a
positive growth on Lowenstein-Jensen medium at 32· C within three to six
weeks of being set up, while tissue removed by punch biopsy from the spreading
edge of the lesion (not the edge of the ulcer, which is usually necrotic and in
which organisms are rarely to be found) can be processed and injected into the
mouse footpad, producing a swelling of tissue within three to four weeks.
The organism is not only acid-fast, staining deeply with the Ziehl-Neelsen
stain, but it can be differentiated from M. leprae and M. tuberculosis in that
it is markedly Gram positive. The Bairnsdale bacillus also stains well in his-
tology sections, as it is markedly hematoxylinophilic and shows up well with
the ordinary hematoxylin and eosin stain.

Histology
This is sometimes confusing, as a biopsy of the necrotic tissue will show nothing
diagnostic (except perhaps a few stained organisms), and biopsies from the
spreading edge may show different forms of granuloma, from the tuberculoid
with Langhans' giant cell to sections that are more suggestive of a lepromatous
reaction, with foam cells and giant cells of a foreign-body type.
Before the ulcer heals, acid-fast bacilli disappear from the tissue. This is
followed by regeneration, with fibroblastic proliferation leading to scar
formation.
Treatment 85

Treatment
The scattered incidence of this disease, which usually occurs in places where
controlled comparison of various therapies is difficult if not impossible, has lead
to diverging claims as to the efficacy of various treatments.

Systemic Treatment
In most countries, neither isonicotinic acid hydrazide nor dapsone has been of
much help, and streptomycin is not recommended. The most commonly used
systemic medications are rifampin (300 mg one to three times a day according
to the size of the patient) either alone or in association with clofazimine (100
mg one to three times daily). Such treatment must be continue for at least six
months. It is often found that the early small lesions heal satisfactorily on this
routine. Larger lesions need local treatment as well.

Local Therapy
It is advisable to remove the gelatinous serosanguinous necrotic mess. This is
best done by cleaning twice daily beneath the undermined edges with a swab
and some form of antiseptic or astringent-eusol or Burow's solution. Care
should be taken that the widespread cleansing extends in all directions. It is
sometimes useful to treat the floor of the ulcer with 1 percent silver nitrate
solution, if granulation tissue seems too proliferative. A silver nitrate stick
moistened with water can also be used.
With this combination of systemic and local therapy it is often found that
the undermined skin reattaches itself to the clean floor of the ulcer. Such adhe-
sion will not occur if the ulcer is sited over a mobile joint (especially the knee
or elbow). Such joints should be immobilized to allow healing. Discharging
necrotic material will rapidly saturate the plaster, making it necessary not only
to immobilize the joint but to cut a window in the plaster to permit continuing
ulcer toilet (Figures 7-6a, b).
As the organism prefers to live at 32· C, heat therapy has been suggested.
In its simplest form, the affected limb can be placed for several hours a day in
a large box with an electric light bulb-100 watts will usually raise the cir-
cumambient air to about 40·C. Electric cradles may be used in more sophis-
ticated areas.

Surgical Treatment
It is traditional for the surgically minded to urge widespread debridement of
the ulcer edges and the necrotic material. There is conflict of opinion as to
whether the unnatural enlargement of an already sizable ulcer can possibly
lead to a more rapid cure. The use of pinch grafts on the ulcer will not be
86 7. Buruli Ulcer (Mycobacterium Ulcerans)

FIGURE 7-6 a,b. Buruli ulcer of the knee immobilized in plaster of Paris with a win-
dow cut to allow draining under the ulcer edge.
Follow-up 87

successful until systemic and local therapy have eliminated at least most of the
pathogens, and by that time spontaneous re-epithelialization frequently will
have started.
There is little doubt that a small early lesion (especially one that has not
ulcerated) can be satisfactorily excised, but such lesions are rarely recognized
until total excision is a practical impossibility.
The following routine is advised:

1. Immobilization of the joint with a skin window to enable ulcer toilet with
eusol or Burow's solution.
2. Suitable doses of rifampin and clofazimine for at least six months.
3. As the necrosis diminishes and the ulcer floor becomes covered with healthy
granulation tissue, pinch grafts may be used.
4. Excision of undermined skin should be avoided until it is certain that the
above routine has not been successful (at least six months).

Follow-up
All patients should be observed for one to two years after apparent cure, since
it is not unknown for a satellite ulcer to appear after treatment is stopped,
probably because fibrosis around a pocket of infection has prevented a suitable
therapeutic level of drug from reaching the area.

Selected Readings
Connor, DR, Lunn, RF: Buruli ulcerations: Clinical study of 38 Ugandans with myco-
bacterial ulcerans ulcerations. Arch Patho11966; 81:183.
Parish, Le, Millikan, LE, Witkowski, JA: Thoughts on tropical dermatology. Int J
Dermatol1983; 22:18.
Pettit, JRS, Rees, RJW, Marchete, NJ: Mycobacterium ulcerans infection: Clinical
and bacteriologic study of cases recognized in Southeast Asia. Br J Dermatol1966;
78:187.
Radford, AJ: Ulcerans ulcer: The sore that heals in vain. Int J Dermatol1975; 14:422.
Ziefer, A, Connor, DR, Gibson, DW: Mycobacterium ulcerans: Infection of two
patients in Liberia. In! J Dermatol1981; 20:362.
CHAPTER 8

Tropical Ulcers

Many dermatoses of worldwide incidence may cause ulcers on the skin, but
ulcers also develop in some diseases that occur predominantly in tropical and
subtropical regions. When these are seen in temperate zones, they can cause
problems in diagnosis. The clinical index (chapter 2) draws attention to a num-
ber of diseases discussed in this book that are known to cause ulceration at
least sometimes during their course; diagnosis and treatment of these condi-
tions are considered in the relevant chapters.
There remain a number of other conditions that have been studied and
described in the past century. Unfortunately, sometimes the same name has
been used to describe more than one picture, and the resulting confusion has
led some dermatologists working in temperate zones to suspect that these con-
ditions are not separate entities. They believe the organisms said to be the cause
of such ulcers are simply secondary invaders of lesions that might have been
diagnosed differently if the observers had better training in dermatology. It has
been suggested that many of these lesions are associated with malnutrition,
anemia, or poor hygiene and that the organisms that have been incriminated
at various times do not necessarily play an etiologic role in the initiation of the
disease.
Certain lesions, however, seem to be persistently associated with some of the
poorer parts of the third world, and descriptions from various sources are sim-
ilar enough for it to be at least possible that some of the ulcers mentioned here
are individual entities.

Some Tropical Ulcers

Some writers use the words tropical ulcer to cover any ulcer that occurs in the
tropics, but others have limited the words to an entity that is perhaps most
often seen in the poorer parts of Africa and India. This is the condition dis-
Some Tropical Ulcers 89

cussed here. The ulcers may occur in epidemic proportions, particularly in pris-
ons, but they are usually endemic and sporadic, most frequently affecting the
legs or ankles. The lesion is usually solitary and starts with a very painful
papule surrounded by a dusky areola that gives way to necrosis. The margins
become somewhat indurated and the ulcerative process spreads deeply into the
dermis. The base of these ulcers is covered with dirty, malodorous granulations
(Figures 8-1, 8-2).
Most of the smaller ulcers resolve spontaneously within three or four
months, leaving a parchmentlike scar. Some, however, become phagedenic
(i.e., they start to erode extensively) and involve muscle, tendon, and bone.
Such cases can remain unhealed for several years, sometimes undergoing
malignant degeneration at the edge. This is one of the more common forms of
cancer in certain parts of Africa.
These ulcers sometimes occur in association with other organisms, but Vin-
cent's organisms (an association of a fusiform bacillus with the Treponema
vincenti) are found so frequently that although there is no firm proof, this clin-
ical picture probably occurs when Vincent's organisms invade traumatized skin
of anemic or malnourished children.

FIGURE 8-1 Ulcers and sinus

tracts with purulent discharge.
(Courtesy Arturo Tapia, M.D.,
Panama City, Panama.)
90 8. Tropical Ulcers

FIGURE 8-2 Ulcer contami-

nated by maggots. (Courtesy
Arturo Tapia, M.D., Panama
City, Panama.)

In the past, various forms of treatment were recommended. Systemic peni-

cillin is effective in some cases, while others, less than 5 em in diameter, usually
respond to a simple regimen of good food, rest, and proper hygiene. Recently,
the use of metronidazole in doses ranging up to 400 mg three times daily for
an adult has been dramatically successful in many cases. The pain and foul-
smelling discharge disappear first, and the ulcer is said to heal within two
weeks. Larger ulcers may need to be excised, especially if they are complicated
by malignant change or pseudoepitheliomatous hyperplasis.

Tropicaloid Ulcer
This condition, sometimes called mycetoid desert sore, was found by Aldo Cas-
tellani to be caused by an organism he called Micrococcus mycetoides, a name
that was later changed to Coccobacillus mycetoides and later still to Coryne-
bacterium mycetoides (Castellani). These small rods are only 1 to 2 II- in length
and less than 0.5 II- thick; they also sometimes show clublike and coccoid forms.
Corynebacterium Pyogenes Ulcers 91

During World War II, the condition was found to be especially prevalent in
military personnel fighting in North Africa, and the ulcer has also been
encountered in other parts of the Mediterranean basin as well as in northern
Australia, where there is a similar climate. It differs from the Vincent form of
tropical ulcer in that there are usually two or three painless, round, shallow
ulcers, 1 to 2 cm in diameter, covered with a thin film of pus and often sur-
rounded by an impetiginized dermatitis.
As it has been claimed that 60 percent of these patients also have impetigo,
it is suggested that tropicaloid ulcers are simply ecthyma with a corynebacter-
ial contaminant.
The condition clears up in two to three months without treatment, but
responds faster to soap, water, and local antibacterial applications.

Diphtheritic Ulcer
Also reported during World War II in North Africa was a similar ulcer that
was known to have been caused by Corynebacterium diphtheriae. Within a few
days of the appearance of a papulopustule, there is necrotic breakdown of the
epidermis. As the ulcer enlarges, a diphtheritic membrane appears on its floor,
which can be removed only with difficulty. Various forms of diphtheritic paral-
ysis (especially of the soft palate) can accompany the ulcers, which heal rapidly
when antidiphtheritic serum is given. With the effective use of vaccines causing
almost complete disappearance of diphtheria, these sores are probably nonex-
istent at present, but they will be seen again if diphtheria epidemics return to
a hot, dry climate.

Veldt Sore
This is probably not an entity. The name has been used at various times for
the tropical mycetoid and the diphtheritic ulcers.

Corynebacterium Pyogenes Ulcers

Corynebacterium pyogenes frequently affects farm animals but is rarely found
in human beings except as a cause of respiratory infections. It has been found
to affect the skin in Thailand, where a number of epidemics of skin ulcers have
occurred in various schools. The children have foul-smelling lesions (usually
solitary and not more than 2 cm in diameter) with an irregular outline, which
contrasts with other tropical ulcers. The ulcers have a granulomatous sloughing
base but do not interfere with the patient's general health. They ae surprisingly
painless.
92 8. Tropical Ulcers

Most cases seem to be self-healing, although simple wet dressings with

Burow's solution will speed things up.

Selected Readings
Bailey, H: Ulcers of the leg and their differential diagnosis. Dermatol Tropica 1962;
1:45.
Girolami, M, Capocaccia, L: Tropicaloid ulcers. Dermatol Tropica 1962; 1:78.
Kotrarjarass, R, Buddhavudhikrai, R, Sokrsongreung, S, et al: Endemic leg ulcers
caused by Corynebacterium pyogenes in Thailand. Int J Dermatol1982; 21:407.
Yesudian, P, Thambiah, AB: Metronidazole in the treatment of tropical phagednic
ulcers. Int J Dermatol1979; 18:755.
PART THREE

Fungal Diseases
CHAPTER 9

Tropical Tineas

Most of the fungal diseases that affect the outer layers of the skin and the hair
can be seen in any part of the world. There are, however, a few that, although
they may develop in temperate zones, are much more common in warmer coun-
tries. Three of these will be discussed here: tinea nigra, first clearly described
in Sri Lanka, tinea imbricata, originally recognized on Oceania; and favus, the
most common cause of tinea capitis in the Middle East and North Africa.
The name tinea is commonly used as a synonym for "ringworm," a der-
matosis caused by keratinophilic fungi of the genera Trichophyton. Micros-
porum. and Epidermophyton. which have an avidity for cornified epidermis,
hair, and nails.
By definition, tinea nigra is a misnomer, as the causative organism is not a
dermatophyte, but the error has been perpetuated for so long that no other
name is widely accepted.

Tinea Nigra
This condition, also called tinea nigra palmaris, is seen most often in Asia and
South America, being relatively rare in Africa. Patients can be found in Europe
and North America, where nearly 80 cases have been reported. It consists sim-
ply of black-brown macules coalescing to form an irregular polycyclic patch
looking like India ink absorbed onto blotting paper. There are no scales or ves-
icles such as are seen in cases of true dermatophyte infection.
In Caucasians, the condition is usually golden-brown, while in darker races
the condition may be black.

Etiology
The causative organism is Cladosporium werneckii. recently renamed Exophi-
ala werneckii. It is a black, almost yeastlike fungus, somewhat like Fonsecaea
dermatiditis. the cause of chromomycoses.
 96 9. Tropical Tineas

Clinical Features
Sharply marginated brown to black macules are seen on the palms or some-
times the plantar surfaces. The lesions are rarely pruritic nor are they often
red. Occasionally, they can occur on the face, neck, or thorax.

Natural History
A recent account described a lesion of tinea nigra that developed on the sole
of a dermatologist twenty years after he had experimentally inoculated the fun-
gus onto the site. It is not known how long it takes for a naturally occurring
disease to become visible, but as case reports of tinea nigra in young people are
hard to find, it is suspected that the incubation period is probably a matter of
years rather than months.

Differential Diagnosis
A junctional nevus may look the same (but it usually appears earlier in life),
and malignant lentigo may also be suspected. Both of the former would not be
easily scraped away.

Investigations
Microscopic examination of a KOH mount of a scraping will easily demon-
strate the presence of the heavily pigmented mycelia of Exophia/a werneckii.
This grows well on Sabouraud's agar, where it produces a shiny black yeastlike
colony, which is why some people group tinea nigra with the chromomycoses.
Later, grey to green aerial hyphae can be seen.
If the diagnosis has not been recognized clinically and a biopsy has been
taken, Gram-positive organisms may be found in the stratum corneum.

Treatment
As the infection is always very superficial, it is surprising that routine epider-
mal turnover does not lead to spontaneous remission of the infection. Despite
its astonishing persistence, there is no reason for such a small and unimportant
lesion to be treated systemically. Often after treatment and clinical cure, the
organism can be recovered from the site. It can be scraped off until no further
discoloration is visible, after which Whitfield's ointment should be applied
twice daily for a month. Relapses with this treatment have not been reported,
probably because the very long incubation period means that relapse takes
many years to become clinically visible.
If the patient objects to the use of a greasy application to a lesion on the
Clinical Features 97

palm, benzoic acid 6 percent and salicylic acid 3 percent in 70 percent alcohol
may be used instead. Other tropical treatment can be used such as clotrimazole
or miconazole cream or lotion, twice daily for two weeks or econazole once
daily for two weeks, but these are often no better than a keratolytic agent.

Tinea Imbricata
This is a true tinea in that it is caused by a member of the trichophyton group
of fungi called Trichophyton concentricum. The disease has innumerable
names: tinea concentricum, tinea imbricata, and Tokelau ringworm being the
most frequently used.
This exotic disease affects some of the most underdeveloped countries in the
world. Probably originating in Southeast Asia, it is found in the Malaysian and
Australian aborigine communities, in the jungle dwellers of New Guinea, Irian
Jaya, and the Amazon basin, in the Vietnamese highlands, and in many islands
of the Pacific, including Samoa, Fiju, and Tokelau. It was during his visit to
the Philippines that Dampier noted its distinctive appearance and described it
in 1727. Curiously, it is absent from Africa and northern Australia, with a few
cases found in South America.

Etiology
The causative organism is an anthropophilic dermatophyte that grows widely
on the skin but is not known to invade the hair or the nails.
In countries where many races live side by side, it is rare to find tinea imbri-
cata in any but the aborigine communities. In Malaysia, where aborigines have
gradually settled into a nonnomadic rural agricultural existence, Tokelau ring-
worm has been dying away.

Clinical Features
Patients who have had the disease for a few years are an unforgettable sight.
The skin is covered with more or less concentric rings of superficial furfura-
ceous scaling. As they extend, the rings finally coalesce to produce large areas
of hypopigmented skin festooned with scaly circles, the whole area looking like
a maritime map in which numerous islands are surrounded by depth soundings.
Patient will usually agree on questioning that the condition is pruritic, but it is
rare to see evidence of excoriation.
Tinea imbricata is common in childhood and early adult life and seems to
be less frequent in older patients, although, of course, in such communities old
age is rarer than it is elsewhere.
98 9. Tropical Tineas

FIGURE 9-1 An early case of tinea imbricata-three lesions extending peripherally.

FIGURE 9-2 An extensive case of tinea imbricata; all affected skin is hypopigmented,
and the few patches of normal skin have kept their color.
Natural History 99

Natural History
Patients rarely ask for treatment while the disease is in its early stages, but
experimental inoculation has shown how it starts. After seven to ten days a
small red macule appears, which turns into an itchy papule that slowly extends
as a circle of peripherally attached scales (Figure 9-1). With the enlargement
of the original ring, new centrifugal circles start in the center, until a patch
may consist of as many as ten concentric rings. The disease easily spreads to
other parts of the body (most affected patients live in communities where little
or no clothing is worn), and the hypopigmented lesions finally coalesce (Figure
9-2). Despite reports to the contrary, lesions can involve the face. The infection
of the limbs may extend onto the sole or palm, where the typical scaliness is
modified by the thicker than average palmar-plantar stratum corneum (Figure
9-3). It is thought that exposure to T. concentricum before the age of two offers
the best means of contracting the disease. On the other hand, there is some
evidence that the tendency to become infected with T. concentricum is due to
an autosomal recessive inheritance pattern.

FIGURE 9-3 Extensive tinea

imbricata spreading down the
arm onto the palm.
 100 9. Tropical Tineas

Differential Diagnosis
The classical picture is unmistakable but in long-standing cases large areas of
skin become so scaly that it may be confused with ichthyosis. The scales of
tinea imbricata are larger and dirty-looking, and ichthyotics give a different
history. A very extensive confluent tinea versicolor can sometimes look the
same-the cellophane-tape test (see Appendix one) will show the true diag-
nosis. The test is negative in tinea imbricata.
Other forms of ringworm may have papules or vesicles at the spreading
edge, neither of which is seen here.

Investigations
Scraping of the skin will produce scales full of mycelial filaments, and culture
on Sabouraud's agar produces a folded, slowly growing thallus somewhat
darker than T. schoenleinii. which it closely resembles. Microscopic examina-
tion of the culture will show branching hyphae, rarely with any spores.

Treatment
The condition responds rapidly to routine forms of antimycotic therapy. 500
mg of fine-particle griseofulvin or ketoconazole (200 mg) given daily will cause
dramatic disappearance of the lesions in 10 to 14 days; Whitfield's ointment,
econazole, miconazole, and clotrimazole cream or lotion have all been success-
ful, but there is an almost immediate relapse in most cases as soon as treatment
has stopped. Treatment should continue for six weeks to reduce the relapse
rate. It is open to debate whether these patients, living as they do in a style
that would not be acceptable in the Western world, have relapsed or have been
reinfected.
Many patients dislike using greasy applications over large areas of skin, and
in Malaysia they prefer to use Whitfield's lotion-a mixture of benzoic acid 6
percent and salicylic acid 3 percent in methylated spirit.

Favus
Most forms of tinea capitis are produced by fungi whose spores invade or sur-
round hair, which, as a result, becomes fragile and breaks off at or near the
scalp level. This causes circular patches of slightly scaly but otherwise unin-
flamed skin. A rare complication known as kerion can cause residual scarring,
but otherwise tinea capitis resolves completely, leaving a normal head of hair.
The condition undergoes natural remission at puberty. Although it is reported
in a few postmenopausal women, it is almost unknown in older people. In con-
Natural History 101

tradistinction to typical tinea capitis, favus, also called tinea favosa, shows no
tendency to spontaneous resolution and spreads slowly but inexorably over the
scalp, leaving a permanently atrophic alopecia.
The condition, once epidemic in the United States and Eastern Europe, is
very common in the Middle Eastern countries and Central America, but is rare
in black Africa. The disease seems to be more at home in the arid subtropical
regions than in the equatorial rain forests. In Iraq, 70 percent of all tinea cap-
itis is favus.

Etiology
Trichophyton schoenleinii is a highly infectious fungus that spreads easily from
child to child, particularly those living or working in cramped quarters. As
there is no tendency for remission, most hairs of the scalp are infected through-
out their length, so pieces snipped off by a barber will contain spores that will
infect others who share a comb, a cap, or a bed. In fact, T. schoenleinii can
live in these cut hairs for even 20 or 30 years. Fortunately, in the Middle East
and North Africa it is socially acceptable to shave children's heads. This not
only diminishes the child's chance of having pediculosis capitis but reduces the
likelihood of favus.

Clinical Features
This is the most socially crippling disease produced by a dermatophyte. It is
not unusual to find communities where more than half the residents have
scarred baldness. Typically, an established active case has patches of wrinkled
atrophy mixed with widespread yellowish crusts which are firmly attached to
the skin by hairs that have not yet fallen out (Figure 9-4a,b). It is among these
crusts that the diagnostic scutula are seen, caused by mycelial overgrowth in
the stratum corneum, producing an accumulation of keratinized and paraker-
atotic cells. This is attached centrally to the underlying epidermis but is periph-
erally detached where it curls away from the skin to give a saucer-shaped crust,
producing a characteristic mousy odor and classically being described as cup-
shaped. In a large series of cases from Iran only about half the patients had
these scutula-their presence is a manifestation of long-standing active disease
but their absence in early cases does not impeach the diagnosis.

Natural History
Spores probably penetrate the hairs at scalp level, and mycelia grow in each
direction. At this early stage, invasion of the hair root and follicle causes mi-
nute red puncta to appear at the follicle mouth, and foci of follicular erythema
 102 9. Tropical Tineas

FIGURE 9-4 a. Extensive favus. In a widespread area of cicatricial alopecia, scattered

patches of cursting persist. b. Marked crusting in an Egyptian man with favus. (Cour-
tesy Mohsen Soliman, M.D., Cairo, Egypt.)
Investigations 103

spread over the scalp, matting together the hairs, which take on a lusterless
appearance. As the disease extends, crusts and, later, scutula develop, which,
if removed, leave moist erythematous puncta in the denuded epidermis.
Finally, as the hair follicles are destroyed and the alopecia spreads across the
scalp, the crusts loose their yellow color and have been graphically described
as being the shade of old mortar-a substance they resemble in dryness and
friability. If left untreated for many years, the condition slowly subsides, leav-
ing an extensive atrophy with islands of normal skin from which grow hairs
that have managed to avoid infection.
Frequently, the edges of the scalp have remained exempt from this process,
and the patient has a circular fringe of normal hair around the alopecia.
There is considerable itching on the scalp during the active stages. As a
result of scratching, infection spreads via the nails to the glabrous skin. When
the fingers are involved, the infection starts subungually and looks indistin-
guishable from other types of tinea unguium, while on the limbs and trunk T.
schoenleinii occasionally produces lesions of tinea circinata with a spreading
vesicular edge. More commonly vesicles are not seen, scaling predominates,
and scutula develop. It is surprising how many patients with long-standing
active disease never produce lesions other than on the scalp.

Differential Diagnosis
An atrophic alopecia studded with yellow, saucer-shaped crusts is easily rec-
ognizable, but in the earliest stages the scattered follicular erythema may be
blamed on bacterial infection and the diagnosis will only become obvious with
time.
Other causes of cicatricial alopecia (lupus erythematosus, lichen planus) are
not so scaly in their active phases, while a history of x-ray therapy will accom-
pany the atrophy that follows excessive irradiation of the scalp.
On some occasions, people with favus may have a diffuse scaliness of the
scalp that can be confused with dandruff or seborrheic dermatitis, in which
case the hair must be examined for evidence of infection.

Investigations
The diagnosis is most easily made by examining the hair under the Wood's
light (see Appendix one), as hairs affected by favus will fluoresce a typical
grey-green. If such hairs are removed and examined under the microscope, the
fungus will be seen. It is an endothrix whose large spores are arranged in chains
among the mycelial elements. The feature that differentiates T. schoenleinii
from all other types of tinea capitis is the collection of rows of small air-bub-
104 9. Tropical Tineas

bles, which can be recognized by their varying sizes as being different from the
spores of uniform diameter.
If hair clippings are transferred to Sabouraud's agar, a slowly growing
folded white colony will develop that microscopically shows hyphae with a form
of branching in which the growing ends expand to look rather like moose
antlers. These are called favic chandeliers.
A biopsy taken from the scalp during the active phase will show an inflam-
matory lesion of the follicle containing foreign-body giant cells, many plasma
cells, hyphae, and spores. When the disease is burnt out, sections will show
fibrosis at right angles to the epidermis as the only remains of the hair follicle.

Treatment
Ketoconazole 200 mg daily or grisofulvin 500 mg for an adult, with smaller
doses for smaller patients, is the preferred treatment. The problem, however,
is to determine a suitable duration of therapy. As infected hairs may grow
almost indefinitely, if treatment is stopped after three to four months, living
spores from the terminal portion of the hair will soon reinfect unprotected hair
at scalp level.
The following routine must be insisted on for both men and women:

1. The scalp must be shaved completely at the start of treatment.

2. Suitable doses of ketoconazole or griseofulvin are administered for four
weeks.
3. Twenty-five days after the start of treatment the scalp must be shaved
again.
4. One month after the end of medication, when the hairs are regrowing, they
should be carefully examined under the Wood's light and, in the unlikely
case that there are still a few showing fluorescence, they may be removed
manually and the patient is cured.

In those parts of the world where favus is endemic, local authorities should be
encouraged to treat all the affected members of a community at the same time.
This, with any luck, will ensure that reinfection from the neighbors is kept to
a minimum.

Selected Readings
Ajello, L: The black yeasts as disease agents: historical perspective. Proceedings of the
Fourth International Congress on the mycoses, PAHO publication No. 356, June
1977.
Blank, H: Tinea nigra-a 20 year incubation period? J Am Acad Dermalol 1979;
1:49.
Treatment 105

Castellani, A, Chalmers, AJ: Manual of Tropical Medicine. New York, William

Wood and Co., 1910.
Conti-Diaz, lA, Civila, E, Asconegui, F: Treatment of superficial and deep-seated
mycoses with oral ketoconazole. Int J Dermatol1984; 23:207.
Khan, A, McIver, FA: A case of tinea nigra palmaris from Charleston, South Caro-
lina. JSC Med Assoc 1980; 76:464.
Miles, WJ, Branom, WT, Frank, SB: Tinea nigra. Arch DermatoI1964; 94:203.
Pettit, JHS: Griseofulvin and favus. Br J Dermatol1962; 74:179.
Ravine, D, Turner, KJ, Alpers, MP: Genetic inheritance of susceptibility to tinea
imbricata. J Med Genet 1980; 17:342.
CHAPTER 10

Chromomycosis

Early in the twentieth century, the term chromoblastomycosis came into being
and was used to cover all skin disease caused by pathogenic fungi that produced
pigmented spores. In the course of time, the name changed to chromomycosis,
and it is now used to denote a dermal infection found predominantly in the
tropics. Pigmented cells of Exophiala werneckii can infect the epidermis, caus-
ing tinea nigra (see Chapter 9), while similar organisms occasionally produce
internal abscesses or even infections of the brain. These conditions will not be
discussed here.
Chromomycosis occurs in the tropical parts of the Americas, in India,
Africa, and Southeast Asia, and is sometimes recognized in temperate climates
(Europe, Taiwan, Japan, or Australia), usually in patients who have acquired
the disease elsewhere.

Etiology
There is considerable confusion about the nomenclature of organisms involved
in this disease. Phialophora, Cladosporium, Fonsecaea, and Hormodendrum,
are all names that have been used at various times and seem to be interchange-
able, while the Exophiala werneckii (also known as Cladosporium werneckii)
does not invade the dermis. It is recommended that the name Fonsecaea be
used for those organisms (F. pedrosi, F. compacta, and F. verucosa) that usu-
ally cause chromomycosis and that the names Phialophora, Cladosporium, and
Hormodendrum be consigned to oblivion.
As these organisms can be found in decaying wood, soil, and vegetable
debris, the disease most commonly affects agricultural workers, farmers, and
gardeners, who develop lesions on the limbs as the result of traumatic
inoculation.
Natural History 107

Clinical Features
Although it is believed that inoculation is the invariable precursor of the infec-
tion, the spread of the lesion is so slow that when the patient finally gets around
to seeking advice the precipitating trauma has often been forgotten.
The classical picture of chromomycosis is of a papilliferous warty lesion. It
can take several forms: a spreading warty granuloma or a reddish-brown
plaque occasionally studded with foul-smelling intraepidermal abscesses. The
dry warty lesions are rarely painful unless they have ulcerated and become
secondarily infected (Figures 10-1 to 10-5).
The infection may spread deep enough to involve the lymphatics, and some-
times the nodules extend up the limb in a sporotrichoid manner to produce a
granulomatous and fibrotic inflammation of the lymph nodes.

Natural History
As most patients seek medical assistance only after the disease has been present
for many years, it is difficult to determine the incubation period, but a case
reported from Tacoma, Washington, showed diagnosable lesions on the hands
only 16 months after the patient stumbled on a macadam driveway.

FIGURE 10-1 Dry verrucosus

infiltration of dorsum of foot.
108 10. Chromomycosis

FIGURE 10-2 Verrucoid le-

sions on hand. (Courtesy
Graeme Beardmore, M.B.,
Brisbane, Australia.)

Slowly, the dermal granuloma and the warty proliferation extend in a mix-
ture of scarring and hypertrophy that can cover the whole limb, although more
often the plaque is only a few centimeters in diameter. In view of the extent
that these lesions may attain, it is suspected that spontaneous resolution does
not occur; there are no persuasive accounts of spontaneous recovery.
Not surprisingly, in such a chronic infection that spreads not only in the
dermis and subcutaneous tissue but also to the lymphatic channels, the final
stages may be complicated by a marked hyperplasia sometimes called lym-
phostasis verrucosa or mossy foot.

Differential Diagnosis
The classical combination of warty hyperkeratosis, papillomatosis, and scarring
is fairly easy to recognize, the most likely confusion being with tuberculosis
verrucosa cutis, which tends to affect the same parts of the body and to extend
equally slowly. In the early stages, a small warty papule is often mistaken for
a verruca vulgaris both by the patient and the physician. The lupoid form of
FIGURE 10-3 Scattered warty
lesions and dermatitis easily
confused with verruca vulgaris
and hand dermatitis. (Courtesy
Graeme Beardmore, M.B.,
Brisbane, Australia.)

FIGURE 10-4 Extensive infec-

tion of the hand. (Courtesy Insti-
tute of Dermatology, Chinese
Academy of Medical Sciences,
Jiangsu, People's Republic of
China.)
 110 10. Chromomycosis

FIGURE 10-5 Verruca growth

and ulceration of several years'
duration on a Chinese man.
(Courtesy Institute of Dermatol-
ogy, Chinese Academy of Medi-
cal Sciences, Jiangsu, People's
Republic of China.)

leishmaniasis rarely affects the same sites and is usually preceded by a recog-
nizable acute leishmaniasis.
If the scarring is extensive, the later stages of syphilis or yaws may be
mimicked.
Lesions with extensive abscess formation have been confused with North
American blastomycosis, but they are usually differentiable as they occur in
widely differing geographic sites.
Hypertrophic skin that is centrally ulcerated may be confused with a squa-
mous or basal cell carcinoma and needs a biopsy to clarify the problem.

Investigations
The organisms causing chromomycosis live in the dermis. It is impossible to
obtain samples by scraping the epidermis; if the organisms are to be recognized
and cultured, it is necessary to examine material either from the discharge of
any complicating abscess or from a biopsy. It is not always easy to grow, but
if a culture can be successfully established, each of the Fonsecaea will produce
soft raised black colonies that can be differentiated from each other only by
experienced mycologists.
The causative organisms can more easily be demonstrated by recognizing
their presence in a biopsy that has been sectioned and stained with hematoxylin
Treatment 111

and eosin. The basic pathology is of a tuberculoid granuloma, usually in the

upper dermis, where the overlying epidermis has been stimulated to a marked
pseudoepitheliomatous overgrowth. In the older cases, chronic fibrosis is found
between the granulomata. This combination of histologic features is not in
itself diagnostic, but fortunately the diagnosis is facilitated by the presence of
golden-brown, thick-walled, septate fungal cells, which are most commonly
seen in the Langhans' cells. These spores, rarely more than 5 IL in diameter,
stand out in the section because of the golden-brown color of their cell wall,
which is markedly thicker than any other cell wall in the neighboring tissue.

Treatment
By far the most successful method of curing small lesions is for them to be
thoroughly excised.
For larger lesions systemic therapy is needed, but none of these is regularly
successful.
Amphotericin B (50 mg injected intralesionally once a week for several
months) or fluorcytosine (given orally 150 mg/kg in three divided doses each
day) may both be tried; griseofulvin is completely ineffective.
The broad-spectrum antifungal drug ketoconazole, given 200 mg daily for
at least three months, seems at least as successful as other therapies. It is also
easier to administer, probably has less severe side effects, and is just as expen-
sive. The drug should not, however, be given during pregnancy.
An ingenious form of therapy has been reported from Japan in which the
large scaly plaques are treated by local heat therapy using an electric bed-
warmer with a surface temperature of 46· C. Either this or a benzene pocket
warmer can be used if all else fails, but treatment will need to be continued for
several months.
Many apparently cured cases have been known to relapse, but if the recur-
rence is small it can be satisfactorily excised.

Selected Readings
Carrion, AL: Chromoblastomycosis and related infections. New concepts, differential
diagnosis, and nomenclatorial implications. lnt J Dermatol1975; 14:27.
Creva-Paz, SA: Chromomicosis. Dermatol Rey Mex 1969; 13:139.
Fan, J, and Tsao, KL: Chromoblastomycosis. Far East Med J 1969; 5:151.
McGinnis, MR; Chromoblastomycosis and phaeohyphomycosis: New concepts, diag-
nosis and mycology. JAm Acad Dermatol1983; 8:1.
Tagami, H, Ginoza, M, Imaizumi, S, et al: Successful treatment of chromoblasto-
mycosis with topical heat therapy. JAm Acad Dermatol1984; 10:615.
Vollum, DI: Chromomycosis: A review. Br J DermatoI1977; 96:454.
CHAPTER 11

Madura Foot and Other Mycetomas

In the middle of the nineteenth century, physicians, especially in India, rec-

ognized a number of somewhat similar clinical conditions, all of which were
associated with sinuses discharging pus in which various colored granules could
be detected. Initially, it was believed that all these grains consisted of aggre-
gates of fungi, and the term mycetoma came into being. Later, it was discov-
ered that of the many different organisms involved some were true fungi
(eumycetes) while others, the actinomycetes, are now considered to be inter-
mediate between fungi and bacteria. These organisms infect the subcutaneous
tissue and produce a number of slightly different clinical appearances, includ-
ing Madura foot, which was described, not for the first time, in 1842 in the
Madurai Dispensary Reports in the Indian Army Medical Reports. If any
eponymous name is to be used, the condition should by rights be called the
Madurai foot, but it is probably too late to alter an established misnomer.
Although Madura foot is most commonly seen in the tropics (India, South-
east Asia, Mexico, Brazil, and Africa), patients have acquired the disease as
far north as California and Bulgaria and as far south as Australia.

Etiology
With the passing years, many members of the eumycete family have been rec-
ognized as causing Madura foot. Other cases, clinically indistinguishable, are
caused by some of the more exotic actinomycetes, which produce white-yellow
granules in the mucopurulent discharge. The eumycetes more frequently pro-
duce brown or black granules.
The condition is usually seen in men, perhaps because in most tropical areas
they form the body of agricultural workers, and the condition is probably
Clinical Features 113

always the result of a penetrating wound. The disease is not known to spread
from person to person or from animal to human.

Clinical Features
Madura Foot
When the condition is fully established, the diagnosis is unmistakable. The dis-
ease starts as a painless nodule that enlarges, softens, and breaks down (Figure
11-1). Other nodules and fistulae develop nearby, and swelling of both dorsal
and plantar surfaces of the foot may be so severe that the toes can no longer
make contact with the ground. The infection spreads deeply to the muscle and
bone. The consequent periostitis, osteomyelitis, and osseous absorption lead to
a dramatic and disabling deformity, which is surprisingly painless (Figure
11-2).
The epidermal hyperplasia seen in the chromomycoses does not occur in
Madura foot. The epidermis between the discharing sinuses is usually normal,
although it is sometimes possible to see a granulomatous proliferation blocking
and surrounding the mouths of the sinuses.

FIGURE 11-1 Painless nodule with purulent discharge in a year-old boy. (Courtesy
Ramon Ruiz-Maldonado, M.D., Mexico City, MexIco.)
 114 11. Madura Foot and Other Mycetomas

FIGURE 11-2 Ulcers and sinus tracts involving the bone in a fourteen-year-old Mex-
ican boy. (Courtesy Ramon Ruiz-Maldonado, M.D., Mexico City, Mexico.)

Other Deep Mycetomas

Any of the organisms that cause Madura foot may, of course, penetrate the
subcutaneous tissue elsewhere. If the hand is involved, deformities of the bone
and muscle will occur, but in other sites the diagnosis is often difficult to estab-
lish if the painless fluctuant swelling of the skin has not yet started to discharge
and the diagnostic granules have not revealed themselves. The difficulty of
diagnosis is probably compounded by the infrequent incidence of the disease
and the consequent low index of suspicion, especially in nonendemic areas.

Actinomycosis
See chapter 13.

Natural History
It is believed that Madura foot invariably follows a penetrating wound into
subcutaneous tissue, and few cases are seen in patients' who are not in the habit
of walking and working barefoot. There are widely differing reports concerning
Differential Diagnosis 115

FIGURE 11-3 Sole of foot studded

with sinus tracts and ulcers in a
Malaysian man.

the incubation period. In a few patients, the lesion starts less than six months
after trauma has occurred, but in many cases the disease is not shown to a
doctor for 20 to 30 years, probably because the combination of nodules, pus-
tules, multiple sinus tracts, fibrosis, and muscle and bone destruction is painful
only if a secondary bacterial infection has invaded the damaged tissue.
There is no tendency to spontaneous cure. Slowly but surely, people with
Madura foot are increasingly immobilized by appalling deformity of the limb
(Figure 11-3). Infections elsewhere are hardly less troublesome.

Differential Diagnosis
A deep mycetoma is not a specific reaction to an individual organism. It is a
nonspecific reaction to chronic infection of subcutaneous tissue. In the early
stages, it may be hard to differentiate a mycetoma from a swollen foot caused
by any bacterial or mycobacterial osteomyelitis, but bacterial infection is usu-
ally associated with fever and pain while mycobacterial osteitis (M. tubercu-
116 11. Madura Foot and Other Mycetomas

losis or M. leprae) usually accompanies other signs of the causative disease.

The diagnosis is established by demonstration of the grains in the mycetoma-
tous discharge or biopsy material.
Some authorities do not attempt to differentiate these mycetomas from acti-
nomycosis, but it is therapeutically helpful to separate the two conditions. Acti-
nomyces israelii is an anaerobic organism that spreads to the subcutaneous
tissue from an underlying lesion, while mycetoma is invariably the result of
inoculation from outside.
Botryomycosis (see Chapter 14) may also mimic a mycetoma clinically.

Investigations
When Madura foot is fully established, the appearance is so typical that inves-
tigations are hardly necessary. In any case, the number of organisms that may
be involved and the wide range of culture media and techniques necessary to
grow them usually prohibit sucessful recognition of the causative agent in the
average third-world clinic. If such attempts are made, it must be remembered
that granules should not be transferred to a suitable culture medium (Litt-
man's ox-gall agar or Sabouraud's agar without cycloheximide) until they have
been removed from the pus, washed in sterile water, and crushed to liberate
the spores from the engulfing accretion that has collected around them.
The eumycetes most commonly recognized are:

Allescheria boydii white granules

Cephalosporium falciforme yellowish granules
Phialophora jeanselmei yellow-brown granules
Madurella mycetomi
or brown-black granules
Madurella grisea

The various form of actinomycetes involved include:

Nocardia braziliensis
Streptomyces madurae
Streptomyces somaliensis

These all produce yellow-white granules.

This is not a complete list, and if other organisms are isolated, it does not
mean that the diagnosis necessarily has to be reconsidered.
There is usually little reason to take a biopsy from a Madura foot, but if it
is done, grains will be seen surrounded by polymorphonuclear leukocytes, his-
tocytes, and fibrocytes, all trying rather unsuccessfully to limit the infection.
Treatment 117

Treatment
Less than 40 years ago, it was believed that potassium iodide was the only
possible treatment, either orally (in increasing doses until iodism developed) or
locally, following curettage of the sinuses. If that did not help, amputation was
the only other method of eradicating the disease.
Since that time, the picture has improved somewhat, and many cases of
Madura foot have responded to oral medication. More frequent isolation of the
causative organism has shown that while lesions caused by Nocardia or StreJr
tomyces respond fairly well to various drugs, the eumycetomas are much more
resistant to therapy, either because they are not sensitive to available drugs or,
equally possible, the grains are relatively impermeable to what seems in vitro
to be a suitable medication.
As the actinomyces are not true fungi, it is not surprising that cotrimoxazole
(two tablets daily for six months and then one daily for a further two years)
has been found to be successful. This may be supplemented by dapsone (100
mg daily) or streptomycin in doses suitable for the size of the patient.
The eumycetes are less susceptible to such regimens, and intralesional injec-
tions of amphotericin B may be used. More recently, ketoconazole (200 mg
twice daily for many months) has sometimes been effective.
The other deep mycetomas are no easier to treat systemically, but their sites
often make it necessary to contemplate eradication of the whole lesion by exci-
sion, amounting even to amputation of foot.

Selected Readings
Barnetson, RSC, Milne, LJR: Mycetoma. Br J Dermatol1978; 99:227.
Klokke, A, Swamidasan, G, Anguli, R, Verghese, A: The causal agents of mycetoma
in South India Trans R Soc Trop Med Hyg 1968; 62:509.
Kotrajaras, R: Mycetoma. A review of seventeen cases seen at the Institute of Der-
matology, Bangkok, Thailand. J Dermatoil981; 8:133.
Magana, M: Mycetoma. Int J Dermato/1984; 23:221.
Palestine, R. Rogers, R: Diagnosis and treatment of mycetoma. JAm Acad Dermatol
1982; 6:107.
Valabinoff, VA, Madurafuss durch nocardia asteroides. Castellania 1977; 5:91.
Zaias, N. Taplin, D, Rebel!, G: Mycetoma. Arch Dermatol1969; 99:215.
 CHAPTER 12

Sporotrichosis

This deep fungus infection can be found anywhere in the world and is not par-
ticularly common in anyone area. Its incidence bears no relationship to race
or skin color. Men are predominantly infected, the disease generally occurring
in the 20- to 50-year age group and more frequently affecting farmers, miners,
construction workers, and gardeners. In one well-recorded epidemic, some
3,000 gold-miners in South Africa acquired the disease from infected wooden
pitprops. It may be seen not only in humans, but also in a wide number of
animals, including rats, cats, dogs, fowl, donkeys, horses, and camels.

Etiology
The offending agent is Sporothrix (formerly Sporotrichum) schenckii, aptly
honoring Benjamin Schenck, who first described the disease in 1898. The
organism is diphasic and aerobic, growing at room temperature on Sabouraud's
agar in as little as five days and producing whitish colonies that rapidly change
to become leathery, heaped-up, and brown or black. Smears show hyphae with
lateral branches and pyriform conidia.
The organism is somewhat comparable to those causing chromomycosis, as
it tends to grow on decaying vegetation, timber, straw, or sphagnum moss. It
can sometimes be detected in soil or in living vegetation. As in the cases of
chromomycosis, the infection usually follows local penetrating trauma
although transmission is generally from the soil, zoonotic methods are
conceivable.
Natural History 119

Clinical Features
When the skin is infected, lesions occur at the site of trauma. Sometimes, the
infection remains localized, but more often the disease spreads up along the
lymphatic system to produce the classical sporotrichoid picture of a primary
ulcerated and crusting granuloma with more recent lesions developing over the
lymphatics and, especially, at the sites of the draining regional lymph nodes.
An infection on the foot, for example, may be associated with others on the
calf and in the popliteal space and even ascend to the inguinal nodes, which,
in the later stages, also develop soft ulcerating granulomata (Figures 12-1
to 12-5).

Natural History
In contrast to chromomycosis, lesions appear on the skin only a few days after
the initial inoculation. Nodules and crusts develop that, frequently being
asymptomatic, may be neglected for a considerable time. If the patient is rea-
sonably successful at combating the infection, the lesion may remain fixed or
localized indefinitely, in which case red, scaling plaques, verrucous lesions, or
even the appearance of pyoderma may develop.
More frequently seen is the cutaneous lymphatic form, in which a chain of

FIGURE 12-1 Chancriform lesion on the thumb. (Courtesy Arturo Tapia, M.D., Pan-
ama City, Panama.)
FIGURE 12-2 Extension of the crusted granulomatous lesions on the hand and wrist.
(Courtesy Graeme Beardmore, M.B., Brisbane, Australia.)

FIGURE 12-3 Crusting and

ulceration on the nose of an
Iranian man who had dissemi-
nated sporotrichosis. (Courtesy
Homayoun Aram, M.D., Jeru-
salem, Israel.)
Natural History 121

FIGURE 12-4 Crusting on the

cheek of a Chinese boy. (Cour-
tesy Institute of Dermatology,
Chinese Academy of Medical
Sciences, Jiangsu, People's Re-
public of China.)

FIGURE 12-5 Draining ulcers on the arm. (Courtesy Institute of Dermatology,

Chinese Academy of Medical Sciences, Jiangsu, People's Republic of China.)
122 12. Sporotrichosis

erythematous nodules or pustules ascend the infected limb, ulcerating and dis-
charging as they go.
Least common is the disseminated type of infection, which sometimes fol-
lows inhalation of S. schenck;;. but is also reported to have arisen by direct
systemic dissemination from a cutaneous lesion. In both instances, the outcome
may be fatal.

Differential Diagnosis
The early lesion may be mistaken for many other diseases: North American
blastomycosis, chromomycosis, cutaneous tuberculosis, or atypical mycobac-
terial infections of the skin. The essential feature is that sporotrichosis develops
much more rapidly after trauma; thus, the disease can usually be recognized
by its history. Sometimes, sporotrichosis can be confused with a pyoderma of
recent onset, which will show all the signs of acute inflammation.
Frequently, the sporotrichoid chain of lesions will indicate the right diag-
nosis, but it must not be forgotten that other deep fungi, particularly chromo-
mycosis, may also extend in a similar way, in which case laboratory investi-
gations will be necessary to clarify the diagnosis.

Investigations
Usually, the most helpful method of investigation in a suspected case of spo-
rotrichosis is to set up cultures from the ulcer exudate, although the fungus is
not particularly plentiful in pus or affected tissue. If present, it will grow rap-
idly, producing a firm chocolate-brown colony.
Biopsies taken from a lesion will heal slowly, leaving considerable scarring,
and should be avoided if the clinical diagnosis has been confirmed by positive
culture. If, however, the diagnosis has not been recognized and a biopsy is
taken, it wll often be found that no diagnostic features are demonstrable. There
will be a mixed purulent and granulomatous reaction with numerous nonspe-
cific microabscesses. Careful study of serial sections stained with the periodic
acid-Schiff technique may reveal the presence of the Sporotrix. but such stud-
ies are frequently unsuccessful.
Rarely, it is possible to demonstrate an asteroid body, in which an eosino-
philic stellate coating of the fungal cells known as the Splendore-Hoeppli phe-
nomenon may be detected. This strange and unexplained abnormality is not
diagnostic. It has been found in botryomycosis and various forms of
phycomycosis.
Intradermal skin tests, complement fixation, and serum agglutination titers
usually confuse clinicians more than they help them.
Treatment 123

Treatment
The traditional method has been the use of a saturated solution of potassium
iodide. The treatment schedule begins with 5 drops three times a day increas-
ing by 1 drop per day per dose up to 30 or 40 drops daily, continued for four
to six weeks or until symptoms of iodism supervene.
When allergy to potassium iodide exists, amphotericin B given intravenously
is probably the best alternative treatment. Recent successful reports about
ketoconazole 200 mg daily for three months suggest that this treatment is
equally effective and easier to give.
Since the parasitic yeast phase of S. schenckii is very intolerant of heat
above 37 C, smaller lesions have been found to respond well to hot compresses.
0

An ingenious physician may wish to devise some method of applying warmth

to larger areas.

Selected Readings
Dellatorre, DL, Lattanand, A, Buckley, HR, Urbach, F.: Fixed cutaneous sporotri-
chosis of the face. JAm Acad Dermatol1982; 6:97.
Dolezal, JF: Blastomycoid sporotrichosis: Response to low-dose amphotericin. J Am
Acad Dermatol1981; 4:523.
Grekin, RH: Sporotrichosis: Two cases of exogenous second infection JAm Acad Der-
matol 1984; 10:233.
Johnson, FB: Splendore-Hoeppli phenomenon, in Binford, CH, Connor, DH (eds),
Pathology of Tropical and Extraordinary Diseases. Washington, DC, Armed
Forces Institute of Pathology, 1976, vol 2, p 681.
Nusbaum, BP, Gulbas, N, Horwitz, N: Sporotrichosis acquired from a cat. J Am
Acad Dermatol1983; 8:386.
Read, SI, Sperling, LC: Feline sporotrichosis: Transmission to man. Arch Dermatol
1982; 118:429.
Smith, PW, Loomis, GW, Luckasen, JL, Osterholm, RK: Disseminated cutaneous
sporotrichosis. Arch Dermatol1981; 117:142.
Sperling, LC, Read, SI: Localized cutaneous sporotrichosis. Int J Dermatol 1983;
22:525.
Trejos, A, Ranirez, 0: Local heat in the treatment of sporotrichosis. Mycopathologia
1966; 30:47.
Vanderveen, EE, Messenger, AL, Voorhees, 11: Sporotrichosis in pregnancy. Cutis
1982; 30:761.
CHAPTER 13

Actinomycosis

As the nineteenth century progressed, workers in many parts of the world took
an interest in discharging dermatological lesions that contained hard granules
made of fungus. In 1877, friable yellow masses, now known as sulfur granules,
were recognized in certain discharges; as they contained radiating filaments,
the organisms were called ray fungi or actinomycetes. More recently, it has
been realized that the actinomycetes are not true fungi but occupy a place
between bacilli and the eumycetes.
Many types are now recognized: they include Nocardia asteroides and
Nocardia brasiliensis, both of which are sometimes found to be the causative
agent in certain cases of Madura foot (see chapter 11), while N. asteroides
may also affect the lung and the brain, given the clinical picture of nocardiosis.
Other forms of ray fungus have from time to time been isolated from skin
lesions, the most important being Actinomyces israelii, an anaerobic organism
that may live symbiotically in the mouth. Under certain conditions, it is respon-
sible for the clinical condition known as actinomycosis.
This disease was first recognized in Europe, but is now rare in the more
affluent countries. Most cases are found in developing countries, although here
too the incidence seems to be decreasing. Men are afflicted more than women,
and poor dental hygiene is a predisposing cause.

Etiology
A ray fungus (Actinomyces bovis), was originally isolated from lesions of the
jaws of cattle, hence, the clinical term lumpy jaw. A few years later in 1878,
James Israel found a similar organism in a similar lesion in a human being and
appropriately named it Actinomyces israelii. There is some disagreement in the
Clinical Features 125

mycologic world as to whether these two are identical. (Mycologists have taken
these organisms into their protective custody, making it necessary for authors
to discuss actinomycosis among the fungus diseases!) Many names have been
given variant actinomycetes isolated from the skin and the mouth. They all
seem to be marginally different in the laboratory, but histopathologically they
cannot be distinguished from A. israelii.
The basic difference between actinomycosis and mycetoma is that the latter
is initiated by inoculation of aerobic organisms that can be found in nature as
saprophytic flora of the soil. Actinomycosis, on the other hand, is caused by an
anaerobic and endogenous actinomycete that affects internal organs before it
spreads to the skin. Primary cutaneous actinomycosis is exceedingly rare.
It is not known how A. israelii spreads from person to person, and there is
no scientific evidence to support the medical myth that the disease results from
chewing straw or grasses.

Clinical Features
A. israelii, living as it does as a saprophyte in the mouth, seems to be able to
invade the body in three sites and therefore shows three different clinical
forms-on the face and neck, on the thorax, and on the abdominal wall.

Cervical-Facial Infections
These are probably caused by the actinomycete invading a periodontal abscess
at the site of a carious tooth or dental extraction. It then spreads to the maxilla
or the mandible, where periostitis and osteomyelitis develop. From there it
extends through the subcutaneous tissue to the skin, where a pinkish-red nodule
appears (Figure 13-1). Even in its earliest stages, this is recognizably adherent
to deeper structures. The swelling slowly softens and fluctuates, becoming
darker in color, and later breaks down to produce one or more sinuses from
which discharges a serosanguinous pus containing the bright yellow granules
giving the disease its name. At the same time, other nodules develop and coa-
lesce, finally producing a board-hard induration traversed by numerous fistu-
lae. The condition is usually painful, particularly during eating. If the disease
spreads far enough, movements of the head and neck become limited. Brain
abscesses even can develop.

Thoracic Actinomycosis
This is seen less frequently and invariably follows actinomycotic invasion of the
lung. It probably cannot occur unless the lung tissue has previously been dam-
aged by such diseases as tuberculosis or chronic bronchiectasis. Once estab-
lished, however, it takes the usual course, with infection spreading outward,
 126 13. Actinomycosis

FIGURE 13-1 Lumpy jaw in a

40-year-old Philadelphia man.

involving first the ribs and then extending to the skin to produce an indurated
area riddled with boggy nodules and discharging fistulae.

Abdominal Actinomycosis
This is the rarest of the three manifestations commonly cited. Somehow, the
actinomycete, reaching the end of the small intestine, which it never seems to
invade, establishes a slowly developing infection in the cecum or appendix. This
then adheres to the abdominal wall, spreads through the musculature, and
appears on the surface (usually in the lower right abdominal quadrant) as a
boardlike induration. The diagnosis will be confirmable clinically only, when
fistulae develop and allow the sulfur granules to surface.

Natural History
In all three of the classical manifestations the onset is insidious, and it takes
many months or even years to produce a clinically recognizable picture.
Extension of infection is not necessarily directed outward (there is no evi-
Investigations 127

dence that the organism has an optimal temperature requirement), as it may

spread to the orbit, the skull, or the brain from cervicofacial lesions, while in
the abdomen direct extension to the liver, ovaries, kidney, and spine have all
been known to complicate the disease.
If a secondary bacterial infection becomes established, a regional lymphad-
enitis may develop. Otherwise, lymph nodes are rarely affected other than by
direct extension from a neighboring infection.
Until the advent of antibiotics, the condition was frequently fatal, and spon-
taneous resolution was not reported.

Differential Diagnosis
When the clinical picture is fully established, the diagnosis is incontrovertible,
but in its early stages the disease may be confused with other chronic inflam-
mations. In the absence of the diagnostic granules, a dental abscess or infected
dental sinus may be suspected, but these are more acute and painful. Cuta-
neous tuberculosis (see Chapter 5) may be confusing early on, but it rarely
leads to such a hard induration. Syphilitic gumma develops more rapidly and
produces a punched-out ulcer, which looks quite different.
Malignant disease, amebic ulcers of the skin (see Chapter 21), and sporo-
trichosis (see Chapter 12) have all to be considered. Mycetoma can usually be
differentiated by the history of the infection starting superficially and pene-
trating deeper as time goes on.
Detailed laboratory studies will be needed to separate actinomycosis from
botryomycosis (see Chapter 14).

Investigations
The diagnosis stands or falls on the demonstration of friable sulfur granules
that differ from those of a mycetoma, which are harder and usually of different
colors. N. asteroides, N. brasiliensis, Streptomyces madurae, and Cephalospo-
rium falciforme are the most difficult to distinguish. They all have yellowish-
white granules, but the A. israelli is a brighter sulfur yellow.
Attempts should always be made to culture the granules in a brain-heart
infusion agar. A rough, dry, creamy-white colony will grow anaerobically,
showing fine filaments and bacillary elements that are Gram positive and not
acid resistant.
Histologically, a biopsy from an actinomycotic lesion will show the granules,
stained purple by hematoxylin and eosin, enveloped by a purulent exudate in
the middle of necrotic tissue. Occasionally, an actinomycotic granule is found
living saprophytically in a crypt of a tonsil that has been removed for a different
reason. In such cases, it will not be surrounded by an adherent pustular
exudate.
128 13. Actinomycosis

Treatment
A. israelii is not a fungus and responds well to most antibiotics-it is rarely
necessary to use anything except penicillin. The dosage must be high, usually
four to five million units intramuscularly every day for at least a year. When
not feasible, similar high doses of oral penicillin may be used. Although this
may successfully eradicate the infection, the subsequent mess of puckered and
scarred tissue is best avoided by widespread excision of the lesion shortly after
the onset of penicillin therapy. When the patient is allergic to penicillin or the
drug is not available, broad-spectrum antibiotics such as tetracycline or eryth-
romycin 250 mg four times a day can be used. Underlying deformities of bone
or spread of infection to abdominal organs may provide a stern challenge to
stern challenge to even the most inventive surgeon. Fortunately, this is less and
less necessary as the twentieth century wears on. It is possible that the decreas-
ing incidence of actinomycosis may be the result of widespread use of anti-
biotics, which kill the saprophyte before it has a chance to become a pathogen.

Follow-up
Patients who have been treated may relapse if any organisms have managed
to take shelter in a nest of necrotic scar tissue. Any suggestion of recurrence
should be treated with a different antibiotic in high doses for a minimum of
three months.

Selected Readings
Binford, CH, Dooley, JR: Actinomycosis, in Binford, CH, Connor, DA (eds): Pathol-
ogy of Tropical and Extraordinary Diseases. Washington, DC, Armed Forces
Institute of Pathology, 1976, pp 552-554.
Israel, J: Neue Beobachtungen auf dem Gebiete der Mykosen des Menchen. Virchows
Arch [Pathol Anatj 1878; 74:15.
Kosh, G, Lalitha, MK, Samraj, T, Mathai, KV: Brain abscess and other protean man-
ifestations of actinomycosis. Am J Trop Med Hyg 1981; 30:139.
Peabody, JW, Seabury, JA: Actinomycosis and nocardiosis. Am J Med 1960; 28:99.
Robbins, TS, Scott, SA: Actinomycosis-the disease and its treatment. Drug lnt Clin
Ph arm 1981; 15:99.
CHAPTER 14

Botryomycosis

There is considerable confusion about the origins of the dermatosis known as

botryomycosis. Some say it was first described by Bollinger in 1870 as a disease
of horses' lungs, while others claim it was originally recognized by veterinary
surgeons as a fungating granuloma found in horses as a complication of cas-
tration. In either case, the name was not used until many years after Bollinger's
description: it was coined because granules seen in the pus somewhat resembled
a bunch of grapes. To add to the confusion, Radcliffe Crocker used the same
name to describe what is now known as granuloma pyogenicum, but this
cherry-red tumor has nothing to do with the condition nowadays called
botryomycosis.
Botryomycosis occurs anywhere in the world. The word is a complete mis-
nomer as the disease it has come to describe is bacterial in origin and not
related in any way to the eumycetes or the actinomycetes. It is discussed here
because of its clinical similarities with actinomycosis, Madura foot, and the
other mycetomas.

Etiology
This chronic suppurative process is caused by organisms that clump together
in the tissue to form granules. A number of different bacteria have been iso-
lated-Staphylococcus pyogenes, Staphylococcus aureus, and Pseudomonas
aeruginosa being most commonly reported. It is not certain what causes these
common organisms to behave in such an atypical way, but there may be a
factor (perhaps antistreptolysin 0) inhibiting normal neutrophil chemotaxis.
Patients often have associated systemic disease-diabetes, active hepatitis, cys-
tic fibrosis, follicular mucinosis, or gross malnutrition.
l30 14. Botryomycosis

Clinical Features
The condition is recognizable only when it occurs in the skin. A similar path-
ologic process in internal organs cannot be diagnosed clinically. A group of
inflammatory nodules appears, becomes larger and proliferates, and then forms
abscesses from which draining sinuses will discharge soft yellow granules.
These lesions may be embedded in a painful inflammatory edema, but the
swelling is usually not extensive (Figure 14-1).
It is not confined to any part of the skin, although a mild predilection for
the hands and feet suggests that traumatic inoculation could playa part in the
causation of the disease. In cases where only the skin is infected, the prognosis
is good, as the lesion may regress; however, in patients with associated systemic
disease, spontaneous cure is less likely.

Differential Diagnosis
The condition can easily be confused with other diseases from which colored
granules are found in pus discharging from deep sinuses in the skin. In Madura
foot and the other so-called mycetomas, the causative agents are true fungi or
anaerobic actinomycetes, and their granules are exceedingly hard. Actinomy-

FIGURE 14-1 Heaped-up granulating tissue that is quite friable.

Treatment 131

cosis, caused by an anaerobic organism that is neither a fungus or a bacterium,

produces bright sulfur-yellow granules, which are more friable than those seen
in the true mycetomas. In botryomycosis, the grapelike granules are softer and
a paler yellow. Other helpful features are that it rarely affects the actinomy-
cosis sites and does not show a board-hard induration.

Investigations
Although it is sometimes necessary to repeat the search on several occasions,
granules will ultimately be found that consist of large clusters of bacteria,
coated by an amorphous eosinophilic material. When cultured, these granules
will reveal diagnosable features.
Histopathologic section will usually show granules to be surrounded by pus
and necrosis; sometimes a liquifying tuberculoid granuloma has caused a mis-
taken diagnosis of sporotrichosis.
In view of the suggestion that there is an associated deficiency of leukocyte
chemotaxis, suitable investigations should be carried out if laboratory facilities
are available.

Treatment
A satisfactory response to antibiotics is to be expected provided the causative
organism is suitably susceptible, and the patient's progress is not complicated
by systemic abnormalities. Without benefit of bacterial cultures, penicillin G
three to four million units daily for several months will usually induce satis-
factory recovery. Some cases have been reported in which penicillin was inef-
fective; this was probably due to bacterial resistance rather than to some com-
plicated immunologic feature of the disease. In such cases, other antibiotics
should be used, such as synthetic penicillins (cloxacillin 500 mg), erythromycin
250 mg, or tetracycline 250 mg all four times a day.
As in actinomycosis, it may be necessary to seek surgical assistance to obtain
the best cosmetic result.

Selected Readings
Bishop, GF, Greer, KE, Horwitz, DA: Pseudomonas botryomycosis. Arch Dermatol
1976; 112:1568.
Bollinger, 0: Mycosis der Lunge Bein Pferde. Virchows Arch [Pathol Anat] 1870;
49:583.
Brunken, RC, Lichon-Chao, N, van den Broek, H: Immunologic abnormalities in
botryomycosis. JAm Acad Dermatol1983; 9:428.
132 14. Botryomycosis

Harman, RRM, English, MP, Halford, M, Saihan, EM, Greenham, LW: Botryomy-
cosis: A complication of extensive follicular mucinosis. Br J Dermatol 1980;
102:215.
Leibowitz, R, Asvat, MS, Kalla, AA, Wing, G: Extensive botryomycosis in a patient
with diabetes and chronic active hepatitis. Arch Dermatol1981; 117:739.
Picou, A, Batres, E, Jarratt, M: Botryomycosis: A bacterial cause of mycetoma. Arch
Dermatol1979; 115:609.
CHAPTER 15

Rhinosporidiosis

Rhinosporidiosis, first recognized in Buenos Aires, Argentina, is caused by an

organism that was originally detected by Seeber in 1896. He thought he had
found a new protozoan organism but it is now believed that the causative agent
is a fungus, probably a member of the phycomycetes, and it has been named
Rhinosporidium seeberi. The disease is endemic in south India and Sri Lanka
and has been seen sporadically in most countries, from the United States to
Malaysia and from Argentina to Poland. It may occur at any age and is more
commonly diagnosed in men than in women in a ratio of 10 to 1.

Etiology
The method of transmission is unknown; some authorities believe that stagnant
water is the chief source of infection, while others believe it is transmitted by
infected dust. A similar condition has been found in cattle and horses, but
transmission to laboratory animals has not been convincing.
The infecting spore is a small, round body approximately 6 to 7 J.L in diam-
eter, with a well-defined limiting membrane, a nucleus, and a karyosome. It
increases in size as repeated nuclear divisions take place. By the time it has
reached 100 J.L in diameter, a thick cellulose layer is deposited on the inner
aspect of the surrounding chitinous membrane: on one point of this a thinning
occurs to form a pore. Further nuclear divisions produce a sporangium ulti-
mately containing several thousand spores. The sporangia are white and are
often 300 J.L in diameter, just visible to the naked eye. Ultimately spores are
liberated by rupture of the sporangium at the pore.
134 15. Rhinosporidiosis

Clinical Features
As the name suggests, this fungus primarily affects the nose and nasopharynx.
A chronic granulomatous reaction produces pedunculated polyps that soon
interfere with breathing. They are friable and bleed easily, the epistaxis often
being combined with a mucinous discharge. When viewed closely, the larger of
the white sporangia are seen scattered in the erythematous polyp, producing
what has been called a strawberrylike lesion (a simile more accurate than
most) (Figure 15-1).
The condition is included in this book because lesions are not necessarily
confined to the nose; they have also been seen on the conjunctivae, mouth, lips,
ears, scalp, penis, vagina, and rectum, where they start as papillomatous or
subcutaneous nodules, frequently pruritic, which later become warty and exude
a mucinous material in which sporangia can be detected with the aid of a hand
lens.
If the conjunctiva is affected, there is initial lacrimation and photophobia
succeeded by the development of different-shaped growths, the lesions being
sessile when growing from the bulbar conjunctiva and pedunculated on the
palpebral conjunctiva.
On the genitalia, they may be mistaken for condyloma latum if the spor-
angia are not recognized.

Natural History
Epistaxis and nasal blockage are the main early symptoms. Slowly the nasal
cavity becomes full of granulomatous polyps that may reach an enormous size,
spilling out into pharynx and protruding through the nostrils to hang over the
upper lip. Occasionally, it has been reported that the disease has regressed
within a few weeks of onset, but other cases are known to have lasted more
than 30 years. Recurrence is likely, even in cases that appear to be doing well,
so it is unwise ever to tell patients that they are completely cured. Rhinospor-
idiosis is rarely fatal, although deaths have been reported following generalized
dissemination of the disease and also from direct obstruction of the trachea
and bronchus.

Differential Diagnosis
In the nose or mouth, the strawberrylike lesions will establish the diagnosis
easily and separate it from the many other conditions that may develop nasal
polyps.
Investigations 135

FIGURE 15-1 Strawberrylike lesions in the nares. (Courtesy Arturo Tapia, M.D.,
Panama City, Panama.)

When it is fully established, the classical hypertrophy and sclerosis of rhi-

noscleroma (see Chapter 16) should not cause too much diagnostic confusion.
Patients with paracoccidioidomycosis, yaws, tertiary syphilis, leishmaniasis,
and lepromatous leprosy may all complain of epistaxis or nasal blockage, but
other signs will usually be visible on the skin.

Investigations
An impression smear from the surface of a polyp mixed with a drop of water
and examined under the microscope will probably reveal characteristic spor-
angia, while the periodic acid-Schiff stain clearly demonstrates the inner por-
tion of the wall, which tends to be birefringent. Nasal discharge may be studied
in the same way or with Romanovsky's stain. Rhinosporidial sporangia differ
from coccidioidomycosis sporangia, which are smaller (up to 80 IL in diameter)
and contain much smaller spores (about 2.5 IL).
Biopsy of one of the polyps, stained routinely with hematoxylin and eosin,
will show sporangia in all stages of development. They are sometimes sur-
rounded by acute inflammation resulting from release of spores into the tissue,
but more commonly a chronic granulomatous reaction is seen with epithelioid
cells and Langhans' cells. As will be expected of such bright red lesions, vas-
cular dilation is a conspicuous histologic feature.
136 15. Rhinosporidiosis

Treatment

There is no known chemotherapeutic or antifungal agent. The only treatment

that can be recommended is the removal of lesions by excision or curettage
followed by electrodesiccation. Some physicians have helped patients by treat-
ing them with intramuscular injections of 2 to 5 percent aqueous tartar emetic
or ethylstilbamidine to a total of 60 to 120 mg. Because the disease is not fatal
and may abate on its own, watchful waiting is an alternative therapy.

Selected Readings
Allen RFWK, Dave, ML: The treatment of rhinosporidiosis in man based on a study
of cases. Indian Med Gaz 1946; 71:376.
Ashworth, JH: On rhinsporidium seeberi (Wernicke, 1903) with special reference to
its sporulation and affinities. Trans R Soc Edin 1923; 53:46.
Chitravel, V, Subramanian, S, Sundaram, 8M, et al: Rhinosporidiosis in a South
Indian village. Sabouraudia 1980; 18:241.
Kannan Kutty, N, Prabakharan, N, Monsurate, J: Oculosporidiosis. Far East Med J
1968; 4:118. _
Ramanathan, K, Ahmad, U, Kutty, M, et al: Rhinosporidiosis in Malaysia. Med J
Malaya 1968; 22:276.
CHAPTER 16

Rhinoscleroma

There is evidence that rhinoscleroma, sometimes simply called scleroma, was

known to the Amerindians of pre-Colombian America. The definitive descrip-
tions were made by Hebra and Kaposi (Kohn) in the 1870s, at which time
endemic areas were found in Galesia, other parts of the Austro-Hungarian
Empire, and Russia. In more recent times, cases have been reported in China,
Egypt, Israel, Iraq, Indonesia, and North America. At present, the highest
incidence seems to be in Venezuela and parts of Central America. Sporadic
cases of this multilating disease probably may be found in any part of the
world.

Etiology
Although Koch's postulates are not entirely fulfilled, since the disease has never
been produced experimentally, most authorities believe that Klebsiella rhino-
scleromatis is the causative organism. It is a Gram-negative, encapsulated
bacillus that is found singly or in short chains.
There is very little evidence that the disease is contagious; occasionally, two
or three cases are seen in a family, but most patients have no such background.
It is possible that climatic or environmental conditions or immunologic incom-
petence playa part in the development of the disease. The incubation period
may be very long. If so, confirmatory history of contact may be difficult to
obtain.

Clinical Features
When the condition is fully established, there is extensive hyperplasia of the
nose and the center of the face. It is an alarming sight. A chronic inflammatory
reaction invades the floor of the nose (Figure 16-1) and the nasal septum and
138 16. Rhinoscleroma

FIGURE 16-1 Early lesions in the nose showing tumorous overgrowth. (Courtesy
Francisco Kerdel-Vegas, M.D., Jacinto Convit, M.D., Bernard Gordon, M.D., and
Mauricio Goihman-Yahr, M.D., Caracas, Venezuela.)

extends outward to the nose and upper lip, downward through the palate, back-
ward to the larynx, or up to the orbit. This massive tumorous overgrowth hin-
ders breathing to such an extent that patients may only be able to breath
through the mouth, while palatal involvement will modify the resonance of
speech.
Occasionally, the condition remains untreated for years, and slowly the
infective element is replaced by the fibrosis that caused it to be called rhino-
scleroma; this may involve the larynx and even the bronchi (Figure 16-2).

Natural History
The whole process of development is prolonged, taking many years after the
appearance of the earliest symptoms. The first stage is a rhinitic infection,
when what seems to be a comon cold becomes more than usually intense, with
headache, respiratory distress, and foul-smelling nasal discharge. The mucous
membranes of the nose become hypertrophied and later atrophy. These
changes are first seen at the base of the nasal cavity. The granulations creep
up the nasal septum and the sides of the nose, slowly obstructing the nasal
cavity. At this stage, the coryzal symptoms disappear, thickening of the tissues
increases, and infiltration steadily produces the nodular and hypertrophic con-
dition that is typical of the established infection. As time goes on, the soft,
boggy granulomatous tissue hardens, leaving the unfortunate patient with a
Differential Diagnosis 139

FIGURE 16-2 Late lesions

showing extensive fibrosis of
nose and lips. (Courtesy Moh-
sen Soliman, M.D., Cairo,
Egypt.)

blocked nose, extensively involved central portions of the face, and a sclerosis
spreading into the larynx and bronchi.

Differential Diagnosis
Although many chronic bacterial diseases affect the nose and center of the
face, most of them tend to leave atrophy rather than hypertrophy. Tuberculo-
sis, yaws, tertiary syphilis, and lepromatous leprosy may all be suspected in the
earlier stages of rhinoscleroma, but when the classical hypertrophy (sometimes
known as Hebra's nose) is fully established, the diagnosis should not be in
doubt.
Certain of the deep mycoses, especially paracoccidioidomycosis, may pro-
duce hypertrophic granulations that bleed easily, and rhinosporidiosis (see
Chapter IS) causes a granuloma that is much softer and studded with clearly
visible sporangiophores.
Several malignant conditions may cause confusion: midline facial granu-
loma, Wegener's granulomatosis, the lymphomata, and even squamous cell
140 16. Rhinoscleroma

carcinoma may all look like hypertrophic tumors blocking the nose, but the
more rapid evolution of these diseases makes it unlikely that the diagnosis will
be mistaken. In all cases, diagnostic features can be seen histologically.

Investigations
Throughout most of the natural history of rhinoscleroma, from the earliest
rhinitic stage onward, the causative organism can be demonstrated in tissue.
Sometimes known as the encapsulated diplococcus of Frisch, it is Gram neg-
ative, 2 to 3 /-L long, and grows aerobically on blood agar. Klebsiella rhino-
scleromatis may be differentiated from the other Klebsiellae, as it is lethal to
mice.
The diagnosis may be more certainly confirmed by the histologic picture,
which shows, in addition to an extensive plasma-cell infiltrate associated with
the Russell colloid bodies found in any infiltrate containing many plasma cells,
numerous Mikulicz' cells, whose presence is diagnostic. There are large, round,
vacuolated histiocytes, often more than 100 /-L in diameter. They have eccentric
nuclei, and despite their foamy appearance, they do not contain lipid. If the
section is stained with a bacterial stain, the Frisch's bacilli will be seen in the
cytoplasm. Mikulicz' cells increase in number as the disease progresses.
Serologic reactions ranging from complement fixation to agglutination tests
are not helpful, and attempts to provoke a cutaneous reaction from suspensions
of the Frisch's bacillus have been indifferently successful.

Treatment
Rhinoscleroma does not respond well to penicillin or the sulfa drugs, but chlor-
amphenicol and tetracycline have both been found helpful if used in large doses
for a long period. Streptomycin is probably the drug of choice and should be
given 1 g daily for at least three months.
As the disease resolves, there may be considerable residual deformity, and
surgical assistance may be needed to reduce the nasal obstruction or cosmetic
damage.

Selected Readings
Goldman, L: Pre-Columbian rhinoscleroma. Arch Dermatol1979; 115:106.
Kerdel-Vegas, F, Convit, J, Gordon, B, et al: Rhinoscleroma. Springfield, Ill, Charles
C Thomas, 1963.
Miller, RH, et al: Klebsiella rhinoscleromatis: A clinical and pathogenic otolaryngeal
enigma. Head Neck Surg 1979; 87:212.
CHAPTER 17

North American Blastomycosis

The deep fungal condition was first recognized in North America. In the early
stages of the disease, the nondescript collection of signs and symptoms is often
misdiagnosed; in fact, when the first known patient was seen in Philadelphia in
the early 1890s the diagnosis was missed. Not until later, in Baltimore, did
Caspar Gilchrist notice the yeast bodies in a histopathologic specimen and
define the disease that sometimes has been called Gilchrist's disease.
Originally found only in North America, particularly along the valleys of
the Mississippi, Missouri, and Ohio rivers, the disease seems to be extending
southward and is being recognized more frequently in Mexico, Central Amer-
ica, and even in South America. Sporadic cases have also been detected in the
Middle East and all parts of Africa from Tunisia to South Africa. It is partic-
ularly prevalent in Zimbabwe.

Etiology
Blastomyces dermatitidis is a dimorphic fungus that grows easily on Sabour-
aud's agar. It is not known how the disease is transmitted, and there is no
evidence that it is contagious. There are a few reports of isolation of the organ-
ism from soil, an important finding, as most patients are men, and more than
three-quarters of them are exposed to soil in their work. An astonishingly high
percentage of patients are over 40 years of age. A few pathologists have
acquired the disease by direct cutaneous inoculation, but such cases are
extremely rare and clinically atypical in that they show a strong tendency to
spontaneous recovery.
142 17. North American Blastomycosis

Clinical Features
Apart from the few cases of direct inoculation, it is believed that in most cases
North American blastomycosis afflicts the skin following infection of the lung.
Starting as a small papule or pustule (or, very rarely, a vesicle), the lesion,
which may be single or multiple, enlarges to form nodules that ulcerate and
discharge pus. The center of the lesion heals, leaving a paper-thin layer of skin,
while crusting and scaling extend peripherally to produce verruciform lesions
interspersed with pustules. As the years go by, the patch extends slowly, leaving
extensively atrophic scarring, ringed with active warty granulomatous lesions.
If the eyelids are affected, an ectropion may occur; mucous membranes are
only rarely involved (Figures 17-1, 17-2).
Single lesions occur on the limbs or face, but if multiple infection occurs,
the areas are frequently symmetrical and usually on the trunk.
At the same time, the disease may spread to subcutaneous tissue and extend
to the bones and joints, the resulting osteomyelitis producing draining sinuses
of the skin. The central nervous system or the renal tract can be affected also.
Such widely disseminated disease usually has a poor prognosis, even if the
cause is recognized and suitable treatment instituted.

Natural History
Pulmonary blastomycosis precedes the appearance of cutaneous lesions in
almost all cases. It is suspected that this is due to the inhalation of spores from
the soil, leading to a respiratory infection that may be symptom-free but more

FIGURE 17-1 Crust lesion with sharp border extending from the eyebrow.
Differential Diagnosis 143

FIGURE 17-2 Crusted lesion with sharp border; some atrophy may already be
perceived.

usually mimics pulmonary tuberculosis, with hemoptysis, dyspnea, loss of

weight, low-grade fever, and sometimes even erythema nodosum. This picture
draws attention to the lungs, and radiographic examination usually shows
widespread miliary lesions but rarely cavitation.
Dissemination of infection to the skin may be delayed for a very long period;
a recent case with multiple skin lesions had an episode of "pneumonia" 50
years previously, when he was working in an endemic area. It is postulated that
with age an impaired immunologic activity can permit a flare-up and dissem-
ination of an infection that has been dormant in the lung for many years. This
theory would explain the late age of onset in such a high percentage of cases.
A less common means of infection is through primary inoculation. Animals,
including horses, dogs, and cats, are known to have had the disease: in a
recorded case, localized blastomycosis developed after a dog bite. In such cases,
the incubation period is only a matter of months, and such lesions do not usu-
ally spread.

Differential Diagnosis
Clinically, the scarring granulomas may be mistaken for tuberculosis, syphilis,
pyoderma gangrenosum, or bromoderma, as well as for other deep fungus
infections. The clinical picture alone is rarely diagnostic. Paracoccidioidomy-
cosis (see chapter 18) usually affects the mouth or nasal cavity, which is rarely
the case in the North American variety of blastomycosis.
144 17. North American Blastomycosis

Investigations
Microscopic examination of pus or of skin scrapings may show Blastomyces
dermatitidis as thick-walled, spherical, budding yeast cells (about 10 Jl in
diamter). They can be differentiated from the spores of chromomycosis, which
are golden-brown. The organism is dimorphic and grows as a yeast at body
temperature. If cultures are established on Sabouraud's agar at room temper-
ature, a mycelial phase predominates in which short pedicules attach the spores
to the hyphae. The organism grows slowly and takes four to six weeks before
dirty-white, fluffy colonies are fully established. The spores can be seen fairly
easily in histologic section, sometimes lying freely in the tissue, but more often
are recognized living in the Langhan's giant cells. If special stains have not
been used, the spores give a punched-out appearance to the cytoplasm. With
the periodic acid-Schiff stain, the budding yeast cells can be clearly seen.
As the clinical diagnosis often remains unsuspected and pus may not be
examined for spores, biopsy is of particular value in establishing the diagnosis.
A typical lesion will show epithelial hyperplasia and acanthosis overlying
extensive tuberculoid granulation tissue, which is mixed with numerous
microabscesses. An unusually high number of Langhan's giant cells may cause
the disease to be suspected, particularly if they have the punched-out appear-
ance produced by unstained intracellular spores. In paracoccidioidomycosis,
the spores are much larger (30 Jl) and show multiple budding.
If a patient is suspected of having North American blastomycosis, the chest
should be x-rayed, and the pulmonary lesions that are almost invariably present
will have to be differentiated from tuberculosis or sarcoidosis by examination
of the sputum, use of the tuberculin test, or even bronchoscopy.
Serologic tests, including complement fixation and immunodiffusion, are
frequently not sensitive or specific enough. Often there is considerable anti-
genic overlap with Histoplasma capsulatum and Coccidioides immitis. The
blastomycin skin test is useful only for epidemiologic purposes.

Treatment
Potassium iodide was formerly used to treat this disease. Later, this was
replaced by 2-hydroxystilbamidine, but many patients relapsed. Amphotericin
B given in standard doses up to 2 g has been more effective, but currently,
ketoconazole 400 mg orally each day for several weeks has been shown to be
curative and is recommended.
It is unwise to treat cases of cutaneous North American blastomycosis with-
out careful watch for deeper infections. Regular chest x-rays should be taken
to observe the progress of any concomitant pulmonary activity. The deeper
infection may still need treatment after the skin lesions have resolved. There is
Treatment 145

a percentage of fatality with all known methods of therapy, and sometimes it

is necessary to use more than one medication.

Selected Readings
Hashimoto, K, Kaplan, RJ, Daman, LA, et al: Pustular blastomycosis. Int J Dermato!
1977; 16:277.
Henchy, FP, Daniel, CR, Omura, EF, Kheir, SM: North American blastomycosis: An
unusual clinical manifestation. Arch Dermato! 1982; 118:287.
Hudson, CP, Callen, JP: Systemic blastomycosis treated with ketonconazole. Arch
Dermato! 1984; 120:536.
Logsdon, MT, Jones, HE: North American blastomycosis: A review. Cutis 1979;
24:524.
McClune, MA, Rogers, RS, Roberts, DG: Laryngeal presentation of blastomycosis.
Int J Dermato! 1980; 19:263.
Sweeney, EW, Franks, A, Silva-Hunter, M: An unusual case of North American blas-
tomycosis in New Jersey. Cutis 1982; 30:199.
CHAPTER 18

Paracoccidioidomycosis

To avoid confusion with North American blastomycosis, it is better that this

disease, which has in the past been called South American or Brazilian blas-
tomycosis, should be known as paracoccidioidomycosis. The disease extends
from Mexico to Chile, with its highest incidence in the state of Sao Paolo in
Brazil. It has probably never been acquired naturally outside this area.

Etiology
As with many of the deep fungus infections, the causative organism, Paracoc-
cidioides braziliensis, is found in the soil; consequently, agricultural workers
are frequently affected. The fact that almost all cases start in the mouth has
stimulated the suggestion that the disease may be acquired as the result of
cleaning teeth with fragments of wood, but this would not explain the greater
incidence in men (90 percent of all cases).

Clinical Features
The typical lesion of paracoccidioidomycosis is seen in a middle-aged man, 45
to 50 years old, who has a very painful granulomatous condition of the buccal
and/ or nasal mucosa (Figure 18-1). An ulcerative stomatitis spreads across the
mouth to the tonsils, and laryngeal and pulmonary lesions are also found.
Authorities disagree as to whether the pulmonary or the oral-nasal lesions are
the first to develop. The ulcerated tissue proliferates to form hyperemic ede-
matous granulations known as mulberry erosions (Figure 18-2) (a mulberry is
Clinical Features 147

FIGURE 18-1 Painful granu-

lomatous crusted lesions on a
Brazilan man. (Courtesy Se-
bastiao Sampaio, M.D., Sao
Paulo, Brazil.)

FIGURE 18-2 Mulberry type of granulation tissue.

 148 18. Paracoccidioidomycosis

FIGURE 18-3 Erosion of the lips and destruction of the gums resulting in loss of teeth.
(Courtesy Jacinto Convit, M.D., and Mauricio Goihman-Yahr, M.D., Caracas,
Venezuela.)

a purple fruit resembling a raspberry), which can be found in the nose, on the
palate, the gums (where as a consequence the teeth frequently fall out) (Figure
18-3), the tongue (Figure 18-4), the tonsils, and the larynx.
At the same time, ulcerated and crusting granulomata may spread to the
skin of the mouth and around the nostrils, and the cervical lymph nodes enlarge
to form an adherent suppurating mass clinically indistinguishable from a
tuberculous adenitis or scrofuloderma.

Natural History
The incubation period is probably from five to ten years. As a result, the disease
is almost completely unknown in children. Spontaneous regression of the con-
dition has not been reported, but many patients seem to have some resistance.
As the infection extends slowly, a degree of delayed hypersensitivity (type iv)
can be shown by suitable skin tests. Less fortunate individuals are anergic, and
the disease not only spreads locally but extends systemically throughout the
body.
In such cases, the lungs and spleen are invariably involved, and lesions are
also seen in the intestines and the liver, while the adrenals, the bones, and the
central nervous system do not escape. About 50 percent of untreated patients
have a slowly progressive fatal disease; the patient may die of peritonitis, men-
ingitis, or even cachexia resulting from the painful oral lesions.
Investigations 149

FIGURE 18-4 Proliferation of granulomatous tissue on the tongue. (Courtesy Sebas-

tiao Sampaio, M.D., Sao Paulo, Brazil.)

Differential Diagnosis
There should be no trouble in differentiating paracoccidioidomycosis from
North American blastomycosis. The latter has a marked tendency to atrophy,
which is not found in the South American disease, while P. braziliensis affects
the mouth, the spleen, and the alimentary tract, three areas rarely if ever trou-
bled by North American blastomycosis.
It is often difficult to determine whether the lung lesions are caused by para-
coccidioidomycosis or tuberculosis. Hypertrophic conditions of the nose (rhi-
nosporidiosis, rhinosceroma, or some cases of fungating squamous cell carci-
noma) do not cause the teeth to fall out, nor are they usually associated with
a suppurating cervical adenitis. Actinomycosis, especially if it invades the
upper ja~, may sometimes mimic paracoccidioidomycosis, but the brawny
swelling and the bright yellow granules should clarify matters. The American
form of mucocutaneous leishmaniasis may also be suspected in the early stages;
it does not, however, spread to the lungs or the abdominal organs.

Investigations
P. braziliensis is another of the diphasic organisms that appear as budding
yeast cells at body temperature and produce mycelia when cultured at room
temperature. Examination of fresh tissue or of discharge from the mulberry
150 18. Paracoccidioidomycosis

lesions or pus from the cervical abscesses can be expected to show typical
spores. They are much larger than those of Blastomyces dermatitidis, ranging
from 30 to 60 IL in diameter. Although they are occasionally seen to be repro-
ducing by single budding, much more frequently many buds surround the cell,
giving an appearance that has been compared to a ship's wheel. It must not be
forgotten that such large cells when seen in a biopsy will themselves have been
sectioned, and the whole spore will not be present.
Attempts to grow the organism on Sabouraud's agar will produce the myce-
lial form. If it is cultured on blood agar at 37°C, the yeast form will
predominate.
Histologic section will show an epithelioid granuloma mixed with a poly-
morphonuclear infiltration, similar to the histology of North American blas-
tomycosis, but here the causative organism is much larger and only rarely
intracellular.
An intradermal skin test with paracoccidiodin will produce a reaction in 48
hours if the patient has any innate resistance to infection. As in leprosy, the
test will be negative in anergic patents with the disseminated form of infection.
There is a complement-fixation test that gives rising titers as the infection
spreads. This investigation, combined with a precipitin test, has demonstrated
antibodies in almost 100 percent of patients.
Patients with this disease may also have pulmonary tuberculosis, and suit-
able studies should be undertaken to exclude the possibility of a double
infection.

Treatment
Oral ketoconazole 200 to 400 mg daily for anything up to a year has produced
total remission or sharp improvement in 96 percent of 75 cases in one study.
Various forms of sulfa drug have been used in the past reasonably successfully,
but sometimes resistance has developed. Cotrimoxazole (one tablet twice daily
for many weeks) is probably a better treatment for patients who are not folate
deficient. Amphotericin B has also been used systemically, but with the advent
of ketoconazole therapy, this drug has diminished in popularity.

Follow-up
Some patients may relapse after cessation of therapy, probably because deep
infection in the spleen or suprarenal does not improve as rapidly as do lesions
on the skin or mucous membrane. Further experience is needed to determine
wheher low doses of ketoconazole should be continued as long-term prophylac-
tic therapy.
Follow-up 151

Selected Readings
Cuco, LC, Wroclawski, EL, Sampaio, SAP: Treatment of paracoccidioidomycosis,
candidiasis, chromomycosis, lobomycosis, and mycetoma with ketoconazole. Int J
Dermatol1980; 19:405.
Fraga, S, Miranda, JL, Marques, A: Clinical pathological study of oral lesions in
South American blastomycosis. Cutis 1974; 14:555.
Furtado, R: Infection versus disease in South American blastomycosis. Int J Dermatol
1975; 14:117.
Furtado, TA, Wilson, JW, Plunkett, OA: South American blastomycosis or paracoc-
cidioidomycosis: The mycosis of Jutz, Splendore, and Almeida. AMA Arch Der-
matol Syphilol1954; 70:166.
Paracoccidioidomycosis. Proceedings of the first Pan American symposium, Washing-
ton, DC, Pan American Health Organization, 1972.
CHAPTER 19

Lobo's Disease

This deep fungal disease, which seems to have affinities with North American
blastomycosis and with paracoccidioidomycosis, was first recorded by Lobo in
a patient from the Amazon valley. In the past 50 years, some 100 cases have
been reported from Brazil and Central America. Although this would imply
that the infection is exceedingly rare, it has been suggested that a greater
awareness of the disease would lead to many more cases being detected.

Etiology
The organism has never been satisfactorily cultured in vitro, while yeastlike
cells seem to grow profusely in patients with the disease. It has been named
Loboa loboi, and a suspension of the affected tissue injected into a hamster's
footpad showed a reduplication of the cells some eight months later. As the
lesions are mostly found on the exposed parts and are most often associated
with a history of trauma, it is believed that, like Blastom)lCes dermatitidis and
Paracoccidiodes braziliensis, the fungus probably lives in soil or vegetation.
There is an extraordinary report by Migaki et al that an organism visually
indistinguishable from that found in Lobo's disease can produce severe gran-
ulomatous disease in the Atlantic bottle-nosed dolphin. Whether the organisms
are identical will not be known until satisfactory culture methods have been
devised.

Clinical Features
The disease shows grouped or isolated nodules that are usually painless, hard,
and smooth, like keloids (Figure 19-1) (the disease has been known as keloidal
blastomycosis), most commonly seen on the limbs and less frequently on the
Differential Diagnosis 153

face. They vary in color from ivory to cafe-au-Iait, and hyperpigmented lesions
are extremely unusual. As time goes on, the nodules extend slowly and may
become edematous, ulcerated, or even verrucous (Figure 19-2). Secondary
lesions, usually appearing in areas easily reached by the fingers, indicate that
the disease may be spread by autoinoculation.

Differential Diagnosis
In fully established cases, the lack of signs or symptoms in the mouth, lungs,
or abdominal viscera completely rules out the diagnoses of North American
blastomycosis or paracoccidioidomycosis. The rarity of ulceration and absence
of lymphatic spread preclude the diagnosis of sporotrichosis. Probably the most
easily confused of the deep fungal infections is chromomycosis, which some-
times can be differentiated only by differences in the biopsies.

FIGURE 19-1 Granulomatous

lesions resembling keloids.
(Courtesy Mauricio Goihman-
Yahr, M.D., Caracas, Vene-
zuela.)
 154 19. Lobo's Disease

FIGURE 19-2 Elevated nodule

becoming verrucous. (Courtesy
J. Sidney Rice, M.D. Collection
of the College of Physicians of
Philadelphia.)

Consideration should be given to the possibility of hypertrophic scars and

keloids. Even if the history is suggestive, the biopsy will not be confirmatory.
Despite the clinical similarity, the histology is quite different; in Lobo's disease
there is an absence of proliferative collagen.

Investigations
So little is known about the disease that nothing can be said about mycologic
investigation. When a new lesion is found, the opportunity should never be
missed to carry out as many investigations as possible.
When biopsies are taken, small ovoid cells, 7 to 10 JL in diameter, with thick
but not pigmented walls, are found in profusion in granulation tissue. Char-
acteristically, the fungi are seen inside huge foreign-body giant cells or large
histiocytes, while lymphocytes are rare and collagen proliferation is not seen.
Sometimes, a chain of fungal cells is seen linked to one another like a chain of
plastic beads.
Although clinically some lesions have been seen to ulcerate and discharge,
the histologic appearance of this complication has not been reported.
Treatment 155

Treatment
The sparsity of cases has ensured that there are only sporadic accounts of sat-
isfactory therapy. Clofazimine 100 mg daily and ketoconazole 400 mg daily
have each shown some therapeutic success, if given for many months. Until
more is known about the organism, the slowly growing, well-defined tumors
are perhaps best treated by local excision.

Selected Readings
Azulay, RD, Carheiro, JA, Da Graca, M, et al: Keloid blastomycosis (Lobo's disease)
with lymphatic involvement: A case report. Int J Dermatol1976; 15:40.
Baruzzi, RG, Castro, RM, D'Andretta, C, et al: Occurrence of Lobo's blastomycosis
among "Caiabi," Brazilian indians. Int J Dermatol1973; 12:95.
Migaki, G., Valerio, MG, Irvine, B, et al: Lobo's disease in an American bottle nosed
dolphin. JAm Vet Med Assoc 1971; 159:578.
Silva, D: Eight new cases of Lobo's keloidal mycosis. Int J Dermatol1973; 12:99.
Tapia, A, Torres-Calcindo, A, Arosemena, R: Keloidal blastomycosis (Lobo's disease
in Panama). Int J Dermatol1978; 17:574.
PART FOUR

Parasitic Diseases
CHAPTER 20

Leishmaniasis

In different parts of the world, widely differing diseases are caused by proto-
zoan parasites known as Leishmania. These parasites have two forms: they
exist in human and other animals in an aflagellate state (amastigote or Leish-
man-Donovan bodies), while the flagellate stage (promastigote) is found in the
insect vector and in culture media. The amastigote is oval or spherical and
measures 2 to 6 /.L in length and 1 to 2 /.L in width. It is an obligate intracellular
parasite. The promastigote is 15 to 25 /.L long and 2 to 5 /.L wide, with a flagellum
that can be up to 30 /.L long.
The various forms of leishmaniasis are transmitted to humans by the Phle-
botomus sandfly and produce two different forms of clinical manifestation, the
cutaneous and the visceral. It has been suspected for many years that the dif-
ferent types of diseases might be caused by various Leishmania species, but
only recently have subtle differences of shape and size of the protozoa and new
techniques of biochemical taxonomy given parasitologists the opportunity to
produce complicated (and somewhat controversial) subdivisions of the genus.
The earliest recognized form of leishmaniasis (the Oriental sore) has been
saddled with several names (Bagdad boil, Biskra button) that remind us of the
areas commonly affected. The disease spreads outward from the Middle East
to northeast India as far as Delhi, and along the coasts of the Mediterranean
to Algeria and beyond. This type of disease is usually self-healing.
Patients whose immunologic defenses are less than complete sometimes pro-
duce a condition mimicking lupus vulgaris usually known as lupoid leishman-
iasis or leishmania recidivans; others are totally unable to defend themselves
against the protozoans and develop a widespread and deforming disease known
as anergic leishmaniasis. In South America, some patients get an Oriental sore
that later spreads to the mucocutaneous areas, producing a deforming muti-
lation known as mucocutaneous leishmaniasis. In India, Bangladesh, some
 160 20. Leishmaniasis

parts of China, and Africa, patients with kala-azar (the visceral form of leish-
maniasis) may later produce post-kala-azar dermal leishmaniasis.
As all these variants have different clinical presentations, are found in dif-
ferent parts of the world, and (probably) are caused by slightly different species
of leishmania, they will each be discussed separately in the following pages.

Oriental Sore
Etiology
Leishmania tropica and its nearest relations can be found as parasites in the
desert rat, dogs, and cats. The disease that they cause is limited to arid zones
in which a sandfty, feeding on an infected gerbil or other reservoir host,
acquires the leishmania. These will change into leishmanids (promastigotes),
which, multiplying profusely in the digestive tract, are inoculated into the skin.
There they are phagocytosed into histiocytes and change into leishmania
(amastigotes), which multiply by binary fission. The histiocytes eventually rup-
ture, and leishmania enter other histiocytes, leading to a pathology that, pro-
ducing an Oriental sore, thus ensures that humans too can be reservoir hosts
for the disease.
Leishmania major affects the gerbil and other wild desert animals and is
said to be the cause of most leishmaniasis found in desert or rural areas. It is
believed that Leishmania tropica is a natural infection of dogs and humans and
is therefore more likely to cause the urban form of Oriental sore. It will of
course surprise no one if patients with rural leishmaniasis are found in an urban
background or vice versa.

Clinical Features
The lesion is usually solitary, appearing at the site of a sandfty bite as an itch-
ing papule somewhat erythematous and indurated, which slowly becomes
crusted with thick, dark, adherent scale through which oozes a sticky serosan-
guinous discharge. Easily differentiable from a pyococcal infection, the nodule
is painless and enlarges slowly, usually taking three to four months to attain
its maximum size, which can be up to 5 cm in diameter. Most patients are
loath to remove the crusted scab, as folklore persuades them that the under-
lying ulcer may become secondarily infected-an unwanted and painful com-
plication. As the months go by, the ulcer begins to heal, the crusts become
separated from the skin, and cicatrization starts at the center of the lesion. This
will slowly spread leaving a somewhat depressed and well-defined hypopig-
mented scar. The whole process of infection, reaction, and spontaneous healing
Natural History 161

will take about a year; indeed in Iran it is known as salak, the one-year disease
(Figures 20-1, 20-2).
As most lesions occur on the face, the scar can be a personal tragedy.
Hypopigmented, irregular, and several centimeters in diameter, it may be
so deep that men may develop cicatricial alopecia of the beard, while occasion-
ally sores on the nostril, ear, or eyelid will cause major facial deformity (Fig-
ures 20-3, 20-4).

Natural History
Although the Oriental sore is usually solitary, sometimes a number of lesions
appear at the same time. It is not known whether these are the results of
numerous bites or whether there has been some endogenous spread. Such mul-
tiple lesions differ from the single sore in that they frequently show neither
crusting nor ulceration.
Some authorities claim that rural leishmaniasis takes longer to run its
course than does the urban variety, but this is of little practical importance, as
the resultant scars are equally unwelcome. While most of the lesions sponta-

FIGURE 20-1 Several lesions

of acute dermal leishmaniasis,
not yet mature enough to break
down and ulcerate.
162 20. Leishmaniasis

FIGURE 20-2 Ulcerating leishmaniasis on wrist and finger. (Courtesy Werner Dutz,
M.D. and Efriede Kohout-Dutz, M.D., Richmond, Virginia.)

FIGURE 20-3 Leishmaniasis

on the face can be associated
with edema and, except for the
long-standing history, might be
confused with anthrax.
Investigations 163

FIGURE 20-4 Oriental sore on the ear.

neously resolve, about 10 percent change their appearance and enter a different
phase, described in the next section (lupoid leishmaniasis).

Differential Diagnosis
As the Oriental sore is a relatively painless, slowly developing condition that
only gradually crusts and rarely ulcerates in much less than three months, it
should not be difficult to differentiate it from acute bacterial diseases (boils,
pyoderma, erysipelas, anthrax), which are much more rapid and usually
painful.
The painless, indolent ulcer occurring in an adult who has recently visited
an endemic area may be mistaken for a basal or squamous cell carcinoma, but
natives of such areas usually acquire leishmaniasis in their early years, when
skin malignancy is unusual.

Investigations
Intracellular parasites will be found in considerable numbers in tissue fluid
either obtained by the skin-slit technique or by impression of the cut edge of a
skin biopsy onto a clean glass slide. If parasites are present, material obtained
by the Dutz technique (Appendix one) may be cultured at 26°C on a blood-
agar medium known as NNN. Parasitologists will recognize the presence of
164 20. Leishmaniasis

promastigotes and the intracellular rodlike nucleus (the kinetoplast), which is

described as setting a tangent to the nucleus. With the Giemsa stain, both the
nucleus and kinetoplast appear bright red.
By the time a nodule has become large enough for the diagnosis to be sus-
pected, biopsy will demonstrate the leishmania to be present in great numbers.
Masses of large histiocytes are packed with organisms, which can also be seen
living extracellularly. Lymphocytes and plasma cells are associated with the
granuloma that underlies a somewhat proliferative epidermis. As immunity
develops, the tuberculoid histology takes over, the histiocytes diminish in size
and number, and in the final stages the organism cannot be found.
The leishmanin or Montenegro test is an intraepidermal test for delayed
hypersensitivity. It may be of use in epidemiologic studies, but as an aid to
clinical diagnosis it is not much help, being negative in the early stages and
only becoming positive when the diagnosis is clinically obvious. Most adults in
endemic areas have a positive Montenegro test due to an earlier infection.

Treatment
If the disease is treated early it may be possile to cause regression of infection
before it has reached a stage where scarring is inevitable. Therapy is not as
successful as might be hoped. Systemically pentavalent antimonials are most
widely used-500 mg of sodium stibogluconate may be given, intramuscularly
or intravenously, for 10 to 14 days. Attempts to treat small lesions by local
intradermal injection are not to be encouraged as the residual scar is in no way
different from that which follows an untreated infection. There have been scat-
tered claims of satisfactory results from the use of amphotericin B or rifamp-
icin, while anecdotal reports of drugs too numerous to mention have usually
not been supported by further studies.
There is, however, an interesting new technique at present being investi-
gated in which the antileishmaniasis drugs are coated with lyposomes and
administered intravenously. Phagocytic cells in the skin rapidly remove lypo-
somes from the bloodstream, and the drug is thereby delivered directly into the
histiocytes that contain the infecting organism. It is not yet known whether
these experiments can lead to a clinically useful therapy.
Small lesions can be surgically excised or destroyed by electrosurgery or
cryosurgery. These techniques are particularly useful as a method of limiting
extension of infection of the nostril or ear.
Parents living in endemic areas believe patients are never infected twice and
frequently seek for their child, particularly if it is a girl, to be vaccinated in a
covered area, preferring a scar on the buttock or thigh to one on the face. It is
now believed that L. major (cause of the rural disease) will protect against L.
tropica, but the opposite is not necessarily true.
While there is no harm in such vaccination in the Old World, it should not
 Differential Diagnosis 165

be recommended in South America, as inoculation with L. braziliensis may be

followed by mucocutaneous leishmaniasis.

Lupoid Leishmaniasis
More than 90 percent of all patients who have Oriental sore overcome the
infection totally at the expense of developing an unsightly scar. Sometimes,
however, as the crust falls away from the healing ulcer the patient finds active
nodules still present in the skin. Less frequently, the sore heals completely and
nodules appear in the scar some time later. This is the start of the condition
that has varyingly been called chronic leishmaniasis, lupoid leishmaniasis, or
leishmaniasis cutis recidivans.

Clinical Features
Scattered throughout the scar are many yellowish-brown translucent nodules
of the apple-jelly type over which the skin is thinned. Sometimes these nodules
develop on an erythematous or hyperpigmented background and gradually
spread peripherally, causing the original scar to extend and producing a picture
that is indistinguishable from lupus vulgaris. In a surprising number of cases
in Iran the patient gives a history of seasonal variation in the lesions and
expects them to get worse in summer. It is not unusual to find that nodules
have ulcerated after exposure to sunshine (Figures 20-5 to 20-7).

Natural History
The Oriental sore takes about a year to run its course. Only in the last stages
is it recognized that some patients are not going to heal normally. There is little
or no tendency for this form of leishmaniasis to regress. In one series of nearly
70 cases all the patients had had the disease for at least eight years, since acute
cutaneous disease had at that time been eradicated, when the sandfties were
fortuitously exterminated during an antimalarial compaign.

Differential Diagnosis
It is extremely difficult to differentiate this from lupus vulgaris if the patient
does not relate that the condition started with an Oriental sore. In endemic
areas, such a history is usually available, as the patients are well aware of the
clinical appearance of primary cutaneous leishmaniasis. If, in sporadic cases
seen elsewhere, this information is not available, the diagnosis may indeed be
166 20. Leishmaniasis

difficult to establish. It may even be necessary to treat the patient with anti-
tuberculosis therapy for a few months: if there is not a dramatic improvement,
leishmaniasis may be suspected.
Except for other causes of tuberculoid granulomata, no other disease need
be considered in the differential diagnosis.

Investigations
Smears taken from an acute Oriental sore abound with leishmania, and culture
produces large numbers of the leptomonad form. This does not apply to lupoid
leishmaniasis, where it is suspected that the body's attempt to eradicate infec-
tion by production of a cell-mediated immunity is less than totally successful,
and (comparable to tuberculoid leprosy or lupus vulgaris) a spreading tuber-
culoid granuloma shows that immunity, although high, is not complete.
Attempts to culture organisms from such granulomata are met with scanty
success. In most patients it is impossible to obtain a positive culture.
Similarly unhelpful are attempts to confirm the diagnosis histologically. The
tuberculoid granuloma is indistinguishable from those found in tuberculosis or
the tuberculoid form of leprosy. Caseation has never been reported in lupoid
leishmaniasis and if seen will rule out the diagnosis. An associated hypertrophy
of the epidermis amounting almost to pseudoepitheliomatous hyperplasia can
produce a histologic appearance similar to that found in chromomycosis, but
without the diagnostic thick-walled intracellular spores.
In most cases, the Montenegro test is positive. This is useful in children, but
not much help diagnostically in areas where almost all adults have a positive
reaction. In cases where the disease afflicts a person who has only fleetingly
visited an endemic area, a positive Montenegro test and a negative tuberculin
test may combine to suggest the diagnosis.

Treatment
Physicians with experience in the Middle East will know that the treatment of
chronic leishmaniasis is depressingly unsuccessful. Spontaneous cure cannot be
expected, and prolonged courses of the usual pentavalent antimonials must be
tried. Intravenous pentostam is the treatment of choice, supplemented if pos-
sible with grenz rays every two to three weeks.
In smaller lesions, the individual apple-jelly nodules may be treated with
liquid phenol or 20 percent trichloracetic acid. The granulomas may be
destroyed in this way, and the resultant cicatrization will not be worse than
that produced by the disease. Cryotherapy can also be used.
Natural History 167

FIGURE 20-5 Lupoid leishmaniasis (resembling lupus vulgaris).

FIGURE 20-6 Lupoid leishmaniasis extending widely over the face.

168 20. Leishmaniasis

FIGURE 20-7 Acute leishmaniasis left a scar on the left cheek. One year later new
apply-jelly nodules appeared and are enlarging.

Anergic Leishmaniasis
The Oriental sore is found mainly in the Middle East and around the borders
of the Mediterranean. Lupoid leishmaniasis, although less frequent, appears in
much the same sites. There is another form of leishmaniasis in which the entire
skin may be covered with nodules, apparently because patients are completely
unable to mount a defensive reaction to the organism. Diffuse anergic leish-
maniasis is limited to central Africa (Ethiopia, the Sudan, Tanzania) and the
equatorial parts of South America. It seems never to have been reported from
the Middle East, but whether these geographic preferences are manifestations
of immunologic differences in the protozoa or in the varying susceptibilities of
the hosts is unknown. It is probably the latter, but it is difficult to explain why
such a defect has not been noted in the Middle East.

Clinical Features
Lesions of lupoid leishmaniasis are in many ways comparable to those of tub-
erculoid leprosy, except of course leprosy granulomata invade the nerves as well
as the dermis. In a similar way, patients who are anergic to leishmaniasis
develop a widespread abnormality that is comparable in almost every way to
Differential Diagnosis 169

lepromatous leprosy; the condition has sometimes been called leproid

leishmaniasis.
When the condition is fully established, there is a symmetrical eruption of
soft bulky nodules on the face and ears with others all over the extremities; the
trunk is less frequently involved. Many lesions resemble soft, shiny keloids, but
others are somewhat scaly or even have a verrucosus surface (Figures 20-5 to
20-7). The outer parts of the eyebrows are missing (madarosis), and patients
may complain of dryness of the nose or epistaxis, but although the mucosa is
often erythematous, intranasal nodules are rarely found. In contrast to lepro-
matous leprosy, the skin between the lesions not only looks normal, but contains
no leishmania.

Natural History
In most cases the disease starts with a small, painless nodule on an exposed
part. This is probably the site of inoculation by a sandfly, but the progress usual
in an Oriental sore does not take place. The nodule enlarges but neither ulcer-
ates nor crusts, and after a few months satellite lesions develop around the
primary one. Over the years a variety of nodules appears all over the body. In
about 20 percent of cases the primary lesion heals, leaving the patient's skin
completely normal for a few months, after which extensive numbers of papules
erupt and enlarge in the classical sites. This temporary healing suggests that
these patients are not primarily anergic, but that their low degree of immu-
nologic defense collapses under the weight of protozoal multiplication and they
become secondarily anergic.
The onset of the disease is not infrequently associated with a period of gen-
eral malaise, but after a few years general symptoms are not seen unless the
patient has entered a phase in which the existing lesions become red and swol-
len in a manner that is exactly comparable to the clinical appearance of leprosy
patients in reaction. Records of such happenings are unclear as to whether
these events are associated with subsequent clinical improvement, analagous to
a reversal reaction.

Differential Diagnosis
Many of these patients have been found living in the world's leprosaria often
diagnosed as having abacterial lepromatous leprosy. Widespread lymphoma
may often cause diagnostic confusion while sarcoidosis and extensive keloids
may also be suspected. The histology should always clarify matters.
170 20. Leishmaniasis

Investigations
These patient., are full of leishmania. Abundant parasites can be found in skin
smears, while culture on the NNN medium is profusely successful. If a biopsy
is taken, the epidermis is normal or mildly thickened, and there is a dense der-
mal infiltrate consisting of numerous vacuolated histiocytes looking like the
foam cells of lepromatous leprosy, but containing masses of parasites that are
easily demonstrated by the Giemsa stain. Lymphocytes and plasma cells are
mixed with the infiltrate, but the granuloma never involves cutaneous nerves.
In anergic patients the Montenegro test is invariably negative. It has been
said that any case diagnosed as lepromatous leprosy in Ethiopia that does not
show acid-fast bacilli should be examined for leishmania; this rule applies
throughout the world.

Treatment
These unfortunate individuals have inherited the grim prognosis that used to
be given for lepromatous leprosy before the use of sulfones. Of the usual anti-
monials, diamidinophenoxypentane (pentamidine) is probably the drug of
choice, but it must be used very carefully because in cases of gross disease a
form of Herxheimer's reaction has been seen.
Rifampicin alone or supplemented with isoniazid or sodium stibogluconate
can be tried; amphotericin Band ketoconazole have also been used. The fact
remains that most of these patients do not respond to any known form of
therapy.

Mucocutaneous Leishmaniasis
Leishmania braziliensis is one of the 13 known forms of leishmania recognized
in South America alone. It can be found in such wild animals as the marmoset
and racoon, particularly those inhabiting the forest areas of the Andes. It pro-
duces in humans a disfiguring disease known as mucocutaneous leishmaniasis,
found mainly in South America. Brazil, Venezuela, and Peru have the most
cases.
Variants of Leishmania braziliensis have been named after the countries in
which they were first detected.

Clinical Features
Although any mucocutaneous site may be involved, including the anus or
vulva, the classical form affects the nasal passages, where redness, induration,
and infiltration lead to a destructive lesion referred to as a camel's nose or
Natural History 171

FIGURE 20-8 Late necrotizing granuloma of mucocutaneous leishmaniasis called

espundia. (Courtesy J. Sidney Rice, M.D. Collection of the College of Physicians of
Philadelphia. )

parrot's beak. Swelling followed by destruction starts in the nasal septum and
extends out to the upper lip and back to the nasal-pharyngeal passage. Later
the tongue, buccal mucosa, and floor of the mouth can be destroyed as the
condition extends to other parts of the face (Figure 20-8). In the later stages,
infection may metastasize to other parts of the body.
Sepsis frequently complicates matters; the patient can become malnourished
because of difficulties in eating, and respiratory failure can follow obstruction
of the bronchotracheal passage and secondary infection of the lung.

Natural History
The classical picture of destructive involvement of the nose and face is not the
beginning of the story since this condition starts as a tropical sore that may be
sited on any part of the skin and runs much the same course as similar lesions
in other parts of the world. The condition caused by L. braziliensis varies from
other forms of leishmaniasis in that anything from a few days to 25 years after
the start of the original infection secondary lesions develop in one or more
mucocutaneous junctions. Most often this extension starts with what the
patient thinks is a chronic cold or epistaxis, later, the nasal cartilage becomes
involved, the nose collapses, and the classic midfacial destruction develops.
172 20. Leishmaniasis

Further extension can even reach the eye, causing granulomatous destruction
of the conjunctiva with corneal ulceration and intersititial keratitis.

Differential Diagnosis
Many diseases give a similar clinical picture, starting with a simple pyoderma,
rhinophyma, rhinoscleroma, and various deep fungal diseases such as sporotri-
chosis and paracoccidiodomycosis. Lupus vulgaris, yaws, and even leprosy pro-
duce a somewhat similar (but less extensive) destruction, while the rare con-
dition known as lethal midline granuloma may have a similar appearance.
The diagnosis cannot be confirmed without suitable investigations.

Investigations
This may be looked on as a disease midway between lupoid and anergic leish-
maniasis. Although leishmania are not difficult to detect they are neither as
rare as they are in lupoid disease nor as profuse as in anergic infection. The
simplest method is to use a skin smear similar to that used to demonstrate
Mycobacterium /eprae (see Appendix one) and stain the tissue fluid with
Giemsa, Wright's, or Leishman's stains. As with leprosy smears it is important
to ensure that the smear is not heavily contaminated with blood, in which case
the relatively rare amastigotes may be missed. As in other forms of leishman-
iasis, culture can be achieved in the Nicolle-Novy-MacNeal (NNN) agar. The
Montegro test is not much use as not all patients are positive, and many normal
people in the region react because of previous exposure.
Biopsy of the erosion will show a necrotizing tuberculoid granuloma that is
only differentiable from lupus vulgaris, leprosy, etc. by virtue of the presence
of the protozoa. As these are relatively scanty it is often necessary to examine
several sections before the diagnosis can be confirmed.
Various serologic tests are known, but are of more value as research tools
than as aids to diagnosis.

Treatment
The condition almost never heals by itself without massive destruction. The
important treatments include the pentavalent antimonial compounds, but a
competent immune system is necessary for any of the drugs to work satisfac-
torily. The most useful is N-methylglucamine antimoniae, which is given 100
mg per day for 20 days, but it has a fairly high failure rate. An alternative
sodium stibogluconate may be needed. It is given intramuscularly daily for two
to three weeks.
Natural History 173

Alternatively, amphotericin B can be given intravenously at an initial dose

of 0.5 mg/kg every three to four hours, gradually raised to 10 mg/kg until a
maximum of 2,5000 to 3,000 mg has been given.
Most recently, ketoconazole 400 mg orally for at least three months has
proved itself a well-tolerated and easily administered modality.
Cryosurgery is useful and rational, as the organisms are known to be sen-
sitive to temperature changes.
There is no known way to immunize people living in endemic areas. The
best hope for prophylaxis is for extensive public health campaigns to eradicate
the sandfly.

Post-Kala-Azar Dermal Leishmaniasis

Kala-azar is the name usually given to a visceral infection caused by Leish-
mania donovani. Not uncommon in northeastern Brazil but found more fre-
quently in central Africa, the borders of the Mediterranean, and parts of Rus-
sia, India, Bangladesh, and China, the established disease shows enormous
hepatosplenomegaly with recurrent fever and a progressive wasting, which, in
fair-skinned patients, is associated with darkening of the skin (kala-azar is
Hindi for "the black fever").

Clinical Features
Some 3 to 30 months after they have had kala-azar some of these patients
develop dermatologic lesions of almost infinite variety. Hypopigmented
macules, nodules, pseudoxanthomata, verrucose lesions, and a sort of prolifer-
ative condylomata have all been reported. Many of these patients are mistak-
enly treated for leprosy despite the absence of acid-fast bacilli or of any neu-
rologic signs.
A butterfly erythema, aggravated by sunlight, may be the earliest sign,
slowly followed by the development of hypopigmented macules covering the
whole body. Later, nodules appear, mainly on the face and ears, that with time
become more disseminated, taking on a warty or even verrucose appearance
(Figures 20-9a,b to 20-11).

Natural History
Kala-azar is becoming a rare disease in most parts of the world, because
attempts to eradicate the sandfly have been successful in many places. In India,
post-kala-azar dermal leishmaniasis is probably now more common than kala-
azar itself, as, once established, the lesions tend to persist or extend for many
years.
 174 20. Leishmaniasis

FIGURE 20-9a,b A case of pulmonary thuberculosis referred for hoarseness of voice

with swelling of lip and tongue for six months. The smear of Leishman-Donovan bod-
ies was positive from lip, tongue, and larynx. -
Natural History 175

FIGURE 20-10 Nodules on

nose being treated as rosacea.
The smear was positive for
Leishman-Donovan bodies.

FIGURE 20-11 Student with post-

kala-azar dermal leishmaniasis
nodules on face and elbows. The
hypopigmented macules were
resistant to antimonials but
resolved well with amphotericin B
(total of 550 mg). There was no
recurrence at a ten-year follow-up.
(Courtesy A. S. Thambiah,
F.R.C.P., and Patrick Yesudian,
F.R.C.P., Madras, India.)
 176 20. Leishmaniasis

This symptom complex is probably a manifestation of immunologic insuffi-

ciency and does not occur in all cases of visceral disease, since most patients
will have some resistance to infection.

Differential Diagnosis
Any form of leprosy may be mimicked by this condition. A previous history of
kala-azar will be helpful, but it is not obtained in many cases. Moreover, there
is of course no reason why, in infected areas, a patient with leprosy cannot also
have a prevous history of kala-azar.
This wide variety of lesions can easily confuse the clinician, but the presence
of firm granulomatous lesions around the mouth and nose and a scattering of
hypopigmented macules elsewhere should be of assistance.

Investigations
In the macular form the causative organisms are frequently not detectable, but
they are present in good numbers in the nodular forms of disease, in which case
positive skin smears stained by Giemsa stain will be enough to confirm the
histology, but if a biopsy is taken it will usually show a histology similar to that
seen in anergic disease with a heavy infiltrate of histiocytes containing numer-
ous parasites.
As usual, the Montenegro test is of little value, as it mayor may not be
positive.

Treatment
As may be expected, if the disease is limited to the macular form it will respond
fairly well to injections of stibophen (2 ml intramuscularly on alternate days).
The nodular varieties are more resistant to antimonials, but may respond to
hydroxystilbamidine isothionate. Amphotericin B therapy has been used suc-
cessfully in Madras.

Chiclero's Ulcer
Leishmania mexicana is usually found on the east coast of Mexico and Central
America. The lesion it causes is similar to an ordinary Oriental sore, but usu-
ally lasts less than six months. If, as is not unusual, the lesion affects the ear,
the infection commonly invades the cartilage and produces a severe erosive
deformity that shows little tendency to spontaneous resolution.
Treatment 177

By far, the best treatment is destruction of the lesion with electrosurgery or

cryosurgery, thus terminating the usual inexorable spread.

Pian Bois
Leishmania braziliensis guyanensis infection produces numerous lesions on the
body that, unlike most Oriental sores, show a sporotrichoid tendency to spread
along the lymphatics and even to infect the regional lymph nodes. The nose
and mouth are not involved.

Selected Readings
Chance, ML: Leishmaniasis. Br Med J 1981; 283:1245.
Connor, DH, Neafie, RC: Cutaneous leishmaniasis, in Binford, CH, Connor, DH
(eds): Pathology of Tropical and Extraordinary Diseases. Washington, DC,
Armed Forces Institute of Pathology, 1976, p 258.
Convit, J, Kerdel-Vegas, F, Gordon, B: Disseminated anergic leishmaniasis. Br J Der-
mato11962; 74:132.
Kerdel-Vegas, F: American leishmaniasis. Int J Dermatol1982; 21:291.
Kern, P: Leishmaniasis antibiotics. Chemotherapy 1981; 30:203.
Lainson, R: The American leishmaniasis: Some observations on their ecology and epi-
demiology. R Soc Trop Med Hyg 1983; 77:569.
The Leishmaniac: A Periodical. Jerusalem, Kuvin Centre for the Study of Infectious
and Tropical Diseases.
Munro, DD, du Vivier, A, Jopling,WH: Post-kala-azar dermal leishmaniasis. Br J
DermatoI1972; 87:374.
Pareek, SS: Combination therapy of sodium stibogluconate and rifampin in cutaneous
leishmaniasis. Int J Dermatol 1984; 23:70.
Pettit, JHS: Chronic (lupoid) leishmaniasis. Br J Dermatol 1962; 74: 127.
Sagher, F: Some basic medical problems illustrate by experiments with cutaneous
leishmaniasis. Trans St. John's Hosp Dermatol Soc 1972; 58:1.
Schewach-Millet, M, Fisher, BK, Semah, D: Leishmaniasis recidivans treated with
sodium stibog1uconate. Cutis 1981; 28:67.
Strick, RA, Borok, M, Basiorowski He: Recurrent cutaneous leishmaniasis. J Am
Acad Dermatol 983; 9:437.
Turk, JL: Leprosy and leishmaniasis. Proc R Soc Med 1970; 63:1053.
Weinrauch, L, Lirshin, R, Even-Pas, Z, et al: Efficacy of ketoconazole in cutaneous
leishmaniasis. Arch Dermatol Res 1983; 275:353.
Urcuyo, FG, Zaias, N: Oral ketoconazole in the treatment of leishmaniasis. Int J Der-
mato11982; 21:414.
Yesudian, P, Thambiah, AS: Amphotericin B therapy in dermalleishmanoid. Arch
Dermatol1974; 109:720.
CHAPTER 21

Amebiasis

Amebiasis is an infection of the gastrointestinal tract, usually the colon, that

may remain localized for many years. At any time, this protozoan infection
can spread to other parts of the lower intestine, the liver, and even additional
internal organs, where it is not unusual for abscesses to form. Cutaneous ame-
biasis is the result of extension of these abscesses to nearby skin; direct inocu-
lation may also produce an amebic ulcer. Both sexes are infected, and there is
no age limit. The duration of the disease varies from a few weeks to several
years. Cutaneous amebiasis occurs worldwide-it is not necessarily limited to
third-world countries, but can even be found in major American metropolitan
areas. It is, however, more common in those parts of the third world where
little attention is paid to sanitation.

Etiology
The condition was first recognized a century ago. It is caused by the protozoan
Entamoeba histolytica. This parasite can exist in two forms: the cyst (10 to
20~ in diameter) and the trophozoite (12 to 50 ~). Both can be found in dogs,
cats, and rabbits, which are known reservoirs of the infection.
Human beings contract the disease by ingesting cysts from contaminated
water or food fertilized with night soil. Trophozoites excyst in the small intes-
tine and enter the colon, where they invade the mucosa. Individuals may have
a few lesions, often asymptomatic, but other patients may be more susceptible
and develop a severe infection. This is probably limited to those in whom mal-
nutrition combines with decreased immunologic competence. The trophozoites,
under certain circumstances, encyst, leave the body, and complete the cycle.
Infection may spread to the liver, where single or multiple cysts develop
Differential Diagnosis 179

varying sizes, containing amorphous necrotic material. These abscesses may

track to the skin, overlying the liver, or sometimes spread to the flank, where
they ulcerate. Ulcers may also occur in the perineum by extension from a rectal
or vaginal infection and have also been reported to arise de novo on the penis;
in the last instance, both heterosexual and homosexual contacts are thought to
playa role in transmission.

Clinical Features
The most common symptom of amebic infection is bloody diarrhea. but this is
not always seen. Jaundice or an enlarged, painful liver may be the first clinical
manifestation. Extraintestinal infection may produce such nonspecific symp-
toms as malaise and fever. It is not unknown for a cutaneous lesion to develop
in a patient whose intestinal and hepatic infection have not been recognized. It
may start with mild itching, but soon definite pain is felt and the skin breaks
down to form an irregular ulcer with a sharply defined border. This may be
masked by overgrowth of granulation tissue or even covered with a necrotic
eschar. The picture can be complicated by the appearance of a nonspecific sen-
sitizing eruption (an amebid lesion), which is an allergic type of response to
the underlying Entamoeba, but in which no organisms can be found.

Natural History
Trophozoites lodging in the intestine will usually cause features of amebic dys-
entery within a few days; the distended abdomen, associated with mucoid or
bloody diarrhea, may persist for months or years if it is untreated, but other
patients may remain undiagnosed for years, particularly if nonspecific abdom-
inal symptoms alternate with periods of relatively good health.
The extension of underlying infection onto the skin causes a painful ulcer,
which extends rapidly with a malodorous necrotic base (Figures 21-1 to 21-3).
Sometimes, the edges produce a warty proliferation, when pseudoepitheliom-
atous hypertrophy develops at the edge of the ulcer. It is most unlikely that
these ulcers will heal spontaneously.

Differential Diagnosis
Other causes of rapidly extending cutaneous ulceration must be excluded;
tuberculous and syphilitiz ulcers are usually painless. Lesions on the penis can
be confused with chancroid, but the most difficult problem is differentiating
180 21. Amebiasis

FIGURE 21-1 Painful ulceration of the groin. (Courtesy Liverpool School of Tropical
Medicine, England.)

this from pyoderma gangrenosum. Condylomata acuminata, skin malignan-

cies, and the deep mycoses are among the wide variety of warty lesions that
can be confused with the hypertrophic cauliftowerlike reaction surrounding the
ulcer. All of these diagnoses can be disproved by demonstration of the Enta-
moeba in the tissues.

FIGURE 21-2 Closer view reveals the extensive necrosis. (Courtesy Liverpool School
of Tropical Medicine, England.)
Treatment 181

FIGURE 21-3 Marked destruction extending onto the perineal area. Note the hyper-
trophic margins. (Courtesy Liverpool School of Tropical Medicine, England.)

Investigations
Although the diagnosis of cutaneous amebiasis may often be made simply by
clinical inspection, it is wise to seek the trophozoites in the discharge as well
as in the stools. If this is not successful, biopsy from the edge of the necrotic
part of the ulcer will usually contain trophozoites that are readily stainable
with hematoxylin and eosin.
If these are not seen in a skin section, the diagnosis will probably not be
made histologically, as the other changes are nonspecific, with necrosis asso-
ciated with lymphocytes and plasma cells somewhat complicated by benign
epidermal proliferation.
A skin test with axenic-amebic antigen will produce a tuberculoid type of
reaction in about 80 percent of cases. Complement-fixation tests, hemagglutin-
ation, indirect immunofluorescence, immunophoresis, and agar gel diffusion
tests, available in some centers, are usually helpful.

Treatment
In the past, various methods of treatment have been reasonably successful.
Chloroquine 600 mg daily for ten weeks along with 650 mg diiodohy-
droxyquin three times a day for three weeks can be used. Dihydroemetine
(I mg/kg intramuscularly daily for ten days) can be used alone or in combi-
nation with chloroquine.
182 21. Amebiasis

Since the development of metronidazole it has become the drug of choice.

Most patients are cured by 750 mg three times a day (20 to 50 mg/kg) for 7
to 21 days.
Large ulcers may show so much necrosis that surgical debridement is nec-
essary to spread resolution.

Follow-up
It is wise to check the feces for Entameba at one month and six months after
cessation of treatment. It should also be remembered that cutaneous amebiasis
is highly contagious. Other members of the household should be examined and
their stools tested.

Selected Readings
Biagi, F: Amebiasis. Antibiot Chemother 1981; 30:20.
Krogstad, DJ, Spencer, HC, Healy, GR: Current concepts in parasitology: Amebiasis.
N Engl J Med 1978; 298:262.
Padilla, CA, Padilla, GM: Amebiasis in Man. Springfield, Ill, Charles C Thomas,
1974.
Saul, A: Amoebiasis cutis. Int J Dermatol1982; 21:472.
Symposium on amebiasis. Bull NY Acad Med, 2nd ser 1981; 57:173.
CHAPTER 22

Toxoplasmosis

This potentially devastating disease can be found in most areas of the world.
It is believed that more than one billion sufferers exist in North and South
America, Australia, and Asia. It is also found in Europe to such an extent that
at least 50 percent of the population of Italy is said to have toxoplasmosis, but
because the infection often remains subclinical, it often is unrecognized.

Etiology
The causative organism is a coccidian parasite that may live in domestic or
farm animals, although the cat is most usually blamed. Toxoplasma gondii is
5 /J- in length and appears as a crescent with a rounded end. This organism
undergoes schizogony and gametogony in intestinal epithelium and is most
commonly found as an intracellular organism in the nervous, muscular, or reti-
culoedothelial systems.
The mechanism of transmission is uncertain, but because there is a more
frequent incidence among butchers and veterinarians, it is believed that direct
transmission from infected animal tissue is possible. Cats, rats, dogs, cattle,
pigs, sheep, and fowl are all known to pass cysts and pseudocysts through the
feces. The disease has also been acquired from eating fresh, uncooked meat.
Infected women have been known to excrete toxoplasma in their menstrual
blood, lochial secretion, maternal milk, and amniotic fluid and so are a source
of intrauterine toxoplasmosis with its triad of symptoms-hydrocephalus, cho-
rioretinitis, and calcification of the brain. In older children, the central nervous
system is chiefly affected by meningitis and encephalitis. In adults the viscera
are most frequently affected, while airborne transmission probably explains the
occasional appearance of lesions in the lung.
184 22. Toxoplasmosis

Clinical Features
Most patients have few or no symptoms. Unfortunately, if the skin is involved,
the morphologic picture of cutaneous toxoplasmosis is generally so nonspecific
that it does not help the diagnosis. There may be a diffuse morbilliform erup-
tion either alone or associated with scattered macules and papules. Purpura,
petechiae, erythema multiforme (Figure 22-1), and scaliness may all be seen,
and gumma formation, nodules, and cysts occur in the later stages (Figure 22-
2).

Natural History
The natural history is always difficult to determine in a disease which is either
asymptomatic or produces only a vague symptomatology. In the noncongenital
form, during the first few weeks of infection, a transient maculopapular erup-
tion is seen. Later, malaise, arthralgia, headache, and fever begin. Immuno-
suppressed patients are more susceptible and may develop a fulminant infec-
tion: tachycardia, febrile episodes, pneumonitis, and inflammation of the
myocardium, the meninges, and the gastrointestinal tract can combine to cause
their death.

FIGURE 22-1 Erythema multiforme-Iike eruption in an 18-year-old Italian woman.

(Courtesy Maurizio Binazzi, M.D., Perugia, Italy.)
Investigations 185

FIGURE 22-2 Nodules and crusting on the legs of a 61-year-old Italian woman.
(Courtesy Maurizio Binazzi, M.D., Perugia, Italy.)

Although most cases are self-limiting, the disease can take a chronic course,
in which case nodules and cysts finally appear in the skin, particularly on the
scalp.

Differential Diagnosis
Fever, vague skin eruptions, and neurologic signs may be confused with tick-
borne typhus or meningococcal meningitis. It must also be remembered that
toxoplasmosis is one of the causes of generalized lymphadenopathy. Cutaneous
lymphomas, dermatomyositis, and lichen planus all at various times can con-
fuse the diagnostically unwary.

Investigations
Organisms are easily recognized in biopsies from infected tissue, as they stain
nicely with methylene blue. Aside from these, the lesion shows nothing but a
nonspecific inflammatory reaction.
The presence of toxoplasma does not indicate whether the infection is recent
or long-standing. It is necessary to resort to serologic tests, of which the indirect
186 22. Toxoplasmosis

fluorescent antibody test is most widely used. High antibody titers suggest an
acute infection, although up to 10 percent of apparently healthy individuals
may also show high readings.
Other tests include the Sabin-Feldman dye test, complement-fixation test,
and indirect hemagglutination tests.
If it is available, 0.1 mg of antigen injected into an infected patient's skin
will produce a flare with pseudopodia within 30 minutes.

Treatment

Cutaneous toxoplasmosis is frequently self-limiting, and treatment is only

needed if there is evidence of eye involvement or other deep manifestations in
the brain or the heart. All immunologically incompetent patients must also be
treated. Unfortunately, success cannot be guaranteed.
Probably the best combination is to give pyrimethamine 25 mg four times
a day together with sulfadiazine 1 gm four times a day for many weeks. Unfor-
tunately, adverse reactions to the folate antagonist are relatively common.
Other treatments reported to be successful include tetracycline in various
doses for various periods, and spiramycin 2 g daily for two months. Spiramycin
may also be used on an alternate-day basis with cotrimoxazole four to six tab-
lets daily.

Selected Readings
Andreev, VC, Angelov, N, Zlatkov, NB: Skin manifestations in toxoplasmosis. Arch
Dermatol1969; 100:196.
Binazzi, M: Patologia dermatologica e toxoplasmos: Ann ltal Dermatol Clin Sper
1980; 34:369.
Binazzi, M, Papini, M: Cutaneous toxoplasmosis. lnt J Dermatol1980; 19:332.
Ippolito, F: Simposio sulla toxoplasmosi. Bull lnt Dermatol S Gall 1981; 9: 1.
Pollock, JL: Toxoplasmosis appearing to be dermatomyositis. Arch Dermatol 1979;
115:736.
Toxoplasmosis. Br Med J 1981; 282:249.
CHAPTER 23

Onchocerciasis

Onchocerciasis, also known as onchocercosis, caused by a filarial nematode, is

probably better known to the lay public by the more graphic name river blind-
ness. It is endemic in many areas throughout the sub-Saharan parts of Africa
from Nigeria to Tanzania and from Angola to Eritrea; in the Americas, it is
most often found in Mexico, Venezuela, and Colombia. Rather surprisingly,
there is small focus in the Yemen, but it seems to be unknown in the rest of
Asia.
The disease can occur at any age, and over 40 million people are known to
be affected, of whom at least 1 percent are now blind. Patients usually live in
areas where rapidly running, shallow streams are the preferred breeding sites
of the black flies that are the intermediate hosts of the infection and that all
belong to the family Simuliidae. These flies need highly oxygenated water in
which to breed. Although various members of the family live in different
places, the disease is epidemic only in riverine areas. One of the African flies,
Simulium damnosum, has been known to fly up to 300 kilometers for breeding
purposes and so is easily able to extend disease to new areas. In South America,
the areas of highest endemicity are usually some 1,000 meters above sea-level,
especially in coffee plantations, but different breeding habits of another inter-
mediate host ensure that in Venezuela mainly the coastal regions are affected.
In those parts of Africa where new dams have been built for hydroelectric
schemes, spread of water often provides new sites for the Simuliidae to breed
and so permits extension of river blindness to previously unaffected popula-
tions. Some of the most fertile valleys in Africa have been completely aban-
doned by the population because of the high incidence of the disease-some-
times as many as 30 percent have impaired vision and more than 5 percent are
blind. The World Health Organization reported in 1966 that in some villages
in Upper Volta more than 25 percent of the population were totally blind.
188 23. Onchocerciasis

Etiology
Onchocerca volvulus is a threadlike filarial worm, the male about 5 cm long
and the female anything up to 50 cm. Although some of them live indepen-
dently in the skin, most of them spend their adult lives clustered in groups being
slowly surrounded by a fibrous and inflammatory reaction that produces firm
dermal nodules up to 5 cm in diameter known as onchocercomata. The adults
cause relatively little trouble; the unpleasant features of the disease are entirely
due to the microfilariae produced by the adult female worm. They exist in
enormous numbers in the dermis, but the life cycle cannot continue unless they
are removed from the skin by one of the Simuliidae that bites an infected host
and ingests the microfilariae along with the rest of its meal. The female fly
bites viciously during the daytime. These flies do not enter houses and curiously
are not much danger to anyone sleeping indoors.
It is in these intermediate hosts that the o. volvulus undergoes the normal
adventures of the filarial family. Piercing the stomach wall, they move to the
thoracic muscles, when, after a series of ecdyses have permitted them to
become infective, they proceed to the fly's proboscis and are returned to the
main host by the bites of the fly. From there they emigrate along the lympatics
into the deeper parts of the skin. About a year later they reach adulthood, start
to breed, and more microfilariae are added to the dermal store in which they
live for up to 3 years. The adult worms have been known to live for 12 to 15
years, producing waves of microfilariae, but finally they too die off. If the
patient has had no further bites from an infected fly the disease will very slowly
have reached a natural cure; by then the clinical features will be well
established.
Onchocerca volvulus is one of the few filariae that has been known to tra-
verse the placenta. In endemic areas, where most of the population is contin-
ually reinfected by repeated bites, it has been said that as many as 5 percent
of the children are actually born with the disease.

Clinical Features
In a fully established case, both skin and eyes are majorly infected.

Skin Changes
Starting with an itching that is later associated with erythema, onchodermatitis
shows numerous small papules often confined in the first instance to a single
area on the trunk or to a single limb. These have at times been mistaken for
scabies. Later, large parts of the skin become lichenified (Figure 23-1), and
Clinical Features 189

FIGURE 23-1 Lichenified le-

sions with scaling and depig-
mentation. (Courtesy Anezi
Okoro, M.D., Enugu, Nigeria.)

destruction of elastic tissue leads to atrophy and the production of a lax. wrin-
kled skin, which, if it affects the face, gives a permanently aged appearance.
Further changes in the skin vary in different parts of the world. In the
American form of the disease, onchocercomata appear most frequently around
the head and neck, perhaps because the Simulium ochraceum (the only mem-
ber of the Simuliidae that is not black) bites mainly this part of the body. In
these countries, gross skin changes occur less frequently than in Africa, but
sometimes pseudoerysipelas may occur on the face (erysipela de la costa (Fig-
ure 23-2). When the lesions lose elasticity and ultimately atrophy, they may
take on a form of leonine facies (mal morado).
In the African type of disease, skin changes of the lower limbs, scrotum, and
190 23. Onchocerciasis

FIGURE 23-2 Dermatitis on face

known as erysipela de la costa.
(Courtesy Arturo Tapia, M.D.,
Panama City, Panama.)

lower abdomen may be extremely marked. The associated onchocercomata

appear most often near the iliac crest; perhaps because the S. damnosum usu-
ally attacks the lower half of the body. As the years go by, residents in endemic
areas will have an increasingly large microfilarial load, which will cause more
and more severe skin changes. Destruction of the skin's elasticity causes baggy
saccular extensions of the skin, festooning the groins and known as hanging
skin. The more severely affected areas often become achromic. This depigmen-
tation is not necessarily persistent. Often the color returns (as it may do in
vitiligo) by extension of pigment from the pilosebaceous follicles. The outward
spread of the scattered brown spots in a white background is sometimes called
leopard skin.
Onchocercomata are usually rubbery, but after the death of the resident
worms a sterile abscess may form, which can be recognized by the development
of fluctuation in a previously solid nodule.
Lymphadenitis is sometimes found in the hanging skin, while in other
patients, inguinal or femoral hernias, hydroceles, and scrotal enlargment may
develop. Elephantiasis of the scrotum and limbs has been reported from some
parts of Africa and South America, but in other parts it is rare or nonexistent.
Clinical Features 191

FIGURE 23-3a,b Infected eyelids leading to blindness. (Courtesy Arturo Tapia,

M.D., Panama City, Panama.)

Eye Changes
The most disastrous aspects of this disease result from invasion of the eye by
microfilariae (Figure 23-3). This most probably occurs by extension from
infected eyelids, as blood-borne spread is unusual. Microfilariae of the O. vol-
vulus, unlike those of other filariae (Wuchereria bancrofti, Brugia malayi, etc.),
do not seem to like living in the bloodstream.
192 23. Onchocerciasis

When the microfilariae die, a toxin is released that causes direct damage to
adjacent tissue. Often, vascular changes affect the eye, producing first a punc-
tate keratitis followed by a sclerosing keratitis and an anterior uveitis. Changes
in the posterior eye are usually not visible because of the anterior uveitis, but
they can include optic neuritis and finally optic atrophy.

Natural History
The natural history of the disease varies according to whether or not the patient
lives continually in an endemic area. People who leave the area after a single
infection will show changes that reflect the course of the life of the parasite.
For 12 to 18 months after a first infection, while the worms are reaching matu-
rity, no signs or symptoms will appear. After the female begins to produce
microfilariae, which enter the skin, an initial itching in the affected areas is
followed by the appearance of pruritic papules sometimes called craw. The
adult worms continue to produce more microfilariae, and for two or three years
(after which the first wave dies out), the numbers will increase steadily and
spread extensively through the skin. After producing microfilariae for some 12
to 15 years, the adult worms finally die off. If there has been no reinfection the
disease stops. During this time, one or more onchocercomata are likely to have
developed around the worms. These will help to focus the attention of physi-
cians outside the endemic sites on the possibility of the disease.
The more severe classical lesions are seen in patients who have been infected
on many occasions: lichenification, pigmentary changes, and hanging skin are
found only when regular superinfection by infected Simuliidae compound the
number of microfilariae. As a result of this, the skin signs become more exag-
gerated, the eye changes more severe, and the disease has no chance of dying
out.
At the same time, the enormous increases of microfilariae in the skin
increases the probability that the flies will be infected whenever they bite, so
there will be a greater likelihood that every fly's bite will be infective.

Differential Diagnosis
In the early stage of the disease, particularly in people who have returned home
after a visit to the tropics, onchodermatitis may be confused with scabies or
pyoderma, while later lichen simplex chronicus, vitiligo, or cutis laxis may all
be misdiagnosed at some time or other. Even lepromatous leprosy may be sus-
pected if the patients develop mal morado.
Onchocercomata are usually easy to recognize. If there are no other signs
and symptoms, they may be mistaken for a fibroma or a lipoma. A form of
hanging skin may also be seen in pseudoxanthoma elasticum.
Treatment 193

A combination of these signs, especially when associated with eye changes,

makes the diagnosis hard to miss.

Investigations
When the diagnosis is suspected, a search for microfilariae is essential. The
skin snip (see Appendix one) easily demonstrates the highly motile microfilar-
iae, but if no microscope is available. another technique may be used to prove
their presence. It is the Mazzotti test, in which 50 mg of diethylcarbamazine
is given by mouth. Within six hours, a sharp increase in pruritis is associated
with the rapid development of small new papules.
Recognition of microfilariae in the anterior chamber of the eye can be
helped by an ophthalmoscopic or slit-lamp examination. When the eye has
been long blind, these organisms are no longer detectable.
A white blood count will invariably show a high eosinophilia. Such a finding
simply suggests the presence of a parasite and can be no more specific, but the
absence of eosinophilia in a patient suspected of having the disease will be evi-
dence against such a diagnosis.
Immunologic tests are of little value because they not only cross-react with
other filarial infections, but almost everybody in an endemic area will show a
positive reaction. If a microfilarial antigen from O. volvulus is available, a pos-
itive reaction may be diagnostically helpful in an early case in someone living
in a nonendemic area (see Appendix two).

Treatment
As for other filarial diseases, diethylcarbamazine is the drug of choice. Two
4 mg/kg doses three times a day for 14 days is highly effective against the
microfilariae, but is not sufficient to kill the adult worms. Repeated courses are
necessary to cover the remorseless production of fresh waves of microfilariae
from adult females loose in the skin or living in the onchocercomata.
As the destruction of intraocular microfilariae may lead to a severe reaction
in the eye, it is suggested that the first course should start slowly.

Day 1 50 mg once (in effect this is a Mazzotti test)

Day 2 50 mg twice
Day 3 50 mg three times
Day 4 100 mg three times
Days 5-14 250 mg three times daily

Even if an ocular reaction is not expected, mydriatics and steroid eyedrops

should always be available.
194 23. Onchocerciasis

As an alternative treatment, suramin is more active against the adult

worms, but it has to be administered with care. Its dosage and limitations are
considered on page 198.
Most patients do not have many onchocercomata. and, as they are not firmly
attached to adjacent tissue their surgical shelling-out is a practical possibility.
If the majority of adult worms can be removed in a single operation there will
be a better chance of rapid cure. In some areas, mass "nodulectomy" has been
followed by a reduction in the incidence of new cases.

Prevention
Mass treatment of communities must be done with great care and suitable
medical back-up, as some people submitted to such prophylaxis may already
be infected, and a severe reaction to diethylcarbamazine can cause severe oph-
thalmic complications.
Destruction of the Simuliidae has been attempted by spraying DDT from
an aircraft over the resting places of S. damnosum. There has so far been no
evidence of DDT resistance.

Selected Readings
Buck, AA: Onchocerciasis: Symptomatology, Pathology, Diagnosis. Geneva, WHO,
1974.
Connor, DH: Current concepts in parasitology: Onchocerciasis. N Engl J Med 1978;
298:379.
Nelson, GS: Onchocerciasis. Adv Parasitol 1970; 8: 173.
Ree, GH: Onchocerciasis treated with diethylcarbamazine. Br J Dermatol 1977;
97:551.
Somorin, AO: Onchocerciasis.lnt J Dermatoll983; 22:182.
CHAPTER 24

Filariasis

Newcomers to the problems caused by filariae may be excused if they find the
nomenclature more than usually confusing, as not all the diseases caused by
these nematodes are called filariasis. A filarial worm known as Onchocerca vol-
vulus causes onchocerciasis and the Loa loa filaria produces loiasis. The con-
dition that is normally known as filariasis is caused by representatives from the
genus Wuchereria and from the genus Brugia (Brug called them Wuchereria,
but the name was changed in his honor). Only one form of Wuchereria is
known (Wuchereria bancrofti). Although many forms of Brugia have been rec-
ognized, most of them are not pathogenic, and only B. malay; and B. timor;
cause natural infection in humans.
W. bancrofti produces Bancroftian filariasis and is found most often in the
tropical areas of Africa, Asia, and Oceania. It was once epidemic in some parts
of the United States but is found now only in the Caribbean and nearby parts
of Central and South America.
Malayan filariasis, caused by B. malayi, occurs in the coastal areas of
Southeast Asia, spreading north to Japan. It has only recently disappeared
from north Australia. Filariasis also occurs in certain Pacific Islands, but par-
asitologists do not agree as to whether it is caused by W. bancrofti or a different
organism called W. pacifica. The disease can affect anyone in the endemic
areas at any time; sex, age, and race are no bar to a sting from an infected
mosquito.

Etiology
The female W. bancrofti is up to 10 cm long, the male about half that size.
These white, threadlike worms are usually found in lymphatic vessels and
lymph nodes, the sexes being coiled together and separable only with difficulty.
196 24. Filariasis

B. malayi is practically indistinguishable from W banerofti; the B. malayi

females seem identical, but perhaps are somewhat shorter, and the difference
between the microfilariae is rather more marked. Differentiation is of little use
to a clinician however, treatment is the same for both infections.
The final host of these filariae is humans, in whom they mate in the con-
nective tissue and lymphatics. the female laying eggs in which larvae have
already formed. To develop further, the microfilariae must enter the blood-
stream, where they are taken up by certain types of mosquito. Many species
of Culex. Aedes. and Anopheles have been shown at various times and in var-
ious places to serve as the intermediate host.
Within a few hours of ingestion, the microfilariae bore their way out of the
stomach and migrate into the thoracic muscle, where following two ecdyses,
they turn into an infective form that then moves to the mosquito's proboscis,
leaving while the mosquito is taking another blood meal. Having returned to
their final host, they proceed to a suitable situation in a lymphatic vessel (espe-
cially the lymph nodes, the testis, and the spermatic cord), where they may live
for a year or more. Toward the end of this time they mature, and the cycle
recommences.
The B. malayi undergoes an essentially similar cycle, but it is known that
on occasion it may invade cats and monkeys as reservoir hosts.
For reasons that are unknown, after the eggs have been laid in humans the
microfilariae only appear in the bloodstream at specific times; W banerofti is
detectable between 10 P.M. and 2 A.M., except in the Polynesian islands, where
they are usually found in the blood in the daytime. B. malayi may show peri-
odicity (around midnight), but sometimes it is subperiodic and appears in the
evening between 6 and 8 P.M.

Clinical Features
In the early days of infection, an acute inflammatory response may develop,
with fever and malaise. Later, orchitis or epididymitis appear if the genitalia
are involved (usually in Bancroftian filariasis), while lymphadenitis and lym-
phangitis of the lower limb is more often seen in Malayan infection. Not infre-
quently, an urticarial eruption occurs in association with eosinophilia.
Slowly, enlarged lymph nodes, lymphedema, or hydrocele may develop, and
there may be repeated attacks of lymphangitis caused by dying worms. As the
condition becomes more fully established, increasing lymphedema is followed
by elephantiasis (Figure 4-1), and the lower limb may ultimately produce a
verrucose hyperplasia known as mossy foot.

Natural History
Most infected individuals never have any signs or symptoms. Sometimes the
disease is recognized only by accidental detection of a microfilaremia. The
development of pathologic changes in the lymphatic system only occurs in a
Natural History 197

FIGURE 24-1 Long term infes-

tation results and fibrosis,
verrucous formation, and ele-
phantiasis. (Courtesy Mohsen
Soliman, M.D., Cairo, Egypt.)

small percentage of hosts, probably because of an immunologic reaction to

infection.
Lymphadenitis and lymphedema of the scrotum or limb, usually unilateral,
may not appear until the infection has been present for many years. Blockage
causes transudation of lymph into the connective tissue, and a subsequent pro-
liferation of fibrous tissue results in elephantiasis. The swelling, which may be
enormous, is usually smooth. Only rarely does mossy foot complicate the
picture.
Other lymphatic complications may be seen: chyluria, chyloceles (in the
scrotum), or even chylothorax.

Tropical Eosinophyllic Lung

Sometimes patients may complain of cough and malaise and are found to have
a diffuse pulmonary infiltration, as well as a very high eosinophilia. It is
believed that many of these patients are suffering from an unrecognized filar-
iasis, but in many cases it is not possible to confirm the presence of
microfilariae.
198 24. Filariasis

Differential Diagnosis
In endemic areas, fevers, malaise, insomnia, fatigue, urticaria, lymphangitis,
lymphadenitis, lymphedema, hydrocele, or chyluria may all indicate a filarial
infection, but if the filaria are not detected such cases may easily remain unrec-
ognized. Those patients with a filarial elephantiasis are more likely to be diag-
nosed, but only if the search for microfilaria is done at a suitable time, and
even then the tests are often negative if the disease is of long standing.

Investigation
Eosinophilia may suggest that a parasite is present, but it is only in tropical
pulmonary eosinophilia that extremely high percentages have been recorded
(up to 70 or 80 percent). The common forms of filariasis stimulate an eosino-
philia of only 10 to 15 percent which is of no specific diagnostic help.
Recognition of the organisms in the blood is the most helpful finding. Thick
blood films may be stained with Giemsa stain, but this is not really necessary
as the microfilariae may be detected with a hand lens if the smear is made with
infected blood. By the time lymphedema and elephantiasis have appeared,
microfilaremia is no longer dependable.
In such cases it may be possible to recognize parts of the worm in a biopsy
from an inguinal lymph node or some other infected tissue, but usually the
section only shows evidence of chronic infection with epithelioid cells, giant
cells, and tissue eosinophilia, and no specific diagnosis can be made.
A skin test made from the dog heartworm Dirofilaria immitis has given
variable results. Similar tests made from W. bancrofti and B. malayi can cross-
react with intestinal helminths and cannot be relied on as a diagnostic aid.

Treatment
Most of the symptoms that cause a patient to be diagnosed as having filariasis
are not helped by successful antifilarial treatment. Diethylcarbamazine (4 to 6
mg/kg) daily for 14 days is highly effective against the microfilariae, but
destruction of the adults will require a further two to three weeks. Mebenda-
zole 1 g twice daily for 28 days is sometimes used instead.
If diethylcarbamazine is not successful, suramin may be given against the
adult worms. It is nephrotoxic and should not be used by people with albumin
or casts in their urine. Other patients can be given suramin intravenously (1 g
in 10 ml water) once a week for eight weeks, but only if they do not respond
adversely to a test dose of 200 mg.
In some cases, repeated febrile episodes will require systemic corticosteroids
for several weeks, while any secondary infection that develops will n~ed appro-
priate antibiotics.
Prevention 199

Local treatment of lymphedema may be helpful; the swelling can be reduced

by firmly binding a previously elevated limb, starting from the foot and includ-
ing the whole leg. Treatment must be maintained for several weeks and pref-
erablya two-way stretch elastic bandage should be used (such as Elastoplast).

Prevention
In most parts of the world, mass treatment can be expected to eradicate filar-
iasis, as there is usually no other reservoir host but humans. Unfortunately,
patient acceptance is not good because the severe reactions that are sometimes
produced by diethylcarbamazine often dissuade many people from accepting
medication. Partial success has been obtained in some areas by adding the
medication to cooking salt.
The other approach to prevention is to undertake mass control of the mos-
quito vectors by suitable techniques. Dieidrin and DDT sprays may be used
against those Anopheles that are not resistant. Careful campaigns to instigate
village control of Aedes breeding sites within 100 meters of the village will
diminish the possibilities of Aedes transmission because of its short flight range.

Selected Readings
Joe, LK: Occult filariasis: Its relationship with tropical pulmonary eosinophilia. Am J
Trop Med Hyg 1962; 11:646.
Maegraith, B: Adams and Maegraith: Clinical Tropical Diseases. London, Blackwell
Scientific, 1980, pp 64-82.
Nelson GS: Current concepts in parasitology: Filariasis. N Engl J Med 1979;
300:1136. t
Neva, FA, Ottesen, EA: Tropical (filarial) eosinophilia. N Engl J Med 1978;
298:1129.
Richards, RN: Verrucous and elephantoid lymphedema. Int J Dermatol1981; 20: 177.
CHAPTER 25

Dracunculosis

Dracunculosis, also known as dracontiasis, dracunculiasis, or guinea-worm dis-

ease, is one of the oldest known diseases, accounts having been found in Egyp-
tian as well as in early Greek and Roman writings. It has been suggested that
the guinea worm was the "fiery serpent" that chased the Israelites during their
wanderings around the Red Sea. It is also believed that the physician's symbol,
the caduceus, which has a worm around a stick, may well have originated as a
depiction of the guinea worm.
The disease exists mainly in the drier parts of the tropics and subtropics of
Africa, the Indian subcontinent, and the Middle East. It also appears in certain
parts of the Caribbean and South America.

Etiology
The disease is caused by the Dracunculus medinensis, which reaches sexual
maturity in its final host, humans. Having mated, the male dies and the female
migrates slowly to the lower part of the leg, where it moves to the surface and
apparently secretes a toxin that causes a blister to develop. This breaks down
when the leg is cooled with water, the worm lying under this erosion discharges
millions of larvae by repeated contractions of the uterus, which takes up most
of its body. The female worm can be more than 60 cm long but is only 2 to 3
mm in diameter.
After exposure to water, the embryo larvae uncurl and become active. They
only survive a few days in clear water but last for up to two to three months in
muddy water or moist soil. If the soil dries up completely, the larvae will
become active again when more water arrives. In this water certain small crus-
tacea of the genus Cyclops are attracted by the movement of the larvae and
ingest thousands of them. Within a few weeks the larvae become infective.
Differential Diagnosis 201

The final host (humans or certain animals) swallows these crustacea by

drinking contaminated water. In the host's alimentary tract, the Cyclops is
destroyed, releasing larvae that migrate through the gastrointestinal mucosa
into surrounding tissue. There, the process of maturation takes up to a year
before the cycle starts again.

Clinical Features
During the phase of maturation, there is little if any evidence that the patient
is infected. When the traveling female arrives in the leg (occasonally it can be
found in the scrotum or elsewhere), the skin begins to itch, and a red papule
develops rapidly into a blister that may be five or more centimeters in diameter.
The base is indurated and edematous. The bulla soon erodes, leaving an ulcer
with a central punctum through which the worm protrudes when provoked by
immersion in water that is below body temperature. The uterus is extruded
through the punctum and discharges a cloudy larvae-containing fluid into the
water or over the ulcer. When the blister begins to appear, there may be an
associated systemic reaction-general malaise, diarrhea, vomiting-probably
in reaction to the toxin that enables the worm to create a bulla.

Natural History
The first clinical evidence that a person has dracunculosis is usually the appear-
ance of a papule on the lower portion of the leg that rapidly develops into a
bulla. It may at that time be possible to palpate the worm lying in the subcu-
taneous tissue (Figure 25-1).
It is not unknown for the worm to become damaged during its migration,
particularly when it has arrived in the subcutaneous tissue but has not yet
caused a blister. If this happens, cellulitis or even a sterile abscess may develop,
which, if it occurs near a joint, may cause effusion or arthritis. It has been
reported that some patients develop a fibrosis constricting the tendons of the
legs.
On other occasions, secondary infection of the ulcerated bulla will produce
a cellulitis around the affected part. When the worm is superficial enough to
be palpated, it can also be visible (especially if the scrotum is involved), and
there may be a superficial resemblance to larva migrans.

Differential Diagnosis
The classic presentation of a single large blister with an erythematous base on
the lower part of the leg or the foot can rarely be mistaken for anything else,
particularly if the limb is put into a bucket of cold water. There is a consequent
cloudy discharge of innumerable larvae.
202 25. Dracunculosis

FIGURE 25-1 The guinea worm exuding from the ankle, which is indurated and ede-
matous. (Courtesy Anezi Okaro, M.D., Enugu, Nigeria.)

There is much more of a diagnostic problem if the classical lesion has not
yet developed and a subcutaneous abscess appears elsewhere. Evacuation of the
pus will usually show that necrosis has been associated with the presence of a
dead guinea worm. If a joint (knee or ankle) is affected, it may be wrongly
taken for rheumatism, traumatic synovitis, or even sciatica, but these relatively
unusual presentations can be detected by an x-ray of the area, which usually
shows a calcified worm in the tissue.
The superficial resemblance to larva migrans does not usually cause diag-
nostic problems, as the history is not the same. In larva migrans, no worm can
be felt in the skin.
Sometimes the bulla is not seen and the patient seeks attention for an
infected ulcer, which may be confused with anything from pyoderma to a
Buruli ulcer. The palpation of the worm will show the true diagnosis.

Investigations
Up to 15 percent eosinophila may be found in many cases. The diagnosis can-
not be based on this finding alone, but it may be of help in confirming suspi-
cions based on other symptoms.
Live, unruptured worms in the deeper tissues usually cannot be detected,
but if the worm dies, they may become calcified and so demonstrable on x-ray.
More often, however, dead worms are simply absorbed.
Prevention 203

It is rarely necessary to biopsy a skin lesion. If this is done, evidence will be

found of acute or chronic infection, including giant cells, epithelioid cells, and
some eosinophils. Some part of a degenerating worm may also be present.
Some workers have used an intradermal test with an antigen made from the
dried powdered worm, but these investigations have not found general
acceptance.

Treatment
Removal of the worm is obviously the best way to correct the situation and the
traditional folk practice, still used in many areas, is to attach the protruding
worm to a stick or a match and slowly to wind it out 2 to 3 cm at a time until
the whole worm has been removed. Unfortunately, not only may the worm be
torn by an enthusiastic operator but sometimes the winding will push eggs back
into the worm until it bursts. In either case, the subsequent painful, angry
inflammation of the subcutaneous tissue can become secondarily infected and
often needs to be treated with systemic antibiotics.
It is better to treat the condition by systemic therapy; metronidazole can be
given (25 mg/kg daily for ten days). Thiabendazole is equally effective but its
unpleasant side effects make it less acceptable.
Urticarial elements are sometimes seen. They respond well to antihista-
mines provided the dracunculus is suppressed at the same time. Surgically ori-
ented doctors have sometimes preferred to dissect the worm out, but this is not
easy if, as may happen, several worms are present at the same time.

Prevention
The disease usually occurs in areas where the same sources are used for wash-
ing and drinking. It will never be eliminated until infected individuals stop con-
taminating their water supply. Provision of good clean piped water is therefore
a prime necessity. If this is not possible, attempts have to be made to destroy
the secondary host (the Cyclops) by suitable treatment of water. They can be
killed by heating the water before it is drunk (a difficult solution in many parts
of the world) or the source can be treated by a molluscicide such as Temephos,
one part per million. Wells can also be treated by perchloron, a bleaching pow-
der substitute. It is claimed that if the barbel fish, which feeds voraciously on
the Cyclops, is introduced into the water supply, guinea-worm disease disap-
pears from the neighborhood.
If such public health precautions are not carried out, the population of
204 25. Dracunculosis

infected areas is liable to be affected many times, as there is no immunologic

protection against the worms or their larvae.

Selected Readings
After small-pox, guinea worm?, editorial. Lancet 1983; 1: 161.
Kale, 00: Clinical evaluation of drugs for dracontiasis. Trop Doct 1977; 7:15.
Muller, R: Dracunculus and dracunculiasis. Ad Parasitoil971; 9:73.
Muller, R: Guinea worm disease: Epidemiology, control and treatment. Bull WHO;
1979; 57:683.
CHAPTER 26

Schistosomiasis

Ten percent of the world's population is infected with schistosomiasis, which

has been known in Egypt for 4,000 years. Often called bilharzia, it is a major
cause of ill health in the tropics and subtropical regions. In 1851, Dr. T. Bilharz
first described the adult form of schistosomal helminths, or flatworms, living in
the portal veins of humans, but not until early in the twentieth century was it
recognized that different forms of watersnails act as intermediate hosts for the
different forms of schistosomiasis. Three of these worms can affect humans:
Schistosoma haematobium, which is prevalent in Africa and the Middle East,
S. mansoni, which occurs both in Africa and South America, and S. japoni-
cum, which is found in the Far East. In certain parts of Africa not only do S.
haematobium and S. mansoni exist together, but it is not unknown, particularly
in the Sudan and in upper Egypt, for patients to be affected by both parasites
at once.
As the snails that are the intermediate hosts for these nematodes prefer to
live in fresh water, a recent change in the method of irrigation in Egypt and
elsewhere has encouraged spread of the disease. Previously, the basin method
of irrigation (depending on the rise and fall of the water level in the rivers) did
not favor these snails. Since the building of the Aswan Dam, however, the irri-
gation has become perennial, and the hosts of both S. mansoni and S. hae-
matobium have thrived and extended through much of the Nile Valley. The
snails prefer the water to be alkaline and to contain calcium; both these needs
are fulfilled in many parts of South America, but as they do not like cold water.
Bilharzia cannot be acquired outside the tropics or at an altitude of much more
than 1,500 meters.
206 26. Schistosomiasis

Etiology
Only three species of Schistosoma cause serious disease. In S. haematobium
humans are the main reservoir and only rarely has this fluke been found in
other animals. This is the organism that causes vesical or urinary bilharzia. S.
mansoni has been found in other primates as well as in humans and is the cause
of intestinal bilharzia. S. japonicum is limited to the Far East and affects dogs,
cats, rats, mice, cattle, buffalo, pigs, and many other animals besides humans.
It has been estimated that in the Phillipines some 25 percent of schistosomiasis
is caused by contamination of water supplies by such animals. In China, rats
living on the river banks are responsible for the spread of the disease and the
use of human feces for fertilizer is an additional public health hazard.
All of these organisms have essentially the same life cycle. Cerceriallarvae
from many other schistosomes are known to penetrate the skin of human beings
who are unwise enough to put themselves or their lower limbs into infected
water but most of these larvae cannot mature in humans and soon die off.
The cerceria from the three pathogens do not die but move via the lym-
phatics into the bloodstream and travel through the heart and lungs into the
hepatic portal vessels, in which they mature. Some 100 to 500 J.L in length, the
leaflike male rolls up to form a tube that encloses a cylindrical female. Having
paired, they migrate to the veins of their choice, S. haematobium going to veins
around the bladder while the others prefer to live in the mesenteric vessels. In
these sites, they lay many hundreds of eggs each day that penetrate through
the walls of the intestine or bladder and ultimately may be found in the urine
or feces, along with which they reach the outside world. When the ova enter
water, a myracidium is hatched that can live for about 48 hours. The cycle
cannot continue unless the myracidium is swallowed by a suitable snail, in
which it develops into a tube-shaped "mother" sporocyst from which emerge
parthenogenitically numerous "daughter" sporocysts, which produce infective
cercarial larvae. These pass out of the respiratory aperture of the snail and
reenter water, where, if they encounter their main host, they cast their forked
tails, penetrate the skin, and complete the cycle.

Clinical Features
Various dermatologic manifestations accompany different stages of infection
and can be divided into three types.

Invasive Schistosomiasis
When the cerceriallarvae penetrate the skin for the first time, an inflammatory
reaction must be expected (especially to those avian species that penetrate the
skin only to die oft). A mixture of irritant and allergic manifestations, some-
Natural History 207

times called schistosome dermatitis, starts with itching as the cercariae touch
the skin. As the water evaporates and penetration is completed, an increased
pruritus is associated with macules, papules, and excoriations that soon become
pustular and crusted. The dermatitis increases in severity for two or three days
and subsides within two weeks. On rare occasions, when these lesions are seen
by a physician, they are usually given a nonspecific name such as swimmer's
itch. The true diagnosis is made only in retrospect.
Patients who live in endemic areas and are continually being reinfected do
not show these early manifestations, having probably acquired an immunity.

Urticarial Schistosomiasis
This too is usually only found in patients who have not previously been infected.
Some four to six weeks after cercarial invasion, the flukes mature, and fever,
arthralgia, cough, eosinophilia, and lymphadenopathy develop, probably
because the sudden appearance of thousands of ova produce an immunologic
cross-reaction with antigens that have developed as a reaction to the growing
worms. On the skin, red macules, itching papules, urticaria, and even angi-
oneurotic edema can be seen. This reaction is most severe with S. japonicum.
In Japan, it is called urticarial fever or Katayama disease.

Cutaneous Schistosomiasis
This will develop after the systemic signs of bilharzia begin to appear.
Although ova most frequently invade the bladder or the gut, they may be found
anywhere in the neighborhood, and in any site they may provoke a slowly grow-
ing granuloma. Sometimes these lesions are seen in the skin (especially the
perineum and adjoining genital region). A fibrotic papilloma with draining
sinuses and fistulae may appear, which in Egypt have been known to extend
through the crural folds to affect the labia and clitoris and even cause a pseu-
doelephantiasis of the vulva (Figure 26-1).
As the infections become more severe, granulations may form around the
umbilicus if the flukes have invaded the periumbilical veins (Figure 26-2) and
hard, flat papules appear on the chest that later coalesce to form a skin-colored
plaque. Later still, a watering-can perineum may result from fistulous connec-
tions between the bladder and the skin.
Dermatologic manifestations of schistosomiasis are rarely diagnosed until
systemic disease has become recognizable.

Natural History
The first symptom of urinary schistosomiasis recognized by the patient is
hematuria, particularly toward the end of micturition. Microscopy of the uri-
nary sediment shows blood cells and the diagnostic ova. As the disease slowly
208 26. Schistosomiasis

FIGURE 26-1 Papules and fi-

brosis. (Courtesy Mohsen Soli- '
man, M.D., Cairo, Egypt.)

progresses, cystitis, bladder hypertrophy, hydronephrosis, calculus formation,

ureteric obstruction, and urinary fistulae may all develop, and ultimately renal
tract infection and uremia may lead to death.
S. mansoni and S. japonicum infections start with typhoid-like symptoms-
bloody stools and hepato-splenomegaly-but in the early stages ova are not to
be found in the feces. As time goes on, acute intestinal complications develop
as a result of the ova penetrating the wall of the gut, and dysenteric fever and
abdominal pain may last for many months. These symptoms seem to be more
prominent in South America than they are in Africa. Later, polyps and pap-
illomata appear in any part of the colon. If they extend to the rectum, soft,
friable, granulomatous lesions appearing at the anus can spread to the
perineum.
The disease shows little tendency to natural remission. It becomes more and
more severe, particularly in patients who are repeatedly infected when fishing,
swimming, or bathing in infested water. Anemia, cirrhosis of the liver, uremia,
and malignant degeneration in the chronically infected areas may all take their
Differential Diagnosis 209

FIGURE 26-2 Swelling and drain-

ing sinuses in groin. (Courtesy
Mohsen Soliman, M.D., Cairo,
Egypt.)

toll unless satisfactory early treatment is available. It must be remembered that

severe symptoms affect only a small portion of the millions of infected people,
and carriers of the disease do not seek medical assistance.

Differential Diagnosis
Invasive schistosomiasis may easily be confused with the cercarial dermatitis
caused by those other schistosomes that do not cause systemic disease, but only
time will tell whether or not a pathogen is involved. If newly infected patients
take their invasive schistosomiasis back to the United States, they may be
thought to have chiggers. Although both scabies and onchocercal dermatitis
may look similar, they have a wider distribution and are not limited to sites
that have been immersed in water.
Urticarial fever may be mistaken for other sorts of toxic erythema or urti-
caria and even for allergic vasculitis. The granulomatous reactions to schisto-
210 26. Schistosomiasis

somal ova in the skin will be diagnosed only if the ova are seen in a biopsy
specimen.

Investigations
It is most unlikely that invasive or urticarial disease will ever be diagnosed
other than retrospectively, and investigations taken in the early stages of infec-
tion are of very little help.
If systemic schistosomiasis is suspected, a search should be made for ova in
the stools or urine. They may be differentiated from each other by the position
of spines on the shell: S. haematobium has a terminal spine at one of the poles
of the oval egg, both S. mansoni and S. japonicum have lateral spines, quite
large in the former and small and barely visible in the latter.
Biopsy of the granuloma will show a chronic inflammatory histology, and,
with luck, the ova will also be found. If the spines are recognizable, the diag-
nosis is completed. A further helpful pointer is that shells of S. mansoni are
acid-fast and the others are not.
Complement-fixation tests, precipitation, and fluorescent antibody tech-
niques are available, but many authorities believe they are of little aid in clin-
ical practice. Intradermal injection of adult worm antigen will produce a pos-
itive reaction in almost every inhabitant of endemic areas. It is of more
diagnostic significance if the test is positive in a patient living in a nonendemic
area who is suspected of having been infected during a visit overseas.

Treatment
In the recent past, different schistosomes responded best to different therapies.
It is now recognized that praziquantel, a heterocyclic pyrazino-isoquinoline, is
effective against all those forms which affect man, being given as a single dose
of 50/mg/kg or two doses of 30 mg/kg at an interval of 12 hours.
If this drug is not available, the treatment of choice against S. hematobium
is metrifonate which is an organophosphorus compound given in doses of 10
mg/kg every 14 days for 3 doses. The alternative treatment for S. mansoni is
oxamniquine 20 mg/kg daily for three days. Neither of these drugs is much
use against the other types of disease.
Until recently, oral niridazole was used against all the parasites, but occa-
sionally it could cause severe toxic effects (especially in patients with hepato-
splenomegaly) and sometimes even caused death from hepatic necrosis. Both
this and hycanthone are now rarely used.
It is a wise precaution when treatment has finished to ensure that the ova
being excreted are no longer viable (see Appendix one). If myracidia are still
found to be hatching from the eggs, a further course of treatment is indicated.
Prevention 211

Prevention
Attempts to destroy snails by molluscicides have not been particularly suc-
cessful. In some communities the introduction of snail-eating ducks to live in
the nearby water has been of some help in reducing the incidence of the disease
in the neighborhood, but the only real way to ensure the eradication of schis-
tosomiasis is by major changes in public health and personal hygiene. Contam-
inated urine and feces must be entirely prevented from entering water in which
human beings immerse themselves.

Selected Readings
Amer, M: Cutaneous schistosomiasis. Int J Dermatol1982; 21:44.
Bayer, HM: Schistosomiasis. Int J Dermatol1980; 19:168.
Gilles, HM: The treatment of schistosomiasis. J Microbiolochem 1981; 7:113.
Jordan, P, Christie, JD, Unrau, GO: Schistosomiasis transmission with particular ref-
erence to possible ecological and biological methods of control. Acta Trop (Basel)
1980: 37:95.
Pearson, RD, Guerrant, RL: Praziquantel: A major advance in anthelminthil therapy.
Ann Int Med 1983; 99:195.
Torres, VM: Dermatologic manifestations of schistosomiasis. Arch Dermatol 1976;
112:1539.
PART Five

Other Dermatoses
CHAPTER 27

Lichen Planus Tropicus

Lichen planus tropicus, also known as lichen planus subtropicus and lichen
planus actinicus, is sometimes confused and categorized with actinic reticuloid.
It is categorized by annular plaques with minimally raised borders and bluish-
brown centers.
Although by definition most of the cases have been reported in tropical
areas, there is increased awareness of this disease. It has been found in the
United States, Italy, and other nontropical countries. The incidence is
unknown, but it does appear to affect patients of all races and both sexes.
It usually begins about the age of 11. Eighty-three percent of the patients
are younger than 41, whereas only 38 percent of patients with regular lichen
planus are that age.
Whether the disease actually exists is open to speCUlation. Lichen planus
itself was first described by Erasmus Wilson in 1869. Over six decades ago,
both John Fordyce in America and Graham Little in the United Kingdom
commented on a peculiar type of lichen planus that existed on exposed areas.
The disease was codified in 1949 by Dostrovsky and Sagher in Jerusalem,
where for 20 years they had followed patients who developed annular pig-
mented patches, generally on the forehead. Lichen planus tropicus is respon-
sible for 30 to 40 percent of the patients with lichen planus in the tropics. The
incidence is slightly higher in women than in men. Some observers have
believed that socioeconomic conditions playa role, since lower- to middle-class
people are aftlicted. Possibly this is due to their excessive exposure to sunlight.

Etiology
The cause of all forms of lichen planus is unknown. Drug reactions and immu-
nologic responses have been postulated for the cause of this papulosquamous
disease, but without confirmation. Sun damage in some form precipitates
216 27. Lichen Planus Tropicus

lichen planus tropicus, as evidenced by the lesions appearing on the exposed

areas, such as the forehead, scalp, and hands. Lesions are known to lessen dur-
ing the cold months.

Clinical Features
Pruritic, red, papular lesions can be found on the forehead, cheeks, the dorsal
portions of the hands and arms, and extensor surfaces of the legs (Figure 27-
la,b). Sometimes the lesions take on an annular appearance. Lesions that are
originally bluish-brown eventually become raised, with a central dell. Some-
times they coalesce and the scaling is minimal (Figure 27-2a,b). The itching is
worse in strong sunlight.
The scalp is affected only when the patient has no protective hair. On occa-
sion, lesions can be found on the covered parts of the body (Figure 27-3) and
in the oral mucosa. The nails do not show the longitudinal ridging character-

FIGURE 27-1a,b Pruritic red

(dark areas) papules on the
a face.
Differential Diagnosis 217

is tic of the regular form of lichen planus. In addition, the fine, lacy streaks
known as Wickham's striae are generally not present.

Natural History
The course of development is slow. Generally, the disease lasts one to two years
but can easily remain for well over a decade.

Differential Diagnosis
The most obvious confusion of this disease occurs with granuloma annulare,
but the morphology and distribution would differentiate the two. Similarly,
basal cell cancer, discoid lupus erythematosus, elastosis perforans serpiginosa,
and porokeratosis of Mibelli head the list of diseases that can mimic lichen
planus tropicus. A variety of lichen planus tropicus has been reported from

b
 218 27. Lichen Planus Tropicus

FIGURE 27-2 Actinic reticu-

loid differs by showing diffuse
lichenification and scaling. (All
courtesy F. Ayala, M.D.,
Naples, Italy.)

Kenya; Lichenoid melanodermatitis seems to differ by disappearing within

eight months. Otherwise, the features are similar.

Investigations
Since the diagnosis is made by inspection, no laboratory tests are necessary,
unless a cutaneous biopsy is taken. Routine staining would show hypergranu-
losis granulosis and thinning and atrophy of the rete ridges, with saw-tooth
acanthosis at the edges. Examination of the dermis may show a bandlike infil-
trate of lymphocytes next to the epidermis.

Treatment
Like the therapy for lichen planus, the treatment for lichen planus tropicus is
not very successful. Topical corticosteroids can reduce the itching, but the dis-
ease will generally take its own course.
Treatment 219

FIGURE 27-3 Lichenification, scaling, and red papules in light exposed and nonex-
posed areas.
220 27. Lichen Planus Tropicus

With more severe itching, systemic steroids can be considered at 30 to 40

mg a day for a two- to three-week period. Antimalarials, such as chloroquine
500 mg a day for two months, can be considered.
Since the condition appears to be triggered by sunlight, the use of a sun-
screen would be indicated.
In any event, the disease generally disappears on its own. Pigmentation can
remain as a sequela.

Selected Readings
Dilaimy, M: Lichen planus subtropicus. Arch Dermatoll976; 112:1251.
Dostrovsky, A, Sagher, F: Lichen planus in subtropical countries. Arch Dermatol
Syphilol1949; 59:308.
Verhagen, ARHB, Koten, JW: Lichenoid melanodermatitis: A clinicopathologic study
of 51 Kenyan patients with so-called tropical lichen planus. Br J Dermatol 1979;
101:651.
Zanca, A, Zanca, A: Lichen planus actinicus. Int J Dermatoll978; 17:506.
CHAPTER 28

Dietary Deficiencies

In the middle of 1983, ministers from 36 member countries of the United

Nations World Food Council were told that of the 500 million Asians who lived
in absolute poverty about 300 million were "endemically undernourished"; that
Africa, which 20 years previously had been self-sufficient in food, has replaced
Asia as the prinicipal recipient of food supplies, and that in Latin America 70
percent of the rural population shared only 35 percent of the rural income and
one in seven was malnourished. Doctors working in western countries should
always remember that starvation is the most widespread deficiency disease in
the world.
It is a common habit in textbooks to enumerate the vitamins that are nec-
essary to maintain health and to describe individual deficiencies, but the
hundreds of millions of people living under starvation circumstances do not
complain of such dermatologic niceties as beriberi or pellagra. Famine, war,
and natural disaster cause a combination of deficiencies in which skin lesions
are the least of the patients' worries, since annually thousands upon thousands
of them die of starvation.
It is only in the more affluent countries that the idiosyncracies of dietary
cranks, the unbalanced intake of the alcoholic, and the pathetic undernourish-
ment of the solitary aged may manifest specific deficiencies of individual vita-
mins. Such conditions may be seen in all parts of the world and are not limited
to the tropical or subtropical areas.

Kwashiorkor
This name was coined by Cicely Williams in 1933, when she described a con-
stellation of symptoms occurring in children with a low-protein diet whose diet
was otherwise balanced, albeit insufficient. The disease may be caused solely
222 28. Dietary Deficiencies

by total lack of protein, but it also affects those whose low intake is further
reduced by recurrent or persistant diarrhea.
An alternative theory has recently been suggested by workers in the Liver-
pool School of Tropical Medicine, who noticed that kwashiorkor frequently
arises when a child, previously the youngest, is superseded at the breast by an
additional younger sibling. Such children not only have a subsequent protein
deficiency, but it is suspected that they may also be affected by an aflatoxin
produced by a mold that commonly affects food in the hot parts of the world.
In the Sudan aflatoxins have been found on food in the markets and even on
plates, and in some children very high amounts have been found in the liver.
This new theory would explain why some children have been known to die
suddenly during the early treatment of the disease-the rapid introduction of
a high-protein diet is dangerous to a damaged liver. Not only is it perhaps wiser
to introduce the protein slowly to a patient with kwashiorkor but search should
be made for a toxoid to stimulate antitoxins to aflatoxin.

Clinical Features
The children are grossly underweight. As the organs of the body fail to develop,
there is first an anemia and then a multiplicity of other symptoms and signs,
including edema of the legs and face, ascites, and a dry, flaky dyschromia of
the skin, sometimes compared to flaky paint. The skin ultimately breaks down,
causing necrosis and atrophy. In most patients the hair thins dramatically and
changes color, so that the fully established case of kwashiorkor shows an under-
developed edematous child with startlingly sparse reddish-yellow hair (Figure
28-la,b).
Associated vitamin deficiencies may be seen, particularly the ocular lesions
(Bitot's spots and keratomalacia) caused by diminished vitamin A intake, while
intercurrent diseases such as bronchopneumonia or gastrointestinal infections-
may cause the condition to end fatally.

Treatment
Patients will respond well to small, frequent feeds of a paste made with
skimmed milk powder supplemented with 20 g of sugar per liter and any avail-
able edible oil (also 20 g per liter). Vitamin supplements should also be
provided.
As the treatment progresses, the edema will disappear in the course of two
to three weeks, during which time, rather alarmingly, the child will lose weight.
After this interlude, when the diagnosis of marasmus may be mistakenly made,
the child improves steadily provided a satisfactorily balanced diet is
maintained.
Treatment 223

b
FIGURE 28-1a,b Kwashiorkor: acute disease in a six-month-old child with scaling,
desquamation, and hyperpigmentation. (Courtesy J. B. S. Coulter, M.D., Liverpool
England.)
 224 28. Dietary Deficiencies

Marasmus

Marasmus is caused by a completely inadequate diet and is the most common

cause of death from starvation in children. Under famine conditions, these
unfortunates are insufficiently breast-fed by undernourished mothers, while
infected food or water given as a dietary supplement may easily cause gastroin-
testinal infections that further reduce the effective diet.
The starving children are grossly underweight and apathetic, with atrophy
of all tissues. They do not show the edema or the discolored hair that is seen
in kwashiorkor.
It must be ensured that food provided for the family is not given only to the
children, as improvement in the diet of the mother is essential if infants are to
be breast-fed. Care must also be taken that dried milk and other dehydrated
foods are mixed with boiled water and administered in clean feeding bottles.

Vitamin A Deficiency
When it was originally described, the condition known as phrynoderma (see
Chapter 29) was attributed to vitamin A deficiency, but it is now doubted that
this is so. Although both retinol and its derivatives, the retinoids, are being
increasingly used in various dermatoses (acne, psoriasis, etc.), there is little
evidence that vitamin A deficiency produces any recognizable skin
abnormality.

Vitamin B Deficiencies
Beriberi
Thiamine is particularly necessary for the maintenance of the nervous system
and the heart. Deficient intake may produce neuromuscular changes (with or
without edema) or cardiovascular conditions. The edematous form, known as
wet beriberi, was common in Southeast Asia, particularly in the prisons of Sin-
gapore and Malaya, but when polished rice in the diet was changed to the
unpolished type the disease rapidly disappeared and is now rare.
Changes in the nervous system may produce wrist-drop or foot-drop, which
can be confused with neural leprosy, but the deficiency is unlikely to produce
any dermatologic change.

Pellagra
This condition is caused by a deficiency of nicotinic acid and is particularly
frequent where maize is the dietary staple. Although it may be associated with
other symptoms, it is classically supposed to show the "three-D syndrome"-
dementia, dermatitis, and diarrhea.
Treatment 225

FIGURE 28-2 Pellagra: scaling and hyperpigmentation on hand.

The dementia is usually mild, amounting to little more than depression, but
sometimes frankly psychotic behavior is seen, which responds rapidly to intra-
venous nicotinic acid. The skin eruption, a dramatic mixture of dryness and
hyperpigmentation, is usually confined to the sun-exposed areas-the backs of
the hands (Figure 28-2) and the face-while classically a well-defined eruption
surrounds the front of the neck to give the "pellagra necklace" (Figure 28-3).

FIGURE 28-3 Pellagra: necklace.

226 28. Dietary Deficiencies

At the same time the mouth and the tongue may become sore and an angular
cheilitis develop. Diarrhea is rarely an early symptom and may not be seen at
all.
It is well known that administration of isoniazid will cause pellagra, prob-
ably because it is so similar structurally to nicotinamide that it competes with
the latter at its site of action. This is of particular importance when under-
nourished patients are being treated for tuberculosis, and the condition must
be especially guarded against when such treatment is being given to those Indi-
ans who are strict vegetarians.

Ariboflavinosis
The main sources of riboflavin are meat and milk. If the dietary intake is so
low that it contains less than 2 mg of riboflavin daily, the tongue will become
raw, the lips sore and fissured, and an angular cheilitis will develop. At the
same time an acute eczematous eruption may appear on the scrotum.

Treatment
As vitamin B deficiencies often appear in combination rather than individually,
it is safer to treat them all with compound vitamin B tablets containing thia-
min, riboflavin, and nicotinic acid.

FIGURE 28-4 Scurvy: note ecchymosis and perifollicular hemorrhages, which can be
confused with purpura. (Courtesy Dr. Thomas Connolly, Philadelphia, Pennsylvania.)
Treatment 227

FIGURE 28-5 Scurvy: the characteristic swollen edentulous gums. (Courtesy Dr.
Thomas Connolly, Philadelphia, Pennsylvania.)

Vitamin C Deficiency
Lack of vitamin C is not particularly common in tropical zones, but in sub-
tropical areas where fresh fruit and vegetables are scarce, scurvy may be seen.
It is probably more frequent in Europe, where it affects those elderly people,
living alone, who limit their diet to what is cheap and easy to prepare and
destroy their vitamin C supply (if any) by boiling vegetables.
Scurvy starts with a loss of weight. Corkscrew hairs appear on the shins
while changes in vascular permeability produce perifollicular hemorrhages that
may be confused with purpura (Figure 28-4). Later, larger ecchymoses are
seen, and if bleeding affects the joints a painful arthritis soon develops. In the
mouth, swollen and perhaps bleeding gums are among the earliest signs (Fig-
ure 28-5).
Relatively small doses of vitamin C (100 mg daily) will soon produce clinical
improvement, but the ecchymoses will fade only slowly and the joints may be
permanently stiffened.

Selected Readings
Brock, JF, Autret, M: Kwashiorkor in Africa. Bull WHO 1952; 5:1.
Meyrick-Thomas, RH, Payne, CMER, Black, MM: Isoniazid induced pellagra. Br
Med J 1981; 283:297.
Sandozia, MK, Haquani, AH, Rajesheri, V, Jasbir,K: Kwashiorkor. Br Med J 1963;
2:83.
Wells, GC: Skin diseases in relation to malabsorption. Br Med J 1962; 2:937.
Williams, CD: A nutritional disease of childhood associated with a maize diet. Arch
Dis Child 1933; 8:423.
CHAPTER 29

Phrynoderma

In 1933, Loewenthal, writing from Africa, and Nicholls, in South India,

described almost simultaneously a condition they both attributed to vitamin A
deficiency. Nicholls suggested the name phrynoderma, meaning toad skin, and
defined it as "a papular dry skin eruption, frequently being accompanied by
mild neuritis and or eye symptoms. The patients are very liable to diarrhea and
dysentery, and when this occurs, the neuritis becomes worse." It was not
unknown for this combination of symptoms to prove fatal.
Since that time, the skin condition has been persistently recognized, more
commonly in the tropics than elsewhere, but nowadays the systemic ill health
that seemed to be an essential accompaniment to the eruption is rarely if ever
found.

Etiology
In 1933, the condition was attributed to vitamin A deficlency, as the skin
lesions were associated with night blindness and xerophthalmia. When an
ounce of cod-liver oil was administered daily to a series of more than 80
patients, all the cases of night blindness got better and all but one of the skin
lesions. Some years later, however, it was reported that not everybody improved
with vitamin A; some only improved when their protein intake was increased
and vitamin B was given. In the 1960s, a discussion arose as to whether the
condition was caused by a general vitamin B deficiency or a specific lack of
riboflavin. Most patients diagnosed as having phrynoderma today are not suf-
fering from any recognizable deficiency, and the etiology remains a mystery.
Differential Diagnosis 229

Clinical Features
In the tropics, most of the patients are under the age of 16. They have dome-
shaped polygonal or circular papules consisting of distended follicles plugged
with keratin, which are on average from 1 to 3 mm in diameter (Fie:ure 29-1).
The eruption is first seen on the extensor surfaces of the limbs, particularly the
knees and elbows, and it slowly spreads to other parts of the limbs but is rel-
atively rare on the trunk or face. Frequently, the papules cluster in more or
less circular patches 3 to 5 cm in diameter. These areas often show obviously
hypopigmented in comparison with the normal skin. Sometimes, especially if
the eruption is unusually extensive, the hypopigmented background is less
clearly noticeable (Figure 29-2).
The original descriptions made great play of the associated symptoms, eye
changes, dysentery, and marasmus, which frequently lead to death. These
other symptoms are not seen today, although the skin lesions seem to be indis-
tinguishable from the original descriptions.

Differential Diagnosis
Phrynoderma is a member of that spectrum of follicular keratoses that ranges
from the small, scaly papules often called keratosis pilaris, which spread dif-
fusely over the trunk and limbs, to keratosis spinulosa, which probably only

FIGURE 29-1 Dome-shaped, plugged papules characteristic of phrynoderma.

230 29. Phrynoderma

FIGURE 29-2 Grouped follicular

keratoses.

FIGURE 29-3 Follicular lesions that resemble lichen spinulosus.

Treatment 231

differs from phrynoderma in that the horny plug protrudes from the follicle in
a spiky way. Sometimes, both the dome-shaped lesions of phrynoderma and
the pointed ones of lichen spinulosus may be seen alongside each other on the
same part of the skin (Figure 29-3).
Pityriasis rubra pilaris has a somewhat similar histologic appearance but is
associated with sufficiently dramatic clinical signs elsewhere for the diagnosis
not to be confused, while lichen planopilaris, if it occurs in the absence of the
diagnostic cicatricial alopecia, may cause problems of diagnosis that can only
be clarified by histologic examination.
The histology shows just what might be clinically expected: a laminated,
horny plug distending the upper part of a follicle.

Treatment
At various times the use of vitamins has apparently been extremely effective
for this condition, but today it seems to respond poorly, if at all, to such ther-
apy. It may even be suspected that, despite the clinical similarities, the toad-
skin eruption seen now has a different etiology than that which was seen in
association with the general state of malnutrition that occurred in Africa and
India during the colonial era.
Mild cases respond slowly to the local application of 2 to 3 percent salicylic
acid and 2 to 3 percent sulfur in a zinc cream base, while larger lesions, more
comedonal in appearance, often improve with the use of 0.05 percent retinoic
acid (tretinoin). This may be too irritating for younger patients, and it can be
diluted with an equal amount of hydrocortisone cream or another of the weaker
corticosteroids.
The condition is rarely seen in patients over 20 years of age, and it is sus-
pected that many cases improve without medical assistance.

Selected Readings
Loewenthal, LJA: A new cutaneous manifestation in the syndrome of vitamin A defi-
ciency. Arch Dermatol Syphilol1933; 28:700.
Nicholls, L: Phrynoderma: A condition due to vitamin deficiency. Indian Med Gaz
1933; 68:681.
Pettit, HIS: Phrynoderma. Int J Dermatol1983; 22:117.
Shrank, AB: Phrynoderma. Br Med J 1966; 1:29.
CHAPTER 30

Brazilian Pemphigus Foliaceous

The words pemphigus braziliensis were used two centuries ago to describe a
bullous disease that was found primarily in Brazil and that has now been rec-
ognized in the adjoining countries of Bolivia, Peru, Venezuela, and Uruguay.
Sometimes known as fogo selvagem (wild fire) and even confused with Tokelau
ringworm (T. concentricum), it is now realized that in many ways the condition
is indistinguishable from pemphigus foliaceous. There are, however, enough
dissimilarities to suggest that Brazilian pemphigus foliaceous may be a distinct
entity. The very high incidence (over 700 cases seen in Brazil in 1974 alone),
the frequent appearance in the young (one-third of all cases start the disease
before they are 20 years old), and the numerous cases with a family history
are all features that suggest the diseases are not quite the same.
Most patients come from the rural areas of Brazil. The state of Sao Paulo
had so many patients that a special hospital was built in the main city, but with
the urbanization of the area, the incidence diminished and now the state of
Goias has the most cases. There is no difference in sex or race of patients, but
there is a predominance of the disease in those people living in agricultural
areas.

Etiology
Like pemphigus foliaceous, the cause of Brazilian pemphigus foliaceous is
unknown. There have been a number of proponents of the theory that there is
a viral etiology. Koch's postulates were in part confirmed when Beutner et al.
produced acantholytic bullae in monkeys that had been inoculated with serum
from Brazilian cases. As is not unusual with diseases that show a distinct
Clinical Features 233

regional localization, insect bites have also been blamed; many patients report
having been previously bitten with borrachudos, a member of the Simuliidae,
well known in Brazil.

Clinical Features
When the disease is fully established, it is characterized by an extensive sym-
metric, scaly eruption (Figure 30-1) amounting almost to an erythroderma
(Figure 30-2). Scattered throughout these patches but perhaps rather more
often found at the periphery are flaccid bullae whose superficial situation in
the epidermis is demonstrated by their brief existence-the roof is rapidly
rubbed off but the scaling and the erythema remain (Figure 30-3).
New bullae continue to erupt and scali ness is widespread, frequently affect-
ing the whole of the scalp and matting the hair, giving a clinical picture similar
to, but more extensive than, tinea amiantacea, which may be followed by a
widespread diffuse alopecia. Large patches of erythema on the butterfly area
of the face may be complicated by hyperpigmentation, while papillomatosis
may be seen on the flexures (axillae, groins, or even the retroauricular folds).
Later, palmar-plantar hyperkeratoses are frequently found.

FIGURE 30-\ Symmetrical scal-

ing lesions. (Courtesy Sebastiao
Sampaio M.D., Sao Paulo,
Brazil.)
234 30. Brazilian Pemphigus Foliaceous

FIGURE 30-2 Diffuse scaling

resembling erythroderma. (Cour-
tesy Sebastiao Sampaio, M.D.,
Sao Paulo, Brazil.

Natural History
The earliest lesions often look more like the Senear-Usher syndrome than a
true case of pemphigus foliaceous, starting as it does with a scaly erythema on
the face, scalp, and the presternal skin on which few if any vesicles are visible;
even at this time, Nikolsky's sign (see Appendix one) is positive. This localized
form may persist unchanged for months or years. Sometimes, it has been
known to resolve spontaneously, the patient having no further trouble.
More often, the eruption extends insidiously, and slowly the classic picture
evolves with erythema, scaling, and bullae anywhere or everywhere on the skin.
At the same time the dermatologic lesions may be accompanied by general
malaise, nocturnal fever, diarrhea, and amenorrhea. Sometimes, secondary
infection of the skin is followed by septicemia and infection in internal organs.
In the extensive presence of such immunocompromised skin, it is not surprising
that viral contamination has been known to cause Kaposi's varicelliform erup-
tion, while scabies, fungal infections, and warts may all complicate the clinical
appearance.
Ultimately, the skin is extensively thickened and hyperpigmented, the nails
become discolored and deformed, the sexual organs atrophy, muscles become
Differential Diagnosis 235

FIGURE 30-3 Typical scaling and

crusitn in a seven-year-old Brazil-
ian boy. (Courtesy Sebastiao Sam-
paio, M.D., Sao Paulo, Brazil.)

weakened, numerous endocrinopathies appear, and if untreated, death follows

in at least 50 percent of the cases.

Differential Diagnosis
Many authors believe that this is simply a variant of pemphigus foliaceous.
Both begin on the face and can initially mimic the Senear-Usher syndrome,
and they continue to be clinically and histologically undifferentiable from each
other. Nowhere else in the world is there an endemic form of pemphigus. Only
the Brazilian disease has a high percentage of natural remissions. These dis-
tinctions are academic, and all patients should be treated. There is so far little
evidence that these diseases, different or not, respond differently to routine
therapy.
Other forms of pemphigus (pemphigus vulgaris, pemphigus vegetans, etc.)
usually have a more rapid course, with large, tense bullae rather than the small
flaccid ones of pemphigus erythematosus-histologically the bulla is sited
closer to the basal layer.
The polymorphic dermatitis herpetiform is, with its symmetrical distribu-
236 30. Brazilian Pemphigus Foliaceous

tion, could perhaps be confused clinically, but it is rare in Brazil, and the his-
tology and immunology are totally different.

Investigations
The diagnosis can be established by histologic examination of a bulla. In all
cases of pemphigus, acantholysis occurs in the epidermis but here the acan-
tholytic split is in the upper part in, or just below, the granular layer. If for
any reason the patient refuses a biopsy, a Tzanck test (see appendix one) will
demonstrate acantholytic cells on the floor of the bulla.
If facilities are available for immunofluorescent studies, direct immunoflu-
orescence will reveal positive pemphigus antibodies. IgG is common and C 3 not
infrequent. Indirect immunofluorescence is usually positive in established cases
but may be negative in the earlier, Senear-Usher-like phase.
It is interesting to note that antiepithelial antibodies have been detected in
healthy people living in endemic areas. This lends credence to the possibility
that the disease is etiologically different from ordinary pemphigus foliaceous.

Treatment
As spontaneous recovery cannot be relied upon, all diagnosed cases must be
treated. It is usually recommended that oral corticosteroids be used, starting
with fairly high doses equivalent to 100 mg of prednisone a day until all new
lesions have been suppressed. The dosage may be slowly reduced until more
bullae start to appear, at which time a mildly raised dosage must be sustained
for a few weeks until diminishing therapy can be reintroduced. Within siJl'
months, it is usually possible to maintain the patient on one or two tablets
a day.
As with all other patients needing prolonged high doses of corticosteroids.
it seems to be wiser to give the drug as a single dose on alternate days. Such
treatment is believed to reduce the side effects of the drug, which may, in long-
term medication, be as dangerous as the disease itself.
An alternative therapy is to give quinacrine 0.3 to 0.6 g daily for several
months, but chloroquine is not so useful.
It should also be remembered that patients are not necessarily exempt from
other diseases. In Brazil more than 10 percent of the patients have associated
pulmonary tuberculosis. It is, of course, imperative that this should be ener-
getically treated. If possible, corticosteroids should be withheld and quinacrine
used until the tuberculosis has been inactivated. In such circumstances, it may
be helpful to supplement therapy with the special tar paint that was used before
the introduction of corticosteroids. It is called jamarsan R and consists of the
following ingredients:
Treatment 237

Sulfur ppt 150 g

Zinc oxide powder 120 g
Boric acid powder 100 g
Calcium hydroxide 100 g
Turpentine 15 g
Crude coal tar 3,000 g
Cottonseed oil 1,500 g

It may be applied twice weekly all over the body for several months.

Selected Readings
Azulay, RD: Brazilian pemphigus foliaceous. Int J Dermato/1982; 21:122.
Beutner, EH, Prigenzi, LS, Hale, W, et al: Immunofluorescent studies of auto-anti-
bodies to intercellular areas of epithelia in Brazilian pemphigus foliaceous. Proc
Soc Exp Bioi Med 1968; 127:81.
Beutner, EH, Wood, GW, Chorzelski, GP, et al: Producao de lesOes semelhantes as
do Penfigo foliaceo pela injecao intradermica am coelhos e macacos, de soros de
doentes com titulo elevado de autoanticorpe. Mem Inst Butantan 1971; 35:79.
Brown, MV: Fogo selvagem (Pemphigus foliaceus): Review of the Brazilian literature.
AMA Arch Dermatol Syphilo/1954; 69:589.
Castro, RM, Roscoe, JT, Sampaio, SAP: Brazilian Pemphigus foliaceus. Clin Der-
mato/1983; 1(2):22.
Martins-Castro, R, Proenca, N, de Salles-Gomes, LF: On the association of some der-
matoses with South American pemphigus foliaceus. Int J Dermato/1974; 13:271.
Sevadjian, C: Nosology of brazilian pemphigus foliaceus. Int J Dermatol 1979;
17:781.
CHAPTER 31

Chronic Arsenical Poisoning

There are three ways in which people may swallow arsenic in sufficient doses
to produce signs of chronic poisoning. First, there may be some criminal inter-
ference in the diet, although the wish to exterminate one's enemies with arsenic
seems to arise less frequently than it did 100 years ago. In any case, it would
be a bungling murderer who gave low doses for such a long time that the vicim
developed chronic arsenism. Second, and also increasingly unusual, medical
practitioners may supply arsenic to their patients as a tonic or as treatment for
psoriasis, lichen planus, or syphilis. Fowler's solution is not a modern form of
therapy, but patients may still be found who were given long courses of ther-
apeutic arsenic 30, 40, or 50 years ago. Quacks have also used arsenic as a
panacea. In Ireland they sold it as a cure for cancer. Finally, there are sporadic
reports of chronic arsenical intoxication following the use of contaminated
drinking water, occurring in groups with a few individuals to a few hundred.
These cases are almost invariably focused around contaminated wells.
In northern Iran dozens of people were affected when a leaking drain from
the public bath affected a series of nearby wells. In the bath, the villagers had
used a locally applied arsenical paste as a pubic hair depilatory. Foci are known
to have occurred in Malaysia in wells that have been sunk in the neighborhood
of tin mines (when tin is removed from the ground, other elements remain in
increased percentages).
Contamination of natural water supply was recognized as early as 1913 in
Argentina and has been reported more recently from Taiwan and from Oregon
in the United States.

Etiology
Although most outbreaks occur in sites where the arsenical content of the avail-
able water is higher than it should be, occasional patients seem to develop
chronic arsenism, when the arsenic in their water supply is within permitted
Clinical Features 239

limits. It is obvious that no one can be poisoned who has no contact with the
chemical, but it may be that there is an individual metabolic trait that plays a
part in the retention of arsenic in tissue. A number of patients with arsenically
induced carcinomata were given arsenic by mouth. The urinary excretion was
lower in carcinoma subjects than in others, suggesting a tendency to increased
storage. This work has not been repeated.
As early as 1888, Hutchison reported six cases of malignancy in patients
whose neoplastic changes were attributed to the therapeutic ingestion of potas-
sium arsenite. In 1922 Leach showed that metastasizing tumors followed
repeated application of potassium arsenite to rat skin. It is possible that these
malignancies were particularly associated with the use of inorganic arsenical
preparations. It is not clear whether the organic trivalent and pentavalent
arsenicals are also to blame. Probably, the arsenic in such formulations is sta-
ble, being attached to a benzene ring, which does not usually liberate organic
arsenic into the system.

Clinical Features
The lesions on the skin usually appear after several years of low-grade arsenical
ingestion; because of this, the condition is rare in children. At first, a slowly
increasing hyperpigmentation appears, affecting large areas of the skin, partic-
ularly on the front or back of the trunk. The scapular areas and limbs are
involved later. This slate-grey pigmentation is usually fairly uniform, but less
frequently it can be patchy. Often, small guttate areas of normal skin are scat-
tered through the diffuse melanosis. They are compared to raindrops on a dusty
road and are sometimes mistakenly taken for hypopigmented areas on a normal
skin; a careful search for the edge of the discoloration will reveal normal skin
for comparison.
Arsenical keratoses develop in every poisoned patient, even if there is little
or no evidence of preceding melanoderms. Scattered lesions on the soles (Fig-
ure 31-1), palms (Figure 31-2), or fingers may look like warts but are usually

FIGURE 31-1 Keratotic lesions

dotting the soles. (Courtesy Ste-
phanie Jablonska, M.D., Warsaw,
Poland.)
240 31. Chronic Arsenical Poisoning

FIGURE 31-2 Keratosis and scal-

ing on the palms. (Courtesy Jer-
ome S. Maliner, M.D., Eugene,
Oregon.)

more protruberant, although punctate lesions are sometimes found. They are
present in such great numbers that confusion with verrucae plantaris is
unlikely. A surprising number of patients have palmar or plantar hyperidrosis,
a finding that has not been explained, but when occurring with multiple kera-
toses is strongly indicative of arsenism.
As time goes on, carcinomas of the skin will develop. They do not usually
start in association with the keratoses, but can be found anywhere on the body.
Bowen's disease, oral leukoplakia, basal cell carcinoma, squamous cell carci-
noma, and keratoacanthoma may all be seen alone or in any combination all
over the skin.

Differential Diagnosis
There is not much problem in reaching a clinical diagnosis of chronic arsenism,
if the history is available; unless arsenic has been administered therapeutically,
almost all the patients will say that other members of their family are involved.
In Iran the community believed the palmar-plantar keratoses to be infectious,
because "if somebody gets it, all his family gets it too." It is also useful to know
Treatment 241

whether a patient comes from an area where other cases of arsenism have been
recognized.
The keratoses have to be differentiated from other forms of plantar kera-
tosis, which usually appear earlier in life, while Darier's disease affects the
trunk as well as the palms. Tylosis palmaris et plantaris is more diffuse, acro-
keratosis verruciformis is more marked on the dorsum of the hands, and epi-
dermodysplasia verruciformis is a generalized disease where there are flat and
elevated warty lesions in many sites.
The slate-grey pigmentation, which in some patients has a more golden
tinge, might be confused with a whole range of hereditary and acquired hyper-
melanoses. Although the raindrop appearance is suggestive of arsenism, other
dyschromatoses may also show a mottled look. The presence of arsenical ker-
atoses clinches the diagnosis.

Investigations
If the suspicion of arsenism has been aroused, analysis of the urine will show
arsenic to be present if the ingestion is continuing, and proof of arsenic remains
in the hair and nails for 2 to 3 years after ingestion has stopped.
The histology, if such facilities are available, will show the types of abnor-
malities that are expected (dyskeratoses, dysplasias, and epitheliomata) but
little or no evidence of their arsenical origin, although Lever suggests that vac-
uolization of epidermal cells (two or three times as large as normal) may be
seen in arsenical keratoses. If such cells occur in considerable numbers in squa-
mous cell carcinoma, the lesion is of arsenical origin.

Treatment
Once started, none of the serious manifestations ever regresses, although there
may in time be a fading of the melanoderma. The gravest complications are
the external and internal malignancies. Clinical attention must be principally
directed to them.
Arsenical keratoses do not respond to topical 5-fluorouracil, and they are
best handled by the local use of 20 percent salicylic acid. Ten percent urea
cream sometimes helps, and we know of patients who smooth down their soles
with sandpaper.
Prophylaxis should be easy in any country, where the public health author-
ities take their work seriously. As soon as a focus of contamination has been
recognized the sources of water must be examined and any that are affected
should be permanently sealed. In the United States, more than 0.05 mg per
liter is considered unsafe, and in Britain the arsenical content of water is not
allowed to excede 0.1 mg per liter. A reliable piped water supply must be pro-
242 31. Chronic Arsenical Poisoning

vided for the area and the inhabitants must be continually reminded that con-
taminated water is not improved by boiling.

Follow-up
Patients whose poisoning ceased many years before will still show melano-
derma, keratoses, and malignancies. There is little evidence that cessation of
intoxication reverses the inexorable process of arsenism. The importance of the
condition does not only lie in the fact that chronic arsenism leads to a range of
dermatologic abnormalities.
A 1978 study of a group of patients who had been treated with arsenic in
the 1930s showed a significant increase in the incidence of malignant internal
neoplasms, mainly in the lungs and gastrointestinal tract. As this finding has
been known for many years in Argentina and is the subject of sporadic reports
from other countries, it is essential that all cases of chronic arsenism be fol-
lowed indefinitely.
Patients must be warned that regular checkups are imperative if possible
complications are to be detected at an early stage.

Selected Readings
Bettley, FR, O'Shea, JD: The absorption of arsenic and its relation to carcinoma. Dr
J Dermatol1975; 92:563.
Reymann, F, Moller, R, Nielsen, A: Relationship between arsenical intake and inter-
nal malignancy. Arch Dermatol1978; 114:378.
Tseng, WP, Chu, HM, How, Sw, et al: Prevalence of skin cancer in an endemic area
of chronic arsenicism in Taiwan. J Natl Cancer [nst 1968; 40:453.
Wagner, SL, Maliner, JS, Morton, WE, et al: Skin cancer and arsenical intoxication
from well-water. Arch Dermatol1979; 115:1205.
ApPENDIX ONE

Useful Techniques

In the body of this book, many investigations have been recommended that are
of help in confirming the various diagnoses. Many of these (routine histology,
bacteriology) are well known to most readers, but we suspect that others are
less widely used. This appendix contains details of a number of procedures that
may be helpful to the nonspecialist.

Cellophane Tape Test

Transparent self-adhesive plastic tape (Cellotape, Scotch tape) is extremely
useful in confirming the diagnosis of pityriasis versicolor. Three to four centi-
meters of the tape are stuck over an active area and firmly rubbed with the
back of a fingernail. When removed, the tape will show an exact replica of the
scaly lesion that it has covered. This in itself is diagnostic of pityriasis versi-
color, but further confirmation can be obtained if the tape is dipped for one
minute into a drop of 1 percent gentian violet, blotted, and mounted on a
microscope slide. Examination will show the spores and germ tubes of the
Pityrosporum.
The cellophane tape test is negative in early cases of tinea imbricata, which
may sometimes be confused with pityriasis versicolor.

Diascopy
It is often helpful to know whether or not a dermal papule has a vascular ele-
ment. This can best be recognized by determining whether it blanches on pres-
sure, but as the pressing finger will entirely cover a small lesion, it is more
244 Appendix One Useful Techniques

helpful if the pressure is exerted with some hard, flat material that is trans-
parent. This permits the nodule to be seen while it is under pressure. Such
instruments may be a plastic tongue depressor or spatula, a magnifying lens,
or some other reasonably thick piece of glass. An ordinary microscope slide can
be used, but they have been known to break under pressure and lacerate the
patient.
Diascopy is of particular value in examination of nodules in a patient sus-
pected of having lupus vulgaris. The apple-jelly nodule is often rather erythe-
matous, and only under diascopy will the typical greenish-yellow color be
clearly revealed.

The Matchstick Test

An even older technique for demonstrating an apple-jelly nodule, located in the

upper part of the dermis, and covered by a taut, stretched epidermis, involves
taking an ordinary wooden match that has been sharpened to a point and plac-
ing it vertical to the papule. Light pressure with a finger will cause the match
to penetrate the epidermis and stand upright without support. If the lesion is
deep in the dermis and the epidermis is not thinned, the point of the match will
break under pressure.
Both these tests are positive in lupus vulgaris and lupoid leishmaniasis and
negative in tuberculoid granulomata.

Dutz Technique
For the many bacterial or parasitic lesions that show crusting or ulceration,
cotton swabs are usually used to obtain suitable material for examination or
culture. This method is often ineffective in ulcerated lesions and of no use at
all if a sample is needed from the depths of a dermal infection. It is better to
use a dental broach. These instruments, used by dentists to abrade dentine, are
steel needles, the distal part being surrounded by metallic barbs of different
sizes. The finer broaches may easily be pushed into the core of an infected area,
producing a very small puncture wound. If they are gently rotated before
removal, they will become coated with tissue, which can be used for a stab
culture, to make a direct smear for bacteriologic examination, or to inoculate
a bacterial plate.
If the lesion is crusted, it is usually possible to insert the broach from the
side into the main body of the swelling and so completely avoid any surface
contamination that may be present. The technique has been found useful for
leishmaniasis, leprosy, anthrax, and yaws. (Reference: Dutz, W, Kohout, E:
Dermatologic diagnosis by using the hemocytometer and the dental broach. Int
J Dermatol1982; 21:410.)
Leprosy Skin Smear 245

Lepromin Test
If lepromin is available and kept at a suitable temperature, it can be used as a
diagnostic aid. It seems to have become traditional to use the left forearm some
two inches distal to the elbow fold to inject 0.1 ml intradermally.
Although the WHO suggests that readings should be taken after 28 days,
those taken after three weeks are acceptable. The diameter of the resultant
papule is measured in millimeters and recorded.

0-3 mm negative
3-6mm +
6-9mm ++
Over 10 mm +++
Unfortunately, both false negative and false positive reactions are possible,
the former perhaps because the injection has been too deep and the latter
because an unclean needle has caused a small intradermal infection.
The combination of clinical, bacteriologic, and histopathologic findings usu-
ally makes the lepromin an unnecessary luxury.

Leprosy Skin Smear

It may be impossible to detect any M. /eprae in a lesion of tuberculoid leprosy,
but in all other types the mycobacterium is present in varying numbers. The
demonstration of its presence is an essential part of the clinical investigation of
borderline and lepromatous disease.

How to Do the Skin-Slit

The following equipment is necessary:

1. a supply of clean, preferably unused microscope slides;

2. an alcohol lamp;
3. numerous gauze or cotton swabs;
4. 1 percent cetrimide or other nonflammable skin cleanser;
5. a scalpel handle fitted with a No. 15 Bard Parker blade.

The purpose of this investigation is to detect the presence of leprosy organ-

isms. It is not a blood test. The lesion should be squeezed between the forefinger
and thumb of one hand until it is suitably blanched. The skin is then cleaned,
an incision 3 to 4 mm long is made, and, the blade being turned at right angles,
one of the walls of the cut is firmly scraped to remove a drop of tissue fluid.
This is smeared onto a clean slide over an area approximately I cm in diameter
246 Appendix One Useful Techniques

(two or three smears can be made on each slide). If the lesion has been firmly
held, the smear will not be bloodstained. Sometimes the incision will bleed after
the smear has been taken-a small wisp of cotton will ensure rapid
coagulation.
The scalpel blade is wiped with cetrimide, flamed on the alcohol lamp, and
cleaned again before the next smear is taken. Which sites are studied should
be recorded so that further investigations in three or six months' time will be
from the same lesions and so be truly comparable.

Where to Do the Skin-Slit

Patients in the borderline group (BT, BB, or BL) will not have a generalized
eruption, and there is no point in taking smears from skin that is not clinically
and visibly involved. Six different sites should be tested to obtain an overall
picture of the activity and severity of the disease. For lepromatous patients, the
following routine is recommended. The shirtless patient sits on a stool with his
back to the operator and smears are taken from the following sites:

1. left ear lobe;

2. right ear lobe;
3. lesion from the back of the left arm;
4. lesion somewhere on the back;
5. lesion from the right arm;
6. the patient turning toward the operator, lesion on the knee or thigh.

It is helpful to take smears from both ear lobes, because the unexpected pres-
ence of bacilli can be taken as evidence that the patient's disease is becoming
completely lepromatous.
This technique is not particularly scientific, as an unmeasured quantity of
fluid is smeared over an unmeasured area on the slide; different operators will
produce smears that differ widely in thickness. It is urged that a patient's
smears always be taken by the same operator, thus minimizing the possibility
of extensive technical variation.

How to Count the Skin-Slit

All smears should be fixed by gentle heating and then stained. Four solutions
are needed:

Solution A 10 percent carbol fuchsin in 90 percent absolute alcohol

Solution B 5 percent phenol in 95 percent distilled water
Solution C 0.5 percent hydrochloric acid in 70 percent alcohol
Solution D 1 percent methylene blue
Leprosy Skin Smear 247

Step 1
Combine 1 ml of solution A with 9 ml of solution B and cover the smear for
20 minutes. It may be gently heated, but not dried out, for a minute at the
start of staining. After this, the slide should be washed with running water.

Step 2
Decolorize the smear by pouring on a small amount of solution C for a few
seconds and wash again with running water. If the smear is still red, decolorize
further, until there is nothing left but a pale pink tinge.

Step 3
Counterstain with solution D for two minutes, wash and leave to dry.
The stain is now ready to be counted. Under an oil-immersion lens, the
mycobacteria should appear as red-stained rods. Other tissues are slightly blue.
Ridley's logarithmic index is used to count the organisms. One hundred oil-
immersion fields are examined on each smear, and the total number of bacilli
are recorded as follows:

1-9 organisms in 100 fields 1+

10-99 organisms in 100 fields 2+
1-9 organisms in every field 3+
10-99 organisms in every field 4+
More than 100 organisms in every field 5+

It is possible but very unusual to find more than 1,000 bacilli in each field. This
must be counted as 6 + .
The bacterial index (BI) is then recorded as the average from all the six
sites examined.

What to Count
Unfortunately, even with successful antileprosy treatment the BI takes a very
long time to diminish significantly, as dead M. /eprae are astonishingly slow to
disintegrate. Three or six monthly estimations of the BI do not give a satisfac-
tory record of the patient's progress. Fortunately, under the oil-immersion lens
it can be seen that all bacteria do not take the stain in the same way-some
bacilli show uniform coloration while others appear fragmented and granular.
It is now known that only the uniform staining bacteria are viable. Use of this
knowledge is another method of measurement, called the morphologic index
(MI). In most untreated cases, 20 to 30 percent of all the bacilli stain uni-
formly. A few weeks after the onset of therapy this percentage will fall to zero.
Reduction in the MI precedes by several months a fall in the BI. Thus, the MI
will show whether or not treatment is being successful.
While the BI is being counted the MI should be estimated at the same time.
248 Appendix One Useful Techniques

One hundred consecutive separately visible organisms should be examined and

the percentage of those that are solidly staining recorded. If six smears are
taken, the average of the bacterial and the morphologic indices will give a gen-
eral statement of the patient's condition. If after several months of supposedly
efficacious therapy the MI has not decreased, either the patient is not taking
the treatment or there is a drug-resistant organism (Reference: Leiker, DL,
McDougall, AC: Technical guide for smear examination for leprosy by direct
microscopy. Amsterdam Leprosy Documentation Service, 1983.)

Nikolsky's Sign
This sometimes helps to differentiate pemphigus from other bullous diseases.
The sign, described by Nikolsky in 1895, is elicited by exerting firm sliding
pressure with a finger on a patient's apparently normal skin. The sign is positive
if there is resulting dislodgement of some or all of the epidermis in the pressure
area. Gentle, direct pressure on a vesicle or a bulla may cause lateral extension
of the lesion, but this is not Nikolsky's sign.
In some other conditions, particularly Lyell's toxic epidermal necrolysis, the
Nikolsky's sign is also positive, but such cases do not show the acantholytic
cells that can be demonstrated by the Tzanck test (see page 249).

Onchocerciasis Skin Snip

The positive detection of microfilariae in the skin is very helpful in the exam-
ination of patients thought to have onchocerciasis. A sharp needle is inserted
into the epidermis and a "tent" of skin is raised that is then shaved off; efficient
practitioners do not cause any bleeding. The snipped piece of epidermis is
placed on a drop of saline on a slide and teased out. Microscopic examination
will show the presence of the microfilariae.

Test of Viabiity of Schistsoma Ova

Urine
The urine should be centrifuged, and the supernatant rejected. Clean water is
added to the sediment and the process repeated as often as necessary until the
supernatant fluid is completely clear. The sediment should be kept in a refrig-
erator overnight, and the next morning warm water added to the tube. The
eggs will soon hatch. The highly motile myracidia can be seen easily with a
hand lens, particularly if the tube is viewed against a dark background.
ApPENDIX Two

Useful Addresses

Culture Media and Laboratory Equipment

General:
Arthur H. Thomas Company
Vine at Third Street
Philadelphia, PA 19106
(01) (215) 574-4500
Dermatologic Lab and Supply Company
201 Ridge
Council Bluffs, IA 51501
(01) (800) 831-6273
Specific:
Baker's DTM
Key Pharmaceuticals, Inc.
P.O. Box 694307
Miami, FL 33169
(01) (800) 327-0592

Surgical Supplies
General:
George Tiemann and Company
80 Newton Plaza
Plainview, NY 11803
(01) (516) 694-6283
Wood's Lght 249

Stool
A few grams of feces are emulsified with saline, strained to remove the coarser
particles, and allowed to stand. The supernatant fluid is decanted, and the sed-
iment washed repeatedly as described above. Addition of warm water after the
sediment has been in a refrigerator will cause the eggs to hatch if they are
viable.
NB. Do not forget (especially in endemic areas) that the demonstration of
viable ova is no proof that the patient's symptoms are due to schistosomiasis.

Tzanck Test
The classical forms of pemphigus are all caused by acantholysis, in which the
cells of the malphighian layer become separated from each other, round off,
and are seen lying separately or in groups in the blister fluid. These are easily
seen in a histologic section, but some patients are unwilling to submit to biopsy.
The Tzanck smear provides a fairly satisfactory alternative method for dem-
onstrating the acantholytic cells.
The roof of an intact bulla is carefully removed, and the floor of the blister
is lightly scraped with a sterile (but preferably blunt) scalpel. The tissue is
spread onto a slide, fixed, and stained with hematoxylin and eosin. Smears from
an active case of pemphigus will contain the diagnostic acantholytic cells. This
test is particularly useful in cases of Brazilian pemphigus foliaceous, as workers
in rural districts may have a microscope but no access to a histopathology
laboratory.

Wood's Light
Certain fungi fluoresce under Wood's light, which is an ultraviolet light, fil-
tered through a nickel-cobalt glass filter. Many forms are available. The easiest
one to use resembles a large electric bulb made of blue glass. It can be effective
only in a completely dark room and should be turned on for a few minutes to
warm up before it is used. Tineas on the body rarely fluoresce, but many of the
causative organisms of tinea capitis will do so.
This is of particular value in cases of favus. Adult patients with a patchy
cicatricial alopecia mayor may not still have an active infection, since the con-
dition does not resolve spontaneously at puberty as happens in other forms of
tinea capitis. Under the light, affected hairs show a grey-green fluorescence,
and even if only one or two hairs are affected, they can be recognized and
submitted to direct microscopy. Without the Wood's light, hairs can only be
randomly selected for microscopy, and negative examination will never fully
persuade the doctor or the patient that the whole scalp is free from infection.
(Reference: Ronchese, F: The Wood light in dermatology. Cutis 1968; 4:1059.)
Drugs, Biologicals, and Medical Sundries 251

Drugs, Biologicals, and Medical Sundries

General:
Doctors Pharmacy
1935 Chestnut Street
Philadelphia, PA 19103
(01) (215) 563-1930
Merieux Institute
17 Rue Bourgelay
69002 Lyon, France

Specific:
Anti-parasitic Drugs
Parasitic Disease Drug Service
Center for Disease Control
Atlanta, GA 30333
(01) (404) 329-3311

Medicated Bandages, Elastoplast

T.J. Smith and Nephew Ltd.
Bessemer Road
Welwyn Garden City
Herts AL7 1HF, England

Praziquantel
Miles Pharmaceuticals
400 Morgan Lane
West Haven, CT 06516
(01) (203) 934-9221
Thalidomide (essential for treatment of erythema nodosum leprosum)
Grunenthal GMBH
5190 Stolberg-im-Rheinland, West Germany
Vaccines (Anthrax)
Department of Health and Social Security
Room H211
14 Russell Square
London WC1B 5EP, England
Department of Public Health
State of Michigan
3500 North Logan
P.O. Box 30030
Lansing, MI 48909
252 Appendix Two Useful Addresses

Skin-Testing Material
General:
Hollister Stier Laboratories
P.O. Box 3145
Spokane, VVA 99220
(01) (800) 992-1120

Society of Interest to Readers

International Society of Tropical Dermatology
Sigfrid A. Muller, M.D., Secretary General
Division of Dermatology
Mayo Clinic
200 First Street, SVV
Rochester, MN 55901
(01)(507) 284-3736

Periodicals of Interest to Readers

International Journal of Dermatology
a. by membership in International Society of Tropical Dermatology
b. or by subscription
J.B. Lippincott Company
East VVashington Square
Philadelphia, PA 19105
(01) (800) 638-3030
International Journal of Leprosy
Business and Circulation Office
1262 Broad Street
Bloomfield, NJ 07003
Quarterly Bibliography of Major Tropical Diseases
National Library of Medicine
Bethesda, MD 20014
 Index

Abdominal actinomycosis, 126, see also investigations of, 170

Actinomycosis natural history of, 167, 169
Actinomyces bovis, 124 treatment of, 170
Actinomyces israelii, 116, 124-125, 128 Anesthesia, of lesions, 52, 53, 63
Actinomycosis Anthrax
clinical features of, 125-126 clinical features of, 22-24
diagnosis of, 127 diagnosis of, 24
etiology of, 124-125 etiologyof,21-22
investigations of, 127 investigations of, 25
natural history of, 126-127 natural history of, 24
treatment and follow-up of, 128 treatment and follow-up of, 25
Aflatoxin, 222 Apple jelly nodule, 41,165
Allescheria boydii, 116 Ariboflavinosis, 226
Alopecia, 103 Arsenical poisoning
cicatrical, 161 chronic, clinical features of, 239-
leprosy, 75 240
scarring, 101 diagnosis of, 240-241
Amastigote, 159 etiology of, 238-239
Amebiasis follow-up of, 242
clinical features of, 179 investigations of, 241
diagnosis of, 179-180 treatment and follow-up of, 241-
etiology of, 178-179 242
investigations of, 181 Avian tuberculosis, 36
natural history of, 179
treatment and follow-up of, 181-182
Amphotericin B Bacillus anthracis, 21, 22, 25
for chromomycosis, 111 Bacillus anthrax, 21
for mucocutaneous leishmaniasis, 173 Bacillus cereus, 25
for North American blastomycosis, Bacterial index (BI), 67-68
144 Bagdad boil, see Oriental sore
for sportrichosis, 123 Bairnsdale bacillus, 78, 84
Anergic leishmaniasis Bancroftian filariasis, 195
clinical features of, 167 Beriberi,224
diagnosis of, 169 Bilharzia, see Schistosomiasis
254 Index

Biskra button, see Oriental sore Cephalosporiumfalciforme. 116

Bitot's spots, 222 Cervical-facial infections, 125, see also
Blastomyces dermatitidis. 141, 144 Actinomycosis
Blastomycosis, see North American Chiclero's ulcer, 176-177
blastomycosis and Chloroquine
Paracoccidiomycosis for amebiasis, 181
Borderline lepromatous (BL) disease, for lichen planus tropicus, 220
59-60 Chromomycosis
Borderline leprosy (BB), 49 clinical features of, 107
clinical features of, 58-60 diagnosis of, 108, 110
diagnosis of, 66 etiology of, 106
Borderline tuberculoid (BT) disease, investigations of, 110-111
58-59 natural history of, 107-108
Botryomycosis treatment of, 111
clinical features of, 130 Cicatrical alopecia, 161
diagnosis of, 130-131 Cladosporium werneckii. 95, 96, 106
etiology of, 129 Clinical index, 6-17
investigations of, 131 Clofazimine
treatment of, 131 for Buruli ulcer, 85
Bovine tuberculosis, 36 for leprosy, 71
Brazilian blastomycosis, see for Lobo's disease, 155
Paracoccidioidomycosis Cloxacillin, for botryomycosis, 131
Brazilian pemphigus foliaceous Coccidioides immitis, 144
clinical features of, 233 Coccobacillus mycetoides, 90
diagnosis of, 235-236 Corynebacterium diphtheriae, 91
etiology of, 232-233 Corynebacterium mycetoides, 90
investigations of, 236 Corynebacterium pyogenes. 83, 91
natural history of, 234-235 Corynebacterium pyogenes ulcers, 91-92
treatment of, 236-237 Cotrimoxazole, for Madura foot, 117
Brugia malayi. 195, 196 Crab yaws, 30, see also Yaws
Brugia timori, 195 Cutaneous anthrax, 22-23, see also
Buruli ulcer Anthrax
bacteriology of, 84 Cutaneous schistosomiasis, 207
clinical features of, 79, 81-83 Cutaneous tuberculosis, 36-37, see also
diagnosis of, 83-84 Tuberculosis, of skin
etiology of, 78-79
follow-up of, 87
histology of, 84 Dapsone
investigations of, 84 for leprosy, 64, 69
local therapy for, 85 for Madura foot, 117
natural history of, 83 Daughter yaws, 29, see also Yaws
surgical treatment for, 85, 87 Dejerine's disease, 65
systemic treatment for, 85 Diarrhea, bloody, 179
Diascopy, 243-244
Dietary deficiencies, 221-227
Camel's nose deformity, 170 Diethylcarbamazine
Cellophane tape test, 243 for filariasis, 198
Cellulitis, 201 for onchoceeiasis, 193
Index 255

Dihydroemetine, 181 Filariasis

Diiodohydroxyquin, 181 clinical features of, 196
Diiodohydroxyquinoline, 182 diagnosis of, 198
Diphtheritic ulcer, 91 eosinophic lung in, 197
Dirofilaria immitis, 198 etiology of, 195-196
Downgrading investigation of, 198
lepromatous disease and, 62, 66 natural history of, 196-197
Dracunculosis prevention of, 199
clinical features of, 201 skin tests for, 198
diagnosis of, 201-202 treatment of, 198-199
etiology of, 200-201 Fogo selvagem, 232
investigations of, 202-203 Fonsecaea compacta, 106
natural history of, 201 Fonsecaea dermatiditis, 95
prevention of, 203-204 Fonsecaea pedrosi, 106
treatment of, 203 Fonsecaea verucose, 106
Dracunculus medinensis, 200 Frambesia, 29
Dutz technique, 244 Frisch's bacilli, 140

Ectropion, 142
Gangrene, synergistic bacterial, 84
Entamoeba histolytica, 178
Gilchrist's disease, 141-145
Eosinophic lung, tropical, in filariasis,
Griseofulvin
197
for favus, 104
Epistaxis, 134, 167
for tinea imbricata, 100
Erythema necrotisans, 74-75
Guinea-worm disease, see Dracunculosis
Erythema nodosum leprosum (ENL),
Gumma, 30-32
63-65
histopathology of, 68-69
lepromatous disease and, 66
treatment of, 72 Hair follicles, destruction of, 101,
Erythromycin 103
for actinomycosis, 128 Hebra's nose deformity, 139
for botryomycosis, 131 Hemorrhagic papule, 22-23
for yaws, 35 Histoplasma capsulatum, 144
Ethambutol, 45 Hyperkeratosis, 34
Ethylstilbamidine, for rhinosporidosis, Hyperplasia, 13 7-13 8
136 Hypopigmentation, in leprosy, 54
Exophiala werneckii, 95
Eye changes, in onchocerciasis, 191-192
Ichthyosis, 75-76
Immunity, and leprosy, 48-49
Favus
Insect bite, 160
clinical features of, 101
Isonicotinic acid hydrazide, 45
diagnosis of, 103
etiology of, 101
investigations of, 103-104
natural history of, 101, 103 Jamarsan R, 236
treatment of, 104 Jaundice, 179
256 Index

Kala-azar, 173 immunologic background and, 48

Katayama disease, 207 incomplete immunity and, 48-49
Keloidal blastomycosis, see Lobo's incubation period, 60-61
disease indeterminate, 73-74
Keloids, 154 investigations of, 67-69
Keratosis pilaris, 229 natural history of, 60-65
Ketoconazole reactions in, 61
for chromomycosis, 111 reversal reactions in, 62
for favus, 104 skin ulceration and, 75
for Lobo's disease, 155 spectrum of, 49, 51
for Madura foot, 117 sulfone-resistant, 69
for mucocutaneous leishmaniasis, 173 treated, progress in, 62-63
for North American blastomycosis, treatment of, 69, 71-72
144 untreated, progress of, 61
for paracoccidioidmycosis, 150 variants of, 73-76
for sporotrichosis, 123 Leprosy alopecia, 75
for tinea imbricata, 100 Leprosy skin smear, 245-248
Klebsiella rhinoscleroma tis, 137, 140 Lichen planus tropicus
Kwashiorkor, 221-222 clinical features of, 216-217
diagnosis of, 217-218
etiologyof,215-216
Leishman-Donovan bodies, 159 investigations of, 218
Leishmania braziliensis, 170 treatment of, 218, 220
Leishmania braziliensis guyanensis, 177 Lobo's disease
Leishmania donovani, 173 clinical features of, 152-153
Leishmania major, 160 diagnosis of, 153-154
Leishmania mexicana, 176 etiology of, 152
Leishmania tropica, 160 investigations of, 154
Leishmaniasis, 159-177 treatment of, 155
Lepra bonita, 74 Loboa loboi, 152
Lepra reactions, 61 Lucio phenomenon, 74-75
Lupoid leishmaniasis, 167, see also Lumpy jaw, 124
Anergic leishmaniasis Lupoid leishmaniasis
Lepromatosis, diffuse, 74 clinical features of, 165
Lepromatous leprosy (LL), 49 diagnosis of, 165-166
clinical features of, 56-58 investigations of, 166
diagnosis of, 66 natural history of, 165
Lepromin test, 69, 245 treatment of, 166
Leprosy, see also Specific types Lupus vulgaris, 39, 41
anergic patients and, 49 diagnosis of, 43
bacteriology of, 67-68 Lymphostasis verrucosa, 63, 108
clinical features of, 51-52, 53-60
diagnosis of, 65-66
downgrading, 62 Madarosis, 57-58, 167
etiology of, 48-49, 51 Madura foot
follow-up of, 73 clinical features of, 113
histopathology of, 68-69 diagnosis of, 115-116
Index 257

etiology of, 112-113 Mycobacterium ulcerans, 44

investigations of, 116 bacteriology of, 84
natural history of, 114-115 phenomena unique to, 79
treatment of, 117
M~durella grisea, 116
Madurella mycetomi, 116 Neural leprosy, 49
Mal morado, 189 clinical features of, 51-52, 54
Malayan filariasis, 195 diagnosis of, 65
Malignancy, arsenic ingestion and, 239 Night blindness, 228
Malignant pustule, 22 Nikolsky's sign, 248
Marasmus, 224 N-methylglucamine antimoniae, 172
Matchstick test, 244 Nocardia asteroides, 124
Mazzotti test, 193 Nocardia brasiliensis, 124
Mebendazole, 198 Nocardia braziliensis, 116
Meleney's burrowing ulcer, 84 North American blastomycosis
Metrifumite,210 clinical features of, 142
Metronidazole diagnosis of, 143
for amebiasis, 182 etiology of, 141
for dracunculosis, 201 investigations of, 144
for tropical ulcers, 90 natural history of, 142-143
Micrococcus mycetoides, 90 treatment of, 144-145
Mikulicz' cells, 140
Miliary tuberculosis, 38-39
Montenegro test, 164 Onchocerca volvulus, 188
Morphologic index (MI), 64 Onchocerciasis
definition of, 68 clinical features of, 188-192
drug therapy and, 69, 71 diagnosis of, 192-193
usetul techniques, 24 etiology of, 188
Mossy foot, 63, 108, 196 investigations of, 193
Mother yaw, 29, see also Yaws natural history of, 192
Mucocutaneous leishmaniasis prevention of, 194
clinical features of, 170-171 treatment of, 193-194
diagnosis of, 172 Onchocerciasis skin snip, 248
investigations of, 172 Oriental sore
natural history of, 171-172 clinical features of, 160-161
treatment of, 172-173 diagnosis of, 163
Mulberry erosions, 146, 148 etiology of, 160
Mycetoid desert sore, 90 investigations of, 163-164
Mycetomas, deep, 114, see also Madura natural history of, 161, 163
foot treatment of, 164-165
Mycobacterium balnei, 43, 44 Orthopedic surgery, for leprosy, 72
Mycobacterium leprae, 44, 48 Oxamniquine,210
bacteriology of 66-67
ENL and, 72
prediliction for nervous tissue, 51
signs and symptoms from, 65-66 Paracoccidioides braziliensis. 146, 149-
Mycobacterium tuberculosis, 36, 44 150
258 Index

Paracoccidioidomycosis Raspberry papule, 29

clinical features of, 146, 148 Reversal reaction
diagnosis of, 149 lepromatous disease and, 66
etiology of, 146 leprosy and, 62
investigations of, 149-150 Rhinoscleroma
natural history of, 148 clinical features of, 137-138
treatment and follow-up of, ISO diagnosis of, 139-140
Parrot's beak deformity, 171 etiology of, 137
Pellagra, 224-226 investigations of, 140
Pellagra necklace, 225 natural history of, 138-139
Pemphigus foliaceous, 232, see also treatment of, 140
Brazilian pemphigus Rhinosporidiosis
foliaceous clinical features of, 134
Penicillin diagnosis of, 134-135
for actinomycosis, 128 etiology of, 133
for yaws, 34-35 investigations of, 135
Phialophora jeanselmei. 116 natural history of, 134
Phrynoderma treatment of, 136
clinical features of, 229 Rhinosporidium seeberi. 133
diagnosis of, 229, 231 Ridley-Jopling classification, of leprosy,
etiology of, 228 49,51
treatment of, 231 Rifampin
Pian bois, 177 for Buruli ulcer, 85
Plastic surgery, for leprosy, 72 for leprosy, 71
Post-kala-azar dermal leishmaniasis for tuberculosis, 45
clinical features of, 173 River blindness, 187
diagnosis of, 176
investigations of, 176
natural history of, 173, 176 Salak, 161
treatment of, 176 Sandfly bite, 160
Praziquantei,210 Schistosoma haematobium. 205, 206
Prednisone Schistosoma japonicum. 205, 206
for Brazilian pemphigus foliaceous, Schistosoma mansoni. 205, 206
236 Schistosome dermatitis, 207
for erythema- nodosum leprosum, Schistosomiasis
72 clinical features of, 206-207
for leprosy, 71-72 cutaneous, 207
Promastigote, 159 diagnosis of, 209-210
Pseudomonas aeruginosa. 129 etiology of, 206
Pullularia werneckii. 106 invasive, 206-207
Pulmonary anthrax, 24, see also investigations of, 210
Anthrax natural history of, 207-209
Pulmonary blastomycosi~,.142-143 prevention of, 211
Pyrimethamine, 186 treatment of, 210
urticarial, 207
Schistosoma ova, viability test of, 248-
Quinacrine, 236 249
Index 259

Scrofuloderma, 38 Tinea captitis, 100

Scurvy, 227 Tinea favosa, see Favus
Simulium damnosum. 187 Tinea imbricata
Simulium ochraceum. 189 clinical features of, 97
Sodium stibogluconate, for Oriental diagnosis of, 100
sore, 164 etiology of, 97
South American blastomycosis, see natural history of, 99
paracoccidioidomycosis treatment of, 100
Spiramycin, for toxoplasmosis, 186 Tinea nigra
Splendore-Hoeppli phenomenon, 122 clinical features of, 96
Sporothrix schenckii. 118 diagnosis of, 96
Sporotrichosis etiology of, 95
clinical features of, 119 treatment of, 96-97
diagnosis of, 122 Tineas tropical, 97-104
etiology of, 118 Tokelau ringworm, see Tinea imbricata
investigations of, 122 Toxoplasma gondii. 183
natural history of, 119, 122 Toxoplasmosis
treatment of, 123 clinical features of, 184
Scrofuloderma, diagnosis of, 43 diagnosis of, 185
Staphylococcus aureus. 129 etiology of, 183
Staphylococcus pyogenes. 129 investigations of, 185-186
Steroid therapy, for lichen planus natural history of, 184-185
tropicus, 220 treatment of, 186
Stibophen, 176 Treponema carateum. 27, 34
Strawberry polyp, 134-135 Treponema pallidum. 27, 34
Streptomyces madurae. 116 Treponema pertenue. 27, 28, 34
Streptomyces somaliensis. 116 Treponema vincenti. 89
Streptomycin, 140 Tretinoin, 231
Sulfadiazine, 186 Trichophyton concentricum. 97, 99
Sulfone therapy, for leprosy, 64 Trichophyton schoenleinii. 100, 101,
resistence of, 69 '103 .
Suramin Tropical ulcers, 88-92
for filariasis, 198 treatment of, 90
for onchoceeiasis, 194 Tropicaloid ulcer, 90-91
Synergistic bacterial gangrene, 84 Tuberculoid leprosy (TT), 49
clinical features of, 54
diagnosis of, 55, 65-66
Tetracycline histopathology of, 68
for actinomycosis, 128 Tuberculosis, of skin
for anthrax, 25 bacteriology of, 44
for botryomycosis, 131 clinical features of, 37-39, 41, 43
for yaws, 35 diagnosis of, 43
Thalidomide, 72 etiology of, 36-37
Thiabendazole, 201 investigations of, 44-45
Thiamin, 224 natural history of, 43
Thoracic actinomycosis, 125-126, see pathology of, 44
also Actinomycosis treatment and follow-up of, 45-46
260 Index

Tuberculosis verrucosa cutis, diagnosis Vitamin B deficiencies, 224-226

of, 38, 43 treatment of, 226
Tuberculous chancre, 37-38 Vitamin C deficiency, 227
Tuberculous lesions, 41, 43
Tuberculous ulcers, 38
Tzanck test, 24'1 Whitfield's lotion
for tinea imbricata, 100
for tinea nigra, 96
Ulcer Wood's light, 249
Buruli, see Buruli ulcer Wuchereria banero/ti, 195, 196
buttock, 83 Wuchereria pacifica, 195
Corynebacterium pyogenes, 91-92
diphtheritic, 91
Meleney's burrowing, 84 Yaws
serpiginous, 31-32 clinical features of, 28-32
tropical, 88-92 crab, 30
tropicaloid, 90-91 daughter, 29
tuberculous, 38 diagnosis of, 33-34
Urticarial schistosomiasis, 207 early, 29-30
etiology of, 27-28
investigation of, 34
Veldt sore, 91 late, 30-32
Vincent's organisms, 89 mother, 29
Vitamin A deficiency, 224 natural history of, 32-33
phrynoderma and, 228 treatment of, 34-35