Concise Dermatology

Concise Dermatology
Edited by
Rashmi Sarkar, MD, MNAMS
Professor
Department of Dermatology
Lady Hardinge Medical College
and
SSK and KSCH Hospitals
New Delhi, India
Associate Editors
Anupam Das, MD
Assistant Professor
Dermatology
KPC Medical College and Hospital
Kolkata, West Bengal, India
Sumit Sethi, MBBS, MD, DNB
Consultant Dermatologist
DermaStation
Janakpuri, New Delhi, India
and
Venkateshwar Hospital
Dwarka, Delhi, India
First edition published 2021
by CRC Press
6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-2742
and by CRC Press
2 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN
© 2021 Taylor & Francis Group, LLC
We acknowledge Ronald Marks and Richard Motley’s 18th Edition of Common Skin Diseases (By Roxburgh).
CRC Press is an imprint of Taylor & Francis Group, LLC

This book contains information obtained from authentic and highly regarded sources. While all reasonable efforts have been
made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal responsibility or
liability for any errors or omissions that may be made. The publishers wish to make clear that any views or opinions expressed
in this book by individual editors, authors, or contributors are personal to them and do not necessarily reflect the views/opinions
of the publishers. The information or guidance contained in this book is intended for use by medical, scientific, or health-care
professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of
the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines. Because of the
rapid advances in medical science, any information or advice on dosages, procedures, or diagnoses should be independently
verified. The reader is strongly urged to consult the relevant national drug formulary and the drug companies’ and device or
material manufacturers’ printed instructions, and their websites, before administering or utilizing any of the drugs, devices, or
materials mentioned in this book. This book does not indicate whether a particular treatment is appropriate or suitable for a
particular individual. Ultimately it is the sole responsibility of the medical professional to make his or her own professional
judgements, so as to advise and treat patients appropriately. The authors and publishers have also attempted to trace the
copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in
this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may
rectify in any future reprint.
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or
utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including
photocopying, microfilming, and recording, or in any information storage or retrieval system, without written
permission from the publishers.
For permission to photocopy or use material electronically from this work, access www.copyright.com or contact the
Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. For works that are
not available on CCC please contact [email protected]
Trademark notice: Product or corporate names may be trademarks or registered trademarks and are used only for
identification and explanation without intent to infringe.
Library of Congress Cataloging-in-Publication Data

Names: Sarkar, Rashmi, editor. | Das, Anupam, editor. | Sethi, Sumit, editor.
Title: Concise dermatology / edited by Rashmi Sarkar, MD,MNAMS, Professor,
Department of Dermatology, Lady Hardinge Medical College and associated
SSK and KSCH Hospital, New Delhi, India, associate editors, Dr. Anupam
Das, MD, Assistant Professor, Dermatology, KPC Medical College and
Hospital, Kolkata, West Bengal, India, Dr. Sumit Sethi, MBBS, MD, DNB,
DermaStation, Janakpuri, New Delhi, India.
Description: First edition. | Boca Raton : CRC Press, 2021. | Summary:
“This concise text from an internationally respected editor presents the
most important points about the most important topics in disease of the
skin, hair, and nails; any medical professional will find here the
material for a solid grounding in the subject”‐‐ Provided by publisher.
Identifiers: LCCN 2020049387 (print) | LCCN 2020049388 (ebook) | ISBN
9780367533656 (hardback) | ISBN 9780367533625 (paperback) | ISBN
9781003081609 (ebook)
Subjects: LCSH: Dermatology. | Skin‐‐Diseases.
Classification: LCC RL72 .C57 2021 (print) | LCC RL72 (ebook) | DDC
616.5‐‐dc23
LC record available at https://lccn.loc.gov/2020049387
LC ebook record available at https://lccn.loc.gov/2020049388
ISBN: 978-0-367-53365-6 (hbk)

ISBN: 978-0-367-53362-5 (pbk)
ISBN: 978-1-003-08160-9 (ebk)
Typeset in Times New Roman

by MPS Limited, Dehradun
Contents
Contributors ............................................................................................................................................... v
1. An introduction to skin and skin disease .................................................................................. 1

Rashmi Sarkar and Anupam Das
2. Signs and symptoms of skin disease........................................................................................... 9

Anupam Das and Rashmi Sarkar
3. Skin infections ............................................................................................................................. 19

Shankila Mittal and Rashmi Sarkar
4. Infestations, insect bites, and stings ......................................................................................... 45

Sumit Sethi
5. Immunologically mediated skin disorders............................................................................... 56

Yasmeen Jabeen Bhat
6. Blistering skin disorders ............................................................................................................ 77

Pooja Agarwal and Rashmi Sarkar
7. Skin disorders in AIDS, immunodeficiency, and venereal disease....................................... 84

Indrashis Podder and Rashmi Sarkar
8. Eczema (dermatitis).................................................................................................................... 96
Sumit Sethi
9. Psoriasis and lichen planus...................................................................................................... 113

Shruti Barde
10. Acne, rosacea, and similar disorders ..................................................................................... 134

Pooja Agarwal
11. Wound healing and ulcers ....................................................................................................... 150

Shekhar Neema
12. Benign tumors ........................................................................................................................... 158

Rashmi Sarkar and Isha Narang
13. Malignant diseases of the skin ................................................................................................ 187

Yasmeen Jabeen Bhat and Anupam Das
14. Skin problems in infancy and old age ................................................................................... 204

Sumit Sethi and Rashmi Sarkar
iii
iv Contents
15. Disorders of keratinization and other genodermatoses ....................................................... 211

Aparajita Ghosh and Anupam Das
16. Metabolic disorders and reticulohistiocytic proliferative disorders................................... 222

Soumya Jagadeesan
17. Hair and nail disorders............................................................................................................ 233

Sumit Sethi
18. Systemic disease and the skin ................................................................................................. 242

Anupam Das
19. Disorders of pigmentation ....................................................................................................... 253

Rashmi Sarkar and Anupam Das
Index ...................................................................................................................................................... 261

Contributors
Dr Pooja Agarwal, MD, Assistant Professor, Department of Skin & Venereal Disease, Smt NHL
Municipal Medical College, Ahmedabad, Gujarat, India
Dr Shruti Barde, MBBS, DCD, MSc (Aesthetic Medicine), Founder & CEO, Studio SkinQ, Mumbai,
Maharashtra, India
Dr Yasmeen Jabeen Bhat, MD, FACP, Associate Professor Department of Dermatology,
Venereology, & Leprosy Government Medical College, Srinagar J&K, India
Dr Aparajita Ghosh, MD, Associate Professor, Dermatology, KPC Medical College and Hospital,
Kolkata, West Bengal, India
Dr Soumya Jagadeesan, MD, Associate Professor, Amrita Institute of Medical Sciences and Research
Centre, Kochi, Kerala, India
Dr Shankila Mittal, MD, DNB, Dermatology, Senior Resident, Safdarjung Hospital, Delhi, India
Dr Isha Narang, MD, DNB, MRCP (SCE) Dermatology, Specialist Registrar, Dermatology University
Hospitals of Derby and Burton, United Kingdom
Dr Shekhar Neema, MD, DNB, MRCP (SCE) Dermatology, Associate Professor, Department of
Dermatology, Armed Forces Medical College, Pune, Maharashtra, India
Dr Indrashis Podder, MD, DNB, Assistant Professor, Department of Dermatology, College of
Medicine and Sagore Dutta Hospital, West Bengal, India
v
1
An introduction to skin and skin
disease
Rashmi Sarkar
Anupam Das
An overview
The skin is an extraordinary structure. It has a surface area of 2 m2 and accounts for 16–20% of the total
body weight. It is made up of several types of tissues that work in harmony with one another
(Figure 1.1). The large number of cell types and functions of the skin and its proximity to numerous
potentially damaging stimuli in the outside environment result in two important consequences. The first
is that the skin is frequently damaged because it is right in the ‘line of fire’, and the second is that each
of the various cell types that it contains can ‘go wrong’ and develop degenerative and neoplastic dis
orders. Knowledge of the structure and functions of the skin is important for the clinician to diagnose
and treat dermatological conditions.
Skin diseases are quite common, and almost every individual suffers from skin disease at least once in
his or her lifetime. Atopic dermatitis affects about 15% of the people under the age of 12, while
psoriasis affects 1–2%. Other conditions that affect a significant number of people are viral warts,
seborrhoeic warts, and solar keratoses. It should be noted that 10–15% of the family physician’s work is
with skin disorders, and that skin diseases are the second most common cause of time taken away from
work. Although skin diseases are not uncommon at any age, they are particularly frequent among the
elderly. The older one gets, the greater the risk of developing skin disease.
Skin disorders are not usually fatal but can cause considerable discomfort and disability. The dis
ability caused can be physical, emotional, and socioeconomic. Patients receive help when their problems
and disabilities are acknowledged and their physician makes attempts to address their various problems.
Skin structure and function

It is difficult to understand abnormal skin and its vagaries without understanding the composition and
function of normal skin. Although, at the first glance, the skin may appear quite complicated, a slightly
deeper look shows that there is an elegant logic behind its architecture, which helps it perform several
vital functions. The skin is composed of epithelial and adipose tissues. The epithelial tissue comprises
the epidermis and the dermis. The adipose tissue, on the other hand, contains the hypodermis. The
accessory structures include hairs, nails, sebaceous, sweat glands, sensory receptors, etc.
The skin surface

The skin surface is a barrier between living processes and the potentially injurious outside world. Thus it
plays the important role of preventing and controlling interactions between the outside and the constant
1
2 Concise Dermatology
SC (15 mm)
E (35–50 mm)
HF
ESG D (1–2 mm)
SFL
FIGURE 1.1 Structure of the skin: HF, hair follicle; ESG, eccrine sweat gland; SC, stratum corneum (15 mm); E,
epidermis (35–50 mm); GCL, granular cell layer; ML, Malpighian layer; BL, basal layer; D, dermis (1–2 mm); SFL,
subcutaneous fat layer.
and vulnerable inside. Its 2 m2 area is modified regionally, which enables it to better perform particular
functions. The skin on the limbs and the trunk is very much the same, but the skin on the palms and
soles, facial skin, scalp skin, and genital skin differ somewhat in structure and function. The surface is
thrown up into a number of intersecting ridges, which make rhomboidal patterns. There are ‘pores’ at
regular intervals opening onto the surface – these are the openings of the eccrine sweat glands. The
diameter of these openings is approximately 25 μm, and there are approximately 150–350 duct openings
per square centimetre (cm2). The hair follicle openings can also be seen at the skin surface and the
diameter of these orifices and the numbers per cm2 vary greatly between anatomical regions. A close
inspection of the follicular opening reveals a distinctive arrangement of the stratum corneum cells
around the orifice.
FIGURE 1.2 Scanning electron micrograph of stratum corneum shows a corneocyte in the process of desquamation (from
Marks and Motley, Common Skin Diseases, 18th edition, with permission).
An introduction to skin and skin disease 3
At magnifications of 500–1000 times, which is possible with scanning electron microscopy (SEM),
individual horn cells (corneocytes) can be seen in the process of desquamation (Figure 1.2).
Corneocytes are approximately 35 μm in diameter, 1 μm thick and shield-like in shape.
The stratum corneum

Also known as the horny layer, this structure is the differentiated end-product of epidermal metabolism
(also known as differentiation or keratinization); the final step in differentiation is the dropping off of
individual corneocytes in the process of desquamation seen in Figure 1.2. The stratum corneum is
composed of 20–25 layers of cornified cells (keratinocytes), which appear as flat cells and do not
possess any nuclei or cytoplasmic organelles. The keratinocytes contain soft keratin. Lamellar bodies
are important structures present around these keratinocytes. Lipids are released from the lamellar
bodies, and these lipids contribute to the permeability of stratum corneum.
The corneocytes are joined together by the lipid and glycoprotein of the intercellular cement material
and by the vestiges of the desmosomes that are well developed in the keratinocytes of the epidermis (see
later). In the stratum corneum, they are known as ‘corneo-desmosomes’. The orderly release of cor
neocytes at the surface in the process of desquamation is not completely characterized, but it appears to
depend on the dissolution of the corneo-desmosomes near the surface by a cascade of enzymes, their
activators, and inhibitors, known collectively as ‘chymotrypsin’, which is activated by the presence of
moisture. On limb and trunk skin, the stratum corneum is some 15–20 cells thick and, as each cor
neocyte is about 1 μm thick, it is about 15–20 μm thick in absolute terms. The stratum corneum of the
palms and soles is about 0.5 μm thick and is, of course, much thicker than that on the trunk and limbs.
The stratum corneum prevents water loss, and when it is deranged, as, for example, in psoriasis or
eczema, water loss is greatly increased so that severe dehydration can occur if enough skin is affected. It
has been estimated that a patient with erythrodermic psoriasis (involvement of more than 90% body
surface area) may lose 6 L of water per day through the disordered stratum corneum, in contrast to 0.5 L
lost normally per day.
The stratum corneum also acts as a barrier to the penetration of chemical agents with which the skin
comes into contact with it. It prevents systemic poisoning from skin contact, although it must be realized
that it is not a complete barrier and percutaneous penetration of most agents does occur at a very slow
rate. Those responsible for formulating drugs in topical formulations are well aware of this rate-limiting
property for percutaneous penetration of the stratum corneum and try to find agents that accelerate the
movement of drugs into the skin. In recent years, as more knowledge has been acquired about the
penetrability of the stratum corneum and the pharmacokinetics of drugs, techniques have been
developed for the administration of drugs systemically via the skin – the transdermal route.
The barrier properties also prevent microbial life invading into the skin; however, the barrier prop
erties are not perfect, and, occasionally, pathogen gains entry via hair follicles or small cracks and
fissures and causes infection. Antimicrobial peptides – the cathelicidins – also play an important role
and some function at the stratum corneum level.
The structure of the stratum corneum is very extensible and compliant in health, permitting movement
of the hands and feet, and is actually quite tough, thus providing a degree of mechanical protection
against minor penetrative injury. The ability to extend is greatly aided by the system of skin surface
markings (varying by the region sampled), which take the form of rectangles and behave like
‘concertinas’ when stretched. The various functions of the skin have been summarized in Table 1.1.
The epidermis
The epidermis mainly contains keratinocytes; but it also contains non-keratinocytes – melanocytes and
Langerhans cells, both of which possess dendrites. This cellular structure is some three to five cell-
layers thick, on average, 35–50 μm thick in absolute terms. Not unexpectedly, the epidermis is about
two to three times thicker on the hands and feet, particularly the palms and soles. The epidermis is
indented by finger-like projections from the dermis known as the dermal papillae and rests on a complex
TABLE 1.1
Functions of the skin
Barrier function
• Permeability barrier to water and electrolytes

• Prevention of entry of microbes and chemicals
• Protection from ultraviolet rays
• Prevention of injury due to blunt objects
Maintenance of body temperature
Sensory functions
• Mechanoreceptors (touch, vibration, pressure)

• Thermoreceptors (heat and cold)
• Nociceptors (pain and itch)
• Free nerve endings
• Corpuscular receptors
Immunological functions
Synthesis of vitamin D and E
Transport of nutrients and metabolites
Sexual attraction
FIGURE 1.3 The junctional zone between epidermis and dermis (from Marks and Motley, Common Skin Diseases, 18E,
with permission).
junctional zone that consists of a basal lamina and a condensation of dermal connective tissue
(Figure 1.3).
The cells of the epidermis are mainly keratinocytes containing keratin tonofilaments, which originate
in the basal generative compartment and ascend through the Malpighian layer to the granular cell layer.
The keratin tonofilaments belong to the group of subcellular structures known as intermediate filaments.
They consist of polypeptides and their molecular weight ranges from 40 to 65 kD. It is thought that they
provide a semi-rigid endoskeleton, and because of their connection to the desmosomal apparatus, they
give strength to the epidermis as a whole. They are joined to the neighbouring keratinocytes by spe
cialized junctions known as desmosomes. These are visible as ‘prickles’ in formalin-fixed sections but
as alternating light and dark bands when viewed by transmission electron microscopy. In the granular
layer, they transform from a plump oval or rectangular shape to a more flattened profile and lose their
nucleus and cytoplasmic organelles. In addition, they develop basophilic granules containing a histidine-
rich protein known as filaggrin and minute, lipid-containing, membrane-bound structures known as
membrane-coating granules of lamellar bodies.
These alterations are part of the process of keratinization, during which the keratinocytes differentiate
into tough, disc-shaped corneocytes. Other changes include a reduction in water content from 70% in
the keratinocytes to 30% in the stratum corneum, and the laying down of a chemically resistant, cross-
linked protein band at the periphery of the corneocyte. This protein band is made up of the polypeptides
involucrin, loricrin, and cornifin. The peptides are cross-linked by gamma-glutamyl transpeptidase. Of
major importance to the barrier function of the stratum corneum is the intercellular lipid which, unlike
the phospholipid of the epidermis below, is mainly polar ceramide and derives from the minute lamellar
bodies of the granular cell layer.
It takes about 28 days for a new keratinocyte to ascend through the epidermis and stratum corneum
and desquamate off at the skin surface. This process is greatly accelerated in some inflammatory skin
disorders, notably psoriasis. Desquamation occurs by the loss of single corneocytes at the skin surface.
This process depends on the dissolution of the desmosomes by the action of chymotryptases, which
become activated near the surface.
Pigment-producing cells
Black pigment (melanin), a polymer synthesized by melanocytes, protects against solar ultraviolet radiation
(UVR). Melanocytes, unlike keratinocytes, do not have desmosomes but have long, branching dendritic
projections that transport the melanin they synthesize to the surrounding cells. They originate from the
embryonic neural crest. Melanocytes account for 5–10% of cells in the basal layer of the epidermis.
Melanin is a polymer that is synthesized from the amino acid tyrosine with the help of a copper-containing
enzyme, tyrosinase. Other pigments contribute rarely (e.g. bilirubin in jaundice or pigments derived from
drugs such as minocycline or chlorpromazine). Exposure to the sun accelerates melanin synthesis, which
explains suntanning. Skin color is mainly due to melanin and blood. The number of melanocytes per unit of
body surface area is variable, depending on the site of the body but the density of melanocytes is the same
in all humans, irrespective of race. The racial differences in complexion are attributed to the distribution
and size of melanosomes, which disperse melanin to the keratinocytes. Melanocytes are completely de
stroyed in vitiligo. In albinism, melanin synthesis is defective. Localized increase in the synthesis of
melanin leads to the development of freckles. Melanocytes in benign proliferation are referred to as nevi,
and the malignant ones are known as melanomas.
Langerhans cells
Langerhans cells are also dendritic cells but are found within the body of the epidermis in the
Malpighian layer rather than in the basal layer. They constitute 2–8% of the total epidermal cell po
pulation. They derive from the reticuloendothelial system and have the function of picking up ‘foreign’
material and presenting it to lymphocytes in the early stages of a delayed hypersensitivity reaction. They
are reduced in number after exposure to solar UVR, partially accounting for the depressed delayed
hypersensitivity reaction in chronically sun-exposed skin. Additionally, the number of Langerhans cells
is also reduced in psoriasis, sarcoidosis, contact dermatitis, etc.
Merkel cells
These are slow-adapting mechanoreceptors located in the basal layer of the epidermis. They are found in
digits, lips, oral cavity, and hair follicles. They have important clinical bearing because of the
association with the development of Merkel cell carcinoma and neuroendocrine carcinoma.
The junctional zone

The junctional zone has considerable functional importance and is vital to understanding the patho
physiology of bullous disorders and many other skin diseases. Figure 1.3 shows the main components of
the junctional zone. Desmosomal processes from the basal keratinocytes, known as hemidesmosomes,
are inserted into an electron-dense lamina (basal lamina). Below the electron-dense lamina, there is an
electron-lucent area (lamina lucida). The dermoepidermal junction is important from the clinical point
of view. When the component molecules do not function properly, the adhesive property of the junction
is lost and this leads to numerous bullous diseases, including bullous pemphigoid, cicatricial pemphi
goid, linear IgA disease, pemphigoid gestationis, epidermolysis bullosa acquisita, etc.
The dermis
The tissues of the dermis beneath the epidermis are important in giving mechanical protection to the
underlying body parts and in binding together all the superficial structures. It is composed primarily of
tough, fibrous collagen and a network of fibres of elastic tissue, as well as the vascular channels and
nerve fibres of the skin. The dermis is thinnest in the eyelids and thickest on the back. It contributes to
15–20% of the total body weight. There are about 20 different types of collagen, but the adult dermis is
made up mainly of types I and III, whereas type IV is a major constituent of the basal lamina of the
dermoepidermal junction. Type V collagen is found in papillary dermis and periadnexal areas. Type VI
collagen is present throughout the dermis and interfibrillar spaces. Type VII collagen is present in the
anchoring fibrils of the dermoepidermal junction. Between the fibres of collagen is a matrix composed
mainly of proteoglycan in which there are scattered fibroblasts that synthesize all the dermal compo
nents. Collagen bundles are composed of polypeptide chains arranged in a triple-helix format, in which
hydroxyproline forms an important constituent amino acid. The important cells of the dermis are
fibroblasts, monocytes, macrophages, dendrocytes, and mast cells.
The dermal vasculature

There are no blood vessels in the epidermis and the necessary oxygen and nutrients diffuse from the
capillaries in the dermal papillae. These capillaries arise from horizontally arranged plexuses in the
dermis. There are tiny arteriovenous shunts in the fingertips and other acral sites, which are referred to
as glomus bodies. Their walls contain abundant plain muscle. The glomus bodies are specially designed
for thermoregulation. The small lymphatic channels follow the blood capillaries but are distinguishable
by the thin delicate lymphatic endothelium. Defective cutaneous vasculature is seen in
Klippel–Trenaunay syndrome, Sturge–Weber syndrome, hereditary lymphedema, etc.
Nerve structures
Recently, very fine nerve fibres have been identified in the epidermis, but most of the fibres run
alongside the blood vessels in the dermal papillae and deeper in the dermis. There are several types of
specialized sensory receptor in the upper dermis that detect particular sensations. Free nerve endings
perceive touch, temperature, pain, and itch. Pacinian corpuscles respond to deep pressure and vibrations.
Other sensory receptors include Golgi-Mazzoni corpuscles, Krause end bulbs, Meissner’s corpuscle
(responding to dynamic pressure), Ruffini corpuscles (responding to stretching of the skin), and
mucocutaneous end organs.
The adnexal structures

The skin possesses specialized epidermal structures that can be regarded as invaginations of the surface
that are embedded in the dermis. These are the hair follicles and the eccrine and apocrine sweat glands.
Hair follicles
Hair follicles are arranged all over the skin surface apart from the palms and soles, the genital mucosa,
and the vermilion of the lips. Hair growth is asynchronous in humans but synchronous in many other
mammals. The hair follicles have a gland attached to them known as the sebaceous gland. The hair
FIGURE 1.4 The hair cycle.
shaft, the canal along which the shaft tracks to the surface, the hair matrix which produces the hair shaft
and sebaceous gland are together known as the pilosebaceous unit. The pilosebaceous units vary greatly
in size. In some areas (e.g. the face) the hair shafts are small and the sebaceous glands quite large. These
are known as sebaceous follicles and have importance in the pathogenesis of acne.
The different phases of our asynchronous hair growth occur independently in individual follicles but
are timed to occur together in synchronous hair growth, accounting for the phenomenon of moulting in
small, furry mammals. The phase of hair growth (anagen) is the longest phase of the hair cycle. A short
transition stage (catagen) is then reached. This is followed by a resting phase (telogen), which is
followed by anagen again somewhat later (Figure 1.4).
The hair shaft grows from highly active, modified epidermal tissue known as the hair matrix. The
shaft traverses the hair follicle canal, which is made up of a series of investing epidermal sheaths, the
most prominent of which is the external root sheath (Figure 1.5). The whole follicular structure is
nourished by a small, indenting cellular and vascular connective tissue papilla, which pokes into the
base of the matrix. The sebaceous gland secretes into the hair canal a lipid-rich substance known as
sebum, whose function is to lubricate the hair. Sebum contains triglycerides, cholesterol esters, wax
FIGURE 1.5 Components of a hair follicle: 1, medulla; 2, cortex; 3, cuticle of the hair; epithelial root sheath: 4, internal root
sheath, 5, external root sheath, 6, dermal root sheath; 7, hair matrix; 8, melanocyte; 9, papilla of the hair; 10, blood vessels.
esters, and squalene. Hair growth and sebum secretion are mainly under the control of androgens,
although other physiological variables may also influence these functions.
Eccrine sweat glands

The eccrine sweat glands are an extremely important part of the body’s homeothermic mechanism in
that the sweat secretion evaporates from the skin surface to produce a cooling effect. Apart from heat,
eccrine sweat secretion may also be stimulated by emotional factors and by fear and anxiety. Certain
body sites, such as the palms, soles, forehead, axillae and inguinal regions, secrete sweat selectively
during emotional stimulation. They are present everywhere in the skin except vermilion border of lips,
nail bed, external auditory canal, clitoris, and labia minora.
The eccrine sweat glands consist of a coiled secretory portion deep in the dermis next to the sub
cutaneous fat and a long, straight, tubular duct whose final portion is coiled and penetrates the epidermis
to drain at the sweat pore on the surface. The gland and its duct are lined by a single layer of secretory
cells and surrounded by myoepithelial cells. The secretion of eccrine sweat glands is basically an
aqueous solution of electrolytes. The disturbance in basic pathophysiology of sweat formation and
secretion leads to hyperhidrosis and hypohidrosis.
Apocrine sweat glands

The apocrine sweat glands drain directly into hair follicles. They are found in axillae, areolae, peri
umbilical areas, prepuce, mons pubis, labia minora, etc. Modified apocrine glands include ceruminous
glands of the ear, Moll’s glands on eyelids, and mammary glands. They are larger than eccrine sweat
glands and the secretion is completely different, being semi-solid and containing odiferous materials
that are thought to have the function of sexual attraction.
2
Signs and symptoms of skin disease
Anupam Das
Rashmi Sarkar
Skin disorders may be generalized, localized to one or several sites of abnormality known as ‘lesions’, or
eruptive, in which case, many lesions appear as spots over the skin. Currently, there are no adequate ex
planations for the distribution of skin lesions in case of most disorders, such as psoriasis or atopic dermatitis.
Any widespread abnormality of the skin may also affect the scalp, the mucosae of the mouth, nose,
eyes, and genitalia, and the nail-forming tissues, and it is important to inspect these sites whenever
possible during the examination of the skin.
The examination of skin revolves around certain terms that are very distinct from one another, and the
knowledge of these terms is quintessential to describing any dermatological entity. The basic lesions of the
skin are classified into three categories: primary, secondary, and special lesions. Primary lesions are basically
the original lesions of disease and need to be identified accurately in order to diagnose a condition.
Secondary lesions are produced as a result of trauma, itching, application of topical medications, etc.
Primary lesions
• Macule: circumscribed flat lesions less than 0.5 cm in diameter, without any elevation or
depression from the surrounding skin, e.g. vitiligo, leprosy, pityriasis versicolor, melasma
(Figure 2.1)
• Patch: circumscribed flat lesions more than 0.5 cm in diameter, without any elevation or
depression from the surrounding skin, e.g. port wine stain, leprosy, vitiligo, fixed drug rash (Figure 2.2)
• Papule: circumscribed solid elevated lesions less than 0.5 cm in diameter, e.g. acne, milium,
molluscum contagiosum, lichen planus, xanthoma, angiokeratoma (Figure 2.3)
• Plaque: circumscribed solid elevated lesions more than 0.5 cm in diameter, with a width greater
than the height, e.g. psoriasis, lupus vulgaris, chromoblastomycosis, cutaneous T cell lymphoma
(Figure 2.4)
• Nodule: circumscribed solid lesions more than 0.5 cm in diameter, with a depth greater than the
width (i.e., it has a definite palpable depth), e.g. leprosy, neurofibroma, nodulocystic acne,
xanthoma disseminatum (Figure 2.5)
• Tumor: soft to firm, fixed or mobile lesion of more than 2 cm diameter, e.g. neurofibroma,
lipoma, fibrolipoma (Figure 2.6)
• Vesicle: circumscribed fluid-filled lesion of less than 0.5 cm diameter, e.g. herpes simplex,
varicella, herpes zoster, pompholyx, contact dermatitis (Figure 2.7)
• Bulla: circumscribed fluid-filled lesion of more than 0.5 cm diameter, e.g. pemphigus vulgaris,
bullous pemphigoid, bullous drug reaction, friction blister (Figure 2.8)
• Pustule: circumscribed lesion of less than 0.5 cm diameter, containing purulent material (pus),
e.g. acne, impetigo, pustular psoriasis, acropustulosis (Figure 2.9)
• Wheal: circumscribed edematous evanescent plateau-like elevations of skin, e.g. urticaria,
bullous pemphigoid, urticarial vasculitis
9
FIGURE 2.1 Macules in vitiligo. FIGURE 2.2 Café-au-lait macules and patches in
neurofibromatosis.
FIGURE 2.3 Discrete papules in lichen nitidus. FIGURE 2.4 Plaque in lupus vulgaris.
Signs and symptoms of skin disease 11
Secondary lesions
• Scale: visible exfoliation of the skin,

e.g. psoriasis, pityriasis versicolor, exfoliative
dermatitis, seborrhoeic dermatitis, ichthyosis
(Figure 2.10)
• Crust: dried serum, pus, or blood admixed
with epithelial debris, e.g. impetigo, favus,
burns
• Excoriation: linear excavation produced as a
result of severe itching and scratching,
e.g. scabies, prurigo simplex, neurotic ex
coriation (Figure 2.11)
• Fissure: well-defined linear cleft in the epi
dermis, e.g. fissured sole, chapped lips
(Figure 2.12)
• Erosion: loss of superficial epidermis as a re
sult of a primary insult, heals without scarring,
e.g. impetigo, herpes simples, varicella
• Ulcer: localized defect in the skin due to loss
FIGURE 2.5 Nodular lesions in steatocystoma. of epidermis and a part of the dermis, heals
with scarring, e.g. venous ulcer, arterial ulcer,
decubitus ulcer, pyoderma gangrenosum
Special lesions
• Comedone: white or black plugs of sebaceous and keratinous material impacted within the pi
losebaceous follicle, e.g. acne, senile comedone (Figure 2.13)
• Burrow: serpiginous tunnel in the stratum corneum, e.g. scabies, larva migrans
• Telangiectasia: permanent superficial dilatation of capillaries, e.g. steroid abuse, discoid lupus
erythematosus, scleroderma
FIGURE 2.6 Tumor in cutaneous B cell lymphoma.

FIGURE 2.7 Grouped vesicles in herpes labialis. FIGURE 2.8 Bullous lesion in senile pemphigoid
[from Marks and Motley, 18th edition].
FIGURE 2.9 Pustules in miliaria pustulosa.

FIGURE 2.10 Furfuraceous scaling in pityriasis versicolor.
FIGURE 2.11 Excoriated papules in prurigo (from Marks and Motley, 18th edition).
• Milium: small superficial cysts with an epidermal lining, e.g. primary milia, epidermolysis
bullosa dystrophica, porphyria cutanea tarda
• Lichenification: a combination of thick skin, increased skin markings, and hyperpigmentation,
e.g. lichen simplex chronicus (Figure 2.14)
• Poikiloderma: combination of hypopigmentation, hyperpigmentation, telangiectasia, and atrophy,
e.g. cutaneous T cell lymphoma, dermatomyositis, radiation dermatitis
Alterations in skin color

The color of normal skin is dependent on melanin pigment production and the blood supply. The color
may also be altered by various exogenous or endogenous pigments. One of the most common
accompaniments of skin disease is redness or erythema.
Erythema
The degree of erythema depends on the degree of oxygenation of the blood, its rate of flow and the site,
and the number and size of the skin’s blood vessels. Different disorders tend to be associated with
particular shades of red due to characteristic alterations in the blood vessels and surrounding tissues.
• Psoriatic plaques: dark red (Figure 2.15)

• Lichen planus: mauve hue
• Dermatomyositis: the color of the heliotrope
flower (Figure 2.16)
FIGURE 2.12 Painful fissures in popliteal fossa in

atopic dermatitis (from Marks and Motley, 18th edition). FIGURE 2.13 Senile comedones.
FIGURE 2.14 Lichenification with scaling and accentuation of skin markings (from Marks and Motley, 18th edition).
Brown–black pigmentation
The degree of brown–black pigmentation de
pends on the activity of melanocytes. It also
depends on the size of the granules and the
distribution of the pigment particles within the
epidermal cells. Shedding of the pigment from
damaged keratinocytes into the dermis is known
as pigmentary incontinence and causes a kind of
tattooing in which the dusky pigment produced
persists for many weeks, months, or even years,
usually in macrophages.
• Brown pigmentation: caused by a break

down product of blood (haemosiderin),
when this has leaked into the tissues
(Figure 2.17)
• Brown–black discoloration of the skin
over cartilaginous structures: alkaptonuria
(Osler’s sign), due to deposition of
homogentisic acid
• Dark brown pigmentation of acne scars or
of areas on the limbs: minocycline
• Generalized darkening of the skin: may be
more pronounced in the flexures in
FIGURE 2.15 Plaques of psoriasis with typical red Addison’s disease, results from increased
color (from Marks and Motley, 18th edition). secretion of melanocyte-stimulating hor
mone and the consequent activation of the
melanocytes to produce more pigment; darkening of the palmar creases and mucosae may be seen
as well
• White color: vitiligo, albinism, leukoderma, etc.
Symptoms of skin disease

Skin disease causes pruritus (itching), pain, soreness and discomfort, difficulty with movements of the
hands and fingers, cosmetic disability, etc.
Pruritus
Itching is the classic symptom of skin disorders, but it may also occur in the apparent absence of
skin disease. Any skin abnormality can give rise to irritation, but some, such as scabies, seem
particularly capable of causing severe pruritus. Most scabies patients complain that their symptom
of itching is much worse at night when they are warm. Itching in atopic dermatitis, senile pruritus,
and senile xerosis is made worse by repeated bathing and vigorous towelling afterwards, as well as
by central heating and air conditioning with low relative humidity. Clothing made from rough
fabrics often aggravates itching – woollen garments are notorious for this problem and patients
should be advised to wear only smooth, silky garments next to the skin. If pruritus is made worse
by aspirin or food additives such as tartrazine, sodium benzoate, or cinnamates, it is quite likely that
urticaria is to blame.
FIGURE 2.17 Lower legs of a patient with chronic

FIGURE 2.16 Reddened areas on the face in derma venous hypertension and brown pigmentation due to
tomyositis, showing typical heliotrope discoloration hemosiderin deposits (from Marks and Motley, 18th
(from Marks and Motley, 18th edition). edition).
Persistent severe pruritus can be the most disabling and distressing symptom and is quite difficult to
treat. Scratching provides partial and transient relief from the symptom and it is fruitless to request
that the patient stops scratching. Scratching itself causes damage to the skin surface, which is
visible as scratch marks (excoriations). In some patients, the repeated scratching and rubbing cause
lichenification and in others, prurigo papules occur. Occasionally, the scratch marks become in
fected. Uncommonly, the underlying disorder occurs at the site of the injury from the scratch. This
phenomenon is found in patients with psoriasis and lichen planus and is known as the isomorphic
response or the Koebner phenomenon. Uncommonly, infection may be spread by scratching and
lines of viral warts or molluscum contagiosa may develop in excoriations.
Painful skin disorders

Most skin disorders do not give rise to pain. The notable exception to this is herpes zoster, which may
cause pain and distorted sensations in the nerve root involved. The pain may be present before the skin
lesions appear, while they are there and, occasionally, afterwards. Pain and tenderness are char
acteristic of acutely inflamed lesions such as boils, acne cysts, cellulitis, and erythema nodosum. Most
skin tumors are not painful, at least until they enlarge and infiltrate nerves. However, there are some
benign tumors that cause pain like blue rubber bleb nevus, leiomyoma, eccrine spiradenoma,
neuroma, dermatofibroma, angiolipoma, neurilemmoma, endometrioma, glomus tumor, granular cell
tumor, etc.
Chronic ulcers are often ‘sore’ and cause a variety of other discomforts, but they are not often the
cause of severe pain. When they do give rise to severe pain, ischaemia is usually the cause. Painful
fissures in the palms and soles develop in patches of eczema and psoriasis due to the inelastic, abnormal,
horny layer in these conditions.
Disabilities from skin disease

Patients with skin disease may experience a surprising degree of disability. A very major cause of
disability is the abnormal appearance of the affected skin. For reasons that are not altogether clear, there
is a primitive fear of diseased skin, which even amounts to feelings of disgust and revulsion. The idea of
touching skin that is scaling or exudative seems inherently distasteful and it is something that most try to
avoid. It is little use pointing out that there is no rational basis for these attitudes, and all that can be
hoped for is that a mixture of comprehension, compassion, and common sense, eventually tinged with
pragmatism, supplants a primitive revulsion based on the contagious nature of leprosy and the
infestations of scabies and lice. It is only too abundantly evident that individuals with obvious skin
disease have social problems: they not only suffer more unemployment overall but also find great
difficulty in obtaining positions that require any kind of interpersonal relationships.
Young patients with acne have particular problems because the disease is visible, as it usually affects
the face. Psoriasis quite often affects the hands, nails, and scalp margin, also causing difficulty for those
whose occupations put them into contact with the public. Numerous other skin disorders put the affected
individual at an economic and social disadvantage. Vascular birthmarks and large neurofibromas are
disfiguring and tend to isolate the bearers. Chronic inflammatory facial disorders, such as rosacea and
discoid lupus erythematosus, also cause problems (Figure 2.18).
To summarize this point, individuals with visibly disordered skin are disabled because of society’s
inherent avoidance reaction. Another aspect of this problem is the sufferer’s own perception of the
impact they are making on all with whom they come in contact. Most individuals who have persistent,
‘unsightly’ skin problems become depressed and isolated. Skin problems are especially damaging for
those in their late teens and twenties who are desperately trying to make relationships at a time when
self-confidence is not at a high point; a disfiguring skin disorder lowers self-esteem further. Many
youngsters with acne and psoriasis find it difficult to conquer their embarrassment sufficiently to have
romantic partners, and that aspect of their development may become stunted. It was once thought that
many skin disorders were caused by neurotic traits,

‘stress’, and personality diseases; it is now increas
ingly appreciated that skin disorders themselves
often cause depression, anxiety, and stress.
Skin disease can be enormously physically dis
abling when it affects the palms or soles. Although
the areas affected only occupy about 1–2% of the
body skin surface, disease of these sites may prevent
walking or even standing and use of the hands for
anything but simple tasks, i.e. they are virtually
completely disabled. Psoriasis and eczema are the
usual causes of this form of disablement because of
the painful fissures that tend to develop in these
conditions. Patients with severe atopic dermatitis
may develop similar painful fissures around the
popliteal and antecubital fossae, so that limb
movements become extremely painful. Those with
severe congenital disorders of keratinization are
often severely troubled by this disordered mobility.
From what has been said so far, it will be appre
ciated that, contrary to popular belief, patients with
skin disorders are often appreciably disabled. They
are disabled on account of society’s and their own
reaction to the appearance of their skin disease and
FIGURE 2.18 Plaques of erythema, scaling and hy because of the physical limitations that the skin
perkeratosis in a man with discoid lupus erythematosus disease puts on them. Skin disease occasionally kills
(from Marks and Motley, 18th edition).
but often produces much unhappiness, usually
through loss of work and social and emotional de
privation, as well as considerable physical
discomfort.
To summarize, it is crucial to meticulously examine each and every patient with a dermatological
problem because, in this era of technologies and investigations, dermatology is the only specialty where
the clinicians rely on their eyes and examination skills to diagnose a disease and, fortunately, the need to
go for investigations is negligible.
3
Skin infections
Shankila Mittal
Rashmi Sarkar
The skin surface and its adnexal structures harbor many commensal organisms, including Gram-positive
cocci (Staphylococcus epidermidis, coagulase-negative staphylococci), Gram-positive lipophilic mi
croaerophilic rods (Propionibacterium acnes), and a Gram-positive yeast-like organism (Malassezia
furfur). However, under special conditions – e.g., excess sebum secretion, depressed immunity, and
compromised stratum corneum barrier protection – they can cause disease. Additionally, various
pathogenic microorganisms can cause skin infection, especially when the skin barrier is disrupted.
Fungal diseases of the skin

Superficial mycoses
Superficial mycoses are limited to the outermost layer of the skin, hair, nails, and are classified as:
• Pityriasis versicolor
• Dermatophytosis
• Tinea nigra
• Black piedra
• White piedra
• Otomycosis
• Onychomycosis
• Superficial mycosis by other non-dermatophytic moulds
• Cutaneous and mucocutaneous candidiasis
Pityriasis versicolor
Incidence
Very common in the tropics. Most commonly seen in adolescence and young adulthood.
Pathogenesis
Lipophilic yeasts, Pityrosporum orbiculare (round form) and Pityrosporum ovale (oval form) (now
invalid and reclassified as Malassezia), are normal inhabitants of the skin. M. sympodialis, M. globosa,
M. restricta, M. slooffiae, M. furfur, M. obtusa, M. dermatis, M. japonica, M. yamotoensis, M. nana,
M. caprae, M. equina, and M. cuniculi are the different species identified by genetic analysis. These
organisms change from the saprophytic spore form to the pathogenic hyphae form by heightened rates
of sebum secretion or depressed immunity. Depigmentation is due to the azelaic acid produced by
Malassezia, which inhibits tyrosinase activity when activated by sunlight.
19
Risk factors
Pregnancy, malnutrition, immunosuppression, oral contraception, excess heat, and humidity (heavy
clothing with perspiration).
Clinical features
• Morphology: lesions are characterized by discrete or confluent, scaly, discolored, or depigmented

areas, mainly on the upper trunk.
• Site: the trunk is the most common site; other sites include the face, upper arm, and groin
(Figure 3.1). Facial lesions are more common in children.
• In the untanned white skin, the affected areas appear darker than normal, but they fail to respond
to light exposure; in the suntanned subject, the affected skin is usually paler, as it usually is in
black people. Lesions may sometimes show some degree of atrophy.
Differential diagnosis
Vitiligo, secondary syphilis, pityriasis alba, seborrheic dermatitis, and pityriasis rosea.
Investigations
Diagnosis is primarily clinical and is confirmed by demonstrating the hyphae and spores of Malassezia
furfur using 10% potassium hydroxide. Large, blunt hyphae and thick-walled, budding spores forming a
‘spaghetti and meatballs’ appearance can be observed under the low power lens of a microscope.
Treatment
• Non-pharmacologic therapy: Sunlight accelerates pigmentation of residual hypopigmented areas

after treatment.
• Acute general Rx: Topical therapy forms the mainstay of treatment and should be the first-line
therapy. Oral treatment is required in cases of extensive involvement and in case recalcitrant
patients do not respond to topical therapy (Table 3.1).
FIGURE 3.1 Hypopigmented macules with furfuraceous scaling in pityriasis versicolor.

Skin infections 21
TABLE 3.1
Treatment modalities for pityriasis versicolor
Topical Systemic
Ketoconazole 2% shampoo for 10 min * 2 weeks Ketoconazole 200 mg OD for 7 days,
or 400-mg stat
Clotrimazole , Econazole , Miconazole BD * 2–3 weeks Fluconazole 400 mg stat
Selenium sulfide 2.5% suspension for 15 min OD * 7 days; Itraconazole 200 mg/day for 5 days
repeated weekly for 1 month, then monthly for maintenance or 400 mg stat
Terbinafine 1% cream BD * 15 days
• Course and complications: The prognosis is good, with the clearance of the fungus after 3–4 weeks
of treatment; however, recurrence is common.
Tinea (Ringworm) infections/Dermatophytic infections

Dermatophyte infections are keratophilic fungi restricted to the stratum corneum, the hair, and the nails
(i.e. horny structures).
Causative organism
Trichophyton, Microsporum, and Epidermophyton species are responsible for this group of dermato
phyte infections. Microsporum affects the skin and hair; epidermophyton affects the skin and nails;
trichophyton affects all three sites.
The species causing dermatophytic infection can be classified as:
• Anthropophilic – e.g., Epidermophyton floccosum, Trichophyton mentagrophytes var. Interdigitale,

Trichophyton rubrum, Trichophyton schoenleinii, Trichophyton soudanense, Trichophyton ton
surans, Trichophyton violaceum, etc.
• Zoophilic – Microsporum canis (dogs, cats), T. verrucosum (cattle) and T. equinum (horses).
• Geophilic – Microsporum gypseum, Microsporum praecox
Morphology of typical lesions

Centrifugally spreading annular/circinate plaque. The centre is clear with papules, papulo-vesicles,
pustules, and scaling on active margin (Figure 3.2).
Tinea infection is classified according to the site infected: the head (capitis), face (faciei), torso
(corporis), hands (manuum), nails (unguium), groin (cruris), or foot (pedis).
Transmission: transmitted by human to human, animal to human, or soil to human contact through
arthrospores shed by a host in skin scales.
Clinical features of ringworm infection

Tinea corporis
This is the ringworm of the skin of the body or limbs. Pruritic, round or annular, red, scaling, well-
marginated patches are typical (Figure 3.3). When an animal species is involved (e.g., T. verrucosum),
the affected skin is inflamed and pustular, and heals spontaneously after a few weeks.
Differential diagnosis: Discoid eczema, psoriasis

(a)
CLEAR CENTRE
OR
LICHENIFICATION
(In Chronic)
SCALES
ANNULAR PLAQUE PAPULES At Margin
PUSTULES (Indicate Activity)
VESICLES
PICTORIAL REPRE SENTATION OF

TYPICAL LESION OF TINEA
(b)
FIGURE 3.2 (a,b) Morphology of typical tinea lesion: annular plaque with papules, papulovesicles, pustules, and scaling
on active margin.
FIGURE 3.3 Well-demarcated scaling patch due to ringworm (from Marks and Motley, 18th edition, with permission).
Skin infections 23
Tinea cruris
Well-defined, itchy, red scaling patches occur asymmetrically on the medial aspects of both groins.
These gradually extend down the thigh and on to the scrotum unless treated. T. rubrum and E. floccosum
are the causative fungi.
• Predisposing factors: Summers, tight-fitting clothes
• Differential diagnosis: Seborrhoeic dermatitis, intertrigo, flexural psoriasis
Tinea pedis
Tinea pedis is very common and particularly so in young and middle-aged men. It tends to be
itchy and persistent. T. rubrum, in particular, and T. mentagrophytes and E. floccosum cause
the infection.
• Predisposing factors: Humidity, occlusive footwear, communal changing rooms, onychomycosis
Ringworm infection of the feet may be

• Vesicular: itchy vesicles occurring on the sides of the feet on a background of erythema
• Dry-type infection: the sole is red and scaly
• Interdigital infection: skin between the fourth and fifth toes, in particular, is scaly and
macerated
• In a patient presenting with pompholyx, always examine the feet as tinea pedis may be associated
with it
Tinea manuum
• Dermatophytic infection of the palmar aspect of the hand

This less common, chronic form mostly caused by T. rubrum usually involves one palm which is dull
red with silvery scales in the palmar creases. One hand–two feet syndrome is the term used for a classic
presentation involving 2 feet and 1 hand by tinea.
Tinea capitis
Ringworm of the scalp is often due to M. canis. In recent years, T. tonsurans has been increasingly seen
as the cause of a subtle form of tinea capitis, particularly in those of African-Caribbean origin.
• Age group: Mainly children
Fungi may invade scalp stratum corneum and the hair cuticle (ectothrix infection), causing pink,
scaling patches on the scalp skin and areas of hair loss due to the breakage of hair shafts (Figure 3.4) or
invade the interior of the hair shaft (endothrix).
Patterns of tinea capitis are recognized as:
• Non-inflammatory
◦ Present as patches of hair loss with scaling and easily pluckable hairs.
◦ Mostly caused by anthropophilic organisms, e.g., T. tonsurans.
◦ Can appear as black dot or grey patch with little inflammation.
• Inflammatory (Kerion)
◦ Present as painful boggy swelling with loss of hairs, studded with pustules with sinus
formation, matted hairs may be present (Figure 3.5).
◦ Mostly caused by zoophilic species but rarely by anthropophilic if a high degree of
hypersensitivity develops.
FIGURE 3.4 Scaling area with hair loss in tinea capitis (from Marks and Motley 18th edition, with permission).
• Favus
◦ Caused by T. schoenleinii.
◦ Presents with yellowish cup-shaped crusts developing round the hairs (scutula).
◦ May develop scarring alopecia.
Tinea unguium
Ringworm infection of the nail plate and the nail bed.
• Causative organism: Dermatophytes associated with hand and foot infections (T. rubrum,
T. mentagrophytes or E. floccosum) or scalp infections (T. tonsurans, T. violaceum, T. soudanensei).
• Predisposing factors: Walking barefoot, wearing ill-fitting shoes, poor peripheral circulation,
trauma to nails.
FIGURE 3.5 Painful boggy swelling with loss of hairs and pustules.
Skin infections 25
FIGURE 3.6 Tinea unguium and pedis.
• Clinical features: It is seen more commonly in the toenails than in the fingernails. Infected nail
plates are discolored yellowish or white and thickened. Onycholysis occurs and subungual debris
collects (subungual hyperkeratosis, Figure 3.6). Tinea unguium has to be distinguished from
psoriasis of the nails.
Tinea incognito
This is extensive ringworm with an atypical appearance due to the inappropriate use of topical corti
costeroids (Figure 3.7). The corticosteroids
suppress the protective inflammatory response
of the skin to the ringworm fungus, allowing it
to spread with absence of typical annular con
figuration and scaling. Fungal infection should
always be ruled out if a suspected eczematous
lesion is not responding to treatment with
steroids.
Diagnosis
Sample collection:
a. Skin: with scalpel blades from the ac

tive margin. If there is no margin, then
scales/generalized scraping taken.
b. Hair: Dermatophytosis: remove hairs
with the roots intact, brush samples can
be taken.
c. Nails:
i. Distal lateral subungual onychomy
FIGURE 3.7 Tinea cruris showing extensive and
cosis: debride from the most proxi
unusual-looking infection due to tinea incognito (from mally involved part of the nail
Marks and Motley, 18th edition, with permission). (undersurface of nails).
FIGURE 3.8 KOH hair mount showing branching fungal hyphae.
ii. Superficial white onychomycosis: superficial scrapings from nail plate.

iii. Proximal subungual onychomycosis: proximal nail plate (undersurface).
• Microscopy: mounted in 10–30% KOH and branching fungal hyphae identified (Figure 3.8). Use
of fluorescent markers like acridine orange, Calcofluor white, or Blankophor in some laboratories
has improved the diagnostic sensitivity of direct microscopy for the identification of fungal
hyphae.
• Culture: culture may be positive when direct microscopy is not, but it takes 2–3 weeks or longer
before the culture is ready to read. Glucose/peptone agar, or Sabouraud’s dextrose agar may be
used. Antibacterial antibiotics like gentamycin (0.0025%) and cycloheximide may be added to
reduce contamination. Avoid cycloheximide if non-dermatophyte moulds are suspected.
• Wood’s lamp examination: helps in diagnosis of tinea capitis as some fungal infections especially
some ectothrix and favus fluoresce green under Wood’s light. It may serve as an important tool for
screening asymptomatic family members and school children during epidemics.
Treatment
Key points for management for tinea infections:
• Avoid excessive heat and moisture

• Wear loose-fitted cotton clothes
• Weight reduction for obese patients
• Avoid sharing of clothes, towel, and combs
• Treat all affected family members
• Treat concomitant onychomycosis or tinea pedis
• Examine pets for focus of fungal infection
• Continue topical management for at least 2 more weeks after resolution of lesions (Table 3.2)
Skin infections 27
TABLE 3.2
Treatment of different types of dermatophytic infections
Infection Drug Dose Duration Others
Tinea capitis Griseofulvin 10–20 mg/kg/d 6–8 wks • Avoid sharing of hairbrushes
(DOC) • Add ketoconazole shampoo to
reduce transmission
Terbinafine 10–20kg to 62.5 mg 6 wks
20–40kg to 125 mg
>40kg to 250 mg
Tinea cruris/ Terbinafine 250 mg OD 1–2 wks Topical therapy preferred
corporis Itraconazole 100 mg OD 1–2 wks Topical Terbinafine or imidazoles BD
for 2 wks
Fluconazole 150 mg/wks 2–4 wks
Systemic therapy when multiple areas
Griseofulvin 500 mg BD 4 wks are affected and topical treatment has
failed
Tinea mannum/ Terbinafine 250 mg OD 2 wks Keep feet dry
pedis Itraconazole 200 mg BD 1–2 wks Topical therapy
Terbinafine or imidazoles BD for
4 wks
Tinea unguium Terbinafine 250 mg OD 6 wks for Topical therapy like amorolfine nail
fingernails lacquer and ciclopirox olamine nail
12 wks for lacquer may be added
toenails
Itraconazole 100 mg BD 6 wks for
fingernails
12 wks for
toenails
200 mg BD (pulse 2 pulses for
for one week for fingernails
each month) 3 pulses for
toenails
Candidiasis (Moniliasis, Thrush)

• Causative organism: Yeast pathogen (Candida albicans) that also resides in the gastrointestinal
tract as a commensal.
• Predisposing factors: Moisture, immunosuppression, pregnancy, oral contraceptives, broad-
spectrum antibiotics for acne, obesity, diabetes mellitus.
Cutaneous candidiasis can present as

• Stomatitis
• Angular cheilitis
• Intertrigo
• Napkin candidiasis in infancy
• Vulvovaginal candidiasis
• Candidal balanitis
• Candidal paronychia
Candidal intertrigo presents with erythema of skin folds with subcorneal pustules and satellite lesions
(Figure 3.9).
• Diagnosis: Potassium hydroxide (KOH) mount showing budding yeast and pseudohyphae. Always
rule out diabetes or immunosuppression in case of recurrent infection.
FIGURE 3.9 Candidiasis showing satellite lesions
• Treatment: Eliminate the predisposing factor and avoid moisture. Topical therapy such as
polyenes (nystatin) and imidazole preparations (miconazole, clotrimazole, and econazole) is
effective. Systemic therapy in various forms of candidiasis is as shown in Table 3.3.
Deep fungul infection

There are several fungal species that cause deep and sometimes life-threatening infection. They can be
subcutaneous (involving dermis, subcutaneous tissue, adjacent bone) or systemic (originate in lungs,
spread to other organs).
Subcutaneous fungal infections include:
• Mycetoma/Madura foot
• Chromoblastomycosis
• Sporotrichosis
• Rhinosporidiosis
• Lobomycosis
• Phaeohyphomycotic cyst
Sporotrichosis may produce a series of inflamed nodules along the line of lymphatic drainage. Deep
fungul infections of this type produce a granulomatous type of inflammation, with many giant cells and
histiocytes as well as polymorphs and lymphocytes. Madura foot is a deep fungul infection of the foot
and is seen in various countries of the African continent and India. The affected foot is swollen and
infiltrated by inflammatory tissue, with many sinuses (Figure 3.10). The infection spreads throughout
the foot, invades bone, and is very destructive and disabling.
TABLE 3.3
Systemic therapy for various forms of candidiasis
Infection Drug Dose Duration
Oropharyngeal candidiasis Fluconazole 100–200 mg OD 7 days
Itraconazole 100 mg OD 7 days
Vulvovaginal candidiasis Fluconazole 150 mg Stat
Candidal onychomycosis Fluconazole 300 mg/wk 4 wks for fingernails
12 wks for toenails
Itraconazole 200 mg BD for 7 days/month 2–3 cycles
Skin infections 29
FIGURE 3.10 Mycetoma with swelling of foot and discharging sinuses.

Systemic fungal infections include
• Aspergillosis • Cerebral chromomycosis
• Blastomycosis • Histoplasmosis
• Candidiasis • Mucormycosis
• Cryptococcosis • Paracoccidioidomycosis
• Coccidioidomycosis • Penicilliosis
They are much more common in immunocompromised patients, including those with acquired immune
deficiency syndrome (AIDS), transplant recipients, those on corticosteroids or immunosuppressive
agents, and those with congenital immunodeficiencies. Some, such as histoplasmosis, cryptococcosis,
and coccidioidomycosis, are widespread systemic infections, which only occasionally involve the skin.
Bacterial infection of the skin

Most skin infections are caused by Gram-positive organisms – staphylococci and streptococci. The
primary skin infections caused by them may or may not be purulent and can be classified as follows.
Direct infection of the skin

• Impetigo • Cellulitis (occasionally)
• Folliculitis • Damage from bacterial toxin
• Furunculosis • Toxic shock syndrome
• Carbuncle • Staphylococcal scalded skin syndrome
• Ecthyma • Staphylococcal scarlatina
• Sycosis • Recurrent toxin-mediated perineal erythema
Predisposing factors: scabies, atopic dermatitis, overcrowding, poor personal hygiene, insect bite,
diabetes, malnutrition.
Impetigo contagiosa
• Causative organism: Staphylococcus aureus in most instances or β-haemolytic streptococci in few.
• Age group: preschool and young children
FIGURE 3.11 Patch of impetigo on the nose (from Marks and Motley, 18th edition, with permission).
• Clinical features: Red, sore areas, which may blister, appear on the exposed skin surface (Figure 3.11).
A yellowish-gold crust surmounts the lesions that appear and spreads within a few days with peripheral
extension without central healing (Figure 3.12). It is, however, not uncommon for the signs of the
lesions to appear over an area of eczema. The condition is then said to be ‘impetiginized’.
Bullous impetigo
• Causative organism: Staphylococcus aureus
• Age group: All ages (common in children)
• Clinical features: Present with bulla lasting
about 2–3 days which rupture and thin brownish
crust forms. Lesions spread with peripheral
extension and central healing forming circinate
lesions
Ecthyma
• Causative organism: β-haemolytic streptococci
(mostly) or staphylococci
• Clinical features: pustule forms on erythematous
skin followed by adherent crusting which on re
moval with difficulty reveals underlying ulcer.
• Complication: risk of post-streptococcal
glomerulonephritis in cases of streptococcal
infection. However, it does not predispose to
rheumatic fever.
• Investigation: routine investigation is not needed.
However, if the infection is recurrent/resistant to
FIGURE 3.12 Yellowish golden crust of nonbullous treatment or MRSA is suspected, then a pus cul
impetigo. ture and sensitivity should be sent.
Skin infections 31
TABLE 3.4
Treatments for bullous impetigo
Specific Management
Topical (for limited disease) Mupirocin (1st line)
Retapamulin
Fusidic acid
Neomycin (staphylococci > streptococci)
Gentian violet
Systemic (ideally 7-day course) Dicloxacillin (250 mg qid)
Cephalexin (250 mg qid)
Amoxyxilllin-clavulanate (500 mg/125 mg tds)
Erythromycin (250 mg qid)
If MRSA suspected:
Cotrimoxazole (800/160 mg bd)
Clindamycin (300–400 mg qid)
Doxycycline (100 mg bd)
Minocycline (100 mg bd)
Linezolid (600 mg bd)
Treatment
General measures
• Clean the area with soap and wash/antiseptic

washes like povidone iodine, chlorhexidine
• Avoid sharing of towels, maintain personal
hygiene
• Treat any underlying skin condition like ec
zema, scabies, pediculosis
Specific management
Some treatment approaches for bullous impetigo
are presented in Table 3.4.
Topical therapy is effective for limited disease.
Indications for systemic therapy include

• Extensive skin involvement
• Fever, lymph node enlargement
• Suspected infection by nephritogenic strep
tococcal strains
Erysipelas (St. Anthony’s Fire)

Erysipelas is a bacterial infection of the dermis and
upper subcutaneous tissue.
FIGURE 3.13 Erysipelas of the right cheek; the area • Causative organism: β-haemolytic
of erythema has been outlined in order to monitor the streptococcus.
response to treatment (from Marks and Motley, 18th • Clinical features: Characterized by sudden
edition, with permission).
onset of a well-marginated, painful, and
swollen erythematous area, usually on the face
or lower limbs (Figure 3.13). The inflamma

tion may be very intense and the area may
become haemorrhagic and even blister. There
is usually accompanying pyrexia and malaise.
Cellulitis
This is a diffuse, inflammatory disorder of the
subcutis and skin.
• Causative organism: this is caused most
commonly by β-haemolytic streptococci;
occasionally, S. areus also implicated. H.
influenza B may be responsible for facial
cellulitis in children
Clinical features
It is relatively common, particularly on the limbs,
and often occurs on legs affected by venous ul
ceration or by lymphoedema. There is pain, ten
derness, slight swelling, and a variable degree of
diffuse erythema. There is often a breach in the skin
surface – frequently fissuring in the toe webs due to
intertrigo – as the portal of entry of the infection.
Treatment of erysipelas and cellulitis

• Rest, elevation of the affected part
• Treating predisposing factors
• Patient has to be admitted if associated with
comorbidities or severe involvement (skin
blistering, necrosis)
• Mild cases: oral antibiotics
◦ Penicillin V, 250 mg qid daily
◦ Dicloxacillin 250 mg qid daily
FIGURE 3.14 (a,b) Folliculitis. ◦ Amoxicillin-clavulanate 625mg TDS
◦ Cephalexin 250 mg qid
• If MRSA is suspected:
◦ Linezolid 600 mg bd
◦ Cotrimoxazole, doxycycline or minocycline along with a β-lactam antibiotic to cover streptococci.
• Severe cases: parenteral antibiotics (ceftriaxone/penicillin/clindamycin/vancomycin) required

followed by oral therapy after clinical improvement.
Folliculitis, furuncles (boils), and carbuncles

• Causative organism: S. aureus
Folliculitis is inflammation of the hair follicle with changes confined to follicular infundibulum (Figure 3.14).
A furuncle is an infection of the hair follicle and perifollicular tissue, which presents as a follicular,
inflammatory nodule with pus formation.
Skin infections 33
A carbuncle is an infection of contiguous hair follicles

presenting as painful red swelling with pus discharging
from multiple follicular orifices (Figure 3.15). Patients
with impaired blood sugar are particularly at risk.
Treatment
•
Gram stain and culture of pus recommended
from carbuncles and furuncle
• Maintain good personal hygiene
• Clean site and hands with soap and water
• Avoid sharing towels, clothes, razors
FIGURE 3.15 Painful red swelling with pus dischar • Incision and drainage
ging from multiple follicular orifices. • Topical antibiotics
• Systemic antibiotics based on sensitivity pattern
may be needed, if abscess is difficult to drain, there is no response to treatment, the patient is
immunocompromised, or there are accompanying cellulitis or systemic symptoms
Antibiotics are effective in various skin and soft tissue infections by staphylococcus and streptococci are
shown in Table 3.5.
Management of recurrent staphylococcal infections
• Send pus culture sensitivity and prescribe antibiotics accordingly.

• Promote regular handwashing with soap and water by the patient as well as the caregivers.
• Regular decontamination of towels and clothes.
• Decolonization
◦ Nasal decolonization may be done with twice daily application of mupirocin for 10 days.
◦ Body decolonization with antiseptic solutions like chlorhexidine (5–14 days) or dilute bleach
baths (1 teaspoon of bleaching powder in 1 gallon of water or ¼ cup of bleaching powder per
¼ tub of water or 13 gallons of water) twice a week for 15 minutes for 3 months.
◦ All carriage sites like nasal, axilla, and perineum should be treated.
◦ Oral rifampicin 600 mg daily for 7–10 days may be used with due caution to the risk of resistance.
TABLE 3.5
Antibiotic treatments for staphylococcal and streptococcal soft tissue infections (1,2)
Sensitivity Antibiotic
MSSA Dicloxacillin
Amoxicillin
Cephalexin
Erythromycin azithromycin
MRSA Topical drugs: mupirocin, retapamulin
Oral drugs: clindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), tetracycline (doxycycline or
minocycline), linezolid, rifampicin
IV drugs: intravenous (IV) vancomycin (A-I), oral (PO) or IV linezolid 600 mg twice daily (A-I),
daptomycin 4 mg/kg/dose IV once daily (A-I), telavancin 10 mg/kg/dose IV once daily (A-I), and
clindamycin 600 mg IV or PO 3 times a day, ceftaroline fosamil, quinupristin-dalfopristin
Newer drugs: tedizolid, dalbavancin, oritavancin
1 Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious
Diseases Society of America.
2 Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant
Staphylococcus aureus Infections in Adults and Children.
TABLE 3.6
Classification of cutaneous tuberculosis
Immunity Multi/Paucibacillary Inoculation Disease
of host (M/P)
Naïve host M Direct inoculation Tuberculosis chancre (primary
inoculation)
Low host M Contiguous spread Scrofuloderma
immunity Autoinoculation Orificial tuberculosis
Haematogenous spread Acute Miliary tuberculosis
Tuberculous gumma (abscess)
High host P Direct inoculation Warty tuberculosis (verruca cutis)
immunity Direct inoculation Lupus vulgaris
Haematogenous spread
Tuberculids Lichen scrofulosorum
Papulonecrotic tuberculid
Erythema induratum (Bazin)
Nodular tuberculid
Anthrax
• Causative organism: Gram-positive bacillus (Bacillus anthracis)
Anthrax is due to a rare, potentially fatal infection-causing black, scabbed sores and septicaemia. It is
spread by farm animals and because the microorganism has a resistant spore form, it can stay on
infected land for years. It has assumed major importance because of its potential for use in bioterrorism.
Tuberculosis
Tuberculosis is a multi-system disease caused by varieties of the waxy-enveloped bacterium
Mycobacterium tuberculosis. Tuberculosis is, unfortunately, now once again becoming common and
multiple-drug resistant strains of M. tuberculosis are becoming a major problem in communities with a
high prevalence of HIV infection. Cutaneous tuberculosis has been classified as shown in Table 3.6.
• Diagnosis: The bacillus can be cultured in special media in vitro, but grows very slowly. Special
stains are needed to detect it in tissue.
Lupus vulgaris
Lupus vulgaris presents as a slowly progressive, granulomatous plaque on the skin, head and neck
followed by arms and legs (buttocks in developing countries) caused by the tubercle bacillus. It slowly
increases in size, over one to three decades. It often has a thickened psoriasiform appearance, grows by
peripheral extension with areas of atrophy and scarring.
Blanching with a glass microscope slide (diascopy) will reveal ‘apple jelly nodules’ due to the un
derlying granulomatous inflammation. Diagnosis can be confirmed with biopsy showing tuberculoid
granulomas.
Tuberculosis verrucosa Cutis (warty tuberculosis)

This is commonly seen on the back of the hands, knees, elbows, and buttocks whenever abrasive contact
with the earth and expectorated tubercle bacilli occurs. Thickened, warty plaques are present, which are
sometimes misdiagnosed as viral warts. Diagnosis is confirmed by biopsy samples showing tuberculoid
granulomata and caseation necrosis.
Skin infections 35
FIGURE 3.16 Puckered scarring of scrofuloderma.
Scrofuloderma
An eroded, weeping area with bluish margins often develops where a tuberculous sinus drains onto the
skin from an underlying focus of tuberculosis infection which heals with puckered scarring
(Figure 3.16).
Other forms of cutaneous tuberculosis

Tuberculous chancre: a persistent ulcer may arise at the site of inoculation as a ‘primary’ infection.
Tuberculides may develop as hypersensitivity to the tubercle bacillus.
• Lichen scrofulosorum: lichenoid eruptions of papules predominantly in children often peri

follicular develop on abdomen, chest, and back (Figure 3.17).
• Papulonecrotic tuberculide: papules arise and develop central necrosis with a black crust.
• Erythema induratum: uncommon disorder, which in many cases appears to fulfil the criterion
of being a response to tuberculous infection. It is characterized by the development of plaque-like
areas of induration and necrosis on the lower calves and occurs predominantly in young women.
Treatment of cutaneous tuberculosis

Intensive phase: isoniazid, rifampicin, ethambutol, and pyrazinamide for 2 months
Continuation phase: isoniazid and rifampicin for 4 months
Some other mycobacterial infections

Swimming pool granuloma
Mycobacterium marinum, which lives in water, is sometimes caught from swimming pools and fish
tanks. It has a 3-week incubation period and causes plaques, abscesses, and erosions on the elbows and
knees, in particular (Figure 3.18).
The condition usually responds to minocycline, although occasionally other antibiotic combinations
are required, as determined by the sensitivity of the cultured organism.
FIGURE 3.17 Lichen scrofulosorum
FIGURE 3.18 Mycobacterium marinum infection in

the dorsum of the hand with ‘sporotrichoid’ spread into
the forearm (from Marks and Motley, 18th edition, with
permission).
Buruli ulcer
Mycobacterium ulcerans is responsible for this disorder occurring in Uganda and south-east Asia.
Large, undermined ulcers form quite rapidly and persist. Surgical removal is currently the best
treatment.
Leprosy (Hansen’s disease)

• Causative organism: Slow-growing bacillus, Mycobacterium leprae, which cannot be grown in
vitro, although it can be passaged in armadillos and small rodents. As with the tubercle bacillus, it
is detected in tissue by the Ziehl–Nielsen stain or by an immunocytochemical test.
• Transmission: The disease is spread by droplet infection and by close contact with an infected
individual.
It is still a serious problem globally, with one to two million people affected, mostly in the poor and
underprivileged countries of Africa and Asia.
Clinical features
The pattern of involvement is highly dependent on the immune status of the individual.
It shows involvement of skin and nerve characterized by hypopigmented lesions and peripheral
nerve thickening. The two extremes are the lepromatous form seen in anergic individuals and the
tuberculoid form seen in individuals with a high resistance. Because there are many gradations be
tween these polar types, the range of clinical signs and the corresponding nomenclature have become
very complicated.
Where the changes are near tuberculoid, the term ‘borderline tuberculoid’ is used; similarly, ‘bor
derline lepromatous’ is used for lesions that are close to the other type. ‘Dimorphic’ refers to
Skin infections 37
characteristics of both types of lesion being present. In tuberculoid lesions, nerves are infected, which
become thickened. The affected areas are well defined, macular and hypopigmented, as well as an
aesthetic because of the nerve involvement. The anaesthesia results in injury, deformity, and disability.
In lepromatous leprosy, the infection is much more extensive, with thickening of the affected tissue as
well as surface changes, with some hypopigmentation. On the face, the thickening gives rise to the
characteristic leonine facies, with accentuation of the soft tissues of the nose and supraorbital areas.
In general, the disease can produce dreadful deformity and disability unless skilfully treated, and it
still evokes great fear in traditional communities. Because the disorder causes patchy hypopigmentation,
the differential diagnosis includes vitiligo, pityriasis versicolor, and pityriasis alba.
In tuberculoid types, there is a striking granulomatous inflammation with many giant cells and only a
few M. leprae to be found. In the lepromatous types, there are many macrophages stuffed with M. leprae
(causing the appearance of foamy macrophages).
Treatment
See Table 3.7.
Lyme disease
• Causative organism: Borrelia burgdorferi
• Spread by (vector): Bite of a tick
This has been described in several areas of Europe, including the UK, and in the United States. It is a
multi-system disease with arthropathy, cardiovascular, and central nervous components, as well as
systemic upset. The skin may be involved in the early stages and show an erythematous ring that
expands outwards (erythema chronicum migrans). In late stages, skin atrophy may be seen (acro
dermatitis chronica atrophicans), or fibrosis in a morphoea-like condition. Diagnosis is made by
identification of the organism in the tissues or by detection of antibodies in the blood.
• Treatment: Doxycycline, 200 mg/day for 3 weeks
Leishmaniasis
This term refers to a group of diseases caused by a genus of closely related protozoal parasites with
complex lifecycles, which include time spent in small rodents. These diseases are spread by biting
arthropods (mostly sandflies) in tropical and subtropical areas. Some forms cause severe systemic
disease and are prevalent in some areas of Africa and South America and the Indian subcontinent; others
cause predominantly cutaneous or mucocutaneous disease.
• Cutaneous forms are found around the Mediterranean littoral and North Africa and in South
America. The ‘Mediterranean’ type is caused by Leishmania major and L. tropica. After an
incubation period of about 2 months, a boil-like lesion appears, usually on an exposed site
(‘Baghdad boil’). Later, this breaks down to produce a sloughy ulcer (‘oriental sore’:
TABLE 3.7
Multidrug therapy for leprosy (WHO regimen)
Type Drug Frequency Adult dose
Paucibacillary Rifampicin Monthly 600 mg
(total duration—6 months) Dapsone Daily 100 mg
Multibacillary Rifampicin Monthly 600 mg
(total duration—12 months) Dapsone Daily 100 mg
Clofazimine Monthly 300 mg
Daily 50 mg
Figure 3.19), which persists for some

months before healing spontaneously, with
scarring and the development of immunity.
• Mucocutaneous forms occur mainly in South
America (New World leishmaniasis) and are
due to L. mexicana and L. brasiliensis. Small
ulcers develop (Chiclero’s ulcer) that seem
more destructive than the Old World types but
also more persistent, and later in the disease
destructive lesions appear, affecting the nasal
mucosa in about half of patients. A cutaneous
component to visceral forms is less common,
but more extensive, and includes a diffuse
cutaneous form with many plaques and no
dules resembling lepromatous leprosy, a re
cidivans form with persistent plaques
resembling lupus vulgaris, and post kala-azar
FIGURE 3.19 Cutaneous leishmaniasis in a boy, (dermal leishmaniasis), occurring after the
showing persistent plaque and papules on the skin of the visceral disease and marked by the appear
cheek (from Marks and Motley, 18th edition, with
ance of numerous small papules.
permission).
Biopsy sections show mixed granulomatous in
flammation. The parasites can be identified by
special stains and can also be cultured in specialized media. There is also an intracutaneous
test (Leishmanin test) which is positive if the skin becomes inflamed and indurated 48–72 hours after
injection of a measured amount of Leishmanin antigen, which indicates present or previous infection.
Treatment
The localized small ulcers heal spontaneously but can be treated by freezing or curettage. Infiltration with
sodium stibogluconate has been used. Amphotericin B deoxycholate, Miltefosine, Liposomal amphotericin B,
Pentavalent antimonial are used in management.
Viral infections of the skin

Herpesviruses
Herpesviruses are enveloped DNA viruses producing typical intranuclear inclusion bodies. They are
classified into α, β, and γ (Table 3.8).
TABLE 3.8
Classification of herpesviruses
Subgroup Virus
α Human simplex virus 1 (HSV1)
Human simplex virus 2 (HSV2)
Varicella zoster virus (VZV)
β Cytomegalovirus (CMV)
Human herpesvirus 6 (HHV6)
Human-herpesvirus 7 (HHV 7)
γ Epstein-Barr virus (EBV)
Human herpesvirus 8 (HHV 8)
Skin infections 39
Herpes simplex
Causative organism: HSV-1, HSV-2
• Herpes labialis: HSV-1 >HSV-2

• Herpes genitalis: HSV-2 >HSV-1
Mode of transmission: Direct contact of skin

or mucosa.
Clinical features
Primary infection has greater severity than re
current episodes.
• Herpetic gingivostomatitis: Commonly, the
lesions occur around the mouth or on the lip.
They start as grouped, tender and/or painful pa
pules or papulovesicles (Figure 3.20) and then
coalesce to form a crusted erosion. The sequence
takes about 7–14 days from initial discomfort to
the final pink macule, marking where lesions
have been. The initial infection may be quite
unpleasant, with severe stomatitis, systemic upset
and pyrexia. Resolution takes place in about 10
days. Reactivation of the herpes infection occurs
in some cases, at varying intervals. Up to 20% of
the population develops recurrent ‘cold sores’, so
named because the disorder is often precipitated
by minor pyrexial episodes.
• Herpes genitalis: Genital herpes in males af
fects the glans penis and the shaft of the penis.
In females, the vulval region or labia minora is
usually involved, but lesions may occur else
where on the buttocks or mons pubis. The dis
order is sexually transmitted and has become
extremely common. Recurrences are more
common with HSV-2 with recurrent episodes
FIGURE 3.20 (a,b) Anogenital warts being less painful and of shorter duration.
• Herpes gladiatorum: Crops of vesicles and
pustules on face, scalp, and upper trunk
transmitted by skin-to-skin contact, common
in wrestlers.
• Precipitating factors for recurrences: Minor trauma, febrile illnesses, upper respiratory tract in
fections, trigeminal neuralgia, laser resurfacing, menstruation.
Diagnosis
• Direct microscopy: Tzanck Smear-acantholytic cells or multinucleated giant cells on giemsa stain
• Immunofluorescent method with antibodies to the herpesvirus
• Viral culture
• Polymerase chain reaction
TABLE 3.9
Treatment of herpes infections
Disease Treatment
First episode Recurrent disease
Episodic disease Suppressive therapy
Herpes labialis Acyclovir 400 mg tds * 10 days Acyclovir 400 mg tds * 5 days Acyclovir 400 mg bd
Acyclovir 200 mg 5 times a Valcyclovir 2 g bd * 1 day
day * 10 days
Valcyclovir 1 g bd * 10 days
Herpes genitalis Acyclovir 400 mg tds * 10 days Acyclovir 400 mg tds * 5 days Acyclovir 400 mg bd
Famciclovir 250 mg tds * Valacyclovir 500 mg bd * 3 days Valacyclovir 500 mg od
10 days OR
Valacyclovir 1 g od
(>10 episode/yr)
Valcyclovir 1 g bd * 10 days Famciclovir 500 mg od, followed Famiciclovir 250 mg bd
by 250 mg bd * 2 days
Varicella & Herpes Oral Acyclovir 800 mg
zoster 5 times a day
Treatment
Most patients do not require treatment. Treatment may be needed for severe episodes and is effective
only if initiated early (Table 3.9).
Herpes zoster (shingles) and chicken pox (varicella)

• Causative organism: Varicella zoster virus is a small DNA virus causing both zoster and chicken
pox, which differ only in the extent of the disease, the symptoms caused, and the immune status of
the individual affected.
Varicella
• Transmission: Highly contagious. Spread by droplets and debris from the lesions. Infectious for
1–2 days before rash to 4–5 days after until all the vesicles crust.
• Incubation period: 4–21 days
• Age group: Childhood, rarely adults
Clinical features
• Prodrome: Fever and malaise
• Rash: Begins on the face and trunk relatively spare extremities (centripetal). Pleomorphic lesions
with macules, papules, papulovesicles which crust, the crust dropping off after some 7–14 days,
leaving pock-type scars in many instances. Oral mucosa may be involved.
Complications
Rarely complicated in children. Secondary bacterial infection, secondary bacterial pneumonia, and otitis
media may occur rarely. Complications are more frequent in adults.
Treatment
For most people, no specific treatment is required apart from keeping the lesions clean and, if necessary,
the application of antimicrobial preparations to prevent or combat secondary infection.
Skin infections 41
Oral acyclovir 800 mg five times a day within 24 hrs of the onset of rash shortens the duration of
disease and decreases its severity.
Prevention
Live attenuated (oka strain) VZV vaccines.
Herpes zoster (shingles)

• Transmission: Due to the reactivation of latent virus in a posterior root ganglion of a spinal nerve.
In immunosuppressed individuals, the disorder is often very severe and may involve several
dermatomes.
• Age group: Mostly affects individuals over the age of 50 years, but it also affects im
munosuppressed individuals, such as patients with AIDS or lymphomas.
• Sites of predilection: Branches of the trigeminal ganglion, dermatomes of the cervical and
thoracic regions.
Clinical features
The disorder often starts with paraesthesias or pain in the distribution of one or more dermatomes.
Erythema followed by vesicles appears in segmental distribution (Figure 3.21). Later, the vesicles
become pustular and then crust.
• Complications
• Post-herpetic neuralgia: about 25–30% of patients with shingles continue to have pain and
paraesthesiae in the affected dermatome long after the skin lesions have disappeared.
• Secondary bacterial infection
• Treatment: Acyclovir reduces duration and severity of pain and healing time for rash if started
within 72 hrs of onset of rash (same dose as varicella).
• Prevention: FDA has approved zoster vaccine in 2006 for adults over 60 years of age.
Viral warts
• Causative organism: Human papillomavirus (a small DNA virus) which has many antigenic types
(Table 3.1). Particular clinical types of wart are caused by particular antigenic types.
• Transmission: Direct contact of skin with wart virus-containing horny debris. Genital warts are
caught mostly (but not exclusively) by venereal contact. Some perianal warts may be transmitted
by homosexual contact or by ‘child abuse’. Vertical transmission can rarely occur from mother to
infant presenting as laryngeal papilloma or genital warts.
Clinical types
• Verruca vulgaris: single/multiple papules with verrucous surface

• Periungual warts
• Verruca plana: multiple flat smooth papules with pseudokoebnerization
• Filiform warts: thin elongated projections
• Palmoplantar warts
• Anogenital warts
The different varieties are illustrated in Figures 3.20, 3.22, and 3.23.
• Histopathology: Epidermal thickening, with acanthosis and koilocytes in upper layers, granular
layer shows a characteristic basophilic, stippled appearance (Figure 3.24).
FIGURE 3.21 (a,b) Herpes zoster in dermatomal distribution.
• Course of disease: All warts disappear spontaneously but may persist for many months or some years.
Treatment
Treatment is not very satisfactory and includes:
• Local tissue destruction

◦ Cryotherapy (tissue freezing with liquid nitrogen or solid carbon dioxide)
◦ Curettage
◦ Cautery
◦ Chemical destruction with topical preparations containing salicylic acid, lactic acid, podo
phyllin, or glutaraldehyde. Popular preparations contain high concentrations of salicylic acid
(12–20%) and lactic acid (4–20%) or podophyllin 10–25% (for genital warts)
• Other methods—intracutaneous injections of cytotoxics such as bleomycin, injections of re
combinant interferon, and use of vesicants such as cantharidin, CO2 laser.
Skin infections 43
FIGURE 3.22 Verruca vulgaris on face. FIGURE 3.23 Giant molluscum contagiosum.
Molluscum contagiosum
• Causative organism: pox virus group (molluscum contagiosum virus)
• Transmission: skin-to-skin contact
• Age group: schoolchildren, immunosuppressed
• Incubation period: 14 days to 6 months
Clinical features
The typical molluscum lesion is a pink-colored or pearly white umbilicated papule (Figure 3.23). There
may be one or many lesions. Pseudokoebnerization is observed. The face and genital regions
(Figure 3.24) are commonly involved.
Pathology
Cells proliferate to form lobulated pear-shaped epi
dermal growths separated by fibrous septa. Cells at the
centre show characteristic degenerative change and
appear as globular eosinophilic bodies in the cyto
plasm (molluscum bodies).
Treatment
Mollusca may resolve spontaneously. Treatment
modalities include curettage and cautery, salicylic acid
preparations, brief applications of cantharidin, or me
FIGURE 3.24 Genital molluscum contagiosum. chanical removal.
Orf (contagious pustular dermatitis of

sheep)
• Casuative organism: Parapox virus that
mostly affects sheep, but also cattle.
• Transmission: Direct inoculation with infected
material. Seen in butchers, meat porters, and
cooks.
• Clinical features: The lesions are solitary,
acute, inflammatory, and blistering and are
mostly on the fingers (Figure 3.25). Following
the attack, a surprisingly high proportion of
patients develop erythema multiforme.
Treatment
Spontaneous recovery occurs. Treat secondary
infection.
FIGURE 3.25 Area of orf infection on the

thumb (from Marks and Motley, 18th edi
tion, with permission).
4
Infestations, insect bites, and stings
Sumit Sethi
The way that the skin reacts to the attacks of arthropods and small invertebrates depends partly on the
extent and severity of the attack and, particularly, on the immune status of the individual attacked.
Each geographical region has its own spectrum of skin problems due to the local fauna. Although
some disorders, such as scabies, are the same the world over, the pattern and incidence of infestations
and bites differ markedly from place to place. In general, the extent of skin problems due to arthropods
is directly related to the sophistication and wealth of the society in question, because of the effects of
personal hygiene, education, effective waste disposal, and prophylaxis.
Scabies
Scabies is caused by infestation with the human scabies mite (Sarcoptes scabiei var. homini). The mite
is a host-specific, obligate parasite and has no separate existence off the human body. The key pre
senting features are intense pruritus and a similar history in close contact. The diagnosis is confirmed by
demonstrating the scabies mite in the patient’s skin.
Aetiology and epidemiology

The female mite burrows into the human stratum corneum and lays eggs within this very superficial
layer. (The male is smaller than the female and dies shortly after impregnating the female.) The
characteristic intense pruritus and eczematous rash in scabies are a result of the affected individual
becoming sensitive to the waste products of the mites within the intra-corneal burrows. This generally
takes 4–6 weeks from the initial invasion of the mite; but subsequent re-infestations cause signs and
symptoms within 24–48 hours, as the individual is already sensitized.
Infestation occurs after close skin-to-skin contact with an infected individual. Fomite transmission is
also possible in case of crusted scabies. In most adults with symptoms, there are no more than 10–15
mites within the skin; however, the number may reach millions in crusted scabies.
There have been several notable pandemics of scabies in recent history, making it notorious as the ‘7-year
itch’. The most recent of these started in the mid-1960s and ended in the early 1970s, although between
peaks of incidence, the disorder continues to appear sporadically and in localized mini-epidemics – such as
within families or in nursing homes.
Clinical features
The diagnosis of scabies is based on a history of pruritus associated with a characteristic dis
tribution of lesions and epidemiologic pattern (e.g. pruritus in close contacts). The pruritus is in
tense and is classically accentuated at night, or after a hot bath, and might be present before any
overt physical signs. Cutaneous lesions comprise small erythematous papules associated with a
variable degree of excoriation (Figure 4.1). They are symmetrically distributed, typically involving
the interdigital webs, sides of fingers, volar aspect of the wrists, lateral palms, axillae, posterior
45
FIGURE 4.1 Papules and excoriations in scabies.
auricular area, elbows, waist (including the umbilicus), ankles, feet, and buttocks. In men, penis and
scrotum are commonly involved, while the areolae, nipples, and vulvar areas are most often affected
in women. The lesions tend to avoid areas with a high density of pilosebaceous follicles; thus, the
head and neck are usually spared in adults while the involvement of these areas is frequent in
infants, the elderly, and the immunocompromised. Eczematous dermatitis, vesicles, indurated no
dules and secondary bacterial infection with Streptococcus pyogenes or Staphylococcus aureus is
commonly seen. The pathognomonic sign of scabies is the burrow, which represents the tunnel
excavated by the female mite while laying eggs. The burrow is a wavy, thread-like, greyish-white
lesion 1–10 mm in length (Figure 4.2). Acral vesiculopustules can represent a clue to the diagnosis
of scabies in infants.
The severity of the eruption depends on the number of mites present on cutaneous surface and the immune
status of the patient. In individuals with defective immunologic or sensory response – such as human im
munodeficiency virus (HIV) infection, patients receiving immunosuppressive drugs, frail elderly, and those
who unable to respond to itch by scratching, due to
paralysis or mental retardation – the infestation is very
severe, known as Norwegian or crusted scabies.
Diagnosis
The burrows of the female scabies mite are pa
thognomonic of the disease, and diagnostic of in
fection. The burrows are grey-white, linear,
slightly raised marks, 1–8 mm long, and present on
the favored sites such as hands, finger webs,
wrists, the instep of feet, and male genitalia
(Figure 4.3). A dermatoscope characteristically
illuminates the burrow and shows the female mite
at one end as a small dark semicircular spot with a
triangular point ‘jet with contrail’ sign. A defini
tive diagnosis can also be made by microscopic
FIGURE 4.2 Scabies burrow on the foot (from Marks identification of the scabies mites, eggs, or fecal
and Motley, 18th edition, with permission). pellets (scybala).
Infestations, insect bites, and stings 47
FIGURE 4.3 Scabies burrow in the interdigital space of the hand.
For patients in whom burrows cannot be identified, a positive family or social history with itching
contacts is helpful evidence and, in the presence of a compatible clinical picture, treatment may be
instituted by the experienced clinician. Unfortunately, it is all too common for patients to be suspected
of having scabies and to be prescribed treatment by inexperienced clinicians when the underlying
diagnosis is, in fact, eczema, and the patient’s skin deteriorates further as a result. The differential
diagnosis is set out in Table 4.1.
Treatment
Treatment should be instituted as soon as the diagnosis has been made to prevent the infestation
from spreading. It should also be offered to everyone who lives with the patient and to all his or
her sexual contacts, who should use the treatment at the same time as the patient. The 5% per
methrin lotion or cream employed are applied to the whole skin surface below the neck and ears.
Treatment should be in contact with the skin for a minimum of 12 hours or overnight. All contacts
of index case should be treated simultaneously, and the treatment should be repeated 7 days later
to kill any new mites that might have emerged from eggs. The particular agents used are set out in
Table 4.2.
Community outbreaks and crusted (Norwegian) scabies

Crusted scabies has a different clinical presentation from sporadic scabies and represents an altered host
response to the infestation; the mite is no different. The term ‘Norwegian’ scabies should be discarded
in favor of ‘crusted’ scabies, which more accurately reflects the clinical presentation. It manifests as
TABLE 4.1
Differential diagnosis of scabies
Disorder Comment
Canine scabies Different distribution – self-limited – not transmitted between humans
Eczematous diseases Particularly atopic dermatitis – usually a history of eczema is present in the patient or family
Dermatitis herpetiformis different distribution; vesicles and urticarial lesions more prominent – biopsy discriminates
Pediculosis Presence of lice and nits
hyperkeratotic crusted plaques developing diffusely on the palmar and plantar surfaces, with thickening
and dystrophy of the fingernails and toenails.
Whenever there is an outbreak of scabies in a community, it is essential to look for patients with
crusted scabies, who act as a reservoir for the condition and perpetuate the outbreak.
Individuals with crusted scabies should be isolated. They may require several repeated courses of
topical permethrin treatment or oral ivermectin and their clothing and bedding should be treated as
infectious and washed at a high temperature.
Community treatment of scabies

When scabies is identified within a community it is important to ensure thorough treatment
of all affected individuals and their contacts to eliminate the condition. Because of the common
occurrence of asymptomatic mite carriers in the household, all family members and close contacts
of the index case should be treated simultaneously. No individual should be permitted to re-enter
the ‘community’ until they have been treated (whether for the condition or as a contact), and
wherever possible, all members of the community should be treated simultaneously to prevent
re-infestation.
Animal scabies
The species of mite that causes scabies in animals is similar to the one that causes human scabies but
does not give rise to scabies infestation in humans. Contact with infested animals may cause transient
lesions in humans skin at the sites of contact, and, occasionally, living animal scabies mites have been
found in human skin but burrows have not been. Sarcoptic mange may be seen in horses, cattle, pigs,
monkeys, guinea pigs, sheep, and goats, but the most common animal scabies to cause problems is
that found in dogs or cats. The correct management approach is to treat the animal appropriately on
veterinary advice and to give any topical anti-itch preparation to the human patient for the affected
site. With proven human scabies infestation, it is important to look for the human contacts, not the
animal contacts.
Pediculosis
Pediculosis is the result of infestation with one of the varieties of the human louse: (1) Pediculus
humanus capitis, the head louse; (2) Pediculus humanus humanus, the body or clothing louse; and
(3) Phthirus pubis, the pubic, or crab, louse.
TABLE 4.2
Treatments used for scabies
Agent Percentage Comment
Permethrin 5% Treatment of choice
Benzyl benzoate 25% Apply twice in 24 hours and repeat on the third day, very irritant
6–10% Sulphur in petrolatum ointment A traditional treatment, irritant but inexpensive
Oral ivermectin Single dose of 200 micrograms/kg: repeated after 7–10 days
For crusted scabies combination of oral with topical treatments is preferred.
Pediculosis capitis (head lice)

Infestation with P. capitis is extremely common and is most frequently seen in children between the
ages of 3 and 12. Although once more often seen in the poorer sections of society, the head louse is now
seen in long-haired schoolchildren, regardless of their social background. It is more common during
times of social upheaval, such as war. The louse is transmitted among children by close head-to-head
contact or by fomites through brushes, combs, blow dryers, hair accessories, pillows, upholstery,
helmets, bedding, or other headgear.
Clinical features
The average incubation period is 4–6 weeks. Itching is the predominant complaint. Some individuals are
asymptomatic, despite infestation and considered to be ‘carriers’. The scratching that results can cause sec
ondary infection with exudation and crusting, but if this does not occur, all that may be seen are excoriations,
erythema, scaling, and red papules on the skin surface. Other clinical findings include a low-grade fever and
regional lymphadenopathy. Examination of the hair will reveal the louse eggs (nits) stuck to the hair shaft
(Figure 4.4). Careful inspection will also detect the adult louse itself, which is less than 1 mm long and greyish
or, after feeding, reddish in hue. When it moves, it deserves the description of ‘mobile dandruff’. Infestations
are diagnosed by demonstrating egg capsules (nits) and live lice. Nits are readily seen by the naked eye, most
commonly in the occipital and retroauricular regions, and are an efficient marker of past or present infestation.
They need to be differentiated from dandruff, hair casts, as nits are not easily dislodged from the hair shaft.
Newly laid or viable eggs are tan to brown in color while the remains of hatched eggs are clear, white, or light
in color. The presence of adult lice or viable nits within 1 inch of the scalp is confirmatory of active infestation.
seborrhoeic dermatitis (dandruff), insect bites, eczema, psoriasis, hair gel spray, pseudonits, piedra.
Treatment
The treatments used are set out in Table 4.3. 1% permethrin cream rinse is recommended as first line
therapy. Ivermectin lotion is approved for children 6 months or older for head lice. Care must be taken
to ensure that all close friends and family are also treated. A further treatment 7 days later is also
FIGURE 4.4 Louse eggs (nits) in hair.

TABLE 4.3
Treatments for pediculosis
Agent Percentage Comment
Malathion 0.5% Both lotion (aqueous and alcoholic) and shampoo
Spinosad 0.9% Topical suspension
Dimethicone 4.0% Asphyxiating agent
Ulesfia 5% Containing benzyl alcohol
Permethrin 1.0% Creamy rinse for head lice
Permethrin 5.0% Dermal crème, for crab lice, not recommended for head lice
Because no treatment is reliably ovicidal, retreatment after 1 week is reasonable.
necessary to kill off all the young lice that may have hatched from the nits that remained alive after the
initial treatment.
Pediculosis corporis (body lice)

Infestation with body lice is common in homeless individuals, victims of war, refugees and natural
disasters, or those forced into crowded living conditions and socially deprived communities with poor
hygiene. Transmission is via infested clothes or bedding or by close contact with the infected subject.
The failure to wash or change clothes after exposure allows the infestation to persist. The body louse is
responsible for the transmission of epidemic typhus, which is due to Rickettsia prowazekii, as well as
trench fever (caused by B. quintana), and relapsing fever due to Borrelia recurrentis. The body louse
spends most of its time attached to the seams of clothing, where the nits should be sought if the disorder
is suspected.
Clinical features
Itching, without a great deal to see to account for the symptom, is usual in the early stages. Some
excoriations mostly linear and primarily on the back, neck, shoulders, and waist; blood crusts and bluish
marks on the skin where the louse has fed may also be seen. Later in the disease, lichenification, and
eczema complete the picture of ‘vagabond’s disease’.
Treatment
Destruction and/or disinfestation of all clothes and bedding of the infested individual, the individual’s
family, friends, and close contacts are necessary. The patient should be treated from head to toe with a
pediculicide (Table 4.3) or given oral ivermectin. Repeat treatment after 1 month is advised.
Pediculosis pubis (pubic lice, crab lice)

The pubic louse (Phthirus pubis) looks different from the head and body lice, as it is broader, with crab-
like rear legs. It is mostly spread by sexual contact. The crab lice cling tenaciously to pubic hair, nipping
down to skin level every so often to have a blood meal. In heavy infestations, the lice spread to body hair
and even to the eyebrows and eyelashes. Sometimes they are found in moustache, beard, axillae, and scalp
hair. Slate grey to bluish, irregular shaped macules about 1 cm in diameter representing haemorrhage from
louse bite named maculae cerulea can be seen. Pediculosis palpebrarum, or phthiriasis palpebrarum, is the
infestation of the eyelashes with crab lice.
Diagnosis is confirmed on finding the louse and/or its nits by microscopic examination of the
plucked hair.
Treatment
A pediculicide (see Table 4.3) should be used, with repeat treatment after 1 month. Ivermectin is the
first-line therapy for phthiriasis palpebrarum. Shaving of pubic hair is sometimes advised but is not
necessary. All sexual contacts should be treated.
Insect bites and stings

A vast number of flying, jumping, and crawling arthropods are capable of causing injury in a variety of
ways to human skin. Some are capable of transmitting disease, and a few important examples of this are
given in Table 4.4 (see also Table 4.5).
Mosquitoes
Mosquito bites tend to be in exposed areas. Some varieties of mosquito (e.g. the culicine mosquitoes)
can cause blisters when they bite. The bites may be extremely itchy and prominent (Figure 4.5) and may
become infected after being scratched.
Fleas
Flea bites are mainly sustained from cat and dog fleas, which occasionally temporarily ‘visit’ a human
host. They drop off their original hosts and live on carpets and rugs, as do their young, and jump up when
they feel the vibration of footsteps. The bites, which are small and itchy, are often, but not exclusively, on
the legs and usually distributed in a linear fashion. Unfed, fleas can enter a state of hibernation and remain
TABLE 4.4
Examples of important arthropod-spread diseases
Disease Arthropod Microorganism
Malaria Mosquitoes (Anopheles species) Malaria parasitea (Plasmodium species)
Trypanosomiasis (sleeping sickness) Tsetse fly Trypanosoma bruceia
Leishmaniasis Sandfly (Phlebotomus species)
Visceral Leishmania donovania
Cutaneous Leishmania tropica
Mucocutaneous Leishmania braziliensisa
Onchocerciasis Blackfly (Similium species) Onchocerca volvulus
Bubonic plague Rat flea Yersinia pestis (formerly Pasteurella pestis)
TABLE 4.5
Examples of methods of injury to the skin by arthropods
Mechanism Arthropod
Bites from piercing and cutting mouthpieces – injection of saliva Mosquitoes, ticks, sandflies, blackflies
Stings from ‘purpose-built’ structures with an injection of toxic materials Wasps, bees, scorpions, jellyfish
Release of toxic body fluids after being on the skin surface, causing ‘Blister beetles’ – cantharidin (Figure 4.10)
blistering crushed
dormant in soft furnishings for up to 2 years, awakening in the presence of a new potential host. As a
result, it is possible for humans to get flea bites long after the departure of the host animal.
Ticks
Ticks stay stuck to the skin for some time after biting and are found mainly in agricultural communities,
as the principal host is mostly sheep. They may be the vector for a variety of infectious conditions, such
as typhus and Lyme disease (Figure 4.6).
Mites
There is a large variety of mites that occasionally may bite humans. Most of these, such as bird mites or
Cheyletellia mites living on cats, dogs, and rabbits (among others) cause small, red, itchy papules and
are quite difficult to identify (Figure 4.7).
FIGURE 4.5 Mosquito bites on the leg (from Marks and Motley, 18th edition, with permission).
FIGURE 4.6 Erythema migrans: annular erythema after a tick bite.

Bedbugs (Cimex lectularius)

This primitive creature lives in the woodwork of old houses and comes out at night to bite its sleeping
victims. The bites are often quite large and inflamed and arranged in straight lines where the creature has
taken a ‘stroll’ over the skin surface. In recent years, bedbug bites have become more frequent and a
problem for hotels.
Wasps and bees

The stings of wasps and bees are usually quite painful. The stung part may become very swollen a short
time after the sting and when hypersensitivity is present, the individual may develop a widespread
reaction. Rarely, such a reaction can cause anaphylactic shock and even death.
Papular urticaria
Papular urticaria is a term used to describe a recurrent, disseminated, itchy papular eruption due to either
insect bites or hypersensitivity to them.
Diagnosis
The lesions themselves should be compatible, i.e., they should be papules or, less commonly, blisters,
and it helps if puncture marks can be found in the lesion. It is commonplace for the patients (or their
parents) to deny the possibility of insect bites being responsible for the lesions, as there seems to be a
social stigma attached to being the recipient of them. A detailed history is necessary, with particular
attention being given to the presence of domestic animals, proximity to farms, the occurrence of similar
lesions in other family members, and the periodicity of lesions.
Biopsy may occasionally be helpful in that it may well rule out other disorders. The presence of a
mixed inflammatory cell infiltrate in the upper and mid-dermis is typical, but the pattern and density of
cellular infiltrate are variable.
Searching for the biting arthropod in the home may be fruitless unless the assistance of trained
personnel is sought. Examination of ‘brushings’ from the coats of dogs by veterinarians may be suc
cessful in identifying the culprit – cheyletellia, for example. Some types of insect bite reaction can be
unusually long-lived and may take many months to resolve.
FIGURE 4.7 Multiple small papules due to mite bites (from Marks and Motley, 18th edition, with permission).
Treatment
Identification of the creature responsible and prevention of further attacks is important. Uncommonly, when
there is evidence of hypersensitivity (as in a bee or wasp sting), systemic antihistamines may be required
and, when there is a severe systemic reaction, systemic steroids and even adrenaline may be needed.
A major problem with insect bites is their intense itchiness. Occasionally, this may result in infection
in the excoriated skin, when treatment is required for this complication. Topical antihistamines (e.g.
diphenhydramine, promethazine) are often prescribed and may have a slight antipruritic effect, but all
that is usually required is calamine or mentholated calamine preparation. Where insect levels are high,
appropriate use of an insect repellent and insect nets is helpful.
Helminthic infestations of the skin

Onchocerciasis
This is caused by the parasite Onchocerca volvulus and is found in equatorial West Africa. The disorder is
spread by the bite of the blackfly Simulium damnosum, which is found around rivers. The larval forms, known
as microfilariae, are injected into the skin by the blackfly and develop after some years into adult onchocercal
worms. These are extremely long (up to 1 m) but very thin (1–2 mm in diameter) creatures that live curled up
in the subcutis surrounded by a palpable, host-supplied fibrous capsule. The adult worm procreates by pro
ducing enormous numbers of microfilariae, which invade the subcutis of large areas of truncal skin.
Clinical features
The disorder is characterized by severe and persistent irritation of the affected skin. Affected
areas become thickened, lichenified, slightly scaly, and often hyperpigmented (Figure 4.8).
The microfilariae may also invade the superficial tissues of the eye and cause blindness
(‘river blindness’).
Diagnosis
Biopsies show non-specific inflammation, but occasionally demonstrate portions of the microfilariae. A
more successful way of identifying the larval forms is by taking a series of skin ‘snips’ with a needle
and scalpel. The tiny portions of the skin are then immersed in saline and observed microscopically to
watch for the emergence of microfilariae. There is usually marked eosinophilia and a complement-
fixation test for antibodies is also available in some centres.
Treatment
The pruritus is much improved by Hetrazan® (diethyl carbamazine). The drug must be given cautiously
because of the possibility of a severe systemic reaction due to the liberation of toxic products from the
dying microfilariae. Hetrazan has no effect on the adult worm and it is necessary to treat with the
potentially toxic drug suramin to kill off the worm and prevent further production of microfilariae.
Ivermectin is also helpful.
Cutaneous larva migrans

This is a distinctive migrating eruption caused by larvae from animal species which temporarily grow
within human skin but cannot complete their life cycle in the human host. It is most commonly caused
by the larvae of Ancylostoma caninum, which are excreted in dog feces and contaminate sandy
beaches (particularly above the high-water line where the sand is never washed). Visitors sitting or
standing on the beach may develop a creeping eruption on the affected skin as the larva moves slowly
FIGURE 4.8 Skin changes of onchocerciasis, with marked

thickening and discoloration (from Marks and Motley, 18th
FIGURE 4.9 Serpiginous track of cutaneous larva
migrans on the dorsum of the foot (from Marks and
Motley, 18th edition, with permission).
FIGURE 4.10 Kissing lesions – blister beetle dermatitis.
within the skin, advancing 1–2 mm per day (Figure 4.9). This creates a dramatic clinical picture and
some irritation of the host skin. The condition may be treated with topical thiabendazole, or oral
ivermectin; untreated, it usually resolves spontaneously after several weeks.
5
Immunologically mediated skin
disorders
Yasmeen Jabeen Bhat
Urticaria and angioedema

Urticaria is characterized by transient, superficial well-defined pruritic wheals of the skin, whereas
angioedema involves oedema of the dermis and subcutaneous or submucosal tissue that is deep and
ill-defined. Urticaria can be acute or chronic. Acute urticaria has a sudden onset and recurs over a period
of less than 6 weeks.
Incidence
Acutely urticaria occurs in 20% of the population, whereas chronic urticaria and angioedema occur
in 0.5%.
Pathogenesis
Both immunologic and non-immunologic mechanisms lead to mast cell activation and release of
mediators like histamine, prostaglandins, and cytokines. Non-immunological activation occurs with
substances like neuropeptides, drugs, opiate derivatives, radiocontrast media, and foods. In im
munologic activation, linkage of two α-subunits of IgE receptors (FcεRIα) of mast cells leads to the
release of histamine, proteases, PGD2, and cytokines. Various bacterial and helminthic infections have
been associated with chronic urticaria.
Clinical features
Urticarias can be classified clinically as:
a. Ordinary urticaria: may be acute, episodic, or chronic. Erythematous wheals occur anywhere
on the body, including scalp, palms, and soles (Figure 5.1). Wheals generally last a few hours
and resolve within 24 hours, leaving the skin with a normal appearance. Patients tend to rub
rather than scratch, so excoriation marks are unusual. Angioedema may be found in 50% of
patients. Urticaria may be associated with systemic symptoms like malaise, vomiting, arthralgia,
dizziness, syncope, and rarely anaphylaxis. The duration of chronic urticaria is more than
6 weeks, and 50% of patients have an idiopathic type with no recognized cause. Pruritic wheals
can occur on an almost daily basis and may greatly impair the patient’s quality of life.
b. Physical and cholinergic urticarias: reproducible wheals induced by a physical stimulus form
the basis of diagnosis. Wheals caused by physical stimuli occur within minutes and persist for
56
Immunologically mediated skin disorders 57
FIGURE 5.1 Erythematous wheals on the trunk of a man.
less than 30–60 min. In many forms of physical urticaria, if the stimulus is sufficiently great,
angioedema may occur upon mediator release. Physical urticarias may be
i) Dermographism: means skin writing. In symptomatic dermographism, patients complain
of whealing and itching at sites of friction with clothing or scratching the skin.
ii) Delayed pressure urticaria: whealing occurs at sites of sustained pressure applied to the
skin after a delay of 30 min to 9 hours and lasts 12–72 hours.
iii) Vibratory urticaria: any vibratory stimulus induces a localized, red, itchy swelling
within minutes and lasting less than a few hours.
iv) Heat or cholinergic urticaria: due to stimulation of the cholinergic postganglionic
sympathetic nerve supply to the sweat glands. The patient complains of itching wheals
that appear within minutes of exertion, when they are hot, experience emotional dis
turbances, or eat spicy food.
v) Cold urticaria: includes a variety of syndromes in which cold induces urticaria. Idiopathic
cold urticaria may be immediate, delayed, localized, familial, or acquired. It may also occur
secondary to serum cryoproteins.
vi) Solar urticaria: wheals develop at the site of exposure within minutes of visible, long or
short-wave ultraviolet radiation and usually fade within 2 hours.
vii) Aquagenic urticaria: contact with water at any temperature induces wheals resembling
cholinergic urticaria.
c. Urticarial vasculitis: In urticarial vasculitis, the cutaneous lesions resemble urticaria but histology
demonstrates vasculitis. The lesions persist for more than 24 hours, have burning or itching
sensation, are tender or painful, and resolve with bruising or staining. Systemic involvement is
common.
d. Contact urticaria: results from skin or mucosal contact with provoking substance.
e. Angioedema without wheals:
i) Idiopathic angioedema (angioneurotic or Quinke’s oedema): a variant of urticaria in
which subcutaneous tissues, rather than dermis, are involved. Common sites involved
are lips, eyelids, and genitalia. Itching is often absent. The lesions last for a few hours or
persist for 2–3 days (Figure 5.2)
ii) Drug-induced angioedema: ACE inhibitors and NSAIDs may cause angioedema, which
affects the face, and oral mucosa, and symptoms may be severe. The ACE inhibitors
prolong bradykinin survival and potentiate its effects by inhibiting ACE. Most cases
develop within 3 weeks of commencing the treatment.
58 Immunologically mediated skin disorders
iii) Hereditary angioedema: a rare disorder with autosomal dominant inheritance. Over
75% present before puberty, but the onset may be delayed into late adult life. There are
recurrent swellings of the skin and mucous membranes throughout life, associated with
nausea, vomiting, colic, and urinary symptoms. These patients have deficiency of a
natural inhibitor of C1 esterase.
Investigations of urticaria
A comprehensive history is of utmost importance. It includes the type of lesions, duration, pruritus,
systemic symptoms (like hoarseness, dyspnea, abdominal pain, and arthralgia), and medications. ASST
(autologous serum skin test) and anti FcεRIα antibody determination can be done for autoimmune
urticaria. Dermographism is evoked by skin stroking; pressure urticaria by application of weight to the
skin; vibratory angioedema by a vibratory stimulus; cholinergic urticaria can be diagnosed by exercise
to sweating; solar urticaria by testing with UVB, UVA, and visible light; cold urticaria by application of
ice cube to skin. Urticarial vasculitis can be diagnosed by histopathology showing features of vasculitis.
Complement levels can also be helpful.
Papular urticaria, systemic capillary leak syndrome, erythema multiforme.
FIGURE 5.2 Marked swelling of the upper lip and eyelids in angioedema.
Angioedema: cellulitis, contact dermatitis, lymphoedema, connective tissue diseases like dermatomyositis.
Course and complications

In 50% of patients, urticaria resolves within 1 year but 20% have lesions for >10 years. Prognosis is
good in most syndromes except hereditary angioedema, which may be fatal if untreated.
Treatment
Elimination of the suspected etiological agent or precipitating factor is important. Antihistamines with
selective H1 receptor blocking activity are the first-line treatment of urticaria. Low-sedating anti
histamines, e.g., cetirizine (10 mg/day), levocetirizine (5 mg/day), loratadine (10 mg/day), fexofenadine
(180 mg/day), etc., are used to reduce urticarial activity with minimal side effects. H2 antihistamines,
such as ranitidine, can be combined with an H1 blocker for a more effective response.
Second-line therapies (targeted therapy) could involve a short course of oral systemic corticosteroids
(in doses of 0.5–1 mg prednisolone/kg/day) for severe urticaria and urticarial vasculitis. For severe
angioedema, epinephrine must be injected intramuscularly. Danazol and stanozolol can be given for
hereditary angioedema.
Third-line therapies (immunomodulatory) could include ciclosporin (2.5–3.5 mg/kg/day), methotrexate
(7.5 mg/week), cyclophosphamide (50 mg/day), omalizumab (anti IgE), IvIg infusion (0.4 g/kg/day for 5 days),
plasmapheresis, etc.
Erythema multiforme
Erythema multiforme (EM) is a cutaneous reaction to a variety of stimuli characterized by classical
‘target lesions’ on the skin and involvement of mucous membranes.
Incidence
EM can occur at any age. It is more frequent in males than in females.
Pathogenesis
It is a reaction pattern to many triggering factors due to immune mechanisms. It has an HLA association,
and immune complexes and autoantibodies have been demonstrated. Delayed hypersensitivity also
plays a role with the predominance of T lymphocytes in the lesions. Infections such as herpes simplex
virus, orf, mycoplasma, coccidioidomycosis, and histoplasmosis; drugs such as sulphonamides and
penicillin; and vaccination may trigger it.
Clinical features
The eruption develops over a few days and resolves in 2–3 weeks. Repeated attacks are associated
with recurrent herpes simplex. In the more common mild form, EM minor, macules, papules or
wheals, and classical ‘target or iris’ lesions are seen symmetrically on the distal extremities
(Figure 5.3). A target lesion has three zones – a central area of dusky erythema or purpura, a middle
paler zone, and an outer well-defined ring of erythema. Mucous membranes may show erosions or
bullae. In the less common severe form, EM major, a more extensive skin and mucosal involvement
with systemic symptoms may be seen.
Investigations
Pathology: The lower epidermis shows vacuolar degeneration and necrotic epidermal cells. The upper
dermis shows oedema and perivascular mononuclear inflammation.
Acute exanthematic eruptions following drugs and infections; autoimmune bullous disorders; vasculitis.

EM minor resolves in 2–3 weeks. EM major may lead to extensive cutaneous involvement, keratitis, and
systemic symptoms.
Treatment
Symptomatic treatment is helpful. Antiviral therapy with acyclovir for recurrent EM following herpes
simplex infection prevents relapse. For more severe cases, prednisolone (30–60 mg/day), decreasing
over a period of 1–4 weeks, is given. Other immunosuppressants may be tried.
Erythema nodosum
A painful inflammatory disorder in which crops of tender nodules occur in response to antigenic stimuli.
FIGURE 5.3 Erythema multiforme with target lesions on right hand and bullae with necrosis on left hand in a child.
Incidence
1–5 in 100,000 people per year, four times more common in women aged 15–40 years.
Pathogenesis
It is a cutaneous reaction pattern (panniculitis) to various infections, drugs like penicillins,
inflammatory diseases like connective tissue diseases, granulomatous diseases like sarcoidosis, and
malignancies like lymphoma.
Clinical features
Crops of painful, bright red, tender nodules, 1–3 cm in size, occur on the shins and rarely arms,
bilaterally. They take 2–6 weeks to resolve and leave a bruised appearance. This is accompanied by
fever, malaise, and arthralgias (Figure 5.4).
Investigations
Hematologic: Elevated ESR, CRP, leucocytosis, ASO titer, throat swab for bacterial culture, X-ray
chest. Pathology shows the septal type of panniculitis.
Other forms of panniculitis, polyarteritis nodosa, nodular vasculitis, pretibial myxedema.
Course
Spontaneous resolution occurs in 6 weeks. Lesions never ulcerate and heal without scarring.
Treatment
Bed rest, elevation of limbs, and NSAIDs. Antibiotics in case of infection and systemic steroids may be
indicated.
Annular erythemas
There are several disorders that are marked by the appearance of erythematous rings, which usually
gradually enlarge and then disappear. Various annular erythemas are granuloma annulare, erythema
annulare centrifugum, erythema gyratum repens, and erythema migrans. Granuloma annulare is the
common type.
Pathogenesis
Immunologically mediated inflammation surrounding the blood vessels and altering collagen and elastic
tissue.
Clinical features
Usually asymptomatic, occurs from months to years, firm, smooth, shiny, skin-colored to erythematous
beaded annular plaques on the body. Single lesions may be seen on dorsum of hand while as multiple
lesions on extremities and trunk (Figure 5.5).
FIGURE 5.4 Erythematous tender nodules distributed FIGURE 5.5 Multiple annular plaques with er
bilaterally on the shins in erythema nodosum. ythematous raised margins and clear centre in granuloma
annulare.
Investigations
Pathology-necrobiosis of connective tissue surrounded by a wall of palisading histiocytes and multi
nucleated giant cells.
Differential Diagnosis
Other annular lesions.
Treatment
Topical and intralesional steroids, topical calcineurin inhibitors like tacrolimus. In generalized type,
phototherapy and systemic steroids may be tried.

Generally, their significance is uncertain, but erythema gyratum repens, signifies the presence of an
underlying visceral neoplasm and erythema chronicum migrans indicates the presence of Lyme disease.
Autoimmune disorders
These disorders are also known as the collagen vascular disorders and the connective tissue
diseases. They arise in the context of a break in the immune tolerance to self where the immune
system fails to ‘recognize’ the individual’s own tissues and mounts an attack on them. In most of
the disorders in this group, the inflammatory process seems to involve the small blood vessels in
particular (vasculitis).
a. Lupus erythematosus: comprises a spectrum ranging from cutaneous disease only in chronic
cutaneous lupus erythematosus to systemic disease only in acute cutaneous lupus.
Systemic lupus erythematosus

Incidence
1–12.5 in 100,000 per year. It is 3 times more common in blacks and much more common in women
than men (9:1).
Pathogenesis
Genetic predisposition with susceptibility genes on the major histocompatibility complex (MHC) loci
HLA-B8, -DR3, A1 and –DR2, autoantibodies, ultraviolet radiation, infections, stress, hormonal factors,
and drugs are implicated.
Clinical features
Include arthralgias or arthritis, renal disease, inflammatory disorder of the pulmonary and cardiovascular
systems, a polyserositis, central nervous system involvement, and skin disorder. Skin lesions of SLE
include facial erythema across the cheeks and nose (butterfly rash or malar rash) (Figure 5.6). Subacute
SLE, a type of SLE, predominantly affects the skin and presents with annular and psoriasiform lesions
on the face and exposed parts.
Investigations
Pathology—atrophy of the epidermis, degeneration of the basal epidermal cells, oedema of dermis,
mononuclear infiltrate around the small blood vessels. Direct immunofluorescence of unexposed, unin
volved skin has granular deposits of immune reactants IgG, IgA, IgM, and C3 at the dermo-epidermal
junction in about 60% of the patients.
Serology—Antinuclear antibodies (>80%), anti-double-stranded DNA antibodies, anti-Sm
antibodies, increase in the level of serum gamma globulins, decreased levels of complement.
FIGURE 5.6 Malar rash involving both cheeks, bridge of nose, and sparing the nasolabial folds.
Hematological—a normocytic normochromic anaemia, neutropenia, lymphopenia, thrombocytopenia,

and elevated ESR. Urinalysis shows persistent proteinuria and casts.
Mixed connective tissue disease, drug hypersensitivity reaction, viral exanthems, photoallergic or
phototoxic reactions.
Treatment
In addition to the general measures like rest and sun-protection, patients require systemic steroids to
suppress the inflammatory process. Immunosuppressants such as azathioprine, methotrexate, myco
phenolate mofetil, ciclosporin, cyclophosphamide, and biological therapies may be needed.

The 5-year survival rate (80–95%) has progressively improved. Poor prognostic signs are hypertension,
nephritis, systemic vasculitis, and CNS disease.
Discoid lupus erythematosus (DLE)

Incidence
4 or 5 in 1000, twice as many females as males affected, common in the fourth decade and severe in
blacks.
Pathogenesis
Genetic factors with environmental factors like UV radiation, viral infection, drugs, and stress may be
responsible. Lesions of DLE can occur in the course of SLE or may be the only manifestation of the
disorder.
Clinical features
Slightly pruritic, sharply marginated red scaly plaques appear on sun-exposed skin of the face and neck
(localized DLE), hands, or arms (disseminated DLE) (Figure 5.7). Follicular involvement is a perma
nent feature and the lifted adherent scales show the ‘Carpet tack’ sign. The plaques develop hy
perpigmentation at the periphery leaving atrophic central scarring, telangiectasia, and
hypopigmentation. On the scalp, scarring alopecia occurs in the affected areas. Mucous membranes may
be involved in 25% of patients.
Investigations
Pathology – the changes are similar to those described for SLE but there is hyperkeratosis with marked
atrophy and epidermal degenerative changes. Also perifolicular and periappendageal lymphocytic
infiltrate can be seen (Figure 5.8).
Lupus vulgaris, hypertrophic lichen planus, sarcoidosis, panniculitis.
FIGURE 5.7 Sharply marginated erythematous scaly FIGURE 5.8 HPE image (100×) showing thinning
plaque on exposed surface in DLE.
Treatment
Sun protection with sunscreens is important. Topical corticosteroids and calcineurin inhibitors are used
for localized lesions. Antimalarials like hydroxychloroquin (200–400 mg per day) are given with
monitoring of ocular side effects. Systemic steroids, immunosuppresants, acitretin, and biological
therapies have been used.

Five per cent patients develop SLE, the risk being higher in patients with disseminated DLE (22%).
Squamous cell carcinoma occasionally occurs in the scars of DLE (Figure 5.9).
Systemic sclerosis
Incidence
A rare disorder with an incidence between 2.3 and 10 per million population, four times more common
in females.
Pathogenesis
Autoimmunity in the presence of genetic factors leads to inflammation, vascular abnormalities, and
deposition of fibrous connective tissue in specialized organs. Depending on the extent of cutaneous
involvement, systemic sclerosis can be divided into diffuse cutaneous systemic sclerosis (dSSc) and
limited cutaneous systemic sclerosis (lSSc).
Clinical features
The disease starts insidiously over years. The earliest feature is Raynaud’s phenomenon and non-pitting
edema of hands and feet with painful ulcerations at fingertips (rat bite necrosis) (Figure 5.10). Fibrosis
of the face results in characteristic mask-like facial appearance, thinning of lips, microstomia, beak-like
nose (Figure 5.11). Macular mat-like telangiectasia appear over the face and deposits of calcium
develop in the skin. The term CREST syndrome –

i.e. calcinosis cutis, Raynaud’s phenomenon, eso
phageal dysfunction, sclerodactyly, and tel
angiectasia – is used. In diffuse cutaneous systemic
sclerosis, involvement of the skin of upper arms,
thigh, chest, and abdomen occurs. High frequency
of pulmonary fibrosis, cardiac involvement, and
scleroderma renal crisis may occur.
Investigations
Pathology – thickening of dermis with hyalinized
collagen and paucity of blood vessels with
thickening and hyalinization of vessel walls.
Anticentomere autoantibodies occur in 71% of
CREST and DNA topoisomerase I (Scl-70) anti
bodies in 30% of dSSc.
Morphea, scleromyxoedema, mixed connective
FIGURE 5.9 Squamous cell carcinoma developing on tissue disease, eosinophilic fasciitis, porphyria cu
the scar of DLE. tanea tarda.
Treatment
There is no specific treatment. Symptomatic management of the patient is very important. Vasodilators
for Raynaud’s phenomenon, penicillamine (750 mg/day), and immunosuppressants like low dose cor
ticosteroids, cyclosporin, and azathioprine appear to help. ACE inhibitors for renal involvement and
cyclophosphamide for pulmonary involvement are useful.

In more rapidly progressive systemic sclerosis, there may be more serious vascular disease affecting the
fingers, resulting in tissue necrosis and even the loss of portions of the digits (Figure 5.12). Renal or
pulmonary disease may eventually cause the death of the patient – the 5-year mortality rate of this
disease is 30% or more.
Morphoea
Morphoea is a localized scleroderma.
Incidence
2.7% in 10,000 with female-to-male ratio of 2.5:1, peak occurrence between 20 and 40 years of age.
Pathogenesis
Unknown; however, infection with borrelial organisms and irradiation may be implicated.
Clinical features
One or more thickened, variably sized sclerotic
plaques develop over the trunk or limbs. Initially
purplish or mauve, they become smooth and
shiny brownish plaques with a lilac-colored edge
(Figure 5.13). The lesions can be linear (en coup
de sabre when present on scalp and face),
guttate, bullous, subcutaneous, or disabling
pansclerotic.
Investigations
Pathology – there is marked replacement of the
subcutaneous fat with new collagen which has
pale, homogenized appearance.
Systemic sclerosis, eosinophilic fasciitis, scleroedema,
Parry Romberg’s syndrome.
FIGURE 5.10 Finger tip ulcers in scleroderma.
Treatment
There is no effective treatment. Topical calcipotriol and topical tacrolimus are beneficial in localized type.

Linear morphea may affect the limbs in children and lead to atrophy and restricted movement.
Generalized morphea leads to a considerable limitation of movement and impedes breathing.
Variants of morphoea
i. Generalized mophoea: A rare type in which widespread idiopathic sclerosis of the skin occurs,
causing considerable limitation of movement without any systemic disturbances.
FIGURE 5.11 Beaked nose, thinning of lips, microstomia, mask-like facies, and mat telangiectasia in dSSc.
FIGURE 5.12 Loss of digits, sclerodactyly, and calcinosis cutis in SSc.
ii. Lichen sclerosus et atrophicus (LSA): Is a disease of adults but occurs in pre-pubertal children.
Females are ten times more affected than men. Aetiology of LSA is unknown. Small, irritating,
whitish, or ivory, sharply demarcated plaques occur on genitalia, around anus, or less commonly,
elsewhere on skin. Dilated pilosebaceous or sweat duct orifices filled with keratin plugs (dells)
and bullae, erosions and telangiectasia may be seen (Figure 5.14). In females, vulva may become
atrophic and in males, it may lead to phimosis.
Topical agents like potent steroids and calcineurin inhibitors have shown good results. Circumcision
may be helpful in males.
Dermatomyositis
Both muscle and skin are affected in this disabling disorder. The skin manifestations may precede, or
occur in isolation from, the muscle inflammation.
Incidence
A rare disease with an incidence of 1.9 per million, occurring twice as frequently in females as in males.
Occurs predominantly between the ages of 40 and 60 years but may occur in children under 16 years
(juvenile).
Pathogenesis
Evolves through multiple phases – a genetically determined susceptibility phase, an induction phase
triggered by environmental stimulus (infection, malignancy, drugs), an autoimmune expansion phase,
and an injury phase involving multiple immunologic effector mechanisms.
Clinical features
Dull red to mauve areas develop over the face, back of the neck, backs of the hands, elbows, knees, and
elsewhere. A particularly characteristic sign is the presence of violaceus erythema and oedema around
the eyes (heliotrope rash, Figure 5.15). Small violaceus flat papules (Gottron’s papules) over knuckles
FIGURE 5.13 Atrophic indurated hypopigmented FIGURE 5.14 Sclerotic plaque with follicular plugs
plaque with voilaceous margins. Bhat YJ, Akhtar S, in LSA.
Hassan I. Dermoscopy of morphea. Indian Dermatol
Online J 2019;10:92-3. Reproduced with permission.
and interphalangeal joints with linear erythema on the dorsa of fingers can be seen (Figure 5.16). Small
areas of necrosis may appear and long-lasting lesions may evolve into poikiloderma and calcification in
subcutaneous tissue. Progressive muscle weakness, pain, and tenderness affecting proximal muscles of
limbs also occur.
Investigations
Muscle enzymes such as creatine kinase, aldolase, and lactate dehydrogenase are increased in the blood.
Urine creatinine is also a good indicator of disease activity. Muscle damage can be assessed by muscle
biopsy and electromyography. Pathology – in the skin, interface dermatitis with mucin accumulation
and in muscles, a characteristic pattern of inflammatory myositis is seen.
Seborrheic dermatitis, lupus erythematosus, steroid myopathy.
Treatment
Rest is essential in acute pain. Oral corticosteroids (prednisolone 60 mg/day) clinically and bio
chemically improve. Immunosuppressive drugs are sometimes required to achieve or maintain
remission.

If progressive, pharyngeal and respiratory muscles are affected. With treatment, the 8-year survival rate
is 70–80%. Poor prognosis is seen in patients with malignancy and pulmonary involvement.
FIGURE 5.15 Confluent voilaceous erythema around eyelids and on v-area of neck in childhood dermatomyositis.
The vasculitis group of diseases

The term ‘vasculitis’ is applied to inflammation and necrosis of blood vessels (small, medium-sized, and
large vessels). Systemic vascular involvement occurs mainly in kidneys, muscles, joints, respiratory
system, skin, gut, and nervous system.
Cutaneous small-vessel vasculitis (CSVV): It is the most common type of vasculitis seen in
dermatology.
Incidence
All ages may be involved, with equal incidence in males and females.
Pathogenesis
A history of drug exposure or recent infection is frequently present. Circulating immune complexes are
deposited in the endothelium of postcapillary venules, leading to activation of the complement system
with activation of inflammatory cascade damaging the vascular tissue.
FIGURE 5.16 Gottron’s papules on knuckles and in

terphalangeal joints of hands. FIGURE 5.17 Palpable purpura on the legs in a pa
tient of cutaneous small cell vasculitis.
Clinical features
The asymptomatic skin lesions typically arrive as a simultaneous ‘crop of palpable purpura’, primarily
localized to legs (Figure 5.17). Mild systemic symptoms including fever, arthralgia, myalgia, and
anorexia may be present.
Investigations
Pathology – deposition of eosinophilic material in the walls of postcapillary venules, extravasation
of erythrocytes, infiltrate of neutrophils with karyorrhexis of nuclei (i.e. leukocytoclasia) are seen. The
endothelium is swollen and shows degenerative changes. Figure 5.18 shows leukocytoclastic vasculitis.
Thrombocytopenic purpura, meningococcemia, pigmented purpuric dermatosis.
Treatment
Disease is usually self-limiting.
Henoch Schönlein purpura (HSP)

Incidence
Although any age group can be affected, children are mainly affected.
FIGURE 5.19 Crops of palpable purpura involving

thighs and buttocks in HSP.
FIGURE 5.18 HPE image (400×) showing perivas

cular neutrophilic infiltrate, eosinophilic fibrinoid
change of vessel walls, and nuclear debris
(leukocytoclasia).
Pathogenesis
Hypersensitivity to streptococcal antigens may play a role as patients have a history of upper respiratory
tract infection.
Clinical features
Classic findings of purpura, arthralgia, and abdominal pain are seen (Figure 5.19). Renal involvement
with HSP is common, presenting as hematuria and proteinuria. Gastrointestinal bleeding may occur.
Painful arthritis affects knees and ankles.
Investigations
HSP is a clinical diagnosis, confirmed by routine histology showing necrotizing vasculitis. In direct
immunofluorescence, perivascular IgA deposits are characteristic.
Treatment
It is mainly supportive. Oral corticosteroids are given to patients with systemic involvement.

Long-term morbidity results from progressive renal disease (5%).
Polyarteritis nodosa
This is a multisystem, necrotizing vasculitis of medium-sized or small arteries.
Incidence
More common in adult males with a ratio of 2.5:1, with an incidence of 4.6–9 per million per year.
Pathogenesis
About 30% of cases are associated with hepatitis B and C antigenemia. Immune complexes lead to
necrotizing inflammation of small and medium-sized arteries, with segmental lesions and involvement
of bifurcations, leading to aneurysmal dilatation, rupture, and ischemic changes.
Clinical features
Cardiovascular, neurological, gastrointestinal, renal, and ocular involvement may be seen in this
potentially fatal disease. Bright red to bluish nodules, ulcers, and livedo-reticularis occur in the skin.
Investigations
Fibrinoid necrosis of vessel wall with thrombosis and infarction of tissues supplied and neutrophilic
infiltrate in all layers of muscular vessel wall and perivascular areas.
Other types of vasculitis and panniculitis.
Treatment
NSAIDs, systemic corticosteroids, and cyclophosphamide are helpful. Surgery may be needed for
complications.

Death from renal failure, bowel infarction, and cardiovascular complications may occur if untreated.
a. Giant cell arteritis

It is a systemic vasculitis of medium and large-sized arteries, notably temporal artery. It is
characterized by headaches, fatigue, fever, high ESR, with necrosis and ulceration on the scalp.
b. Other types of cutaneous vasculitis
The development of crops of purple purpuric papules with darker and occasionally crusted
central areas and sometimes pustules occur in the course of subacute bacterial endocarditis,
gonococcaemia, and meningococcaemia. Drugs such as the thiazides may also cause a
vasculitis. Renal involvement sometimes accompanies skin lesions. The importance of such
lesions is that they are signs of an underlying systemic disorder, demanding rapid diagnosis
and treatment.
c. Capillaritis
This is a group of benign, persistent, mildly inflammatory skin disorders in which the focus of
the abnormality appears to be in the papillary dermis and the immediately subepidermal capillary
vasculature. The term ‘persistent pigmented purpuric eruption’ seems appropriate, as they are
persistent and because of the damage to capillaries, causing leakage of blood and pigmentation
from haemosiderin staining. The lesions mostly occur on the lower legs and vary from a macular,
spattered appearance (Schamberg’s disease; Figure 5.20) to an itchy, papular eruption (lichenoid
purpuric eruption) or a macular golden eruption (lichen aureus). These disorders generally cause
little disability and remit spontaneously after a variable period.
Drug eruptions
Drug eruptions are skin disorders resulting from drug side effects, ranging from common skin eruptions
to rare or life-threatening drug-induced diseases.
Incidence
The incidence of cutaneous adverse drug reactions (CADRs) is 5.5 per 100,000 of the population.
Pathogenesis
New drugs started within the preceding 6 weeks are potential causative agents. Both immunological and
non-immunological mechanisms are involved. They may be provoked by systemic or topical admin
istration of a drug. Variation in drug-metabolizing enzymes and HLA associations are the constitutional
factors. Acquired facts like active viral infection and concurrent use of other medications also alter the
frequency of drug-associated eruptions.
Clinical features
There are various patterns of cutaneous adverse drug reactions.
• Exanthematic (maculopapular) reactions: Most frequent of all cutaneous reactions to drugs, usually
within 2 weeks after administration. The lesions may be scarlatiniform, rubelliform, morbilliform,
or profuse eruption of small macules and papules. The distribution is generally symmetrical. The
trunk and extremities are usually involved in comparison to viral rashes which may start on the face
and progress to involve trunk, accompanied by conjunctivitis, lymphadenopathy, and fever.
Maculopapular drug eruption usually fades with desquamation (Figure 5.21). Ampicillin, the
psychotropic drugs, and the non-steroidal anti-inflammatory agents commonly cause this type
of rash.
FIGURE 5.20 Pigmented purpuric eruption in

Schamberg’s disease. FIGURE 5.21 Exanthematic drug eruption.
• Exfoliative dermatitis: is one of the most dangerous patterns of CADR, characterized by gen
eralized uniform redness and scaling of entire skin usually associated with fever, malaise, and
lymphadenopathy.
• Urticaria, angioedema, and anaphylaxis: this systemic reaction may have constitutional symptoms
in addition to cutaneous lesions and in severe cases, hypotension, bronchospasm, and laryngeal
oedema.
• Erythema multiforme, Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis: (TEN)
Characterized by target lesions in EM, involvement of skin as well as mucous membranes in SJS by
bullae and erosions, and necrosis of sheets of the epidermis in case of TEN (Figure 5.22). SJS and
TEN have immunologic pathogenesis. Genetic differences in the metabolism of some drugs may lead
to idiosyncratic toxicity. Drugs causing SJS and TEN include sulphonamides, tetracycline, peni
cillins, and NSAIDs.
• Drug rash with eosinophilia and systemic symptoms (DRESS syndrome): Also known as drug
hypersensitivity syndrome. It begins within 3–8 weeks of drug intake (mostly anticonvulsant
drugs). It presents with constitutional symptoms, maculopapular exanthema, lymphadenopathy,
eosinophilia, and multiple organ involvement.
• Acute generalized exanthematous pustulosis (AGEP or toxic pustuloderma): is characterized by
sudden onset of multiple sterile non-follicular pustules on the background of diffuse erythema,
starting in the flexural areas and face. Fever and neutrophilia are associated. Drugs causing AGEP
include penicillins and NSAIDs.
• Fixed drug eruption: characterized by the repeated onset of a single (occasionally multiple) er
ythematous plaque at the same site. The skin lesion can be bullous or erosive and heals with
hyperpigmentation. Numerous drugs – including dapsone, the sulfonamides, tetracycline, and
mefenamic acid – may be responsible.
• Photosensitivity reactions to drugs (phototoxic dermatitis): results from exposure to certain drugs
by ingestion or topical application and to UV radiation or visible light. It presents as an exaggerated
sunburn response – erythema, oedema, vesicles, and bullae. Tetracyclines and sulfonamides may
cause a phototoxic response. The phenothiazines may cause either a phototoxic or a photoallergic
reaction.
FIGURE 5.22 Denudation of the skin in toxic epidermal necrolysis.

• Drug-induced pigmentation: drug-induced alterations in pigmentation may occur from the

deposition of a variety of endogenous and exogenous pigments in the skin. The pigmentation
usually has a slate-grey hue on sun-exposed sites.
• Lichenoid drug eruption: Lichenoid drug eruption can be seen with many medications,
including hydrochlorothiazide, NSAIDs, furosemide, antihypertensives (ACE inhibitors,
β-blockers, CCBs), proton pump inhibitors, phenothiazines, anticonvulsants, antituberculous
drugs, sildenafil, imatinib, and antimalarials. Lichenoid drug reactions may be photodistributed
(lichenoid photoeruption) or generalized.
• Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE): It is a delayed hy
persensitivity immune response to drugs like antibiotics, characterised by well demarcated sym
metrical erythema of intertriginous areas without systemic symptoms.
Investigations
History of drug exposure, the interval between the introduction of a drug, and onset of rash and improvement
after drug withdrawal may give a clue. Skin testing, radioallergosorbent test, and patch test can be done.
Viral exanthems.
Treatment
Drugs implicated in a previous reaction should be avoided. For minor conditions, withdrawal of the
suspected drug and symptomatic therapy with emollients, topical steroids, and systemic antihistamines
may help. For severe reactions, maintenance of body temperature, fluid and electrolyte balance,
prednisolone 40–60 mg/day should be given.

Severe CADRs may lead to hypothermia, fluid and electrolyte loss, infection, high-output cardiac
failure, stress ulceration, malabsorption, and venous thrombosis.
6
Blistering skin disorders
Pooja Agarwal
Rashmi Sarkar
Many inflammatory skin disorders can produce blistering at some stage in their natural history. In
primary blistering diseases, blistering, a direct result of the initial pathological process, is a major
feature. The different primary blistering diseases are listed in Table 6.1.
Bullous pemphigoid (senile pemphigoid)

Bullous pemphigoid (BP) is an uncommon blistering disease that occurs mainly in people over 60 years
of age. Large, tense, often bloodstained blisters develop over a few days anywhere on the skin surface
(Figure 6.1). A history of skin lesions like urticaria, papules, or pruritus can be found in many cases.
Mucosal lesions can be seen in 10–30% of patients. New crops of blisters continue to appear for many
months without adequate treatment, and the disease is painful and disabling. Rarely, the disorder is a
sign of an underlying malignancy and can be associated with some neurological disorders (Table 6.2).
Laboratory findings
There is a circulating antibody directed to the epidermal basement membrane zone in 85–90% of
patients, which can be detected using the immunofluorescence method. The titre of this antibody is to,
some extent, a reflection of the activity of the disease. Antibodies of the IgG type and the complement
component C3 are also deposited in the subepidermal zone around the lesions in the majority of patients
and can also be detected using the direct immunofluorescence technique. Biopsy reveals that there is
subepidermal fluid, with polymorphs and eosinophils, present in the infiltrate subepidermally.
Treatment
Patients with widespread blistering may need to be hospitalized and treated as though they had severe
burns. Milder cases may be treated with potent topical corticosteroid ointments, and many patients
respond, albeit slowly, over several weeks, to doxycycline. High doses of corticosteroids (40 mg per day
of prednisone, or more) may be needed to control the disease, and immunosuppressive treatment with
azathioprine, methotrexate, or mycophenolate mofetil may be used to allow a reduced dose of systemic
steroids. Anti-inflammatory agents administered with dapsone or nicotinamide may also be beneficial.
Mucous membrane pemphigoid

It is not a single disease, but a group of heterogeneous, chronic blistering diseases primarily affecting
mucosal surfaces. It is the second most common autoimmune blistering disorder in central Europe.
Historically, because of the scarring complications that may develop clinically, it was described as
cicatricial pemphigoid but is now categorized as mucous membrane pemphigoid. Cicatricial pemphigoid is
77
TABLE 6.1
The ‘primary’ blistering disorders
Subepidermal Intraepidermal
Bullous pemphigoid Pemphigus and its variants
Mucous membrane pemphigoid Pemphigus vulgaris
Dermatitis herpetiformis Pemphigus vegetans
Linear IgA disease and chronic bullous disorder of childhood Pemphigus foliaceus
Anti-p200 pemphigoid Endemic pemphigus foliaceus
Epidermolysis bullosa Intercelluar IgA Dermatosis
Epidermolysis bullosa acquisita Paraneoplastic pemphigus
Pemphigoid gestationis
Bullous systemic lupus erythematosus
TABLE 6.2
Diseases associated with bullous pemphigoid
Malignancy Neurologic disorder
Gastric cancer Parkinson’s disease
Renal cancer Dementia
Leukemia Unipolar or bipolar disorder
Lymphoma Multiple scelrosis
now used for blistering disorders where skin lesions heal with scarring, but mucosal lesions are absent. The
mucous membranes that are most frequently affected are the oral cavity, the eyes, and nasopharynx.
MMP typically presents as remitting and relapsing mucosal inflammation and erosions. Intact vesicles
or bullae are seen less frequently. Cutaneous lesions may resemble pemphigoid but are differentiated as
they heal with scarring.
Dermatitis herpetiformis
Intensely itchy vesicles, papulovesicles, and urticarial papules appear in crops over the knees, elbows,
scalp, buttocks, and around the axillae (Figure 6.2). Most patients with dermatitis herpetiformis (DH)
have a mild, asymptomatic gastrointestinal absorptive defect due to gluten enteropathy, as in patients
with coeliac disease. Some diseases with an immunopathogenetic component are more common in
patients with DH, including thyrotoxicosis, rheumatoid arthritis, myasthenia gravis, and ulcerative
colitis. The disorder is persistent but fluctuates in intensity.
Laboratory findings
Small-bowel mucosal biopsy reveals partial villous atrophy in 70–80% of patients with DH. Minor
abnormalities of small-bowel absorptive function are also common. Biopsy of new cutaneous lesions
demonstrates that the vesicle forms subepidermally and develops from collections of neutrophils in the
papillary tips (the papillary tip abscess). Direct immunofluorescent examination from perilesional skin
reveals the presence of IgA in the papillary tips in the skin around the lesions in all patients.
Treatment
The most important therapeutic interventions include a gluten-free diet and oral dapsone therapy.
Blistering skin disorders 79
FIGURE 6.2 Vesiculopapules in dermatitis herpetiformis

FIGURE 6.1 Tense blister due to bullous pemphigoid
(from Marks and Motley, 18th edition with permission).
(from Marks and Motley, 18th edition with permission).
Skin lesions respond rapidly to the drug dapsone (50–200 mg per day) in most patients. However,
dapsone has several potential toxic side effects, including haemolysis, methaemoglobinaemia, and
sulfaemoglobinaemia, and may itself cause rashes such as fixed drug eruption. It should not be given to
patients with glucose 6-phosphate dehydrogenase deficiency. A gluten-free diet will improve the gas
trointestinal lesion and skin disorder in many patients after some months. Topical superpotent corti
costeroids, though not useful alone, may help alleviate pruritus when given along with dapsone.
Linear IgA disease

This is an interesting condition, which may present with clinical features mimicking both bullous
pemphigoid and dermatitis herpetiformis. It was recognized by the characteristic findings on direct
immunofluorescent examination of the skin, which reveal a linear deposition of IgA antibodies at the
dermoepidermal junction. In children, it is seen as a condition known as ‘chronic bullous disease of
childhood’. In adults, it may occur spontaneously or occasionally be induced by drugs such as non-
steroidal anti-inflammatory drugs or vancomycin. Clinically, there are vesicles or bullae on normal skin.
New blisters form at the periphery of healing lesions, resulting in an annular appearance frequently
described as strings of pearls or crowns of jewels. Common sites of affliction are the trunk, buttocks,
extensor extremities, and the perioral area. Treatment is outlined in Table 6.3.
Epidermolysis bullosa
This is not a single disorder, but a group of similar, inherited blistering diseases. The blistering is caused
by various congenital structural and metabolic defects. It can be present since birth as a result of
80
TABLE 6.3
Subepidermal blistering disorders
Disease Bullous Mucous Linear IgA disease and Dermatitis Anti‐p200/ Epidermolysis Bullous systemic Pemphigoid
pemphigoid membrane chronic bullous herpetiformis Laminin γ1 bullosa acquisita lupus gestationis
pemphigoid disorder of childhood pemphigoid erythematosus
(SLE)
Clinical Old age (>75 years); Erosions with Tense blisters, erosions, Intensely pruritic <75 years of age; Erosions, blisters, SLE patient, tense Pregnancy or
features tense blisters, predominant mucosal involvement grouped tense blisters, and scars on blisters, postpartum
erosions, intense mucosal rare, blisters arranged vesicles on erosions; trauma‐prone areas erosions; period;
pruritus, mucosal involvement, in annular pattern extensor sites mucosal in mechanobullous photoexposed erythemia,
involvement rare scarring in like’string of pearls’ involvement rare variant. Lesions areas papules, bullae,
severe cases resembling BP in intense pruritus
inflammatory
variant
Special Association with Ocular, laryngeal Can be drug-induced, Association with Rare association Rare association with Precipitating Recurrence with
features neurologic complications most commonly celiac disease with psoriasis inflammatory drugs include pregnancy or
disorders and due to scarring vancomycin, bowel disease, hydralazine, with
rarely malignant NSAIDs, and haematological penicillamine hydatidiform
penicillin malignancies mole
Treatment
1st line Potent topical Potent topical Oral dapsone Gluten-free diet Potent topical Prednisolone Dapsone Topical steroids
steroid steroid steroid
Prednisolone Dapsone Potent topical Dapsone Prednisolone Colchicines Oral
Dapsone Cyclophosphamide corticosteroids Potent topical Dapsone Dapsone antihistaminics
Oral prednisolone steroid
2nd Line Azathioprine, Mycophenolate Tetracycline ± Other sulfa Doxycycline, Mycophenolate Azathioprine Prednisolone
Doxycycline, mofeil nicotinamide drugs azathioprine Cyclosporine Prednisolone
Methotrexate,
Mycophenolate
Mycophenolate
3rd line Immunoglobulins Immunoglobulins Mycophenolate mofetil Immunoglobulins Immunoglobulins Methotrexate Azathioprine
Immunoadsorption Immunoadsorption Immunoglobulins Immunoadsorption Immunoadsorption Rituximab Immunoglobulins
Rituximab Rituximab Rituximab
Concise Dermatology
mutations in genes coding for structural elements in the basement membrane, or can present later in life
as a result of antibodies produced against collagen VII. The various forms of epidermolysis bullosa are
summarized in Table 6.4.
There is no effective treatment other than to avoid trauma and to keep the blistered areas clean and dry.
Epidermolysis bullosa acquisita

This condition has only been recognized in the last 25 years. As the name implies, it is an acquired
blistering disorder, often affecting middle-aged to elderly individuals, which, at the first sight, resembles
bullous pemphigoid. It has two variants – mechanobullous type which resembles epidermolysis bullosa
and an inflammatory variant resembling pemphigoid. It is more resistant to treatment than pemphigoid
and many cases originally diagnosed as pemphigoid, which were thought to be resistant to treatment,
were most probably epidermolysis bullosa acquisita. Confirmation of the diagnosis is made by im
munofluorescent tests on salt-split skin (skin which is incubated in hypertonic saline to induce a split at
the dermoepidermal junction). The antibodies in epidermolysis bullosa acquisita bind to the dermal side
of the split; in bullous pemphigoid, they bind to the epidermal side.
Anti-p200 pemphigoid
It is a distinct bullous skin disorder characterized by autoantibodies against p200 protein at the der
moepidermal junction. Clinically, the disease resembles pemphigoid with tense cutaneous blisters.
TABLE 6.4
Major variants of epidermolysis bullosa
Variant Cleavage plane Clinical features
Epidermolysis bullosa simplex Intraepidermal Most common subtype
Friction-induced blistering
Palms and soles most commonly affected
Blisters in herpetiform pattern in severe disease
Erosions heal without scarring
Residual pigmentary changes may remain
Milia and atrophy can occur after healing
Junctional epidermolysis bullosa At the level of lamina lucida Extensive mucocuatneous blistering at birth
Nails and hair are affected frequently, resulting in
complete loss
Scarring, webbing, milia, and atrophy occur
commonly after healing
Dystrophic epidermolysis bullosa Dermal Extensive mucocutaneous blistering, severe skin
fragility
Nail dystrophy, alopecia common
Pseudosyndactyly is characteristic
Oral, esophageal, anal mucosa also affected
Kindler syndrome Mixed Trauma induced blistering in childhood
Poikiloderma and atrophy seen in adults
Photosensitivity
Gingivitis and periodontitis common
Diagnosis can be made only by detecting antibodies against p200 by Western blot against an extract of
the upper dermis.
The subepidermal blistering disorders are summarized in Table 6.3.
Pemphigus
Pemphigus is a group of blistering disorders, which is characterized by acantholysis, i.e. loss of ker
atinocyte to keratinocyte adhesion, which results in the formation of epidermal blisters in mucosae and
skin. Acantholysis is induced by autoantibodies against intercellular adhesion molecules. There are
several types (Table 6.5), out of which pemphigus vulgaris (PV) is the most common. The average age
of onset is 40 to 60 years. The lesions are thin-walled, delicate blisters that usually rapidly rupture and
erode (Figure 6.3). They occur anywhere on the skin surface and very frequently occur within the mouth
and throat, where they cause much discomfort and disability. The disorder is persistent, although
fluctuating in intensity. Before adequate treatment became available, it was usually fatal. Pemphigus
foliaceus is another variant where blistering occurs in the superficial layers of the epidermis. Clinically,
blisters are seen rarely and erosions with crusting are seen mainly over the scalp, face, and seborrheic
areas. It can sometimes become generalized and the patient may go into erythroderma. Though a chronic
disease, its course is more benign than pemphigus vulgaris.
Laboratory findings
In more than 90% of patients, there is a detectable circulating antibody directed to the intercellular adhesion
molecules. The titre of the antibody reflects the severity of the disease. The presence of the antibody and its
titre are determined by indirect immunofluorescence methods. Biopsy reveals the intraepidermal split, with
rounded up epidermal cells, known as acantholytic cells. The cells over the basement membrane lose in
tercellular adhesion and appear as a ‘row of tombstones’. Direct immunofluorescence examination of the
perilesional involved skin is the gold standard and will show the presence of antibody of the IgG class in a
fishnet pattern and the complement component C3 between epidermal cells.
TABLE 6.5
Intraepidermal blistering diseases
Disease Cutaneous Mucosal Clinical features Special features
distribution involvement
Pemphigus Face, scalp, trunk May be severe Flaccid bullae, erosions Rare association with
vulgaris thymoma, may be drug-
induced
Pemphigus Flexures Less severe Vegetating lesions in Cerebriform tongue
vegetans flexures
Pemphigus Scalp, seborrheic None Erosions with crusting, May go into erythroderma
foliaceus areas blisters seen rarely
Endemic Upper body None Flaccid blisters, erosions Endemic to South America,
pemphigus may progress into
foliaceus erythroderma
Intercelluar IgA Flexures, scalp, none Flaccid pustules, IgA monoclonal gammopathy
Dermatosis proximal limbs Circinate appearance
Paraneoplastic Significant Severe Polymorphic lesions- Lymphoproliferative disease,
Pemphigus palmoplantar bullae, erosions,
involvement, ‘target lesions’,
generalized lesions lichenoid lesions
may be there
FIGURE 6.3 Eroded areas on the face due to pemphigus vulgaris.
Treatment
The patients should be treated as though they had burns and, if severely affected, need inpatient care.
High doses of systemic steroids are the mainstay of therapy as they provide rapid improvement in the
disease. Immunosuppressive therapy with azathioprine or mycophenolate mofetil should be started
simultaneously to reduce the steroid dose gradually. In resistant cases, other therapeutic modalities
should be used, which include cyclophosphamide, rituximab, intravenous immunoglobulins, plasma
pheresis, and immunoadsorption.
7
Skin disorders in AIDS,
immunodeficiency, and venereal
disease
Indrashis Podder
Rashmi Sarkar
Introduction
Acquired immune deficiency syndrome (AIDS) is a symptom complex caused by a lymphotropic ret
rovirus, now known as the human immunodeficiency virus (HIV). The virus is acquired either by sexual
intercourse (homosexual or heterosexual) or from the accidental introduction of material contaminated
by HIV into systemic circulation. Although unprotected sexual intercourse remains the major route of
transmission of this deadly condition, intravenous drug abuse, and contaminated blood transfusion
facilitate its spread.
Epidemiology
Today, this disorder has reached epidemic proportions, with approximately 36.7 million people living
with HIV/AIDS at the end of 2015 worldwide. Amongst them, 1.8 million were found to be children
(<15 years), most of them acquiring the infection from their HIV-positive mothers during pregnancy,
childbirth, or breastfeeding. The vast majority of these people live in low- and middle-income countries,
with sub-Saharan Africa being the worst affected region, accounting for almost 70% of these cases (25.6
million).
Pathogenesis
The virus incapacitates the T-helper lymphocytes, thus preventing the proper functioning of the cell-
mediated immune response. It uses the CD4 antigen as its receptor and employs the T-cell’s genomic
apparatus to replicate, destroying the cell as it does so. It can also infect reticuloendothelial cells
(including Langerhans cells) and B-lymphocytes.
After gaining access, the virus usually stays latent and the infected individual remains free of
symptoms for a long period, but the virus may cause a systemic illness in a relatively short time after
infection and before or at the time of seroconversion. This illness is characterized by pyrexia, malaise,
and a rash resembling infectious mononucleosis. The median period for progression from HIV infection
to AIDS is 9–10 years but is very variable.
Usually, there are no symptoms for several years, even after an antibody response develops until the
virus is ‘activated’ by an intercurrent infection such as herpes simplex. AIDS is characterized by
84
Skin disorders in AIDS, immunodeficiency, and venereal disease 85
TABLE 7.1
Dermatological manifestations of HIV/AIDS
Infectious conditions Non-infectious conditions
• Fungal infections (characteristic deep fungal • Cutaneous malignancy (Kaposi sarcoma, non-
infections viz. histoplasmosis, blastomycosis, melanoma skin cancers, etc.)
dermatophytosis, etc.)
• Viral infections (warts, molluscum • Seborrhoeic dermatitis (more severe and more
contagiosum, etc.) common)
• Bacterial infections (exaggerated • Psoriasis (increased incidence of

manifestations of tuberculosis, syphilis, bacillary psoriatic arthritis)
angiomatosis, etc.)
• Parasitic infestation (crusted/Norwegian scabies, • Reiter’s syndrome

acanthamoebiasis)
• Generalized pruritus
• Ichthyosis/xerosis
• Drug reactions (more severe than in normal

patients; SJS, TEN)
• Acne conglobata
• Mucosal changes (increased occurrence of oral

aphthae)
• Hair changes (thin lustreless hair, different

varieties of alopecia, long eyelashes)
• Nail changes (characteristic finding is proximal

subungal onychomycosis)
• IRIS (immune reconstitution inflammatory

syndrome)
depressed delayed hypersensitivity, and a reduction in the number of circulating T-helper cells is a
constant finding. Indeed, the progress of the disease can be monitored by checking the lymphocyte count
and estimating the viral RNA load. Skin disorders are prominent in AIDS, and patients often present
with a skin complaint.
Some important dermatological manifestations of HIV/AIDS are given in Table 7.1.
Infectious conditions
When the disease is activated, the patient becomes subject to opportunistic infections as well as to an
increased incidence and severity of usually mild and commonplace infections, such as viral warts and
oral thrush, as a result of profound immunosuppression.
The introduction of highly active antiretroviral therapy (HAART) has greatly reduced the develop
ment of these complications in patients with HIV infection. However, these complications may become
severe or life-threatening in the absence of proper and adequate treatment.
Fungal infections
Dermatophyte infections, including nail infection, become extensive and are difficult to clear. Recurrent
candidiasis is often a major problem, especially in the mouth and oropharynx with varied clinical
presentations (erosive, membranous, vegetative, and angular cheilitis). Even systemic spread of
Candida infection, especially oesophageal involvement (an AIDS-defining criterion), is not uncommon
and often a terminal event. Occasionally, it may result in disseminated disease or sepsis, which is
characterized by the occurrence of proximal muscle tenderness along with maculopapular rash.
Proximal subungual onychomycosis is the characteristic pattern of fungal nail infection in these patients.
Pityrosporum ovale may cause extensive pityriasis versicolor, thus resulting in troublesome and per
sistent truncal folliculitis (Figure 7.1) in some patients and severe seborrhoeic dermatitis in others.
Various ‘deep fungal’ infections like histoplasmosis, blastomycosis, cryptococcosis have gained pro
minence, particularly in hot and humid parts of the world. Organisms that do not usually infect humans
may sometimes cause problems – such as the Penicillium species. Invasive deep fungal infections have
been reported to be one of the major causes of mortality in HIV/AIDS patients, accounting to almost
50% of all AIDS-related deaths globally.
Viral infections
Viral warts may become very extensive and troublesome. Molluscum contagiosum lesions may be larger
than usual and present in very large numbers, often on the face and eyelid. Inflamed lesions are common.
Recurrent herpes simplex infection may be a par
ticular problem, with extensive bilateral and per
sistent skin involvement often resulting in scarring.
Severe, chronic, and progressive orolabial, genital,
or anorectal ulcers may occur. Even an un
suspecting lesion of chronic herpetic whitlow may
be the first manifestation of HIV/AIDS.
Herpes zoster is similarly a troublesome infec
tion in AIDS and maybe the initial manifestation.
It may not resemble ‘ordinary’ herpes zoster,
typically resulting in echthymatous, verrucous, and
necrotic lesions, causing considerable pain and
tissue destruction, as well as spreading outside the
dermatomes in which it began (non-contiguous
dermatomes). A characteristic pattern called dis
seminated zoster often occurs in these patients
(more than 2 non-contiguous, scattered lesions
outside the affected dermatome). Epstein-Barr
virus (EBV) causes a characteristic condition in
these patients called oral hairy leukoplakia (OHL),
which serves as a marker for HIV/AIDS.
Bacterial infections
Severe and extensive staphylococcal infections
FIGURE 7.1 Folliculitis due to Pityrosporum ovale (pyoderma) are common (Figure 7.2). Tuberculosis
infection in a patient with human immunodeficiency and syphilis are both major problems for individuals
virus infection (from Marks and Motley, 18th edition). with AIDS. Both disorders progress rapidly and are
responsible for extensive and severe disease in AIDS patients. Extrapulmonary disease is quite common in
late HIV disease. It has been reported that these patients are 30 times more likely to develop active TB,
compared to the general population. Cutaneous TB also occurs more frequently in these patients. The most
common form is military tuberculosis in contrast to scrofuloderma being the most common form in non-
reactive patients. Infections with mycobacterial species that do not generally infect humans may also be
seen in these patients. Bacillary angiomatosis, a characteristic feature of HIV/AIDS, occurs due to infection
with a bacterial microorganism similar to the bacillus-causing ‘cat-scratch’ disease. It causes Kaposi’s
sarcoma-like lesions and a widespread eruption of red papules. Another infection characteristic of HIV/
AIDS is pneumonia due to Pnemocystis jiroveci. Recently, trials are going on the long-term use of co
trimoxazole to prevent serious bacterial infections in HIV-infected children. A group of researchers are also
exploring the role of vaginal microbiota in HIV transmission and infection. Syphilis can also present with
some unusual manifestations in immunosuppressed AIDS patients like multiple, painful and giant chancres,
increased chance of lues maligna (secondary syphilis with vasculitis and systemic involvement) and more
rapid progression to tertiary syphilis. There might be limited antibody response to treponemal antigens or
false-negative non-treponemal tests, making the serologic diagnosis of syphilis unreliable in these patients.
Parasitic infestations
Scabies seems to spread very quickly and cause extensive and severe skin involvement in patients
with AIDS, leading to the formation of hyperkeratotic lesions called ‘crusted or Norwegian’
scabies. Erythroderma may occur and itching may be almost non-existent. Other rare parasitic
FIGURE 7.2 Severe, extensive pyoderma in an HIV-positive child (courtesy of Dr. Nidhi Gupta, Medical College,
Kolkata, India).
infections may also occur with increased frequency in these patients viz. acanthamoebiasis,
onchocerciasis, etc.
Skin cancers
Depressed delayed hypersensitivity also results in failure of ‘immune surveillance’ and the development
and rapid progression of many forms of skin cancer. Viral infection may also be at work in the de
velopment of the disorder known as Kaposi’s sarcoma, which mainly accompanies AIDS contracted
from homosexual contact. A herpes-type virus is suspected of being responsible for this (HHV-8).
Mauve, red, purple, or brown macules, nodules, or plaques may ulcerate and may spread to involve the
viscera. Kaposi’s sarcoma is a frequent cause of death in patients with AIDS. Other common skin
cancers seen in HIV-positive patients include superficial basal cell carcinomas (BCCs) of the trunk,
SCCs in sun-exposed areas, genital HPV-induced SCC, and extranodal B- and T-cell lymphomas.
Other skin manifestations

Pruritus and dryness of skin (xerosis)
The skin of patients with AIDS may become dry and ichthyotic, making AIDS one of the causes of
‘acquired ichthyosis’, which, in turn, is one of the causes of persistent pruritus. Pruritus occurs in almost
30% of AIDS patients and is considered to be one of its markers. However, pruritus is not usually
caused by the disease itself but is rather related to the associated inflammatory dermatoses. The most
common type of lesions are papular, pruritic eruptionpapules, collectively called ‘papular pruritic
eruption,’ which can be either follicular (temperate regions) or non-follicular (tropical and subtropical
regions). Eosinophilic folliculitis (EF) is the most common type of follicular pruritic eruption, clinically
characterized by the development of urticarial papules on the upper trunk, face, neck, and scalp; while
the histologic hallmark is eosinophilic infiltration around the upper part of hair follicles. Non-follicular
pruritic eruptions are mostly insect-bite reactions, followed by scabies, prurigo nodularis, atopic der
matitis, seborrheic dermatitis, and transient acantholytic dermatosis (Grover’s disease). These lesions
are treated using topical corticosteroids, phototherapy (UVB or PUVA), and antihistamines.
Seborrhoeic dermatitis
Seborrhoeic dermatitis is one of the common causes of chronic, itchy scaly eruption in these patients. Its
incidence is much more than in seronegative patients, affecting also 85% of all seropositive patients at
some point of their disease. It is quite often the presenting feature of HIV (Figure 7.3). Often this
condition becomes extensive in patients with AIDS, presumably due to massive overgrowth of
Pityrosporum ovale other causative microorganisms, occasionally resulting in erythroderma.
Psoriasis
Pre-existing psoriasis may develop an ‘explosive phase’, or psoriasis may develop de novo as an ag
gressive, rapidly spreading eruption. Severe psoriatic variants like psoriatic arthritis, pustular psoriasis,
and erythrodermic psoriasis are more common in HIV-infected patients. Several explanations have been
proposed lately for this “psoriasis HIV-1 paradox” including HIV-1induced destruction of regulatory
CD4 + T cells, an increase in the number of memory CD8 + T cells late in disease, or HIV-1 proteins
acting as superantigens.
Reiter’s syndrome
Patients often present with migratory arthritis along with keratotic limpet-like scales. Circinate balanitis
and plantar fasciitis are common, but urethritis and uveitis are often absent.
FIGURE 7.3 Extensive seborrhoeic dermatitis in an AIDS patient (courtesy of Dr. Nidhi Gupta, Medical College,
Kolkata, India).
Drug reactions
Cutaneous adverse drug reactions (CADRs) occur more frequently in patients suffering from HIV/AIDS;
ranging from morbilliform eruptions to erythroderma and even Stevens–Johnson syndrome. Commonly
implicated drugs include sulphonamides (cotrimoxazole), nevirapine, abacavir, rifampicin, and
carbamazepine.
Acne conglobata
This is a severe and extensive form of acne responding well to oral retinoids or HAART (Figure 7.4).
Mucosal lesions
Mucosal lesions like aphthae occur more frequently in these patients.
Hair changes
Lustreless hair, thin hair, various types of alopecia, discoloration, premature greying, and long eyelashes
have been described.
Nail changes
Some of the important nail changes reported to occur more frequently in seropositive patients are
leukonychia, pigmentation, half and half nail, clubbing, yellow nail syndrome, paronychia, and proximal
subungual onychomycosis (PSO). PSO is a marker of HIV infection.
IRIS (Immune reconstitution inflammatory syndrome)

IRIS refers to a paradoxical worsening of a known condition or the appearance of a new condition in
HIV positive patients after initiation of antiretroviral therapy occurring as a result of restored immunity.
Mycobacterial infections have been reported to be the commonest triggering factor for IRIS, apart from
viral (herpetic, HPV, hepatitis group, etc.), fungal (cryptococcal, histoplasma), parasitic (Strongyloides
FIGURE 7.4 Acne conglobata in an HIV-positive boy (from Marks and Motley, 18th edition).
infestation), and other non-infectious conditions like Guillain–Barre syndrome, autoimmune thyroiditis,
non-Hodgkin’s lymphoma, and myopathy. HAART must be continued along with symptomatic treat
ment in all cases apart from a few life-threatening cases which may require discontinuation of HAART
along with systemic corticosteroids.
Treatment of skin manifestations of AIDS

Treatment of the cutaneous manifestations include treatment of the disease proper (AIDS) and symp
tomatic treatment of the cutaneous condition (infections, pruritus, etc.)
Treatment of the disease proper (HIV/AIDS)

Several drugs have shown efficacy in treating HIV infection; some of the important antiretroviral drugs
are tabulated in Table 7.2.
The first effective treatment for AIDS was zidovudine (AZT, azidothymidine), a reverse transcriptase
inhibitor, given at 500–1500 mg per day in four to five divided doses. The drug slows down the progress
of the HIV infection but comes nowhere near eliminating the viral infection. Unfortunately, it causes
nausea, malaise, headache, and rash as well as many other side effects. Several other classes of anti
retroviral drugs are now available. Other nucleoside analogue reverse transcriptase inhibitors include
lamivudine, nevirapine, stavudine, delavirdine, and efavirenz. Other classes of drugs in use include
protease inhibitors and non-nucleoside reverse transcriptase inhibitors. Optimal regimens now usually
consist of at least three drugs from two classes of antiretroviral agents. The newer antiviral drugs
include enfuviritide (fusion inhibitor), maraviroc (blocks the entry of virus into cell by blocking the
CD4 protein), and the integrase inhibitors (raltegravir, dolutegravir). Although promising, trials are
going on to assess the efficacy of these drugs.
Symptomatic treatment of cutaneous conditions

Ganciclovir and foscarnet are indicated for cytomegalovirus complications. Aciclovir is used for herpes
simplex and herpes zoster. Various antibiotics and other antimicrobials are used as indicated for bac
terial infections. Fluconazole, itraconazole, and ketoconazole are particularly useful for serious and life-
threatening Candida infections. Recombinant interferon-alpha 2B and other interferons have been used
with some success in Kaposi’s sarcoma. The new retinoid bexarotene (Targretin®) is used topically to
TABLE 7.2
Important antiretroviral drugs
Category/Family of drugs Principal mechanism of action Names of drugs
Nucleoside reverse After phosphorylation, gets incorporated into Zidovudine, Didanosine, Zalcitabine,
transcriptase the growing viral DNA to cause premature Stavudine, Lamivudine, Abacavir,
inhibitors (NRTI) chain termination Emtricitabine
Non-nucleoside reverse Binds directly to the viral (HIV) reverse Nevirapine, Delavirdine, Efavirenz
transcriptase inhibitors transcriptase enzyme and blocks its function
(NNRTI)
Nucleotide reverse Prevents the entry of viral DNA into the host Tenofovir
transcriptase inhibitors cell nucleus
Protease inhibitors Inhibit protease enzymes resulting in the Indinavir, Ritonavir, Saquinavir,
formation of immature, defective viral Nelfinavir, Amprenavir,
particles Atazanavir, Tipranavir, etc.
Fusion inhibitor Blocks the fusion of viral membrane with the Enfuvirtide
host cell membrane
Entry inhibitor Blocks receptors on the host cell (CD4) Maraviroc
Integrase inhibitors Blocks the integration of viral DNA into host Raltegravir, Dolutegravir, Elvitegravir
cell DNA
induce regression in individual lesions. Other cutaneous manifestations also require symptomatic
treatment like topical corticosteroids (psoriasis), antipruritics (generalized pruritus), and emollients
(xerosis and ichthyosis).
Drug-induced immunodeficiency
Patients who undergo organ transplantation and those suffering from chronic disorders like auto
immune disorders such as systemic lupus erythematosus, rheumatoid arthritis, and some eczematous
diseases, including severe recalcitrant atopic dermatitis, receive immunosuppressive drugs like cor
ticosteroids and azathioprine, ciclosporin, or tacrolimus for varying lengths of time. The cutaneous
side effects from the immunosuppression are not usually as prominent as in AIDS patients but depend
on the extent and length of the immunosuppression. They include severe and extensive bacterial and
other opportunistic infections.
Patients with renal allografts have most problems, perhaps because they are treated continuously for
longer periods than most of the other groups. They are prone to the development of numerous warty
lesions on the hands and face. These are either viral warts or solar keratoses, or lesions in which it is
really quite difficult to determine their nature. It may be that many viral warts directly transform into
premalignant lesions (Figure 7.5).
It should be noted that photochemotherapy with ultraviolet radiation of the ‘A’ type (PUVA) treat
ment also causes depression in delayed hypersensitivity due to depletion of antigen-presenting cells of
the skin (Langerhans cells), and this probably results in the delayed development of skin cancer in few
patients with psoriasis treated with PUVA.
Other causes of acquired immunodeficiency

Lymphoreticular proliferative diseases such as Hodgkin’s disease, leukemias, and sarcoidosis also result
in depressed delayed hypersensitivity. Hypovitaminosis A, chronic malnutrition, and chronic alcoholism
also result in depressed immune defences, although the depressed immunity in these instances is
contributory to causing disease rather than being directly causative.
Congenital immunodeficiencies
Some congenital/primary immunodeficiency disorders present with eczematous dermatitis as the
cutaneous manifestation. Some of such prominent disorders are listed in Table 7.3.
Dermatological aspects of venereal disease

Several skin infections, although not exclusively ‘venereal’, are nonetheless spread by venereal contact. Such
disorders include genital warts, herpes simplex (type II virus), molluscum contagiosum, scabies, and pubic lice.
Reiter’s syndrome
This disorder occurs as a sequel to non-specific urethritis in men and, less commonly, to bowel in
fection, and probably results from infection with a Mycoplasma organism. There is usually accom
panying migratory arthritis with spondylitis and occasionally conjunctivitis. Thick, red psoriasiform
skin lesions develop on the soles and elsewhere on the feet. These are often severe, persistent, ag
gressive, and pustular (keratoderma blenorrhagica). Inflamed red scaling patches may also develop on
the glans penis (circinate balanitis). There is a curious and unexplained preponderance of patients with
the human leucocyte antigen (HLA) B27 haplotype. Although arthritis in a characteristic involvement is
the most common presentation, urethritis and conjunctivitis may or may not be present; thus the
classical triad of arthritis, urethritis, and conjunctivitis is extremely rare in occurrence.
Gonorrhoea
This venereal disease, which predominantly af
fects urethral epithelium, is caused by a delicate
intracellular Gram-positive diplococcus – the
gonococcus. The skin is only affected during
gonococcaemia, when small purpuric and pust
ular vasculitic lesions suddenly appear in the
course of a pyrexial illness (Figure 7.6). These
are similar to the purpuric pustular lesions that
develop in meningococcaemia and subacute
bacterial endocarditis.
Chancroid (soft sore)

This venereal infection is caused by the Gram-
negative bacillus Haemophilus ducreyi. One to 5
days post-infection, a soft sloughy ulcer appears on
the areas of contact on the penis or vulva. Other
sites may be affected, and inguinal adenitis occurs
in 50% of patients, usually unilateral in distribution.
Both the genital ulcer and lymphadenopathy are
painful, a characteristic feature of this condition.
Differential diagnosis includes syphilitic
chancre, herpetic ulceration, granuloma inguinale,
FIGURE 7.5 Warty lesions on the hands in a patient and traumatic ulcers. The treatment of choice is
after 8 years on azathioprine and prednisolone fol Azithromycin (1 gm orally in a single dose) or
lowing renal allograft; the lesions are either viral warts Injection Ceftriaxone 250 mg i.m. in a single dose
or solar keratoses, or somewhere in between (from or Ciprofloxacin (500 mg twice daily for 3 days) or
Marks and Motley, 18th edition). Erythromycin (500 mg 6-hourly for 14 days).
TABLE 7.3
Important immunodeficiency disorders
Disorders Features
1. Infantile/X-linked agammaglobulinaemia X-linked recessive disorder; absence of plasma
cells in the marrow making patients more
susceptible to severe pyoderma and numerous
warts.
2. Severe combined immunodeficiency (SCID) Sex-linked recessive or autosomal recessive
inheritance, complete deficiency of both
cell-mediated and humoral immunity due
to depression of circulating lymphocytes,
increased susceptibility to all infections
leading to death between the ages of 1 and 2 years.
3. Ataxia telangiectasia Autosomal recessive disorder characterized by cerebellar
degeneration, telangiectasia on exposed skin developing
progressively, lymphopenia and depressed circulating
levels of IgA antibody.
4. Hyper-IgE syndrome (HIES)/Job Autosomal dominant disorder, mutation in STAT3 gene;
syndrome/Buckley syndrome recurrent cutaneous and sinopulmonary infections,
dermatitis from birth or early childhood, coarse
facial features, and very high levels of
immunoglobulin E (IgE).
5. Wiskott–Aldrich syndrome X-linked recessive inheritance, mutation in
WAS gene, life-threatening primary
immunodeficiency associated with a
bleeding tendency, eczema, and recurrent
pyogenic infection.
Syphilis
Syphilis has recently generated renewed interest because of the rising incidence of AIDS; the syphilitic
chancre serves as a portal of entry for the HIV virus as well as the more dramatic presentation of
syphilis in AIDS patients. The disease is caused by the delicate spirochaetal microorganism Treponema
pallidum, which is transmitted by contact between mucosal surfaces.
Clinical features
Characteristically, the incubation period is 9–90 days and the first sign is the appearance of the chancre
at the site of inoculation, usually on the glans penis, prepuce or, less often, on the shaft of the penis in
men and on the vulva in women. In homosexuals, the chancre may appear around or in the anus. The
chancre is of variable size (0.5–3 cm in diameter) and has a sloughy and markedly indurated base.
Untreated, it heals after 3–8 weeks.
This primary stage of the disease is followed by a brief quiescent phase of from 2 months to up to
3 years before the secondary stage occurs. In secondary syphilis, there are signs of a usually mild
systemic upset with slight fever, headache, mild arthralgia, and generalized lymphadenopathy. In ad
dition, there are skin manifestations, which include an early widespread pink macular rash, involving the
palms and soles (Figure 7.7) and a later papular or lichenoid eruption. Thickened, broad-based warty
areas (condylomata) appear perianally and in other moist flexural sites (Figure 7.8). Ulcers appear on the
oral mucosa (snail-track ulcers).
After resolution of the secondary stage, there is a latent period without signs or symptoms, lasting for 5–50
years. The tertiary stage takes protean forms and includes cardiovascular disease with aneurysm formation
(particularly aortic aneurysm), central nervous disorder, either as tabes dorsalis or general paralysis of the
insane, and ulcerative or gummatous lesions that may occur on the skin or on mucosal surfaces.
FIGURE 7.6 Vasculitis (from Marks and Motley, 18th edition).
Diagnosis
Diagnosis is made by identification of the spirochaete from wet preparations of the chancre or moist
secondary-stage lesions (dark ground illumination microscopy) and by serological tests detecting either
lipoidal substance liberated by infected tissues (non-treponemal tests) or the presence of antibodies to
the microorganism (treponemal tests).
The older Wassermann reaction (WR) has been replaced by the Venereal Disease Reference
Laboratory (VDRL) test, a flocculation test, which, although not specific, is quite sensitive and becomes
FIGURE 7.7 Palmar rash in secondary syphilis (from

Marks and Motley, 18th edition). FIGURE 7.8 Perianal condylomata in secondary sy
philis (from Marks and Motley, 18th edition).
positive early in the disease. It can also be used to monitor therapy as it becomes negative around 6
months following adequate therapy. The WR and the VDRL tests (and other similar tests) depend on
lipoidal antigens. The T. pallidum haemagglutination assay (TPHA) is currently the most widely used
specific test and depends on antibodies to the microorganism.
Treatment
The treatment of syphilis includes one dose of Benzathene penicillin (240000 IU) intramuscular for
early stages or 3 weekly 240000 IU intramuscular doses for late latent/unknown duration disease.
Recently, comparable efficacy has been reported with oral Doxycycline 100 mg twice daily for 14 days
for early stages and 100 mg twice daily for 28 days for late latent/unknown duration stages (Antonio
MB, Cuba GT, Vasconcelos RP, Alves AP, da Silva BO, Avelino-Silva VI. Natural experiment of
syphilis treatment with doxycycline or benzathine penicillin in HIV-infected patients. Aids.
2019; 33:77–81). A proportion of patients develop a fever and possibly a rash after starting treatment
(Jarisch–Herxheimer reaction). More serious reactions can also occur. However, in penicillin-sensitive
patients, the drug of choice is erythromycin.
8
Eczema (dermatitis)
Sumit Sethi
The term ‘eczema’ includes several disorders (Table 8.1) in which inflammation is focused on the
epidermis. Typically, epidermal cells become swollen and accumulate oedema fluid between them
(spongiosis), leading to the formation of vesicles in acute cases. Odema, vasodilation along with
perivascular mononuclear infiltrate, is seen in the dermis.
Some types of eczema stem from yet uncharacterized constitutional factors (‘endogenous’ or con
stitutional eczema), whereas others are the result of an external injury (exogenous). The clinical picture
varies according to the nature of the provocation, the acuity of the process, the susceptibility of the
individual, and the site of involvement.
Atopic dermatitis
Definition
This is a very common, chronic relapsing inflammatory skin condition characterized by extreme itching.
The eczematous lesions typically affect the face and extensors in infants, while flexural surfaces are
involved in children, adolescents, and young adults. It is often associated with a personal or family
history of other atopic disorders, such as asthma and allergic rhinoconjunctivitis.
Clinical features
Signs and symptoms
Atopic dermatitis (AD) is a highly pruritic inflammatory skin disease characterized by a chronic or
chronically relapsing course that begins during infancy (early onset) but occasionally may present in
adulthood (late-onset). Dry lackluster skin, intense pruritus, and cutaneous hyperreactivity are cardinal
features of AD. Pruritus may be present intermittently throughout the day but is usually worse in the
evening and night. The itchiness is made worse by changes in temperature, by rough clothing (such as
woollens), and by other minor environmental alterations. The incessant scratching gives the fingernails a
‘polished’ appearance and results in eczematous lesions, prurigo papules, and lichenification. Early/
acute skin lesions appear as intensely pruritic papules and vesicles on erythematous base, associated
with excoriations, vesicles, and serous exudate (Figure 8.1). Erythematous, excoriated, scaling papules
characterize subacute dermatitis (Figure 8.2). Chronic AD is characterized by thickened hyperpig
mented plaques of skin with accentuated skin markings (lichenification) and pruritic papules
(Figure 8.3). The distribution pattern of eczema varies according to the patient’s age. During infancy,
the lesions are more acute and primarily involve the face, scalp, and extensor surfaces of the extremities.
The diaper area is usually spared. Older children, and those with long-standing skin disease, develop a
chronic form of AD, with lichenification and distribution of the rash to the flexural folds of the ex
tremities. AD often decreases in severity as the patient grows older, leaving an adult with skin that is
prone to itching and inflammation when exposed to exogenous irritants. Chronic hand eczema may be
the presenting manifestation of many adults with AD.
96
Eczema (dermatitis) 97
TABLE 8.1
Common types of eczema
Type Synonyms Frequency/Age group Cause
Atopic dermatitis Neurodermatitis Very common, mostly Unknown, but appears to be
Besnier’s prurigo occurs in infants and the immunologically mediated
Infantile eczema very young
Seborrhoeic dermatitis Infectious eczematoid Very common in all age Probably microbial with
dermatitis groups overgrowth of normal skin flora
being responsible
Discoid eczema Nummular eczema Uncommon, mainly in Unknown
middle-aged individuals
Lichen simplex Circumscribed Quite common, mainly in Initially appears to be a localized
chronicus neurodermatitis young and middle-aged itch causing an ‘itch–scratch
adults cycle’
Eczema craquelée Asteatotic eczema Uncommon, restricted to Low humidity and vigorous
the elderly washing
Venous eczema Stasis dermatitis Common in the age group Multiple; a common variety is
Gravitational eczema that has gravitational allergic contact dermatitis to
syndrome medicament
Allergic contact Common in all adult age Delayed hypersensitivity to a
dermatitis groups except the specific agent
very old
Primary irritant contact Occupational dermatitis Very common in all adult Both mechanical and chemical
dermatitis Housewives’ eczema age groups except the trauma
very elderly
Photosensitivity Not uncommon, mainly in Both phototoxic and photoallergic
eczema adults types occur
FIGURE 8.1 Inflamed, thickened eyelids and some loss of eyebrows and eyelashes due to perpetual eye rubbing in atopic
dermatitis (from Marks and Motley, 18th edition, with permission).
In many patients, there is a widespread fine scaling of the skin, described as ‘dryness’ or xerosis; it is
sometimes incorrectly diagnosed as ichthyosis, but is really the result of the eczematous process itself.
Another feature sometimes incorrectly ascribed to ichthyosis is the presence of increased prominence of
the skin markings on the palms Figure 8.4) – the so-called hyperlinear palms. The cheeks are often pale,
FIGURE 8.2 Excoriations of the wrists in atopic dermatitis (from Marks and Motley, 18th edition, with permission).
with crease lines just below the eyes (known as

Dennie Morgan folds) due to continual rubbing,
making the facial appearance quite characteristic
(Figure 8.5). In addition, the eyebrows tend to be
sparse. Running a blunt instrument (such as a key)
over affected skin produces a white line in about
70% of patients, known as ‘white dermato
graphism’. This is the reverse of the normal triple
response and disappears when the condition im
proves. This paradoxical blanching is similar to
that seen after intracutaneous injection of metha
choline in atopic dermatitis patients.
Clinical variants
In patients with black skin, there are often nu
merous small follicular papules in affected areas.
In lichenified areas in black-skinned patients,
there may be irregular pigmentation, with hy
perpigmentation at some sites and loss of pigment
at others.
Some individuals lose their childhood eczema
only to develop chronic palmar eczema in later
years with scaling, hyperkeratosis, and cracking.
FIGURE 8.3 Exaggeration of skin surface marking
This is also believed to be a manifestation of
(lichenification) due to scratching (from Marks and
Motley, 18th edition, with permission). atopic disease.
Associated disorders
Atopic dermatitis, asthma, and hay fever seem to share pathogenetic mechanisms in which aberrant immune
processes play an important part. These three ‘atopic’ disorders cluster in families and the tendency to one or
FIGURE 8.4 Prominent skin surface markings of the palms (hyperlinear palms) in atopic dermatitis (from Marks and
FIGURE 8.5 Prominent crease beneath the eyes in a child with atopic dermatitis – Denny Morgan fold (from Marks and
the other or all is inherited in an as-of-yet uncharacterized way. Chronic urticaria and alopecia areata occur
more often in atopic dermatitis patients. The skin of patients with atopic dermatitis is more vulnerable to both
chemical and mechanical trauma and has an unfortunate tendency to develop irritant dermatitis. Many of these
associated problems may be due to a general defect in the barrier function of atopic skin.
Occupational and chronic hand eczema are much more common in patients with atopic dermatitis.
Complications
Patients with atopic dermatitis are frequently troubled by skin infections. Pustules and impetiginized
areas represent bacterial infection (mostly staphylococcal) and are the most common expression of this
propensity. They are easily treated but tend to recur. Cellulitis may also develop, giving rise to fever and
systemic upset. Viral warts and molluscum contagiosum are also more frequent and more extensive than
in non-eczematous subjects.
Herpes simplex sometimes causes a severe and extensive rash in atopic dermatitis patients, who may
develop fever and severe systemic upset, but recover after 10–14 days.
Epidemiology and natural history

Atopic dermatitis occurs in families, but the mode of inheritance has been difficult to work out.
AD is very common and has 15–20% prevalence in some developed countries. It typically begins
during infancy; 50% of patients present it by 1 year of life and an additional 30% between the ages of 1
and 5 years. Between 50–80% of patients with AD develop allergic rhinitis or asthma later in childhood.
Many of these patients outgrow their AD as they develop respiratory allergy.
Laboratory findings and aetiopathogenesis

Skin biopsy of an acute eczematous lesion reveals spongiosis, epidermal thickening, parakeratosis and
an inflammatory cell infiltrate (mostly lymphocytes), oedema, and vasodilatation in the dermis.
Elevation of serum IgE antibodies is seen in approximately 70–80% of AD patients. These are ‘re
aginic’, precipitating antibodies to various environmental allergens, including foods and inhaled materials,
which become fixed to mast cells. Atopic patients often have multiple positive reactions to various foods,
house dust mite allergen, and pollens.
The susceptibility to skin infection, association with other disorders with immunopathogenetic
component, and elevated IgE level, suggest an abnormality of the immune system in the pathogenesis of
atopic dermatitis. Part of the problem may be an imbalance in the relative proportions of two sub
populations of T-helper lymphocytes – TH1 and TH2. The TH1 subset typically secretes gamma in
terferon and is important in turning off the secretion of immunoglobulins by B-lymphocytes. TH2 cells
predominantly secrete interleukin-4 (IL-4) and are thought to be dominant in atopic dermatitis.
A marked decrease in skin barrier function is observed in AD patients due to the downregulation of cornified
envelope genes (filaggrin and loricrin), reduced ceramide levels in epidermis, enhanced transepidermal water
loss, and increased levels of endogenous proteolytic enzymes. Frequent use of alkaline soap and detergents
raise the pH of skin, increasing the activity of endogenous protease enzymes, leading to further decrease of
epidermal barrier function. Exogenous proteases from Staphylococcus aureus (S. aureus) and house dust mites
also take a toll on the epidermal barrier. Deficiency of few endogenous protease inhibitors in atopic skin
worsens the situation. The defective epidermal barrier leads to increased allergen absorption and microbial
colonization of the skin. Epicutaneous sensitization to these environmental allergens, chemicals, and antigens
results in inflammatory responses and a high level of immunologic memory, thus predisposing these children to
the development of respiratory allergy and food allergy later in life.
Management
Several points need to be kept firmly in mind.
The disease is persistent but unpredictably active and subject to recurrent flares, making it important
to develop a good relationship with patients and their immediate relatives over what may be many years.
The disorder causes discomfort and disability because of the intense and persistent itching, resulting
in anxiety and depression in those affected by it. The sleep disturbance associated with intense pruritus
affects the entire family.
The use of bland, greasy emollients gives symptomatic relief and provides protection from further
antigenic insults.
Infection plays an important role in the aggravation of the disease and antimicrobial therapy, both local
and systemic, may help to rapidly terminate an exacerbation. This is particularly true in cases of
Staphylococcus aureus infections, to which there appears to be a specific susceptibility in atopic patients.
Topical corticosteroids
Topical corticosteroids are the most useful topical agents for the treatment of atopic dermatitis.
However, these drugs are only suppressive and may need to be given over long periods to maintain a
reasonable quality of life. Toxic side effects include skin atrophy, striae distensae, and pituitary–adrenal
axis suppression, with the possibility of adrenal collapse and masked infection. Sudden withdrawal of
corticosteroids can lead to a severe ‘rebound’ aggravation of eczema, and, thus, it is prudent to use the
least potent corticosteroid preparation that is effective. Acquired tolerance or tachyphylaxis is another
problem associated with the use of topical corticosteroids, which makes them less effective with
continued use. However, changing to another preparation of similar potency will help regain control.
Steroid formulations specifically tested for safety and approved by the US Federal Drug
Administration (FDA) for use in younger children include desonide hydrogel and nonethanolic foam,
fluticasone 0.05% cream, and fluocinolone acetonide oil. Mometasone cream and ointment are approved
for children aged 2 years and older. Ointments are preferred over creams, lotions, and gels as vehicles
for steroids, as they do not contain preservatives and tend to have a better emollient effect.
Non-steroidal topical immunosuppressive agents – like tacrolimus (Protopic® 0.03% and 0.1%) and
pimecrolimus (Elidel® 1.0%) – are alternatives to topical steroids and particularly useful for the treatment
of areas such as the face and intertriginous regions. Tacrolimus ointment 0.03% has been approved for
intermittent treatment of moderate to severe AD in children aged 2 years and older, with tacrolimus
ointment 0.1% approved for use in adults; pimecrolimus cream 1% is approved for the treatment of
patients aged 2 years and older with mild-to-moderate AD. These agents are effective, but expensive, and
should only be used when the corticosteroids are contraindicated or prolonged application is required.
Topical phosphodiesterase inhibitors

Crisaborole is a topical PDE4 inhibitor indicated for the treatment of mild to moderate atopic dermatitis
in adult and pediatric patients 3 months of age and older. It can be used on the face and skinfolds but
may sting when applied. It is most useful as maintenance therapy for mild to moderate eczema.
Moisturizers
Moisturizers have hydrating effects on the skin in eczema because of their occlusive and emollient
properties. Many moisturizers also contain ‘humectants’, which attract and retain water. They reduce
scaling and improve skin texture and appearance. They improve the elasticity of skin, reduce fissuring,
and decrease the pruritus and inflammation.
All moisturizers seem to have the same degree of efficacy, provided they are sufficiently greasy and
occlude the skin surface. The most important issues are how frequently they are applied and patient
compliance. They should ideally be applied within 3 minutes of a warm soaking bath to retain moisture.
Hydration of skin improves its barrier function and decreases transepidermal water loss.
Tar preparations
Coal tar has anti-inflammmatory and anti-pruritic properties. The generic preparations (e.g. tar ointment
or tar and salicylic acid ointment BP) are not popular because of the smell and messiness associated with
their use. Modern proprietary preparations are more acceptable (e.g. Exorex® cream). They are not to be
used on inflamed skin and are best employed for chronic lichenified type of eczema. Side effects include
folliculitis, irritation, and photosensitivity.
Systemic agents
Patients with severe recalcitrant disease do not respond to topical measures. For this group, options
include NBUVB (narrowband UVB), systemic steroids, cyclosporine, ‘biologicals’, and other im
munosuppressants (methotrexate and azathioprine).
Some patients improve after sun exposure, and in 50%–75% of severely affected patients, phototherapy of
some type may be of assistance, but has to be balanced against the long-term hazards of skin ageing and
cutaneous malignancy. In a hot and humid climate, sunlight may trigger sweating and pruritus, thereby being
deleterious to atopic patients. Systemic steroids suppress eczema, but have long-term side effects, including
osteoporosis, skin fragility, susceptibility to infection, and pituitary–adrenal axis suppression, which prob
ably outweigh the short-term benefits. They are appropriate to manage short-term exacerbation and should
be gradually tapered followed by an intensive regimen of skincare to prevent rebound phenomenon.
Cyclosporine is a fungal metabolite peptide with immunosuppressive effects, which is helpful for
patients with severe, generalized atopic dermatitis at a dose of 3–5 mg/kg body weight per day.
Nephrotoxicity and hypertension are side effects of cyclosporine and therapy requires regular blood
pressure and kidney function test-monitoring.
Alitretinoin
This is an oral retinoid drug that has been shown to be helpful in the treatment of chronic hand eczema.
The recommended dose is 30 mg daily for a 12–24-week period. The drug has many of the retinoid
group toxicities, including teratogenicity.
Dupilumab
This is an IL-4 alpha receptor inhibitor that blocks the function of IL-4 and IL-13. It is a targeted therapy
approved by the FDA for the treatment of moderate-to-severe atopic dermatitis in patients aged 12 years and
older whose disease is not adequately controlled with topical prescription treatments. It is injected every
2 weeks after a loading dose and decreases pruritus and Eczema Area and Severity Index (EASI) scores. The
most common significant side-effects are injection site reactions, eye and eyelid inflammation, and cold sores.
Antimicrobial agents
Patients with atopic dermatitis are particularly prone to skin infection, which contributes to the flare-up
of dermatitis. Infection with staphylococci and possibly other bacteria cause pustules, impetiginized
lesions, and cellulitis. Bacterial swabs from suspected infected lesions should be taken before starting
treatment with either topical or systemic antibacterial agents. Diluted bleach baths may reduce the
bacterial load and decrease skin infections. The infected area can be soaked or bathed in 1 in 8000
potassium permanganate solution or aluminium subacetate solution. Topical mupirocin may be used,
but other antibiotics should be avoided because of the risk of inducing microbial resistance and allergic
contact dermatitis. If the infection is severe, systemic antibiotics should be given.
Definition
This is a common, chronic, superficial inflammatory disorder that characteristically affects regions with
high sebum production and the flexural areas of the body. Both infantile (Figure 8.6) and adult forms
exist. It is believed to be due to the overgrowth of lipophilic yeast Malessezia, sebaceous activity,
immunologic abnormality, and patient susceptibility.
Clinical features
Signs and symptoms
Sharply demarcated patches or thin plaques varying in color from pink-yellow to dull red to red-brown
appear at predisposed sites rich in the sebaceous gland, like the scalp, face, ears, presternal region – and
FIGURE 8.6 Cradle cap.
body folds. Depending on the acuteness and severity, scaling may be bran-like in dandruff (pityriasis
sicca) to flaky “greasy” scaling in frank seborrhoeic dermatitis or exudative and crusted in severe
involvement. Scaling and erythema of the eyelid margins (marginal blepharitis) may also occur.
Seborrhoeic folliculitis is marked by numerous small monomorphic itchy papules and papulopustules
originating in the hair follicles of scalp and beard. The usually commensal yeast-like microorganism
Malassezia ovalis (Pityrosporum ovale) seems to have taken on an aggressive role, causing the in
flammatory lesions.
Other sites involved

The condition may erupt suddenly to cause exudative lesions in the major body flexures. This is
especially likely to occur in the summer months in overweight elderly individuals. In the elderly,
seborrhoeic dermatitis may spread rapidly to become generalized. This ‘erythrodermic’ picture is quite
disabling, but fortunately quite uncommon.
The disorder causes mild itching and discomfort as compared to other eczematous disorders. It can
give rise to severe soreness and discomfort when it is exudative and affects the major flexures. Round or
annular scaling patches, which develop over the central chest and the central upper back, are particularly
common in the middle-aged and the elderly, as are erythematous areas in the groins, especially in
overweight people.
In the groin area, it is important to distinguish from flexural psoriasis and ringworm infection (tinea
cruris; Table 8.2). Ringworm is usually asymmetrical and does not reach up into the groin apices. There
is usually a raised, slightly scaly advancing edge to ringworm and a tendency to clear centrally.
Mycological testing is simple and prevents misdiagnosis. Psoriatic lesions have more pronounced er
ythema with silvery-white scales that peel in layers. Characteristic psoriasis lesions elsewhere and nail
involvement may differentiate from seborrheic dermatitis.
Aetiopathogenesis
The current view is that seborrheic dermatitis is an inflammatory response to the overgrowth of yeast-
like microorganism, Malassezia ovalis (Pityrosporon ovale). This is a ‘normal’ denizen of human hair
TABLE 8.2
Differential diagnosis of rashes in the groin
Diagnosis Clinical features Tests
Ringworm Often not symmetrical, very itchy, rapidly spreading Microscopy and culture of
scales
Seborrhoeic dermatitis/ Tends to be symmetrical and to involve apices of groins; None available
intertrigo other areas may be affected
Clothing dermatitis May resemble seborrhoeic dermatitis; likely to affect Patch testing
other areas
Flexural psoriasis Psoriasis elsewhere tends to be symmetrical surface None available
scaling
follicles. In the human immunodeficiency virus (HIV) disease, Parkinson’s and stroke patients, the
M. furfur population increases and causes dermatitis.
Natural history and epidemiology

The condition is common at all ages and in both sexes. Severe and widespread seborrhoeic dermatitis is
a particular problem for elderly men, but the milder forms are no more common in the elderly than in
younger age groups. In the newborn, yellow or brown scaly lesions with adherent epithelial debris are
known as ‘cradle cap’. There is no racial predilection for the disorder and it appears to affect all social
groups and occupations. Left untreated, the condition waxes and wanes over many years.
Treatment
The major aim of treatment in seborrhoeic dermatitis is the removal of the precipitating microbial cause
and the suppression of the eczematous response. Topical preparations containing both corticosteroids or
an imidazole, such as miconazole, econazole, or clotrimazole may be all that is required for patients
with limited glabrous disease. Topical antifungal agents or topical calcineurin inhibitors are preferred on
facial and intertriginous skin.
Exudative intertriginous areas in the major body fold respond rapidly to bed-rest, which avoids further
friction between opposing skin surfaces, and weak, non-irritating antimicrobial solutions for bathing and
wet dressings.
Discoid eczema (nummular eczema)

Definition
Discoid eczema is a common eczematous disorder of unknown cause, characterized by the appearance
of erythematous, round, scaly patches on the arms, legs, and, less frequently, the trunk.
Clinical features
Signs and symptoms
Slightly raised, pink–red, well-defined, scaly discs, varying in diameter from 1 to 4 cm, appear on the
extensor arms and lower legs and dorsum of hands (Figure 8.7). The disorder is quite itchy and is often
associated with dry skin on arms and legs.

Discoid eczema is most common in middle-aged and
elderly people and presents as an intensely itchy
outbreak of three or four discoid lesions on the leg.
The condition responds to potent topical steroid
therapy. Regular use of emollients is important to
prevent recurrence.
The condition has to be distinguished from psoriasis,
in which the margins are more distinct; from ring
worm, which usually spreads peripherally and has a
raised margin; and from Bowen’s disease, which is
mostly restricted to the light-exposed areas and is
usually manifested as one or two solitary red,
scaling patches (Table 8.3) that gradually increase
in size.
Treatment
Potent topical steroid ointments with regular emollients
FIGURE 8.7 Discoid eczema. and emollient cleansers are required.
Eczema craquelée (asteatotic eczema)

Definition
Eczema craquelée is an eczematous disorder that occurs on the extensor aspects of the limbs of elderly
individuals and is characterized by very dry skin and a ‘crazy pavement’ appearance.
Clinical features
Signs and symptoms
The most common affected sites are the shins, the fronts and sides of the thighs, extensor aspects of the
upper arms and forearms, and the upper and mid-back. The involved skin is pink, roughened, and super
ficially fissured, giving a ‘cracked’ appearance (Figure 8.8). The areas affected are more sore than itchy.

The disorder is restricted to the elderly and is more common in winters, when there is low ambient
relative humidity. Vigorous prolonged hot baths and use of harsh soaps aggravate the condition.
TABLE 8.3
Differential diagnosis of round, red, scaling patches
Dianosis Features
Psoriasis Well-defined, thickened, scaly plaques, usually multiple
Discoid eczema Only a moderately well-defined edge; slightly scaly, pink patches, limited in number
Ringworm May be annular with central clearing; microscopy and culture of scales will reveal fungal mycelium
Bowen’s disease Often slightly irregular in shape; edge is well-defined; biopsy is decisive
Treatment
The condition responds to the frequent use of emollients and, if necessary, corticosteroid ointment.
Taking short tepid showers, using acid pH synthetic detergent soaps, and application of emollient after
bathing prevent recurrence.
Lichen simplex chronicus (circumscribed neurodermatitis)

Definition
Lichen simplex chronicus is an intensely pruritic rash, sharply localized to one or a few sites. Affected
areas are characterized by hyperpigmentation, thickening, and exaggeration of the skin surface markings.
Clinical features
The medial aspect of the ankle, the back and sides of neck, scalp, the elbows, and adjoining extensor
aspects of the forearms, the wrists, and the genitalia are among the areas of skin that are prone to develop
patches of this disorder. The individual lesions vary greatly in size but are mostly 2.5–7.5 cm in diameter.
Characteristically, the lesions are raised hyperpigmented scaling plaques with a well-defined, if somewhat
irregular, margin. They are intensely itchy, often bearing excoriations, and the perpetual rubbing and
scratching causes skin hypertrophy with exaggeration of the skin surface markings (Figure 8.9). In
extreme cases, large nodules form, and the condition is known as prurigo nodularis (Figure 8.10).

The disorder is quite common in middle-aged
individuals regardless of sex or race. It is a very
stubborn disorder, which is very resistant to
treatment and recurrences are frequent. Prurigo
nodularis is similarly persistent.
Hypertrophic lichen planus may be difficult to
distinguish, although this disorder tends to be more
mauve or pigmented and be less regularly licheni
fied than lichen simplex chronicus. Biopsy may be
needed to distinguish these disorders with certainty.
Lichen simplex chronicus may also resemble a
patch of psoriasis or a patch of Bowen’s disease.
Pathology and pathogenesis

Histologically, there may be striking epidermal hy
pertrophy, which, in extreme cases, may resemble
epitheliomatous change (pseudoepitheliomatous hy
perplasia). More usually, the hypertrophy is quite
regular and may resemble psoriasis (psoriasiform).
The persistent scratching causes an increased rate of
FIGURE 8.8 Eczema craquelée; note the ‘crazed ap epidermal cell production and accounts for the hy
pearance’ (from Marks and Motley, 18th edition, with pertrophy; there is always marked hyperkeratosis
permission). and some parakeratosis.
FIGURE 8.9 Lichen simplex chronicus affecting FIGURE 8.10 Prurigo papules with excoriations in
scrotum; note the hyperpigmentation and exaggerated volving the knee.
skin surface markings.
Treatment
The condition tends to persist and recur regardless of the treatment prescribed. High-potency topical
corticosteroids, intralesional corticosteroids, or preparations of coal tar are sometimes helpful. Medium
potency steroid impregnated tape can be particularly helpful. It is applied to affected skin overnight for
several weeks until the lesions remit.
Contact dermatitis
Contact dermatitis may be caused by direct toxic action of a substance on the skin, the so-called primary
irritant dermatitis, or by a substance inducing a delayed hypersensitivity reaction, allergic contact
dermatitis. Both are common and cause considerable loss of work and disability.
Primary irritant dermatitis

Definition
Primary irritant dermatitis is a non-specific inflammatory rash that results from direct contact with toxic
‘irritating’ materials. The degree and the severity of damage are dependent on both the concentration of
the toxic material, duration of contact as well as the condition of the skin at the time of contact.
Clinical features
Scaly, red, and fissured areas appear on the irritated skin (Figures 8.11 and 8.12). The hands are the most
frequently affected. The palmar skin is often affected, but the areas between the fingers and elsewhere
on the hands may also be involved. The condition may become exudative and very inflamed if the
substances contacted are very toxic. This form of

contact dermatitis causes considerable soreness
and irritation. The fissures make movement very
difficult and effectively disable the victims.
The condition must be distinguished from al
lergic contact dermatitis by a carefully taken
history and patch testing. Psoriasis of the palms
may resemble contact dermatitis, but the areas
affected are better marginated and nearer to the
wrist and are usually accompanied by signs of
psoriasis elsewhere. Ringworm usually affects
one palm only and is marked by diffuse
erythema and silvery scaling. If there is any
doubt, scales should be examined for fungal
mycelium under the microscope.

An ‘irritant’ substance will injure anyone’s skin
FIGURE 8.11 Primary irritant contact dermatitis to if there is sufficient contact. The duration of the
chloroxylenol containing antiseptic on scrotum. contact is as important as is its intimacy.
Occlusion enhances the penetration of irritants
and so worsens dermatitis. The simultaneous application of more than one irritant will often
compound an irritant reaction synergistically. However, some individuals are more prone to develop
primary irritant contact dermatitis – especially atopic subjects.
The disorder is seen particularly often in manual workers (occupational dermatitis) and housewives
(housewives’ dermatitis). Builders, mechanics, hairdressers, cooks, and laundry workers are some of the
FIGURE 8.12 Primary irritant contact dermatitis affecting the back of the hand.
groups that are frequently affected. The condition causes considerable economic loss due to loss of
work. Contact with alkalis, organic solvents, detergent substances, cement, and particulate waste is often
responsible.
Prevention and management

The identification of potential irritant substances, use of non-toxic substances as substitutes for
more irritating traditional agents, prevention of skin contact, use of protective gloves, use of
emollients and worker education are all important in prevention. When present, the cause must be
identified and further contact should be prevented. When the condition is severe, rest from manual
work is required.
Moisturizers are an important component of treatment. They prevent contact with irritants by forming
a barrier and minimize fissuring. Moderately potent to potent corticosteroids should help reduce the
inflammation and accelerate healing.
Allergic contact dermatitis

Definition
Allergic contact dermatitis is an eczematous rash that develops after contact with an agent to which
delayed (cellular) hypersensitivity has developed.
Clinical features
The rash develops at the sites of skin contact with the ‘allergen’ but occasionally spreads outside
these limits for unknown reasons. The severity and area of involvement vary enormously de
pending on the ‘dose’ of allergen to which the patient has been exposed and the susceptibility of
the individual. When very acute, the reaction develops within a few hours of contacting the
responsible substance; e.g. with ‘poison ivy’, which is common in the USA. Itching is noticed as a
sign after exposure first and then the area involved becomes red, swollen, and vesicular. Later, the
area becomes scaly and fissured.
An enormous number of substances are capable of causing allergic contact dermatitis. Nickel dermatitis
is one of the most common examples – about 5% of women (or more) in the UK are said to be sensitive to
nickel. Affected individuals cannot wear stainless-steel jewellery because of the nickel content in the steel
(Figure 8.13) and develop a rash beneath steel studs, clips, and buckles.
Other examples include allergy to chemicals in rubber, e.g. mercaptobenzthiazole (MBT) and
thiouram. Allergies to lanolin (in sheep-wool fat and in many ointments and creams) and to perfumes
can cause dermatitis after the wearing of cosmetics. Modern-day ‘lanolin’ is much less of a problem
because the potent allergenic components of natural wool have been removed during
purification. Lanolin, ethylenediamine, Vioform, neomycin fragrances, and local anaesthetics are
amongst the many substances that may cause dermatitis after using in a cream or an ointment (dermatitis
medicamentosa). Dyes (such as the black hair dye paraphenylenediamine) can also be the cause of
allergic contact dermatitis (Figure 8.14). Some materials are notorious for causing sensitivity and are not
often used topically because of this, e.g. penicillin and sulfonamides.

Allergic contact dermatitis is quite common but not as common as primary irritant dermatitis. It is rare
in children and uncommon in the elderly. It is seen in all racial groups, although less so in black-skinned
individuals. Once allergic dermatitis has developed, the sensitivity persists throughout life.
FIGURE 8.13 Allergic contact dermatitis to nickel in metal bangles.
Diagnosis of allergic contact hypersensitivity

Accurate history taking and careful clinical examination to identify all involved areas are very
important. The definitive technique for diagnosing allergic contact hypersensitivity is patch testing.
In this test, possible allergens are placed in occlusive contact with the skin for 48-hour periods, and
the area is inspected 48–72 hours after removal of the patch. A positive test is revealed by
the development of an eczematous patch with erythema, swelling, and vesicles at the site of
application. In practice, low concentrations of allergen are applied to avoid false-positive primary
irritant reactions.
In most cases, a battery of the commonest allergens causing allergic contact dermatitis in that
community is applied in appropriate concentrations (Table 8.4).
FIGURE 8.14 Allergic contact dermatitis due to paraphenylenediamine hair dye.


The sensitizing chemical (antigen) crosses the stratum corneum barrier and is picked up by the
Langerhans cells in the epidermis. The antigen is then ‘processed’ by the Langerhans cell and passed
on to T-lymphocytes in the peripheral lymph nodes. Here, some of the T-lymphocytes develop a
specific ‘memory’ for the particular antigen and their population expands. This process of sensiti
zation takes some 10–14 days in humans. After this period, when the particular antigen contacts the
skin once again, the primed T-lymphocytes with the ‘memory’ for this chemical antigen rush to
the contacted site and liberate cytokines and mediators that injure the epidermis and cause the
eczematous reaction.
Treatment
It is vital to identify the sensitizing material and prevent further contact with it. Eczema will subside
rapidly in most cases after removal from the antigen. The use of weak or moderately potent topical
corticosteroids and emollients will speed the resolution of the eczematous patches.
Venous eczema (gravitational eczema; stasis dermatitis)

Definition
Venous eczema occurs on the lower legs and is the result of chronic venous hypertension.
TABLE 8.4
Common antigens and concentrations used in patch testing and concentrations
Antigen Percent
Balsam of Peru 25
Benzocaine 5
Chlorocresol 1
Chloroxylenol 1
Cobalt chloride 1
Colophony 1
Dowicil 200 1
Epoxy resin 1
Ethylene diamine 1
Formalin 1
Kanthon CG 0.67
Mercaptobenzthiazole 2
Mercapto-mix 2
Neomycin 20
Nickel sulfate 5
Parabens 15
Paraphenylene diamine base 1
Perfume-mix 8
Potassium dichromate 0.5
Primin 0.01
Thiuram-mix 1
Wool alcohols 30
Clinical features
Itchy, pink scaling areas develop on a background of the changes of chronic venous hypertension. The
affected areas are often around venous ulcers, but the margins of the eczematous process are poorly
defined. Occasionally, the process spreads to the contralateral leg and even to the thighs and arms.
In most cases, venous eczema is actually an allergic contact hypersensitivity to one of the substances
used to treat the venous ulcer. Such substances include lanolin, neomycin, ethylenediamine, and rubber
additives (in the dressings and bandages). Allergy to topical steroids may also develop.
Treatment
The presence of allergic contact hypersensitivity must be identified and the patient should be advised to
avoid using the agent responsible. The simplest of topical applications should be used – white soft
paraffin is suitable as an emollient and 1% hydrocortisone ointment is suitable as an anti-inflammatory
agent.
9
Psoriasis and lichen planus
Shruti Barde
Introduction
Psoriasis is a multisystem inflammatory syndrome that affects people of all ages globally. It is more
usually seen in adults than in children, with two peaks of presentation in the age groups 16–22 years and
57–60 years. There is no gender difference in the morbidity profile of psoriasis, although females
reportedly develop it earlier than males. Geographically, its prevalence increases farther away from the
equator. Prevalence rates are between 0.09% and 11.4% globally, whereas in developed nations, the
rates are between 1.5% and 5%. Studies also show differences in prevalence based on ethnic origin, with
the rates being higher in Caucasians compared to those in Africans, Hispanics, and people of other
ethnic origins. Due to its chronicity, recurrent, and disfiguring nature, and multisystem involvement,
psoriasis has a deep psychological impact on the patients and their Quality of Life (QoL).
Presentation
Psoriasis presents itself with well-defined, raised, pinkish, scaly patches predominantly on the extensor
aspects of the body like elbows and knees, lower back, and scalp, mostly symmetrical in distribution
(Figure 9.1). Scalp involvement does not cause alopecia (Figure 9.2). Lesions are mildly pruritic or non-
pruritic. The scales are due to the dead cell build-up, giving it a shiny silvery-white appearance
(Figure 9.3). The lesions vary considerably in shape and size, and mucosal involvement is almost never
seen. When lesions cover the joints, fissuring may be seen. Facial skin is usually not affected, except the
scalp margins, retro auricular folds, and sometimes the nasal folds.
Auspitz’s sign
Pinpoint bleeding is seen after removing psoriatic scales by glass slide, due to breach in the suprapapillary
epithelium. The bleeding occurs when the glistening white Bulkeley’s membrane is scraped off from the
lesions, exposing the dilated suprapapillary blood vessels. This is a quick test useful for diagnosis in the OPD.
Woronoff’s ring
A clear halo surrounding a psoriatic plaque due to vasoconstriction.
Nails
Pitted, discolored, and deformed nail plates can be seen in psoriatic patients, often due to nail plate
separation from the nail bed (onycholysis). Nail changes are seen in about 50% of the patients with
psoriasis, sometimes after as long as a decade of onset of the cutaneous lesions (Figure 9.4).
113
FIGURE 9.1 Typical red, scaling plaques of psoriasis on the leg.
FIGURE 9.2 Scalp psoriasis.
Koebner’s phenomenon/Isomorphic response

This involves the appearance of new psoriatic patches at the site of cutaneous trauma (scratching, burns,
cuts, etc.) and scars (Figure 9.5). The lesions appear about a week or two after the injury. This can also
be seen in other conditions such as vitiligo and lichen planus. Pseudokoebnerization is seen in warts and
molluscum contagiosum due to autoinoculation. The lesions appear about a week or two after the injury.
Psoriasis and lichen planus 115
FIGURE 9.3 Psoriasis on the dorsum of hand – a site of predilection.
FIGURE 9.4 Nail psoriasis with discoloration, subungual hyperkeratosis, and oil spot/salmon patch.
Genetics
The chance of children being affected varies according to family history. With one positive parent
history, chances are 14%, which goes up to about 41% with both parents being clinically affected.
A range of “susceptibility genes” in the MHC (major histocompatibility complex) determine the in
cidence and severity of psoriasis in a person. HLA-C (mainly HLA Cw6) is the main gene associated
with the disease. HLA-B27 is a marker for sacroiliitis associated with psoriasis.
Pathogenesis
The two main pathological processes involved in dermal lesions are epidermal proliferation and dermal
inflammation. One very obvious abnormality in psoriasis is the hyperplastic epidermis with increased
FIGURE 9.5 Psoriasis appearing at sites of injury (from scratching) – the isomorphic response (from Marks and
Motley,18th edition, with permission).
mitotic activity, and initial therapeutic interventions were directed at the control of epidermal cell
production in this disease. Attention has now diverted to dermal inflammation and immune-suppression
to control the disease since increased mitotic activity and epidermal thickness were found to be
secondary phenomena.
In histologic sections, epidermal findings include parakeratosis (epidermal nuclei are retained in the
inefficient horny layer), hyperkeratosis, and marked exaggeration of the rete pattern. Collection of
polymorphs in the parakeratotic stratum corneum results in the formation of Munro’s microabscesses,
which is the most important diagnostic sign to clinch the diagnosis. Epidermal cell turnover is faster and
is about 3–4 days instead of about 28–30 days. Inflammation results from lymphocyte infiltration and an
increased number of tortuous capillaries in the dermis.
Morphological classification of psoriasis

Plaque psoriasis
This is the most common type of psoriasis, has an onset in the second or third decade of life, can involve
other systems (metabolic syndrome), and can be resistant to treatment (Figure 9.6). Small plaque
psoriasis (plaques < 2 mm) occurs at any age and responds well to treatment such as phototherapy.
Guttate psoriasis
This type of psoriasis is seen in children and young adults usually after acute streptococcal infections of
throat. It presents with small lesions of 2 mm–1 cm distributed uniformly throughout the body, but
mainly on the trunk, arms, and legs (Figure 9.7). Palms and sole involvement is rare. An elevated
antistreptolysin O, streptozyme or anti-DNase B titer is found in nearly half of the patients, indicating a
recent streptococcal infection. Resolution occurs within 2–3 months.
FIGURE 9.6 Well-defined erythematous, scaly patch on the palm due to psoriasis.
FIGURE 9.7 Multiple small papules of guttate psoriasis seen after a streptococcal tonsillitis.
Flexural/Inverse psoriasis
As the name suggests, this type of psoriasis is seen on the flexural aspects on the body, namely groin,
gluteal clefts, axilla, and inframammary folds (Figure 9.8). This presentation is common in overweight
or obese people with psoriasis. The lesions often are shiny and without appreciable scales due to these
areas being humid. Failure of anti-fungals and antibiotics in suspected candidal or bacterial infections
should arouse suspicion. Another common differential is seborrhoeic dermatitis and both conditions can
coexist simultaneously.
FIGURE 9.8 Flexural psoriasis.
Uncommon types of psoriasis
• Elephantine type: As the name suggests, the skin becomes very thick and scaly. It is usually
seen on back, hips, or thighs.
• Rupioid type: Here the lesions resemble the oyster shells and have a conical thick crust. They
appear waxy and yellowish and could resemble the lesions of secondary syphilis or keratotic
scabies. Biopsy is needed to confirm.
• Lichenified type: Due to repeated scratching and rubbing the area, the skin becomes thicker and
darker in these lesions.
• Koebnerized type: Lesions can develop on the areas that have suffered cutaneous trauma due to
scratching or itching and on previous scars.
• Photosensitive type: UV Light is helpful in most but in some, it could worsen the condition,
causing an increased inflammatory response.
Erythrodermic psoriasis
In erythrodermic psoriasis, the characteristic plaque-like lesions disappear and progress to general
ized, diffuse skin involvement. The skin becomes red and scaly throughout the body. It is a very
severe subtype of psoriasis that could be fatal; hence, close monitoring is advised. Some provocating
factors include blatant use of topical and oral corticosteroids and the use of irritant agents such as
dithranol and tar. There are also reports of induction of erythrodermic psoriasis due to bupropion and
intereferon alpha and ribavarin. Due to excessive inflammation in the skin, there is a lot of heat loss
and water loss resulting in dehydration. Because of shunting the blood to the skin, there is hy
perdynamic circulation which could result in cardiac failure and loss of protein, electrolytes, and
metabolites via the shed scales.
Drug aggravated and drug-induced psoriasis

Some drugs (Table 9.1) can aggravate existing psoriasis, precipitate psoriasis, cause recurrence in pa
tients, and even lead to the development of treatment-resistant psoriasis; beta-blockers, in particular, are
known to cause psoriasiform eruptions.
TABLE 9.1
Drugs associated with psoriasis
ACE inhibitors/AT II antagonists
Antimalarials
Beta-blockers
Calcium channel blockers
Carbamazapine
Corticosteroids
Imiquimod
Interferon-alpha/interferon-gamma
Lithium
Metformin/gemfibrozil
NSAIDs
Sodium valproate
Pustular psoriasis
This is classified further into three classes: palmoplantar pustulosis, generalized pustulosis, and others.
Palmoplantar pustulosis
Patients with palmoplantar pustulosis develop yellowish-white, sterile pustules on the central parts of
the palms and soles (Figure 9.9). Older lesions after 1–2 weeks take on a brownish appearance and are
later shed on a scale at the surface (Figure 9.10). The affected area can become generally inflamed,
scaly, and fissured and, although relatively small areas of skin are affected, the condition can be very
disabling.
FIGURE 9.9 Typical pustular psoriasis affecting the palms.

FIGURE 9.10 Pustular psoriasis of the sole of the foot with several older brown scaling lesions that were pustules (from
Marks and Motley,18th edition, with permission).
The disorder is common in smokers and resistant to treatment.
Generalized pustular psoriasis

This is also known eponymously as Von Zumbusch’s disease and is one of the most potentially serious
disorders dealt with by dermatologists. In its classic form, attacks occur suddenly and are characterized
by severe systemic upset, swinging pyrexia, arthralgia, and a high polymorphonuclear leucocytosis
accompanying the skin disorder.
The skin first becomes erythrodermic and then develops sheets of sterile pustules 2–4 mm in diameter
over the trunk and limbs. Sometimes, the pustules become confluent so that ‘lakes of pus’ develop just
beneath the skin surface. Various provoking agents include infections, hypocalcemia, irritating topical
treatment (Koebner phenomenon), and sudden withdrawal of oral corticosteroids. These patients are
very unwell and require hospitalization. They can usually be brought into remission by modern treat
ments but are subject to recurrent attacks.
Other forms of pustular psoriasis

Occasionally, pustules may develop locally after strong topical corticosteroids have been used or be
come widespread after systemic corticosteroids have been administered and then abruptly withdrawn.
Other rare variants of pustular psoriasis include:
TABLE 9.2
Types of psoriasis arthritis
Presentation Involvement
Asymmetric Distal interphalangeal, metacarpophalangeal joints
Rheumatoid arthritis Symmetrical polyarthritis
Axial Resembling ankylosing spondylitis (+/− peripheral joints)
Arthritis mutilans Joint destruction
• Acrodermatitis continua, in which there is a recalcitrant pustular erosive disorder on the fingers
and toes around the ends of the fingers and the nails and occasionally elsewhere.
• Pustular psoriasis in pregnancy is known as impetigo herpetiformis.
Associations
It has been seen that psoriasis results in systemic inflammation which results in the following:
• Arthritis: the various types of presentation are given in Table 9.2. Psoriatic arthritis can range
from mild inflammation to a severe mutilating form known as arthritis mutilans (Figure 9.11).
The rheumatoid factor is absent in this arthritis and it is accompanied with tendon, ligament, and
joint capsule inflammations (enthesitis) and dactylitis.
• Inflammatory bowel disease
• Cardiovascular disease: psoriasis has been known to cause an increase in CRP levels and BMI,
resulting in hyperlipidemia and increased waist circumference which increases the risk of an
adverse cardiovascular event.
• Depression
FIGURE 9.11 The results of psoriatic arthropathy (arthritis mutilans) (from Marks and Motley, 18th edition, with permission).
FIGURE 9.12 Psoriasiform plaque in the leg in reactive arthritis.
Scaly rash in plaque psoriasis can be confused with conditions like seborrhoeic dermatitis, discoid
eczema, lichen simplex chronicus, Bowen’s disease, ringworm infection, psoriasiform napkin dermatitis
etc. (Figure 9.12). In seborrhoeic dermatitis, the rash is rather diffuse unlike the distinct plaques of
psoriasis. In Lichen simplex, the history of intense itching results in excessive rubbing and lichenified
skin which is often dark and pigmented. Ringworm infection can be confused with flexural psoriasis but
the KOH treated scrapings can provide the distinction.
Mycosis fungoides – a T-cell lymphoma of skin – often evolves through a phase in which there are
many red psoriasiform lesions on the trunk, but these differ from psoriasis by being more varied in
thickness and more irregular in shape and persistent.
On the legs, raised, round, red, scaling psoriasiform patches often turn out to be patches of Bowen’s
disease in the elderly or discoid eczema. Lichen simplex chronicus around the ankles may also be
difficult to distinguish.
Pityriasis rubra pilaris is an uncommon disorder of no known cause, which may mimic psoriasis in
some cases. It is characterized by large red scaling areas on the face and trunk often with an orangish
tinge and prominent follicular orifices containing keratinous debris. Psoriasis of the palms may be
difficult to distinguish from eczema but typically has a sharper border.
Superficial basal cell carcinoma lesions are sometimes several centimetres in diameter and quite
psoriasiform in appearance, but have a fine raised, ‘hair-like’, ‘pearly’ margin.
Treatment
Inflammatory reactions in psoriasis affect many systems in the body, the symptoms of which may
arise at random points in the course of the diseases. It has been reported that the cases of psoriasis are
often undertreated and physicians often do not have a long-term and customized perspective in tai
loring treatments. Many factors need to be considered before deciding on treatment options for
TABLE 9.3
Factors to be considered before treatment
1 Age
2 Occupation
3 Psychosocial disability
4 Extent of disease
5 Financial backing
6 Pregnancy
7 Treatment history
8 Need for monotherapy
9 Other comorbidities
10 Patient preferences
psoriasis (Table 9.3). Treatment of psoriasis includes topical and systemic treatment options
(Table 9.4).
Correct and long-term treatment planning, initiating oral treatments at the right time and referral to
the dermatologist at the correct time are imperative.
Topical therapy
Topical treatments for skin lesions aim at decreasing the rate of mitosis and keratolysis of the thickened
stratum corneum, thus improving the appearance of lesions. However, in severe disease, topicals are not
the first-line treatments and systemic treatments are preferably started with topicals.
Patients with just a few small plaques do well with an emollient such as white soft paraffin, by itself or
with 3–6% salicylic acid twice daily. Salicylic acid, combined with topical steroids, has a higher efficacy.
With more lesions and symptoms, more active topical treatment is needed. Tar-containing preparations
are less popular because of stinging, unpleasant smell, and staining of clothes. Tar has anti-inflammatory
and cytostatic activity and certainly has a mild anti-psoriatic effect. Proprietary tar preparations have some
advantages over the British National Formulary formulations with regard to aesthetic qualities. Tar
shampoos for scalp involvement are still popular.
Analogues of vitamin D3 are effective topical treatments; calcipotriol used once or twice daily results
in an improvement in some 60% patients after 6 weeks of treatment. Used alongside medium-potency
corticosteroids, the efficacy is increased and the skin irritation decreased. Apart from skin irritation,
there is the concern that a sufficient amount of these D3 analogues will be absorbed to cause hy
percalcaemia. Fortunately, this has not proved to be a frequent problem thus far. Other vitamin D
analogues being tried for topical therapy include maxacalcitol and tacalcitol. Calcipotriol with steroid
combinations has been shown to be better than either of them used alone.
Anthralin (dithranol) is a potent reducing agent that has marked therapeutic activity in psoriasis. It is
generally used in ascending concentrations, starting at 0.1% or 0.05% and rising to 5.0%. Dithranol
often irritates and burns the skin and care must be taken to match the concentration used to the in
dividual patient’s tolerance. It also causes a distinctive brown–purple staining of clothes (Figure 9.13),
towels, and skin. Apart from the irritation and staining, dithranol has no serious side effects.
The role of topical corticosteroids in the treatment of psoriasis is limited owing to their side effect
profile and rebound flare-up of the disease after stopping them. Life-threatening generalized pustular
psoriasis can result after sudden withdrawal. They are useful for patients with flexural lesions for which
other irritant preparations are not suitable. For the same reason, weak topical corticosteroids are also
suitable for lesions on the genitalia and the face where potent topical corticosteroids cannot be used.
124
TABLE 9.4
Treatment options for psoriasis
Grade BSA Treatment Side effects and monitoring Assessment Other support
requirements
Mild <10% Topical Corticosteroids Atrophy, striae, telangiectasia, PASI score calculated before • Psychological
therapies tachyphylaxis, and after 6–24 weeks for support
hypopigmentation assessment • Rehabilitative
Anthralin Irritation, staining dermatitis Improvement assessed as support
follows: • Nursing care
Tar Irritant dermatitis PASI score • Climatotherapy
Tazarotene Retinoid dermatitis >= 75%: GOOD response • Day care treatment:
Calcipotriene Slight irritation, staining 50–75%: PARTIAL response modified
Goeckerman
Emollients Liquid paraffin and other
hydrating moisturizers
Moderate 10–30% Systemic Methotrexate KFT, LFT, CBC, platelet counts
to be monitored monthly
Retinoids (Acitretin) LFT, Cholesterol monthly,
pregnancy tests if indicated
Cyclosporine A KFT, BP, LFT, Uric acid every
2–4 weeks (short-term use
preferred)
Moderate 10–30% Systemic Others: Mycophenolate Mofetil, <50%: FAILED treatment

Hydroxyurea Other assessment tools are
Sulfasalazine DQLI (Dermatology
Cellcept etc. Quality Life Index), PGA,
SKINDEX-16
Phototherapy PUVA Nausea after ingestion of
NBUVB psoralen, burns (start after In case of incomplete
24hours of exposure), response or compliance
BBUVB
development of lentigenes, issues, consider
malignant melanoma, eye combination treatments or
irritation, and dryness. use of Biologicals.
Lasers: Excimer (308 nm) Burns
(Continued on next page)
Concise Dermatology
TABLE 9.4 (Continued)
Grade BSA Treatment Side effects and monitoring Assessment Other support
requirements
Biologics Given below If ADL affected, consider
Severe >30% Systemic +/− Phototherapy As above more potent treatment.
Biologics Alefacept CD4 levels monitored weekly
Platelet counts monitored weekly
Etanercept LFT
Psoriasis and lichen planus
Infliximab Latent screening, KFT, PPD,

LFT TB
Adalimumab Latent screening, KFT, PPD,
LFT TB
Severe: Erythrodermic Systemic Acitretin (most common),
psoriasis/Pustular methotrexate, cyclosporine A,
psoriasis anti-TNF agents, systemic
steriods (occasionally)
Note: BSA: body surface area; PASI: Psoriasis Area and Severity Index; KFT: kidney function tests; LFT: liver function tests; CBC: complete blood counts; BP: blood pressure; PUVA:
psoralen + ultraviolet A; NBUVB: narrow-band ultraviolet B; BBUVB: broad-band ultraviolet B; ADL: activities of daily living.
125
FIGURE 9.13 Brownish-purple staining on the skin due to dithranol (from Marks and Motley, 18th edition, with permission).
Systemic steroids can be used ONLY in the following indications:
• Generalized pustular psoriasis of pregnancy/erythroderma: this is the ONLY definitive indication

for using oral steroids.
• Persistent and uncontrolled erythrodermic psoriasis causing metabolic complications.
• Generalized pustular psoriasis if other drugs are contraindicated or not effective.
• Severe polyarthritis that could lead to irreversible joint damage.
Another, quite different, treatment is a topical retinoid analogue called tazarotene (0.05% or 0.1%). This is quite
an effective agent, showing 65% improvement in 6 weeks. When used alongside medium-potency topical
corticosteroids, its efficiency is increased and the irritation experienced by around 15% of users is decreased.
Both the vitamin D3 analogues and tazarotene may improve psoriasis by modulating gene activity and
redirecting differentiation and by reducing the epidermal proliferation. When more than 10% of the
body surface area is involved, topical treatment becomes very difficult. The same is true of ery
throdermic psoriasis and generalized pustular psoriasis, which require systemic treatment.
TABLE 9.5
The use of methotrexate in psoriasis
Indications
• Severe psoriasis involving >20% BSA
• Resistant psoriasis (resistant to topicals, retinoids, PUVA)
• Erythroderma
• Pustular psoriasis
• Psoriatic arthritis
Contraindications
• Compromised liver functions (cirrhosis, acute hepatitis, etc.)
• Compromised renal function
• Pregnancy or nursing
• Decreased blood counts (anaemia, leukopenia, thrombocytopenia)
Methotrexate
This antimetabolite is a competitive antagonist of tetrahydrofolate reductase, blocking the formation of
thymidine and thus DNA. It is thought that this anti-proliferative activity may be important in reducing
epidermal and lymphocyte proliferation. It is also quite toxic, producing hepatotoxicity in patients who
stay on the drug for long periods. The drug also suppresses haematopoiesis and may cause gastro
intestinal upset. Hence, it is used in moderate to severe cases of erythrodemic or pustular psoriasis,
where psoriasis involves >20% BSA, is resistant to topicals therapies, or in debilitating psoriatic ar
thritis. The indications and contraindications for using methotrexate in psoriasis are listed in Table 9.5.
It is given once weekly in doses of 5–25 mg orally, subcutaneously, or intramuscularly. To minimize
the possibility of serious side effects, patients must be monitored frequently (preferably monthly) by
blood counts and blood biochemistry.
It is recommended that a liver biopsy be performed both before treatment begins and after a cu
mulated dose of 1.5 gm in patients at high risk of methotrexate toxicity and after a 3.5 gm cumulative
dose in low-risk individuals. Many clinicians believe that information concerning incipient hepatic
toxicity can be obtained by measuring blood levels of procollagen peptides. Ultrasound scanning has
also been used to assess hepatic damage non-invasively. Methotrexate is also a teratogen, and fertile
women should use contraceptive measures. It is mainly suitable for those who would otherwise be
disabled by the disease, and for some elderly patients with severe psoriasis.
Retinoids are analogues of retinol (vitamin A). They exert important actions on cell division and
maturation, and acitretin is of particular value in psoriasis. The drug benefits patients with all types of
severe psoriasis after 3–4 weeks of administration but is most effective when used in combination with
some form of ultraviolet treatment. Its major drawback is that it is markedly teratogenic and can only be
given to fertile women if they use contraception and are prepared to continue using efficient and reliable
contraceptive measures for 3 years after stopping treatment. Other significant toxicities include hy
perlipidaemia and a possibility of hyperostosis and extraosseous calcification. In addition, it does have
some hepatotoxicity in a few patients. These ‘significant’ toxicities are not common; but minor mucosal
side effects occur in all patients, including drying of the lips and the buccal, nasal, and conjunctival
mucosae. Minor generalized pruritus and slight hair loss also occur. Oral retinoids should only be
prescribed by dermatologists, i.e. those who are familiar with their actions and effects.
Cyclosporin
Cyclosporin is an immunosuppressive agent and appears to work by inhibiting the synthesis of cytokines
by T-lymphocytes. It is also dramatically effective in psoriasis when given in doses of 3–5 mg/kg per day.
Its toxic side effects include severe renal damage, hypertension, hyperlipidemia, and hypertrichosis.
Its place in the treatment of disabling and severe psoriasis is assured, but great care and constant mon
itoring are required.
Treatment with ultraviolet radiation

A form of UVR treatment known as PUVA (photochemotherapy with ultraviolet radiation of the
A [long-wave] type) is used in psoriasis. The UVA is supplied by special fluorescent lamps that emit at
wavelengths of 300–400 nm, housed in cabinets or special frames over beds.
A photosensitizing psoralen drug is given orally 2 hours before exposure or topically shortly before
irradiation. The main psoralen used is 8-methoxy psoralen, but 5-methoxy psoralen and trimethoxy
psoralen are also sometimes used. The dose of 8-methoxy psoralen is 0.6 mg/kg.
Alternatively, the patient bathes in water containing a psoralen and is then exposed to UVR a
few minutes later. Ordinary ‘sun lamps’ emitting UVB (290–320 nm) can also be used to treat
psoriasis. The dangers of burning may be greater and the dangers of skin cancer are similar
to PUVA.
Narrowband UVB light (311 nm) is increasingly the phototherapy treatment of choice, especially in
extensive involvement of more than 30% surface area. It is given 3 times a week. Both PUVA and UVB
can be combined with topical dithranol, calcipotriol, and tazarotene or oral acitretin. These combina
tions reduce the cumulative dose and side effects of these therapies.
The dose of UVA is calculated (in joules) from the output of the lamps and the time of exposure. The
dose required for clearance is approximately 50–100 J/cm2, and care is taken to keep the dose as low as
possible and certainly below a total cumulated dose of 1500 J/cm2 to reduce the possibility of long-term
side effects, which are as follows:
• Increased incidence of squamous cell carcinoma of the skin – up to 10 or 12 times that in a

control group of patients with psoriasis after 10 years. Carcinoma of the external genitalia in men
is a particular problem. There is an increased incidence of basal cell carcinoma and melanoma in
PUVA-treated psoriatic patients as well.
• Increased solar elastotic degenerative change, with the appearance of ageing and alteration of
skin elasticity.
• Cataracts can develop and all patients who receive PUVA must wear effective UVA protective
goggles or sunglasses during exposure and for 24 hours afterwards.
In the short term, nausea is often experienced and, if too long an exposure is given, burning can occur.
Patients who are ‘sensitive to the sun’ or who coincidently have a disorder that can be aggravated by
UVA exposure, such as lupus erythematosus or porphyria cutanea tarda, should not be treated by any
form of UVR.
Biological treatments
It appears that tumor necrosis factor (TNF)-alpha is an important cytokine component in the patho
genesis of psoriasis, and since 2004, agents have been available that block the action of this factor.
They are all quite effective and can be given IM, SC, or IV. Since they do not disturb the Cyt.P450
system, there are no drug interactions seen when they are administered along with other systemic
therapies such as methotrexate, etc. The agents concerned are of three types: ‘humanized’ mono
clonalantibodies to TNF-alpha (such as adalimumab or infliximab); recombinant human cytokines;
and fusion proteins.
Biologicals are usually considered in patients having 5–10% BSA involvement with a Psoriasis Area
and Severity Index (PASI) score of 10–12. Prior to the start of treatment it is essential to do baseline
counts and rule out any chronic infections such as tuberculosis (TB). The treatment cycles are generally
12–14 weeks and results are evaluated on PASI score, Dermatology Quality of Life Index (DQOLI),
and lesion improvement. Although short-term use of biologicals does not show any renal or hepatic
side effects, the long-term safety profile, especially with respect to immunosuppression is not well
documented and will need further studies.
Lasers in psoriasis
Xenon chloride excimer laser (308 nm) is the laser of choice for treating the dermal lesions in
psoriasis. Laser provides a targeted phototherapy and this treatment can be initiated in children as well
as adults. The energy given (J/cm2) depends upon the lesion’s thickness and the response achieved.
The target chromophore is cellular DNA. Laser causes death of the T cells and regulates epidermal
proliferation. The advantage of laser over other phototherapies is that it is more site-specific, reduces
UV exposure to normal skin, thereby reducing side effects, and hence allows a higher dosage of
energy per session.
Importance of attention for psychological health

Psoriasis is known to be associated with depression. This is not only because of the extent of the disease
and its disabling nature, but also because of the stigma attached to it, which prevents patients from
taking the treatment in the first place. Social morbidity leading to employment worsen the burden. QoL
is affected, especially in those having lesions on exposed body parts, particularly scalp and face. WHO
has raised concerns due to the increasing incidence and prevalence of psoriasis over the years and is
urging health organizations to increase awareness about the same. Physicians are also encouraged to
refer patients for group therapy or psychotherapy sessions.
Pityriasis rubra pilaris

Definition
Pityriasis rubra pilaris (PRP) is an uncommon papulosquamous skin disorder of unknown etiology,
presenting with follicular keratosis, erythema, and palmoplantar hyperkeratosis.
Clinical features and histology

PRP is divided into six clinical subtypes: adult type (classical and atypical), juvenile type (classical,
circumscribed, and atypical) and HIV-virus associated. Adult type is the most common. Usually, the
disease begins on the face and scalp after trauma or bacterial infection and progresses in the cephalo-
caudal direction. It is associated with pinkness and scaling, and spreads within a few days or a week to
involve the rest of the body. There is a characteristic orange hue to the redness, and on the thickened
palms there is a characteristic yellowish discoloration (Figure 9.14). Scattered among the red, scaling
rash are islands of spared white skin on the hands and thighs, and sometimes elsewhere there is a
typical follicular accentuation due to the presence of hyperkeratotic spines. Typical lesions called
nutmeg papules are seen on the dorsum of hands on the knuckles. The juvenile type of pityriasis rubra
pilaris, although similar in many ways to the adult form, tends to be much more stubborn and resistant
to treatment.
The histological appearance is distinctive in that, although there is considerable epidermal thickening,
the accentuation of the dermal papillae and the undulations of the dermo-epidermal junction are much
less marked than in psoriasis.
FIGURE 9.14 Waxy palmar thickening due to hy FIGURE 9.15 Lichen planus papules affecting the
perkeratosis in pityriasis rubra pilaris (PRP Sandle). tongue.
Treatment
Treatment is challenging; however, patients respond well to TNF inhibitors, oral retinoids (acitretin and
isotretinoin), and anti-IL 12/23 because of their anti-proliferative anti-inflammatory and immune
modifying properties. Recently, alitretinoin has been tried with very good results. Treatment with
methotrexate or cyclosporine has also been advocated.
Lichen planus
Lichen planus (Greek leichen, ‘tree moss’; Latin planus,‘flat’) is an inflammatory disease affecting skin,
mucosa (Figure 9.15), scalp, and nails. The term ‘lichenoid’ refers to the histologic description of
inflammatory infiltrate and basal cell liquefaction and used to characterize the pathology of diseases
resembling lichen planus. This is the only papulosquamous disorder that presents itself without scales.
Epidemiology
Lichen planus occurs between the third and the fifth decades of life without any specific gender or race
predilection.
Aetiology
The exact aetiology of LP is unknown; however, it results from an immune response to the basal layer of
epidermis. The following are associated with the onset of this autoimmune disorder:
• Drugs: diuretics (thiazides, spirolactone, furosemide), gold, anitmalarials, β−blockers, penicillamine,

phenothiazines, ACE-inhibitors, quinidine
• Infections: hepatitis C infection and post viral chronic active hepatitis
• Immunological disorders: primary biliary cirrhosis, autoimmune chronic active hepatitis
FIGURE 9.16 Red–mauve papules of lichen planus in linear distribution. Some of these have a faint white network
pattern on the surface (Wickham’s striae).
Lesions
A classical cutaneous lesion of lichen planus (LP) is a pruritic polygonal, purple, flat-topped papule or
plaque often having a whitish lace pattern on it (Wickham’s striae, Figure 9.16). Lichen planus tends to
involve the flexor aspects of extremities, wrists, arms, and legs in a bilaterally symmetric distribution.
Koebner’s phenomenon is seen in LP too (Figure 9.17). Nails, mucosa, and scalp should always be
examined. Nail involvement is seen in 10% of the cases and presents as thinning, longitudinal ridging,
pterygium formation (Figure 9.18), distal splitting, onycholysis, and anonychia (in long-standing cases)
of the nail plate.
Lichen planus is one of the primary causes of scarring alopecia on the scalp. Lesions heal with a
pigmented patch, which persists for some weeks.
FIGURE 9.17 Many papules of lichen planus affecting the arm, showing Koebner phenomenon.
Variants
Hypertrophic lichen planus (Figure 9.19) is commonly present on extremities with thickened, hy
perpigmented, extremely pruritic plaques while in Annular lichen planus lesions individual papules fuse
to give a ring-type configuration. This presents mostly in blacks and commonly involves genitalia.
Lichen nitidus is a variant of lichen planus in which many tiny, pale, flat-topped papules develop in
clusters. Bullous lichen planus is a very rare variant in which blistering occurs due to bullae forming
sub-epidermally in some lesions. Lichen planopilaris involves the hair follicles resulting in scarring
alopecia and affected sites look like horny spines with perifollicular scaling and pigmentation. Atophic
lichen planus presents with bluish to erythematous papules and plaques with central superficial atrophy.
Ulcerative type is a progression of bullous lichen planus and results in extensive scarring of feet. Nail
and mucosal involvement is common.
Histopathology
The exact prevalence of lichen planus is unknown but it is a rather common disease in Asian countries.
T-cell mediated proinflammatory and counterregulatory mechanisms against an unknown antigen in
epidermis, function in the pathogenesis of lichen planus. Ultimately there is damage to the basal cells,
leading to their hydropic degeneration.
• A band of lymphocytes and histiocytes is seen subepidermally. Among the inflammatory cell
infiltrate are clumps of melanin pigment as a result of damage to the epidermis.
• Damage to the basal epidermal cells causes a ‘sawtooth’ profile, vacuolar degenerative change,
and scattered eosinophilic cytoid bodies representing dead epidermal cells. A cleft formed due
to epidermal separation is called a Max Joseph histological cleft.
• Variable epidermal thickening with increase in thickness of the granular cell layer and
hyperkeratosis is seen.
Immunofluorescence studies show a dense, ragged band of fibrin at the dermoepidermal junction
and clumps of IgM deposit. The basic process is thought of as an immunological attack on the basal
layer; the presence of inflammatory cells and the other epidermal alterations is believed to be a
secondary event.
FIGURE 9.18 Pterygium of the nail in lichen planus.

FIGURE 9.19 Hypertrophic lichen planus.
TABLE 9.6
Treatment overview for lichen planus
Lesion Treatment of choice
1 Localized LP Topical corticosteroids, Tacrolimus ointment
2 Extensive LP Oral corticosteroids/PUVA/acitretin
3 LP of nail and scalp Oral corticosteroids
4 Mucosal LP Oral corticosteroids/cyclosporine/acitretin
The disease mostly remits spontaneously, so that most patients require very little treatment. Despite
severe pruritis, LP patients are not seen to scratch as much, since scratching induces pain. This is called
Brocq’s phenomenon. When patients are severely affected with a generalized eruption, systemic cor
ticosteroids are sometimes helpful, as are the oral retinoids such as acitretin for the more recalcitrant
patients. Treatment options depend on the type of LP and its severity (Table 9.6).
10
Acne, rosacea, and similar disorders
Pooja Agarwal
The disorders described in this chapter are common, inflammatory, characterized clinically by papules,
and occur on the face pre-eminently. Traditionally disorders of this kind were given the term ‘acne’ as a
prefix. However, we now no longer subscribe to the view that they are related in any significant way, and
it is better to reserve the term ‘acne’ for the common disorder characterized by seborrhoea and comedones.
Acne
Acne is one of the most common skin disorders. It has been estimated that the prevalence of acne ranges
from 35% to 90% in adolescents. There are some differences in the prevalence in different ethnic types – it
is uncommon, for example, among the Inuit. It is mostly a disorder of puberty but can occur at any age.
Definition
Acne (acne vulgaris) is a disorder in which hair follicles develop, obstructing horny plugs (comedones).
Later, inflammation may develop around the obstructed follicles, which can lead to surrounding tissue
inflammation also and scar formation.
Clinical features
The earliest feature of the disorder is an increased rate of sebum secretion at puberty, making the skin
look greasy (seborrhoea). Comedones usually accompany the greasiness. They often occur over the
sides of the nose and the forehead but can occur anywhere. Comedones are follicular plugs composed of
follicular debris, desquamated corneocytes, and compacted sebum. They have pigmented tips from the
melanin pigment deposited by the follicular epithelium at this level (Figure 10.1).
Inflamed, erythematous papules develop from blocked follicles. These are a shade of bright red, often
irregular in shape, and quite tender to the touch and may be set quite deep within the skin (Figure 10.2).
Sometimes, they develop pus at their tips (pustular acne), but these may also arise independently
(Figure 10.3). In a few patients, some of the papules become quite large and persist for long periods –
they are then referred to as nodules.
In severely affected patients, the nodules liquefy centrally so that fluctuant cysts are formed. In
reality, the lesions are pseudocysts, as they have no epithelial lining. These lesions are seen in the most
severely affected patients, and they cause the worst scarring. This type of severe acne is known as cystic
or nodulocystic acne and can be very disabling and disfiguring (Figure 10.4).
When the large nodules and cysts eventually subside, they leave in their wake firm, fibrotic, nodular
scars, which sometimes become hypertrophic or even keloidal. The scars are often quite irregular and tend
to form ‘bridges’ (Figure 10.5). Even the smaller inflamed papules can cause scars, and these tend to be
pock-like (Figure 10.6) or are triangular indentations (‘ice-pick scars’, Figure 10.7). Other types of scars
that can be seen in acne are rolling scars – which are broad depressions with sloping edges (Figure 10.8) –
and boxcar scars – which are broad depressions with sharply defined edges (Figure 10.9).
134
Acne, rosacea, and similar disorders 135
FIGURE 10.2 Multiple acne papules over the forehead.
FIGURE 10.1 Multiple open and closed comedones;

note the blackened tips from melanin.
There is a very rare and severe type of cystic acne known as acne fulminans, in which the acne lesions
quite suddenly become very inflamed. At the same time, the affected individual is unwell and develops
fever and arthralgia. Laboratory investigation often reveals a polymorphonuclear leucocytosis and odd
osteolytic lesions in the bony skeleton. The cause of this disorder is not clear, although it has been
FIGURE 10.4 Cystic acne over cheek; note the sur

FIGURE 10.3 Acne papules with scattered pustules. rounding inflammation.
FIGURE 10.5 Hypertrophic scarring in a bridging pattern FIGURE 10.6 Pock scarring of acne (from Marks and
(from Marks and Motley, 18th edition). Motley, 18th edition).
FIGURE 10.7 Ice pick scars with active acne lesions. FIGURE 10.8 Multiple rolling scars.
suggested that it is due to the presence of a vascu

litis that is somehow precipitated as a result of the
underlying acne. Rarely, Gram-negative folliculitis
can develop in acne patients where topical anti
microbials are inadvertently used (Figures 10.10
and 10.11).
Sites affected
Any hair-bearing skin can develop acne, but the
areas on the front and back of the trunk and the face
are much more vulnerable than others. These acne-
prone areas tend to have hair follicles with small
terminal hairs and larger sebaceous glands (sebac
FIGURE 10.9 Boxcar scars. eous follicles). The face and, particularly, the skin
of the cheeks, lower jaw, chin, nose, and forehead
are usually affected. The scalp is usually not in
volved. In patients with severe acne, it is quite common for other areas to be affected, including the
outer aspects of the upper arms, the buttocks, and thighs.
Clinical course
For most of those affected, the disorder is annoying, troublesome, and persistent, with wave after wave
of new lesions. Although the natural tendency is for resolution, it is difficult to know in any individual
patient when the condition will improve. The majority lose their acne by the age of 25 years, but some
tend to have the occasional lesion for much longer. In some women, there is a pronounced premenstrual
flare of their acne some 7–10 days before the menses begin and right through their reproductive life.
Occasionally, acne may make an unwelcome appearance (sometimes for the first time) in the fifth or
sixth decades.
FIGURE 10.10 Gram-negative folliculitis with severe FIGURE 10.11 Gram-negative folliculitis with acne
erythema. lesions.
People with acne in hot, humid climates often become disabled by its suddenly worsening, with large
areas of skin covered by inflamed and exuding acne lesions. This is termed as tropical acne.
Epidemiology
About 35–90% of the population develops a degree of clinically evident acne at some point during
adolescence and early adult life, but perhaps only 10–20% seek medical attention for the problem. This
proportion varies in different parts of the world, depending on the racial background, affluence, and the
sophistication of medical services. The variations in incidence in different ethnic groups have not been
well-characterized, although it does appear that Eskimos and Japanese experience less acne than do
Western Caucasians.
Onset is usually at puberty or a little later, although many patients do not appear troubled until the age
of 16 or 17 years. Men appear to be affected earlier and more severely than women. However, in post-
adolescent ages, females are affected predominantly. Older age groups are not immune, and it certainly
is not rare to develop acne in the sixth, seventh, or even eighth decade of life.
Special types of acne

Acne conglobata
It is a severe form of acne, which most commonly affects young males. Back, chest, and buttocks are
the most severely affected sites. Large nodular-cystic lesions with draining sinuses and resultant
severe scarring occur. In contrast to acne fulminans, systemic symptoms are absent in acne
conglobata.
Acne induced by drugs

Androgens provide the main normal ‘drive’ to the sebaceous glands. It is the increased secretion of these
hormones that is responsible for the increased sebum secretion at puberty.
The systemic use of glucocorticoids induces troublesome acne (Figure 10.12). The acne that results is
curiously monomorphic in that sheets of acne lesions appear (unlike ordinary acne) all at the same stage
of development. Interestingly, corticosteroid creams can, uncommonly, also cause acne spots at the site
of application. Paradoxically, corticosteroids are sometimes required for their anti-inflammatory actions
in the treatment of severe acne and are given for a short duration.
Occupational acne/Chloracne
Workers who come into contact with lubricating and cutting oils develop an acne-like eruption at the
sites of contact, consisting of small papules, pustules, and comedones. This is often observed on the
fronts of the thighs and forearms, where oil-soaked overalls come in contact with the skin. A similar
‘acneiform folliculitis’ sometimes arises at sites of application of tar-containing ointments during the
treatment of skin diseases (Figure 10.13).
Chloracne is an extremely severe form of industrial acne caused due to exposure to complex
chlorinated naphthalenic compounds and dioxin. Typically, numerous large cystic-type lesions occur in
this form of industrial-acne-causing massive cosmetic disability.
Acne cosmetica
Some cosmetics contain comedo-inducing (comedogenic) agents, such as cocoa butter, iso
propylmyristate, derivatives and some mineral oils, which can induce acne. With the availability of less
comedogenic cosmetics, its prevalence has lessened. Use of thick, oil-based hair products contributes to
acne development on the forehead, which is termed as pomade acne.
FIGURE 10.12 Steroid acne. The lesions tend to be FIGURE 10.13 Comedones and inflamed follicular
more uniform in appearance than in ‘ordinary’ acne (from papules from tar application (from Marks and Motley,
Marks and Motley, 18th edition). 18th edition).
Excoriated acne
This disorder is most often seen in young women.
Small acne spots around the chin, forehead, and on
the jawline are picked, squeezed, and otherwise
altered by manual interference. The resulting pa
pules are crusted and often more inflamed than
routine acne spots. Often, the patients have little
true acne and the main cosmetic problem is the
result of the labour of their fingers! Mostly, this is
a minor problem, which can be improved by
counselling, but there are some more seriously
affected patients in whom the problem is
persistent.
Other rare variants of acne
1. Acne mechanica: it is the result of blocked

pilosebaceous ducts as a result of repeated
friction, such as by backpack straps, etc.
2. Neonatal and infantile acne: a benign
self-resolving condition occurring in
FIGURE 10.14 Infantile acne (from Marks and Motley,
18th edition).
FIGURE 10.15 Senile comedones.
children under the influence of maternal androgens (Figure 10.14)

3. Senile comedones: comedones seen in old age, usually in periorbital area due to laxity of skin
(Figure 10.15)
4. SAPHO syndrome: synovitis, acne, pustulosis, hyperostosis, and osteitis
5. PAPA syndrome: sterile pyogenic arthritis, pyoderma gangrenosum, and acne
6. SAHA syndrome: seborrhea, acne, hirsutism, and alopecia
Pathology, aetiology, and pathogenesis

Histologically, the essential features are those of a folliculitis with considerable inflammation. The exact
histological picture depends on the stage reached at the time of biopsy. Usually, it is possible to make
out the remnants of a ruptured follicle. In the earliest stages, a follicular plug of the horn (comedone)
can be identified. Later, fragments of horn appear to have provoked a violent mixed inflammatory
reaction with many polymorphs and, in places, a granulomatous reaction with many giant cells and
histiocytes (Figure 10.16). In older lesions, fibrous tissue is deposited, indicating scar formation.
The sequence of events leading to acne development is not yet fully understood. However, it is agreed
upon that sebum production, follicular hyperkeratinization, growth of Propionibacterium acnes, and
inflammation are the key events involved in the pathogenesis. Acne first appears at puberty, at which
time there is a sudden increase in the level of circulating androgens. Sebaceous glands are pre
dominantly ‘androgen-driven,’ and thus sebum production increases at puberty. However, the com
position of sebum lipids is more influential for acne development than the amount of sebum produced.
Alterations in sebum lipid composition (increased levels of desaturated free fatty acids and decreased
levels of linoleic acid) are seen to be associated with follicular hypercornification through modulation of
the immune system. Lipid peroxidation products also have a proinflammatory effect.
Follicular obstruction plays an important role in the development of acne lesions. Micro comedones
are the earliest lesions, and inflammation has been seen at the microcomedone level also. Previously it
was thought that abnormal follicular keratinization occurred first, but studies have recently demon
strated expression of IL-1α and other cytokines preceding abnormal keratinization. These local cyto
kines along with the alteration of serum lipid composition, sensitivity to androgens, and P. acnes
overgrowth cause epithelial hyperproliferation.
P. acnes is a Gram-positive bacilli

thriving in the anaerobic environment pro
vided by sebum lipids and the pilosebac
eous apparatus. Earlier thought to be
nonpathogenic, P. acnes-driven in
flammatory responses lead to acne.
Enzymes secreted by P. acnes promote the
follicular wall degradation and follicle
rupture. These also digest the sebum lipids
into fatty acids, which have a pro-
inflammatory action by stimulating the
antimicrobial peptides (defensins, cathe
licidin, and granulysin). P. acnes also di
rectly engages the Toll-like receptors
located on keratinocytes and inflammatory
cells and leads to the recruitment of neu
trophils and macrophages to the follicle. P.
acnes also promotes follicular hyperker
atinization by inducing integrin and filag
grin and biofilm production. An acceptable
hypothesis is that the important in
flammatory lesions of acne are the result of
follicular leakage and eventually rupture.
FIGURE 10.16 Pathology of inflamed acne papules showing The role of diet in acne pathogenesis
a ruptured follicle and a dense inflammatory cell infiltrate still remains controversial. Stress, on the
composed predominantly of polymorphs (from Marks and Motley, other hand, appears to have a slight cor
18th edition). relation with acne development.
Treatment
Perhaps no other dermatological ailment demands as much attention as teenager’s acne. Although not
physically disabling, the psychological impact of acne can be striking, leading to low self-esteem and
depression. The appropriate course of acne treatment requires a detailed assessment of clinical type and
severity of acne, previous treatments, aggravating factors, and the presence of post-inflammatory changes.
Basic principles
Medical therapies for acne target the four key factors involved in acne pathogenesis.
• Follicular hyperproliferation and abnormal desquamation, encouraging the shedding of the fol
licular horny plugs to free the obstruction (comedolytic agents)
• Increased sebum production – reducing the rate of sebum production, either directly by acting on
the sebaceous glands (sebotrophic agents) or indirectly by inhibiting the effects of androgens on
the sebaceous glands (anti-androgens)
• Propionibacterium acnes proliferation – reducing the bacterial population of the hair follicles to
cut down the hydrolysis of lipids (antimicrobial agents)
• Inflammation – reducing the damaging effects of acne inflammation on the skin with anti-
inflammatory agents
General measures
Patients with acne are often depressed and may need sympathetic counselling and support. There is no
evidence that particular foodstuffs have any deleterious effect or that washing vigorously will help remove
lesions. These and other myths should be dispelled and replaced with a straightforward explanation of the
nature of the disorder, its natural history, and treatment, with firm reassurance that they will improve.
Topical treatment
Currently, the most popular form of topical preparation is a gel, cream, or alcohol-based lotion.
1. Topical retinoids
These enhance desquamation and facilitate the removal of comedones (comedolytic). They are
useful for the treatment of both inflammatory and non-inflammatory acne and preferably should
be used as the first-line management. Tretinoin and its cis-isomer – isotretinoin (systemic) – both
are used successfully for the treatment of acne. Adapalene and tazarotene are the newer retinoids.
The side effects from the use of retinoid preparations include some pinkness and slight scaling
of the skin surface, especially in fair, sensitive-skinned individuals. For the most part, this
‘dryness’ of the treated area is tolerable and decreases after continued usage. It is the same with
both tretinoin and isotretinoin. All the topical retinoids cause increased sensitivity to the sun – due
to the thinning of the stratum corneum. Though tazarotene is considered as the most effective, it is
also the most irritating topical retinoid, while adapalene is the best-tolerated one.
In addition to the treatment of active acne, retinoids also fasten the resolution of post-
inflammatory hyperpigmentation. They are also used as maintenance therapy in the patients.
2. Topical antimicrobials
Clindamycin (1%) preparations are quite effective for mild and moderate types of acne.
Bacterial resistance to clindamycin frequently develops when used as monotherapy. Topical
dapsone (5% and 7.5% gel) is a novel and effective treatment for acne vulgaris. The greatest
improvement is seen in inflammatory lesions. Nadifloxacin, a potent synthetic bactericidal
fluoroquinolone, is also reported as having potent action against P. acne.
Other antimicrobial compounds

Benzoyl peroxide (2.5–10.0%) is quite effective and is used as a cream, gel, or lotion. Its prime action is
as an antibacterial agent but it also has some comedolytic action. It is quite irritating and causes some
pinkness, scaling, and soreness. Combination of other antibiotics with benzoyl peroxide reduces the
chances of development of antibiotic resistance.
3. Other topical preparations

a. Azelaic acid: it is a natural dicarboxylic acid with comedolytic, antimicrobial, and mild anti-
inflammatory action. Due to its inhibitory effect on tyrosinase, it is also useful in improving
post-acne pigmentation. It is available as a 15% gel and 20% cream.
b. Salicylic acid: in patients who are not able to tolerate topical retinoids, topical salicylic acid
(0.5–2%) gel can be used as an alternative comedolytic agent.
Systemic treatment
Antibiotics: they are mainly indicated in patients with moderate and severe inflammatory acne and acne
resistant to topical treatment.
Tetracyclines
Systemic tetracyclines have been the sheet anchor of treatment for moderate and severe acne for many
years. Patients with many papular inflammatory lesions involving several sites are suitable for systemic
tetracyclines. In the past, tetracycline was the primary agent used, but with the advent of newer tet
racyclines, its use has been reduced greatly. The newer minocycline and doxycycline are given in
smaller doses (50 mg or 100 mg) once or twice per day, and their absorption does not seem to be
affected by food. Extended-release formulation of minocycline given once a day is now an additional
option available for the treatment of acne.
Side effects of the tetracyclines are few and not usually serious. Gastrointestinal discomfort and
diarrhoea occasionally occur. Photosensitivity was mainly a problem with older, now no longer used,
analogues. Fixed drug eruption and, rarely, other acute drug rashes develop. Minocycline can cause a
dark-brown pigmentation of the skin or acne scars or acral areas on the exposed parts of the skin after
long-continued use in a small number of patients. Minocycline may also provoke a rare reaction similar
to drug-induced lupus erythematosus with hepatitis, arthritis, and pneumonitis.
Tetracyclines must not be given to pregnant women, as they are teratogenic, and must not be given to
children and adolescents, as they cause a bone and tooth dystrophy, in which these structures become
deformed and discolored.
Macrolides
Erythromycin, earlier considered as one of the main agents for treating acne, is now being used less
because of development of antibiotic resistance. The efficacy of erythromycin in acne is similar to that
of the tetracyclines, and its use is now recommended only in patients with contraindication to tetra
cycline and its derivatives. Azithromycin, another macrolide antibiotic, has proved efficacious in the
treatment of acne.
Other antibiotics and antimicrobials

Clindamycin, quinolones, dapsone, and sulfonamides are other drugs that have been used systemically
for acne. None is more effective than the tetracyclines, but they may be suitable for patients who are
either intolerant or who no longer respond to the tetracyclines or erythromycin. Side effects are more
common and sometimes of a serious nature (e.g. blood dyscrasias).
Isotretinoin (13-cis-retinoic acid)

The large majority of patients with acne will respond to topical or some combination of topical and
systemic drugs. However, some severely affected patients may not, and for them there is another drug
that can offer relief. This agent is the cis-isomer of tretinoin – isotretinoin. It reduces sebum secretion by
shrinking the sebaceous glands and may also alter keratinization of the mouth of the hair follicle and
have an anti-inflammatory action.
In order to reduce treatment-induced flares, it is typically started at 0.5 mg/kd/day during the first
month, and then slowly increased to 1 mg/kg/day. The total treatment goal is to achieve 120 to 150 mg/kg
cumulative dose, which is usually reached in four to six months.
The response after a few weeks is to inhibit new lesions in more than 80% of patients. Patients with
many large cystic lesions affecting the trunk, as well as the head and neck region, take longer to respond
and may need more than one 4-month course. Isotretinoin is the only acne medication that can alter the
natural course of acne permanently.
Unfortunately, side effects are frequent. They range from common drying and cracking of the lips,
to the very serious, which include teratogenicity, hepatotoxicity, bone toxicity, and a blood lipid-
elevating effect. The teratogenic effects are very worrisome, as the acne age group is almost identical
to the reproductive age group. The effects on the fetus include facial, cardiac, renal, and neural
defects and are most likely to arise if the drug is taken during the first trimester. Some 30–50% of
TABLE 10.1
Treatments for acne
Topical Oral
Antimicrobial Comedolytic Antimicrobial Sebum suppressive
Benzoyl peroxide Tretinoin Tetracycline Isotretinoin
Erythromycin Adapalene Minocycline Cyproterone
Clindamycin Tazarotene Doxycycline Ethinylestradiol
Azelaic acid Erythromycin Spironolactone
Dapsone
Nadifloxacin
pregnancies during which the drug was taken have been affected. Because of this, it is strongly
recommended that if it is planned to prescribe isotretinoin for women who can conceive, effective
contraceptive measures must also be planned and used during and for 1 month after stopping
the drug.
Hepatotoxicity is rare, although a small rise in liver enzymes is common. A rise in triglycerides and
cholesterol, such that the ratio of very-low-density lipoproteins to high-density lipoproteins is increased,
regularly occurs, and overall there is a 30% rise in lipid levels. This is not likely to be a problem for
most patients with acne, but maybe for older patients. The same is true of bone toxicity. A variety of
bone anomalies have been described, including disseminated interstitial skeletal hyperostosis and os
teoporosis, but these are not likely to be a problem for acne subjects. The drug has also been accused of
causing severe depression, leading to suicide in some cases. The evidence for this is not strong, as
patients with severe acne are often depressed before starting treatment.
Hormonal therapy
Hormonal treatments include inhibitors of androgen production, either from the ovary (oral contra
ceptives) or adrenal gland (low‐dose corticosteroids), anti-androgens blocking the androgen receptors
effect on the sebaceous gland.
Oral contraceptives containing a combination of progestin and oestrogen are used in women with
resistant acne. The commonly used progestins are cyproterone acetate and drospirenone. They are not
suitable for men because of the feminizing properties. Acne improvement is seen after some 6–8 weeks
of use, but is not as effective as isotretinoin. It is associated with a number of minor side effects,
essentially those associated with taking oral contraceptives.
Spironolactone, a potassium-sparing diuretic, has also been found to have anti-androgenic effects and
has occasionally been used as a treatment for acne.
Treatment of acne is summarized in Table 10.1.
Rosacea
Definition
Rosacea is a chronic inflammatory disorder of the skin of the facial convexities, characterized by
persistent erythema and telangiectasia punctuated by acute episodes of flushing, papules, and pustules.
Classification
There are four subtypes of rosacea: erythematotelangiectatic (facial redness and visible blood vessels),
papulopustular (acne), rhinophymatous (thickening of the skin on the nose), and ocular rosacea (the eye
area). Patients may present with features suggestive of one or multiple subtypes.
Epidemiology
Rosacea is quite a common disorder, but its exact prevalence is not known and varies in different
communities. The disorder is essentially one of fair-skinned Caucasians. It seems particularly common
in Celtic peoples and in individuals from northwest Europe. It is only occasionally seen in darker-
skinned and Asian skin types and is rare in black-skinned individuals. It occurs primarily in adults over
the age of 30. Women are more frequently affected, except in the case of rhinophymatous rosacea,
where males are predominantly affected.
Aetiology and pathogenesis

The cause of rosacea remains uncertain. Various contributing factors have been proposed, which
include abnormalities in the immune system, ultraviolet damage, various microorganisms, and vas
cular dysfunction.
a. Immune response – dysfunction of the innate immunity may contribute to the development of
vascular abnormalities and chronic inflammation in rosacea. This is proposed to occur through
the production of cathelicidin peptides, which have inflammatory and vasoactive properties.
b. Microorganisms – the role of the mite Demodex folliculorum, a normal commensal of the hair
follicle, is quite unclear. Although it is found in vastly increased numbers in rosacea, this in
crease may result from the underlying disorder in which there is follicular distortion and dila
tation. The mite is a normal inhabitant of adult facial hair follicles, but it does not seem to do any
harm. Similarly, gastrointestinal colonization by the microorganism Helicobacter pylori has
been suspected (but not confirmed) of having a role in the aetiopathogenesis.
c. Ultraviolet damage – ultraviolet radiations through stimulation of reactive oxygen species and
angiogenic peptides are believed to contribute to rosacea development. The disorganization of
the upper dermal collagen, the excess of solar elastotic degenerative change, and the pre
dominance in fair-skinned types all point to the importance of solar damage to the upper dermis.
d. Vascular dysfunction – vascular hyperactivity is seen in patients with rosacea.
Clinical features
Sites affected
The cheeks, forehead, nose, and chin are the most frequently affected areas, making a typical
cruciate pattern of skin involvement (Figure 10.17). The flexures and periocular areas are con
spicuously spared. Occasionally, the front of the neck and the bald area of the scalp in men are
also affected. Sometimes only one or two areas of the face are affected, and this makes diagnosis
quite difficult.
The lesions
The most characteristic physical sign is that of persistent erythema, often accompanied by marked
telangiectasia. The disorder may not progress beyond this ‘erythemato-telangiectatic’ state but, even if it
does not, the bright red face causes considerable social discomfort and often marked depression. Such
patients also complain of frequent flushing at the most trivial stimuli.
Superimposed on this persistent background of erythema are episodes of swelling and papules
(Figure 10.18). The papules are dull red, dome-shaped, and non-tender, in contrast to acne, in which
they tend to be irregular and tender. Pustules also occur, but are less frequent than in acne; blackheads,
cysts, and scars do not occur in rosacea.
FIGURE 10.17 Typical rosacea with the involvement

of the cheeks, forehead, and chin. Note the sparing of the FIGURE 10.18 Papules of facial skin in rosacea (from
periocular area and flexural sites (from Marks and Marks and Motley, 18th edition).
Motley, 18th edition).
Natural history
Rosacea tends to be a persistent disease and the tendency for patients to develop episodes of acute
rosacea remains for many years after appropriate treatment has calmed down an attack. However, the
disease becomes less common in the seventh decade and seems quite rare in the elderly.
Pathology
A characteristic constellation of features seen in histological sections makes skin biopsy a useful test when
the clinical diagnosis is uncertain. A feature common to all rosacea skin samples is the presence of dermal
disorganization, solar damage, and oedema and telangiectasia in the upper dermis. When there are in
flammatory papules, the blood vessels are encircled by lymphocytes and histiocytes, among which giant
cell systems are sometimes found. In a small proportion of biopsies, the granulomatous aspect is striking
and may even resemble a tuberculous granuloma. In rhinophyma, apart from abnormalities in the fibrous
dermis and inflammation, there is also marked sebaceous gland hyperplasia.
Any red rash of the face may be confused with rosacea. Papular rashes of the face seem to cause most
problems. The most common differential diagnoses are summarized in Table 10.2.
TABLE 10.2
Differential diagnosis of rosacea
Disorder Positive discriminants
Skin disorders
Acne Scars, seborrhoea, cysts, back and chest involvement
Seborrhoeic dermatitis Greasy scaling, involvement of nasolabial, retroauricular areas
Perioral dermatitis Micropapules, perioral and paranasal involvement
Systemic disorders
Systemic lupus erythematosus Rash on light-exposed areas, arthropathy, positive antinuclear factor, haematological
findings
Dermatomyositis Mauve–lilac rash around the eyes, with swelling, rash on backs of fingers, muscle
tenderness, pain, and weakness, positive laboratory findings
Carcinoid syndrome Marked telangiectasia, flushing attacks, hepatomegaly
Polycythaemia rubra vera General facial redness and suffusion, possibly hepatosplenomegaly
Superior vena caval obstruction Facial suffusion, distended neck veins
Complications
Rhinophyma
This occurs mainly in elderly men, although it occasionally occurs in women too. The nose becomes irre
gularly enlarged and ‘craggy’, with accentuation of the pilosebaceous orifices. The nose also develops a dull-
red discoloration with prominent telangiectatic
vessels (Figure 10.19). Popular names for this in
clude ‘whisky-drinkers nose’ and ‘grog blossom’.
Rarely, the chin, the earlobes, and the forehead are
similarly affected.
Lymphoedema
Persistent lymphoedema is another unpleasant,
though uncommon, complication of rosacea seen
predominantly in men. The swollen areas are
usually a shade of dull red and may persist when
the other manifestations of rosacea have
remitted.
Ocular complications
About 30–50% of patients with acute papular
rosacea have a blepharoconjunctivitis. This is
usually mild, but some patients complain bitterly
of soreness and grittiness of the eyes. Some of
this may be the result of keratoconjunctivitis
sicca, which appears to be quite common in
rosacea. Styes and chalazion are also more
common in rosacea. Keratitis is a rare, painful
complication occurring in men, in which a vas
cular pannus moves across the cornea, producing
FIGURE 10.19 Rhinophyma with prominent tel severe visual defects and, ultimately, blindness.
angiectasia (from Marks and Motley 18E).
General management
Patients with rosacea are often very sensitive about their appearance and may be depressed. They should
be strongly reassured and managed sympathetically. Regular use of sunscreens, mild facial cleansers,
emollients, and avoidance of aggravating factors are advised in every subtype.
Treatment
Treatment depends on the subtype of rosacea
Erythemato-telangiectatic rosacea: Topical alpha receptor agonists like brimonidine (0.5%) have shown
the strongest efficacy in controlling facial erythema in rosacea. Another alpha receptor agonist, oxy
metazoline, has also shown good results. Topical tacrolimus has been shown to cause improvement in a
small number of cases. In patients not responding to topical treatment, low‐dose β‐blocking medica
tions, e.g. propranolol should be considered. Laser therapy (using pulse dye laser, intense pulsed light)
can also be used to eliminate the malar telangiectatic vessels. In recalcitrant lesions, botulinum toxins
have been found to be helpful to reduce facial flushing.
Papulopustular rosacea: Most patients with active inflammatory lesions can be managed with topical
therapies. Metronidazole (0.75%) gel or cream, azelaic acid (15%) gel, ivermectin(1%) cream and
sulfacetamide (10%) with sulphur 5% preparations are the commonly used agents. Topical retinoids and
benzoyl peroxide-clindamycin combinations have also been found useful. Systemic therapy is typically
used in patients with unsatisfactory response to topical therapy. Tetracycline, doxycycline, and mino
cycline are the first-line antibiotics for papulopustular rosacea. In patients who cannot tolerate tetra
cyclines, alternative antibiotics include macrolides (erythromycin) and oral metroronidazole. Low-dose
isotretinoin can be considered in resistant cases.
Rhinophymatous rosacea: Early cases with inflammation benefit with topical therapies. Chemical
peels and low dose isotretinoin are useful to reduce seborrhoea. In severe cases, debulking with carbon
dioxide laser, or surgical remodelling are indicated.
Ocular rosacea: Daily lid hygiene in form of lid massage and warm compression, along with the use
of lubricant eye drops is recommended. Topical antibiotics like metronidazole may improve mild lid
inflammation. Topical cyclosporine is also seen to minimize inflammation. For moderate to severe
ocular rosacea, oral tetracyclines or macrolides, or metronidazole are often needed.
Perioral dermatitis
Definition
Perioral dermatitis is a common inflammatory disorder of the skin around the mouth, characterized by
the occurrence of micropapules and pustules.
Epidemiology
Perioral dermatitis is most common in young women aged 15–25 years, being quite uncommon in men
and in older women.
Pathogenesis
The pathways leading to the development of perioral dermatitis are unclear. Topical corticosteroid use is
commonly reported with perioral dermatitis. The classic history is of a popular facial eruption which
initially improves with corticosteroid use and then worsens or recurs upon continued use. Several other
factors have also been proposed as contributors to its development e.g. fluoridated toothpaste, cosmetic
products, Candida albicans, and oral contraceptive therapy.
Clinical features
Many minute, slightly pink scaly papules and pus
tules develop around the mouth, sparing the area
immediately next to the vermillion of the lips
(Figure 10.20). Lesions sometimes involve the na
solabial grooves and, in severely affected patients,
also affect the skin at the sides of the nose. There is
no background of erythema, distinguishing the
condition from rosacea.
Treatment
No definitive treatment has been recommended for
perioral dermatitis. Tapering followed by dis
FIGURE 10.20 Perioral dermatitis. There are many tiny continuation of topical corticosteroids is advised.
papules around the mouth (from Marks and Motley,
18th edition).
Use of a milder corticosteroid cream is re
commended to avoid flare of disease. Topical cal
cineurin inhibitors, e.g. pimecrolimus (1%), topical erythromycin, and topical metronidazole 1% have
been used in mild-to-moderate cases. In severe cases, oral tetracyclines or low dose isotretinoin may be
indicated.
11
Wound healing and ulcers
Shekhar Neema
Principles of wound healing

Wound healing is fundamental to the survival of an organism. Injury to tissue initiates a complex
cellular and biochemical activity, which results in wound healing. Wound healing is divided into three
distinct, but overlapping, phases: (a) hemostasis and inflammation; (b) proliferation; (c) the remodelling
phase (Figure 11.1).
Wounds that do not progress through normal stages of wound healing become chronic and result in
poor anatomical and functional outcomes. Non-healing wounds are a major cause of morbidity and have
an enormous impact on healthcare expenditures.
Factors affecting wound healing

There are various local as well as systemic factors that affect the process of wound healing.
Oxygenation and nutrition are important for the wound healing process. The presence of infection or of
a foreign body in the wound results in impaired wound healing. Advanced age, obesity, stress, diseases
such as diabetes, chronic renal disease, chronic liver disease, smoking, medications such as gluco
corticoids, and chemotherapeutic agents negatively impact wound healing.
Venous ulcers
The common causes of leg ulcers are listed in Table 11.1.
Epidemiology
Venous leg ulcers account for 70% of chronic leg ulcers. The prevalence of venous leg ulcers increases
with increasing age and is more common in men more than 60 years of age and in women.
Pathogenesis
The venous system in lower extremity comprises superficial, communicating, and deep veins. It contains
bicuspid valves, which ensure the unidirectional flow of blood towards the heart. In a standing position,
the pressure in the venous system is equal to the hydrostatic pressure in the legs (80 mm Hg). During
muscle contraction, calf muscles exert pressure on deep veins, and blood is pushed upwards. Normal
valve functioning maintains a unidirectional flow of blood and prevents transmission of high venous
pressure to the superficial venous system. After the deep venous system empties, the pressure reduces
and blood flows from the superficial venous system to the deep venous system through its
150
Wound healing and ulcers 151
FIGURE 11.1 The sequence of events after incisional wounding of the skin. (a) 0 to 12 hours. Initially, the small blood
vessels constrict and then platelets plug the endothelial gaps. The extravasated blood clots form a temporary plug for the
wound. White cells accumulate at the interface between the damaged and the normal tissue. (b) 12 hours to 4 days. After
about 18–24 hours, epidermal cells actively move on to the surface of the defect. Epidermal cells at the sides of the wound
divide some hours later to make up for the loss. Epidermis also sprouts from the cut ends of the sweat coils and hair
follicles. After 2–4 days, new capillaries start to sprout and vascularize the granulation tissue in the wound cavity. Damaged
connective tissue is destroyed and removed by macrophages, and new collagen is secreted by fibroblasts. Myofibroblasts
are fibroblastic cells that develop the power to contract and are responsible for wound contraction. (c) 4 to 10 days. Between
4 and 10 days after wounding, the wound cavity becomes covered with the new epidermis, whose stratum corneum does not
possess normal barrier efficiency until the end of this period. The granulation tissue is replaced by a new dermis whose
collagenous fibres are not yet orientated. In the later stages, remodelling takes place so that the orientation of the dermal
collagenous bundles to the original lines of stress occurs. Scar formation occurs when there has been significant damage to
the dermis. The epidermis ultimately develops a normal profile and the vasculature is also restored to normal contractility.
E = epidermis; DCT = dermal connective tissue; BV = blood vessel; FC = fibrin clot; ME = migrating epidermis; F =
fibroblasts; MF = myofibroblasts; M = macrophages; GT = granulation tissue; SC = sweat coil; DC = dermal collagen.
(From Marks and Motley, 18th edition, with permission.)
communicating system. In cases where there is any obstruction in the deep venous system, valve
dysfunction or reflux, it will result in ambulatory venous hypertension.
The exact pathomechanism for venous ulceration is not known. Various theories have been proposed,
one being the fibrin cuff theory, which postulates that increased intraluminal pressure in capillaries
causes leakage of fibrinogen and formation of fibrin cuff, thereby impairing oxygen and nutrition
diffusion to tissues. Another theory proposes that trapped white cells release proteolytic enzymes, which
promote ulceration. Extravasation of red blood cells results in the deposition of a hemosiderin pigment
in macrophages, resulting in a brownish pigment of the skin (Figure 11.2).
Clinical features
The patient complaints of heaviness or a dull ache in the lower legs, which is increased after prolonged
standing and relieved after rest or leg elevation. Pitting ankle oedema is usually the earliest sign. Dilated
TABLE 11.1
Common causes of leg ulcers
Vascular Venous, arterial, mixed
Vasculitis – polyarteritis nodosa, rheumatoid arthritis, Wegener’s granulomatosis
Livedoid vasculopathy
Neuropathic Diabetes, syringomyelia, leprosy, peripheral neuropathy
Decubitus ulcer Elderly, bedbound, spinal cord injury
Hematologic Sickle cell disease, polycythemia rubra vera, thalassemia, cryoglobulinemia
Infection Mycobacterium tuberculosis, atypical mycobacteria, leishmaniasis, fungal – blastomycosis,
cryptococcosis, coccidioidomycosis, histoplasmosis, sporotrichosis
Neoplastic Marjolin’s ulcer, squamous cell carcinoma, basal cell carcinoma, melanoma, Kaposi sarcoma
Metabolic Diabetes mellitus, alpha-1 antitrypsin deficiency, prolidase deficiency
Misc Pyoderma gangrenosum, trauma, factitious, cold injury, radiation, burns, panniculitis, medications –
hydroxyurea
tortuous veins can be visualized best with the patient in the standing position. In prolonged disease, the
skin develops a brownish discoloration and becomes thick and hard, which is known as lipodermato
sclerosis. A venous ulcer is usually solitary, develops on the lower one-third of leg and is superficial
(Figure 11.3).
Complications
Infection: The ulcer may get infected.
Eczema: Allergic contact dermatitis is commonly
seen in patients with a venous ulcer. It results from
various medications applied for the treatment of
ulcer (e.g. neomycin, sisomycin).
Malignant change: Malignant transformation can
occur in any chronic wound; however, such trans
formation in venous ulcer is extremely rare.
Bleeding
Lipodermatosclerosis – hyperpigmentation and in
duration of the skin.
Treatment
Treatment is aimed at wound care and improving
venous drainage.
Wound care
• Clean the wound with normal saline.

• Wound debridement, if required, may be
FIGURE 11.2 Venous hypertension; note the pigmen
surgical, autolytic or mechanical.
tation and appearance of the skin, suggesting that it is • The infected ulcer should be treated with
bound down to the underlying tissues (from Marks and appropriate antibiotics based on swab culture
Motley, 18th edition, with permission). and sensitivity.
• A dressing that maintains a moist wound bed

should be used; topical antimicrobial should
be avoided.
Improving venous drainage
•
Compression therapy increases the leg ulcer
healing rate. It also reduces the risk of re
currence. Multicomponent compression ban
dages are more effective than single-
component bandages. The presence of ar
FIGURE 11.3 Typical venous ulcer. terial insufficiency is a contraindication for
compression therapy.
• Sclerotherapy, superficial endoscopic perforator surgery, endovenous ablation, or sapheno-
femoral junction ligation can be performed for the treatment of reflux.
Supportive therapy consists of weight reduction; exercise to improve the calf muscle pump; pentox
ifylline, flavonoid, doxycycline, or zinc help in ulcer healing; split-thickness skin grafting can be used
for ulcers with a healthy wound bed; or stanozolol or danazol for lipodermatosclerosis.
Ischemic ulceration
Ischemic ulcers are also a common clinical problem; however, they occur more commonly as mixed
ulcers in combination with a venous ulcer or a diabetic ulcer.
Pathogenesis
Arterial insufficiency can be acute or chronic. Acute limb ischemia results from an embolic phenom
enon and results in gangrene and acute ulceration. Progressive atherosclerosis is the commonest ae
tiology resulting in chronic ischemia. It affects large vessels. Other diseases that can cause ischemic
ulceration are thromboangiitis obliterans, vasculitis, livedoid vasculopathy, and cryoglobulinemia.
Clinical features
Arterial ulcers usually occur in a patient older than 45 years, who have risk factors for atherosclerosis
such as diabetes mellitus, smoking, hypertension, hyperlipidemia, or obesity and a sedentary lifestyle.
Patients present with intermittent claudication. Arterial ulcers are extremely painful and the pain
worsens on leg elevation and improves on dependency.
Ulcers are punched out, have a sharply demarcated border and are present over sites of pressure or
trauma. They may be associated with diminished peripheral pulses and a prolonged capillary
filling time.
Treatment
Treatment in arterial ulcers is aimed at the treatment of the underlying atherosclerosis. It is of utmost
importance to cease smoking and control diabetes, blood pressure, or dyslipidemia and reduce weight.
A gradual increase in the walking distance improves the blood supply to ischemic extremities. Wound
care includes moist wound dressing, sharp debridement, and systemic antibiotics for infection. An
interventional vascular procedure like percutaneous transluminal angioplasty or bypass surgery can be
performed for stenotic vessels. Aspirin is effective for the secondary prevention of coronary artery
disease and cerebrovascular disease.
Decubitus ulcers
This is better known as the pressure ulcer. It is defined as an area of unrelieved pressure over a defined
area, usually over a bony prominence, resulting in ischemia and tissue necrosis.
Pathophysiology
Pressure ulcers result from constant pressure, which impairs local blood flow to soft tissue for an
extended period. The arterial capillary closing pressure is 32 mm Hg, and the venous capillary closing
pressure is 8–12 mm Hg. The external pressure exerted should be more than 32 mm Hg, and for an
extended time, so as to impair inflow and the resultant ischemia. Ischemia results in pain and patients
shift position; however, in the unconscious or immobile patient, this protection is lost and a pressure
ulcer is produced. Poor nutritional status, incontinence, or maceration increase the vulnerability of tissue
to develop pressure ulcers.
Clinical features
Pressure ulcer occurs on pressure points in patients who are unconscious, unable to move or bed-bound
due to some reason. The National Pressure Ulcer Advisory Panel (NPUAP) has classified pressure ulcer
into four stages.
STAGE 1: Intact skin with signs of impending ulceration; this presents as non-blanchable
erythema
STAGE 2: Partial-thickness skin loss; this presents as a shallow ulcer with a pink wound bed
STAGE 3: Full-thickness skin loss with extension into the subcutaneous tissue
STAGE 4: Full-thickness tissue loss with extension into muscle, bone, tendon, or joint capsule
Treatment
It is of utmost importance to prevent pressure sore in an immobile, unconscious patient by good nursing
care. Changing position regularly, proper bed positioning, protection of vulnerable bony prominences,
removal of skin secretions and nutritional support are some of the interventions to prevent the formation
of pressure ulcers.
The treatment of pressure ulcers depends on the stage of an ulcer. Stages 1 and 2 can be treated
conservatively by moist wound dressing, while stages 3 and 4 require surgical intervention such as flap
reconstruction. Antibiotics are used if the wound is infected.
Neuropathic ulcers
Neuropathic ulcers result from repeated inadvertent injury to an anaesthetic or hyperesthetic area
of skin, subsequent to nerve injury. Nerve injury can result from various causes such as metabolic,
infections, or toxic causes. The most common causes are diabetes mellitus and leprosy.
Clinical features
Ulcers usually occur in long-standing cases of uncontrolled diabetes mellitus or lepromatous leprosy.
Neuropathic ulcers usually occur on the soles of the feet as punched out, deeply penetrating, painless
ulcers (Figure 11.4).
FIGURE 11.4 Neuropathic ulcer in a patient of leprosy.
Treatment
The treatment of neuropathic ulcers requires offloading of the affected limb, wound care by appropriate
dressing to maintain moist wound environment, antibiotic for wound infection, optimal control of blood
glucose in cases of diabetes, and multi-drug therapy in cases of leprosy.
Less common causes of ulceration

Pyoderma gangrenosum
This is a rare disease of uncertain etiology, associated with an underlying systemic condition in almost
50% cases. Diagnosis is made by excluding other causes of ulceration.
Aetiopathogenesis
Commonly associated diseases are inflammatory bowel disease, rheumatoid arthritis, leukemia, and
monoclonal gammopathy. Dysregulation of the immune system – especially neutrophil chemotaxis –
occurs, which results in ulceration and the pathergy phenomenon.
Clinical features
A patient presents with red papules or pustules, which ulcerate and then increase in size. It is associated
with pain, arthralgia, and malaise. Ulcers have a violaceous border and undermined edges (Figure 11.5).
Treatment
Treatments include systemic therapies such as corticosteroids, cyclosporine, mycophenolate mofetil,
azathioprine, or dapsone. Topical therapies include gentle wound care, topical tacrolimus and pime
crolimus. Surgical debridement should be avoided as the pathergy phenomenon can lead to enlargement
of the wound.
FIGURE 11.6 Vasculitic ulcer (from Marks and

FIGURE 11.5 Multiple ulcers of the leg in pyoderma Motley, 18th edition, with permission).
gangrenosum that developed over a 3-day period (from
Marks and Motley, 18th edition, with permission).
Vasculitic ulcer
Ulceration may occur when small or medium vessels become thrombosed due to inflammation of
the vessel wall. Vasculitic ulcers are wedge-shaped, have irregular borders and are usually bilateral
(Figure 11.6). Inflammation of the vessel wall may occur due to primary vasculitis like polyarteritis
nodosa or Wegener’s granulomatosis or vasculitis secondary to other illnesses, such as rheumatoid
TABLE 11.2
Diagnosis of ulcers based on clinical examination
1. Venous ulcer Location – ulcer in the lower third of the calf and 1 inch below malleolus (Gaiter area), sloping
edges.
Surrounding skin – telangiectasia, varicose vein, eczema, lipodermatosclerosis, oedema
2. Arterial ulcer Location – distal regions, bony prominences
Vertical edges
Surrounding skin – poor capillary refill time, diminished peripheral pulses
Pain increases on elevating limb
3. Neuropathic ulcer Location – sole of feet (heel or base of great toe), punched out edges
Surrounding skin – hypoaesthetic or anesthetic, deformity might be present
4. Vasculitic ulcer Presence of livedo reticularis and thigh ulcers in polyarteritis nodosa, stellate ulcers in livedoid
vasculopathy
5. Miscellaneous Rolled out edges in basal cell carcinoma
Violaceous border and undermined edges in pyoderma gangrenosum
TABLE 11.3
Investigations in a patient with a leg ulcer.
Sr No Clinical suspicion First-line investigation
1. Venous ulcer Imaging
• Duplex ultrasonography to diagnose venous reflux and rule out deep
venous thrombosis
• Contrast venography
2. Arterial ulcer Ankle – brachial index
Imaging
• Arterial duplex ultrasonography
• Magnetic resonance angiography
• CT angiography
• Conventional angiography
3. Neuropathic ulcer Nerve conduction studies
Electromyography
4. Pyoderma gangrenosum or Biopsy from the edge of the ulceration
malignant ulcer
5. Vasculitic ulcer Serology – ANA, ANCA, APLA
6. Miscellaneous investigations • Wound swab and culture – should be done in all cases where the
infection is suspected
• Biopsy from the edge of the ulcer can be done in cases where the
exact cause is not known
• Complete blood count, blood sugar fasting and postprandial
• Coagulation studies including protein C, protein S, Factor V leiden,
Antithrombin III levels in cases where vasculopathy is suspected
• Special test for sickle cell anaemia
arthritis, scleroderma, or systemic lupus erythematosus. The treatment of vasculitic ulcer is by wound care
and treatment of underlying vasculitis, usually by immunosuppressive therapy such as corticosteroids.
Malignant disease
In rare cases, basal cell carcinoma or squamous cell carcinoma can present as a non-healing ulcer.
Kaposi sarcoma in immunosuppressed individuals can also present as leg ulcers. Squamous cell car
cinoma can develop in a burn wound, radiation injury, lichen planus hypertrophicus, or other chronic
dermatoses.
Infective causes
Tuberculosis, leishmaniasis, tertiary syphilis, or deep fungal infection can result in leg ulcers.
Diagnosis and assessment of leg ulcers

Diagnosis of leg ulcer is very important before a specific therapy is planned. Diagnosis depends on the
appearance of the ulcer and physical examination (Table 11.2) and special investigation (Table 11.3).
12
Benign tumors
Rashmi Sarkar
Isha Narang
Many different cell and tissue types in the skin are responsible for the enormous number of tumors
that may arise from it (Figure 12.1). Some important benign tumors of dermatological relevance
(Figure 12.2) are discussed in this chapter. Treatment of benign tumors is summarized in Table 12.1.
Adipocytic tumors
Lipoma
Lipomata are common, solitary, or sometimes multiple, slowly growing benign tumors of fat,
mostly found in the subcutaneous tissue. Histologically, they consist of mature fat cells.
Clinical features
They are soft, skin-colored subcutaneous nodules and have poorly defined edges. They may be en
ormous in size or only 1–2 cm in diameter and can occur anywhere (Figure 12.3). Multiple lipomas can
be found in association with Proteus syndrome, Cowden’s disease, and Bannayan’s syndrome.
Lipomatosis is diffuse infiltration with non-encapsulated adipose tissue. It is found in conditions like
multiple symmetrical lipomatosis, Dercum’s disease, etc.
Fibrohistiocytic tumors
Dermatofibroma (fibrous histiocytoma, histiocytoma, sclerosing haemangioma)
It is a benign dermal or subcutaneous tumor. Its line of differentiation is uncertain, and it is also not certain
whether the dermatofibroma is a benign neoplasm or some form of a localized chronic inflammatory
disorder. The lesions have no serious clinical significance but are sometimes mistaken for melanomas.
These lesions are classified as fibrohistiocytic tumors due to their histopathology. It consists of many
spindle-shaped and banana-shaped mononuclear cells in a whorled pattern, which may be fibroblast-
derived, and there is a variable amount of new collagenous dermal connective tissue. There are also
many histiocytic cells present, which often contain lipid or iron pigment, both of which may derive from
the large number of small blood vessels also contained in the lesion. The presence of Touton giant cells
loaded with hemosiderin is thought to be pathognomonic of dermatofibroma.
Clinical features
They are firm or hard intracutaneous nodules. They are usually found on the limbs as solitary lesions, but
sometimes two or three or even more are found in the same patient. Generally, they are brownish in color
(from the haemosiderin pigment) and have a rough or warty surface because these dermal nodules have the
158
Benign tumors 159
FIGURE 12.1 Classification of soft-tissue tumors.
FIGURE 12.2 Classification of benign tumors.
propensity to thicken up the epidermis immediately above them. On squeezing the overlying epidermis, the
‘dimple sign or Fitzpatrick sign’ is seen, due to tethering of the overlying epidermis to the underlying lesion
(Figure 12.4). Multiple dermatofibromas are associated with systemic lupus erythematosus, chronic myeloid
leukemia, HIV, and patients on immunosuppressive therapy.
Pericytic (Perivascular) tumors

Glomus cell tumor or glomangioma
This uncommon, benign vascular tumor arises from the glomus cells controlling tiny vascular shunts
between arterial and venous capillaries at the periphery, having a close relation to the Sucquet-Hoyer
canal. The constituent cells have a characteristic cuboidal appearance.
TABLE 12.1
Treatments for benign tumors
Tumor Treatment
Dermatofibroma • Poses only cosmetic problem: treatment unnecessary
• Surgical excision can be done
Glomus cell tumor • Surgical excision
• local recurrence rare
Pyogenic granuloma • Curettage and cautery under local anaesthesia
• Recurrences common
Senile angioma • Requires no treatment
• For cosmesis, larger lesions can be excised
• Vascular laser under local anaesthesia
Spider naevus • Lesions developing in pregnancy disappear spontaneously
• In healthy children, they persist
• Respond quickly to the tuned dye 595 nm laser
Neurofibroma • Genetic counselling
• Treatment is symptomatic
• Lesions causing disfigurement can be excised
• Carbon dioxide laser is used
Neurilemmomma • Surgical excision
Leiomyoma • Surgical excision
Lipoma • Surgical excision
Seborrhoeic keratoses • Removal by curettage, cautery, or diathermy
• Recurrence is the rule
Syringoma • Cauterisation or diathermy for cosmesis
Cylindroma • Surgical excision
Apocrine hidrocystoma • Surgical excision
Eccrine hidrocystoma • Surgical excision
• Cauterisation or diathermy
• Carbon dioxide laser and pulse dye laser
Eccrine poroma • Surgical excision
Pilomatrixoma • Surgical excision
Trichoepithelioma • For cosmetic reasons: Surgical excision, curettage, pulsed carbon dioxide laser,
cryotherapy, and dermabrasion
• If malignancy is suspected adequate excision and histological examination
Sebaceous gland hyperplasia • For cosmetic purpose, gentle cautery, cryotherapy, carbon dioxide, and pulsed
dye laser and trichloroacetic acid
Clear cell acanthoma • Surgical excision
Clinical features
The lesion is an exquisitely tender pink or purple nodule, which often presents in adults. It occurs
usually on the hands, commonly around the fingertips, on the head, neck, and penis.
Vascular tumors
Senile angioma (Campbell De Morgan spot, cherry angioma)
As with seborrhoeic warts and skin tags, senile angioma is a frequent accompaniment of skin ageing.
Abrupt onset of numerous lesions has been reported with chemotherapy, mostly nitrogen mustards.
Histologically, it resembles the capillary angioma.
Benign tumors 161
FIGURE 12.3 A lipoma situated deep to the frontalis muscle (from Marks and Motley, 18th edition).
FIGURE 12.5 Dome-shaped, red-haemorrhagic nodule

of pyogenic granuloma.
Clinical features
These are smooth-surfaced, dome-shaped, pur
plish, or cherry-red papules on the trunk of the
FIGURE 12.4 Dermatofibroma: demonstrating char middle-aged or the elderly (Figure 12.6). Many
acteristic ‘dipping’ on lateral pressure (from Marks and lesions may appear over a period of some
Motley, 18th edition). months, but apart from the distress that their
appearance seems to cause, they have no special
significance for general health.
Capillary aneurysm
Since the most common presentation of this tiny vascular lesion is of a suddenly appearing black
pinhead spot, it is sometimes mistaken for an early malignant melanoma. If left, it gradually fades.
FIGURE 12.6 Senile angioma on the trunk in a man

aged 63 years (from Marks and Motley, 18th edition). FIGURE 12.7 Spider naevus (from Marks and Motley,
18th edition).
Spider naevus (spider telangiectases, naevus araneus, spider angioma)

It is found in association with liver disease and pregnancy. It is thought to be related to increased
oestrogen.
Clinical features
This is a small prominent pulsatile blood vessel, which appears at the skin surface frequently with radiating
capillary branches. The ascending central arteriole represents the body of the spider and the fine vessels that
radiate from the centre represent the legs of the spider. It is frequently solitary or maybe multiple, seen
usually on the upper half of the body in children, and may develop in women during pregnancy
(Figure 12.7).
Neural tumors
Neurofibroma and von Recklinghausen’s disease
The neurofibromas can be solitary or multiple. Multiple neurofibromas are present in several dis
tinct genetic disorders. The two main forms are NF1 (Neurofibromatosis 1 or von Recklinghausen’s
disease) and NF2 (Neurofibromatosis 2). It is inherited as an autosomal dominant condition, but
30–50% of patients do not give a family history, suggesting that there is a high rate of new gene
mutation.
Histologically, the typical picture is of a non-encapsulated dermal mass composed of interla
cing bundles of spindle-shaped cells, often in a ‘nerve-like’ arrangement, set in a homogeneous
matrix amid which mast cells may be seen.
Benign tumors 163
Clinical features
Individual lesions are often quite large, soft,
compressible, and skin-colored (Figure 12.8).
Neurofibromata start to appear in childhood
and increase in number during adolescence.
They are cosmetically very disabling and, in
the worst cases, result in gross deformity.
Ultimately, large numbers may be present.
Some of these lesions become very large, soft,
diffuse swellings; others become pedunculated
and pendulous. Alongside the neurofibromata,
light-brown, uniformly pigmented, irregular
macular patches appear (café-au-lait patches)
over the trunk and limbs (Figure 12.9). A
useful diagnostic point is the presence of small
pigmented macules at the apices of the axillae
(so-called axillary freckling). There is a greatly
increased risk of tumors affecting the central
and peripheral nervous systems as well as of
tumors of sympathetic tissue, such as
phaeochromocytoma.
The National Institute of Health Consensus
Development Conference Statement requires two
or more of the following criteria to be fulfilled to
FIGURE 12.8 Soft mauve or pink, compressible lesions be called NF-1:
of neurofibroma (from Marks and Motley, 8th edition).
1. Six or more café-au-lait macules of over 5 mm in greatest diameter in prepubertal individuals

and over 15 mm in greatest diameter in postpubertal individuals
2. Two or more neurofibromas of any type or one plexiform neurofibroma
3. Freckling in the axillary or inguinal regions (Crowe’s sign)
4. Optic glioma
5. Two or more Lisch nodules
FIGURE 12.9 Café-au-lait patch in von Recklinghausen’s disease (from Marks and Motley, 18th edition).
6. A distinctive osseous lesion such as sphenoid dysplasia or thinning of the long bone cortex with
or without pseudoarthrosis
7. A first-degree relative (parent, sibling, offspring) with NF1 by the preceding criteria
Neurilemmoma (Schwannoma)
The neurilemmoma is an uncommon benign tumor of neural connective tissue and is composed of
Schwann cells.
Microscopically, they consist of thin, spindle-shaped cells arranged in a stacked or ‘storiform’
manner.
Clinical features
The lesions vary in size, are usually slow-growing, and occur anywhere on the skin surface. They are
usually pink-grey or yellowish, firm, well-circumscribed, rounded nodules, and sometimes painful.
Neuroma
This rare benign neural tumor is the most differentiated of all the neural connective tissue tumors and
consists of well-formed nerve elements. It occurs at the site of nerve injury and occasionally seems to
arise spontaneously and is frequently tender.
Muscle tumors
Leiomyoma
This is an uncommon benign tumor of smooth muscle that arises either from arrector pili muscle of
hair follicles or from the smooth muscle of blood vessel walls. It can be confused histologically
because of its spindle-shaped and strap-shaped plain muscle cells, which may look like fibrous or
neural tissue. They are classified into piloleiomyomas, genital leiomyomas, and angioleiomyomas.
Eruptive leiomyomas are reported in patients with haematological malignancies, especially chronic
lymphocytic leukaemia.
Clinical features
It is mostly smooth, tender, oval, and bluish red in color nodules or plaques, varying in size from
1 cm to 3 cm in length and 0.5 cm to 1.5 cm in breadth, present usually on extremities and trunk. It
may be spontaneously painful, especially in the cold, and indeed can sometimes be seen to contract
when cooled. Leiomyomas have been associated with type II papillary renal carcinomas and
Alport syndrome.
Tumors of epidermal origin

Seborrhoeic keratoses (basal cell papillomas, seborrhoeic warts)
They are extremely common benign tumors of ageing skin. Most patients are over 40 years, have
multiple lesions, and may have a familial tendency. They seem to be most common in Caucasians, but
similar lesions are seen in black-skinned and Asian peoples.
Histologically, there is epidermal thickening, with the predominant cell being rather like the normal
basal epidermal cell. Surmounting the thickened epidermis, there is a warty hyperkeratosis whose
Benign tumors 165
FIGURE 12.10 Pathology of a flat seborrhoeic wart showing ‘church spire’ arrangement (from Marks and Motley,
18th edition).
arrangement has been likened to a series of church spires (Figure 12.10). Within the lesion are foci of
keratinization and horn cysts.
Clinical features
They are solitary or multiple brownish, warty nodule, or plaque on the upper trunk or head and neck
regions; their pigmentation varies from light fawn to black (Figure 12.11). They often have a greasy and
‘stuck on’ look. In black-skinned people, they may appear as multiple, blackish, dome-shaped warty
papules over the face, a condition known as dermatosis papulosa nigra. The differential diagnosis
of warty lesions is given in Table 12.2. When deeply pigmented, they are sometimes mistaken for
malignant melanoma.
They usually cause no symptoms, but patients complain that they catch in clothing and are un
sightly. They may also irritate and, less frequently, become inflamed and cause soreness and pain
and may be mistaken for a squamous cell carcinoma. Eruptive seborrhoeic keratoses have been
referred to as Leser Trelat sign, and this is a marker of an underlying malignancy. The changes are
referred to as an irritated seborrhoeic keratosis and are a common reason for patient anxiety and
referral for specialist advice.
Benign tumors of sweat gland origin

The more common benign tumors of sweat gland origin are listed in Table 12.3. The most common are
described next.
Syringoma (Syringocystoma)
They are benign skin tumors, usually multiple. Histologically, there are tiny, comma-shaped (tadpole-like)
epithelial structures, some of which appear cuticle-lined, forming microcysts (Figure 12.12).
Clinical features
They are multiple small white or skin-colored papules that are typically seen on the skin below the eyes
(Figure 12.13) in young adults. Occasionally, they are also evident on the arms and lower trunk. They
may be associated with Down’s syndrome.
Cylindroma (Turban tumor, Spiegler’s tumor)

This is a slow-growing benign tumor arising from
apocrine sweat glands that, like syringoma, is often
multiple. It has an autosomal dominant inheritance in
familial cases. Oval and rounded masses of basaloid
epidermal cells surrounded by an eosinophilic band
of homogeneous connective tissue characterize the
histological appearance (‘jigsaw-puzzle’ appearance).
Clinical features
Smooth pink and skin-colored nodules and papules
occur over the scalp and face in young adults,
which are sometimes painful. Multiple tumors may
arise and cause considerable cosmetic distress.
Apocrine hidrocystoma
A benign tumor arising from cystic dilatation of
the apocrine gland.
Clinical features
It is an uncommon cyst, usually solitary, and may
have skin to greyish-blue color, usually seen
FIGURE 12.11 Typical brown/black, ‘stuck-on’ warty around the eyelids. It is often confused with basal
lesions known as seborrhoeic warts (from Marks and
cell carcinoma (Figure 12.14).
TABLE 12.2
Differential diagnosis of warty tumors
Lesion Comment
Seborrhoeic keratosis Mostly in elderly individuals and multiple; may have a greasy, ‘stuck-on’ appearance
Viral wart Not usually pigmented; mostly in younger individuals on hands, feet, face, and genitalia
Solar keratosis Flat, pink, and scaly usually, but can have a horny or warty surface; mostly on the backs of
hands and face
Epidermal naevus Usually since birth; anywhere on the body; often a linear arrangement
TABLE 12.3
Benign tumors of sweat gland origin
Lesion Comment
Syringoma Multiple white papules beneath eyes; composed of tiny cysts and comma-shaped
epithelial clumps
Cylindroma Solitary or multiple nodules on face or scalp; clumps of basaloid cells with
eosinophilic colloid material
Syringocystadenoma papilliferum Mostly develop in naevus sebaceous on the scalp or on mons pubis
Apocrine hidrocystoma Small thin-walled, bluish cyst found around eyelids
Eccrine poroma Solitary nodule on palms or soles or, rarely, elsewhere; basaloid clumps in the upper
dermis
Eccrine spiradenoma Tender and painful solitary nodule
Benign tumors 167
FIGURE 12.12 Pathology of syringoma showing many comma-shaped epithelial structures and tiny cysts (from Marks
and Motley, 18th edition).
FIGURE 12.13 Syringoma lesions around the eyes.
FIGURE 12.14 An apocrine hidrocystoma: this example is larger than usually seen in the periorbital skin (from Marks
and Motley, 18th edition).
Eccrine hidrocystoma
A benign tumor arising from dilatation of eccrine gland units.
Clinical features
This is also a solitary, uncommon cyst and a close differential of apocrine hidrocystoma. It has the skin
of greyish-blue color, usually seen around the eyelids and cheeks. A history of an increase in size on
exposure to heat and improvement when the skin is exposed to cold is present.
Eccrine poroma
It is an eccrine sweat duct-derived tumor. Histologically, the lesion appears contiguous with the surface
epidermis and consists of basaloid cells in which there are cuticularly lined duct-like structures.
Clinical features
They are pink-red, moist exophytic lesions arising predominantly on the palms and soles in adults.
Benign tumors of hair follicle origin

Pilomatricoma (calcifying epithelioma of Malherbe, trichomatricoma)
It is a benign tumor of hair matrix cells. Clumps of basal cells progressively become calcified and
eventually ossified, leaving behind their cell walls only (ghost cells).
Clinical features
It is a solitary, smooth, skin-colored or bluish
nodule present around the head, neck, and
upper trunk in children and young adults
(Figure 12.15). The hard nature of the lesion is a
strong clue to the diagnosis. Stretching of the
skin over the tumor with multiple angles results
in a ‘tent sign’.
Trichoepithelioma (Brooke’s tumor)

It is a benign tumor of hair germ cells. There may
be a familial tendency to develop these lesions.
Histologically, it consists of the most part of
clumps of epithelial cells and horn-filled cysts; it
may transform into basal cell carcinoma.
Clinical features
Trichoepithelioma are small, pearly papules more
often multiple than solitary and usually occur over
the scalp and central face with a predisposition to
the skin around the nose (Figure 12.16).
FIGURE 12.15 Pilomatrixoma (from Marks and

Benign tumors 169
FIGURE 12.16 Trichoepithelioma.
Sebaceous gland hyperplasia

It is a common feature of elderly skin representing
benign proliferation of sebaceous gland and has
been suspected to be due to chronic solar damage
rather than ageing. FIGURE 12.17 Sebaceous gland hyperplasia. Note the
Histologically, it consists of hypertrophied central ‘punctum’ within a yellowish papule on the face
lobules of normal sebaceous gland tissue. (from Marks and Motley, 18th edition).
Clinical features
One or, more often, several yellowish, skin-colored papules develop over the skin of the face, some of
which have central puncta (Figure 12.17). They are often mistaken for basal cell carcinomata or dermal
cellular naevi.
Clear cell acanthoma (Degos acanthoma)

The name derives from the epidermal thickening composed of large cells that, when stained with
periodic acid–Schiff reagent, are found to be stuffed with glycogen (Figure 12.18) and infiltrated with
polymorphonuclear leucocytes.
Clinical features
This is usually a solitary moist, pink papule or nodule on the upper arms, thighs, or trunk that has been
present, unchanging, for several years in adults.
Naevi
The term ‘naevus’ is used for a fixed lesion present at or soon after birth. These are developmental
anomalies consisting of immature melanocytes in abnormal numbers and sites within the skin. They are
very common and, on average, white-skinned Caucasians have 16 over the skin surface. Melanocytic
FIGURE 12.18 Pathology of clear cell acanthoma showing hypertrophied epidermis with areas of large, pale epithelial
cells (from Marks and Motley, 18th edition).
naevi come in a wide variety of shapes and sizes and the main types are summarized in Table 12.4. The
treatment of various naevi is provided in Table 12.5.
Congenital naevi
They are deeply pigmented lesions present at birth or appear a few months after birth and grows in
proportion to the growth of the child. The size of the naevi determines the risk of development
of melanoma. American National Institutes of Health (NIH) consensus definition categorizes
these naevi into small (<1.5 cm in diameter), large (1.5–20 cm in diameter), and giant naevi
(>20 cm in diameter)
Histologically, these lesions consist of numerous ‘packets’ (theques) of naevus cells
(Figure 12.19), which may be small and basophilic (lymphocytoid), large and less intensely
staining (epithelioid), or spindle-shaped. They may also coalesce to form naevus giant cells or
after they have been present for many years, may show degenerative changes, including fatty
degeneration and calcification. Naevus cells tend to be faceted together in a rather character
istic way.
Clinical features
These lesions, which are present at birth, are usually solitary and dark brown and are more than 1 cm2 in
size. They are plaque-like or nodular and may contain hair (Figure 12.20). The surface of large naevus
may become warty and develop nodules with the growth of the infant. They share with the limb-girdle
naevus the increased tendency to malignant transformation. It has been suggested that 10% of the larger
congenital naevi develop malignant melanoma. The most deforming congenital melanocytic naevi are
those that cover large areas of skin in the pelvic region and adjoining back (bathing trunk naevi) or over
the shoulder region and upper limb.
Acquired naevi (mole, naevocytic naevus, cellular naevus)

Acquired naevi appear after birth, usually during adolescence or young adult life. Potential diffi
culty arises when an adult notices a brown lesion for the first time. Has it been there for many years
before being noticed? Or is it a new benign mole, some other pigmented lesion, or a malignant
melanoma?
Benign tumors 171
TABLE 12.4
Main varieties of melanocytic naevi
Type Clinical features Comment
Congenital/simple Present since birth, tend to be larger Compare with acquired naevi
than acquired naevi, often hairy
Girdle Cover large areas around pelvic or Increased tendency for malignant
pectoral zone (bathing trunk or cape transformation – especially if very large
naevus)
Acquired Develop mainly in late childhood and
early adolescence
Junctional Macular, brown/black Anywhere on skin or mucosae
Dermal cellular Papular or nodular, may be hairy; Very common on face and scalp
usually light brown or skin-colored
Compound Combination of dermal, cellular, and
junctional
Naevus spilus Large, speckled, light-brown naevus Uncommon, increased risk of malignant
change
Dysplastic naevus Many moles with irregular margins Increased tendency to malignant
syndrome and pigmentation; may be sporadic melanoma
but also familial
Juvenile melanoma Orange–pink nodule or plaque in Histological picture may simulate
childhood; also known as ‘Spitz’ melanoma
naevus
Blue naevus Blue due to depth of pigment in dermis
Cellular blue naevus Bluish nodule on scalp, hands, or feet
Mongolian spot Large, flat, greyish blue macule Present at birth over sacrum; may fade
Naevus of Ota or Ito Flat, blue–grey areas on face and neck Predominantly in Asians
They are benign proliferation of melanocytes at the dermal–epidermal junction. If the cluster remains
in dermo-epidermal junction it is known as junctional naevus and migration of some of the cells to
dermis gives rise to compound naevus. It is called dermal cellular naevi when the whole cluster lies in
the dermis.
The differential diagnosis for this situation is given in Table 12.6.
Junctional naevi
These are flat, brown, or black moles. It is presumed that this is the first stage in the ‘lifecycle’ of
the ordinary mole. This type of mole is seen most frequently on the palms and soles, especially
in children.
Compound naevi
These have the characteristics of a dermal cellular naevus, but there are areas of ‘junctional ac
tivity’. It is presumed that these lesions are intermediary in development between the junctional
naevus and the dermal cellular naevus.
Dermal cellular naevi

They are fawn or light-brown or just skin-colored papular or nodular lesions. They are common on the
face and are often ‘hairy’, accounting for occasional episodes of pain, redness, and swelling due to
TABLE 12.5
Treatment of naevi
Naevus Treatment
Congenital naevi • Aimed at improving cosmetic effect and to reduce the risk of malignant
transformation
• Various plastic surgery techniques are utilized.
• Both these aims are difficult to attain in large melanoma
• Choice of intervention has to be balanced, keeping in mind the need for
cosmesis
Acquired naevi • Aim is to differentiate benign from atypical naevi
• History, examination, and dermoscopy should be utilized to differentiate
• Excision should be followed by histopathology
• Lasers and various surgical methods can be utilized if excision is done
for cosmetic purpose
Spitz naevus • Local excision with a narrow margin
Naevus of Ota • Q-switch ruby laser is effective
Verrucous epidermal naevus • Surgical excision, shave excision, dermabrasion can be done
• Cryotherapy and lasers (Er:Yag and CO2) can be utilized
• Recurrence is common
Becker’s naevus • Q-switched Nd:YAG laser can be done
Naevus sebaceous • Excision of scalp lesions with primary closure
Shagreen patch • Surgical excision
• Laser ablation
Naevus lipomatodes cutaneus • Surgical excision
superficialis • Laser ablation
Adenoma sebaceum • Surgical excision
• Laser ablation
Port wine stain • Laser treatment (pulse dye laser) can be dramatically effective
• Not all lesions respond equally to treatment
Lymphangioma circumscriptum • Sclerotherapy
• Laser ablation
Infantile haemangioma • Depends on the location, stage of evolution, morphology, risk of
functional or cosmetic disfigurement, and comorbidities
• If situated on the face they have the potential to grow and interfere with
vision (Figure 15.42) or upper airway haemangioma can cause breathing
difficulties
• Under these circumstances early intervention is necessary
• Systemic and topical steroids have been replaced by oral propranolol
with better efficacy and side effect profile
• Topical timolol has been tried with some success
• Surgery is rarely required. They are undertaken if results are likely to be
superior and to restore the contour and anatomy of a structure
• Tuned dye 595 nm lasers may have a minor role in ‘toughening’ the
surface of these lesions, particularly those prone to bleeding
• There has been some success using Nd:YAG lasers
Angiokeratoma • Smaller lesions to be treated with curettage and cautery
• Larger lesions are excised surgically or by laser
Benign tumors 173
FIGURE 12.19 Pathology of congenital melanocytic naevus showing packets or theques of naevus cells, some of which
are ‘naevus giant cells’ (from Marks and Motley, 18th edition).
FIGURE 12.20 Large congenital melanocytic naevus (from Marks and Motley, 18th edition).
TABLE 12.6
Differential diagnosis of an acquired naevus
Diagnosis Comments
Acquired naevus (mole) Usually light brown, static
Seborrhoeic keratosis (basal cell papilloma) Brown, warty
Dermatofi broma (histiocytoma) Firm, light brown
Malignant melanoma Enlarging, irregular, variegate
Pigmented basal cell carcinoma Smooth, pigmented nodule
folliculitis. In some, there is a deep component with many spindle-shaped naevus cells that may su
perficially resemble the cellular component of a neurofibroma. In the elderly, when there is a little
pigment, they may be misdiagnosed as basal cell carcinoma.
Degenerative changes in naevi

Naevus cell naevi gradually become fewer during the ageing process and it is believed that
moles develop involutional changes before disappearing. Some develop lipid vacuoles in their
substance, others develop a type of foamy change, and others appear to calcify before finally
disappearing.
Dermal (blue) naevi

Cellular blue naevus
The melanin pigment and the bulk of the naevus cells are in the mid and deep dermis. The striking blue
color given by the pigment is due to the red wavelengths being filtered out by the superficial dermis and
epidermis known as the Tyndall effect.
Clinical features
A raised, smooth area of diffuse pigmentation is found to be present over the back of the hands or feet
and scalp, usually appearing at puberty (Figure 12.21).
Mongolian spot
A type of blue naevus commonly found in Asians. It occurs as a greyish discoloration over the sacral
area in the newborn, becoming less prominent in later life. The dermal melanocytes in persistent
Mongolian spots have an extracellular sheath and are frequently associated with disorders of inborn
errors of metabolism and vascular birthmarks.
Naevus of Ota
Blue-grey to brown pigmentation affecting face usually unilaterally in the area supplied by the oph
thalmic and maxillary divisions of the trigeminal nerve. Ocular involvement is present, most commonly
of the sclera (Figure 12.22).
FIGURE 12.21 Blue naevus (from Marks and Motley, 18th edition).
Benign tumors 175
FIGURE 12.22 Naevus of Ota.
Naevus of Ito
Similar to naevus of Ota but situated in the dis FIGURE 12.23 Multiple dysplastic moles with the irre
tribution of posterior supraclavicular and lateral gularity of shape and pigmentation (from Marks and
brachial cutaneous nerves. Motley, 18th edition).
Dysplastic naevus syndrome (atypical mole syndrome)

Recognition of this syndrome is important because of the increased frequency of malignant melanoma
associated with it. The condition may occur sporadically but is also familial in many patients. It is said that
the risk of a melanoma developing is approximately 1%, but it is certainly much more than that in the
familial form if one of the affected members of the family has had a melanoma – perhaps 10%. It is even
greater – possibly 100% – if the individual has already had one melanoma.
These lesions often have what the dermatopathologists call a ‘worrying appearance’, meaning that
many have one or more features suggesting melanoma. There may be a degree of cytological atypia and
excessive mitoses. These patients should be reviewed regularly and any suspicious moles removed for
histological examination. It is helpful to take detailed clinical photographs and dermatoscopy photo
graphs of their moles for future comparison.
Clinical features
The lesions are variable in number and may be quite large compared with ordinary moles. They have
irregular margins and irregular brown pigmentation, some having an orange-red hue (Figure 12.23). The
ABCDE algorithm is a quick way of obtaining a diagnostic clue to pick suspected melanoma lesions.
• Asymmetry
• Border irregularity
• Color variegation
• Diameter >6 mm
• Evolution
However, despite these clinical clues, the diag

nostic accuracy remains low. In such a scenario,
dermoscopy is a useful tool for the evaluation of
skin lesions. It has increased sensitivity and
specificity for melanoma, allowing detection at
an early stage. It acts as a bridge between clin
ical suspicion and biopsy, thereby reducing the
number of unnecessary biopsies of naevi.
Spitz naevus (juvenile melanoma)

This is an uncommon, benign lesion of
childhood and adolescence; its alternative
name derives from its histological appear
ance, which may look frighteningly like a
melanoma to the uninitiated.
Clinical features
Usually, solitary, occasionally multiple red,
pink, or orange papules, nodules, or small pla
ques (Figure 12.24), which may have a corru
gated or peau d’orange surface present on the
face, generally the cheeks, and the legs (in
FIGURE 12.24 Juvenile melanoma: a red nodule on the young adults).
arm of a 9-year-old boy (from Marks and Motley, 18th
edition).
Epidermal naevus
Epidermal naevi are an uncommon, localized
malformations of the epidermis, composed of keratinocytes and classified as hamartomata. They are
congenital in origin, represent genetic mosaicism, and are usually present at birth. Histologically, there
is regular epidermal thickening and hyperkeratosis, often in a church-spire pattern.
Clinical features
Many epidermal naevi are arranged linearly and are warty, known as verrucous epidermal naevus
(Figure 12.25). Sometimes they track along with a limb and adjoining trunk and are extensive and
disfiguring. This type is known as naevus unius lateris (Figure 12.26).
Variants
Becker’s naevus
Becker’s naevus is an odd type of hamartomatous lesion that develops in adolescence or early adult life
and sometimes shows increased androgen sensitivity. It consists of hypertrophy of all the epidermal
structures, including the hair follicles and melanocytes.
Clinical features
A comparatively large area of skin is affected by a brownish and sometimes hairy plaque usually
occurring around the shoulders or upper arms (Figure 12.27).
Benign tumors 177
FIGURE 12.25 Verrucous epidermal naevus on the back FIGURE 12.26 Naevus unius lateris – linear warty lesion
of the neck. (from Marks and Motley, 18th edition).
Naevus sebaceous
These are epidermal hamartomas consisting of sebaceous glands (Figure 12.28).
FIGURE 12.27 Becker’s naevus on the upper back. The affected area is pigmented, thickened, and hairy.
FIGURE 12.28 Typical orange plaque of naevus sebaceous on the scalp (from Marks and Motley, 18th edition).
Clinical features
Lesions are yellowish orange-brown plaques on the scalp, either present at birth or shortly
afterwards, and may enlarge, thicken, and develop other lesions in them, such as basal cell carcinoma
in adult life.
Connective tissue naevi

These are rare intracutaneous plaques and nodules, often with a knobbly or corrugated skin
surface. They are very difficult to identify histologically because they are composed of normal
connective tissue.
Shagreen patch
Plaque-type collagenoma most often occurring in the lumbosacral area (Figure 12.29).
FIGURE 12.29 Shagreen patch on back in a patient of tuberous sclerosis.

Benign tumors 179
FIGURE 12.30 Skin colored to pink-red dome-shaped papules in a patient of adenoma sebaceum.
Adenoma sebaceum
‘Adenoma sebaceum’ is a misnomer as it is not an adenoma and is not derived from sebaceous glands.
It occurs on the cheeks and the central part of the face of patients with tuberous sclerosis and consists
of pink or red, firm papular lesions (Figure 12.30) in which vascular fibrous tissue is found rather than
(as the name would suggest) an excess of sebaceous glands.
Tuberous sclerosis (epiloia)

This dominantly inherited syndrome is a neurocutaneous disorder.
Clinical features
The cutaneous components include shagreen patches, ash leaf-shaped hypopigmented patches on the
trunk, subungual fibromata, which are fibrous nodules that develop beneath the toenails and fingernails,
and adenoma sebaceum (see the earlier discussion).
Fat naevi
Naevus lipomatodes cutaneus superficialis
This is a rare disorder with ectopic collections of mature lipocytes in the dermis.
Clinical features
They can be either in form of clusters of soft, fleshy, yellow to skin-colored papules or nodules found
commonly on the lower trunk and on the upper posterior thighs or as solitary, domed, or sessile papule
at sites other than the lower trunk (Figure 12.31).
FIGURE 12.31 Naevus lipomatoses on the lower back.
Vascular naevi
According to the International Society for the Study of Vascular Anomalies (ISSVA),
vascular birthmarks can be broadly divided into vascular tumors and vascular malformations
(Table 12.7).
Vascular malformations
Soft, compressible, mauvish-blue swellings composed of large vascular spaces may occur. These
lesions show little tendency to reduce in size in later life and may extend widely through the local
tissues.
Capillary malformations
Stork mark (Salmon patch, Nuchal stain)
It is a popular name for the red discoloration at the back of the neck in a high proportion of newborns.
It fades in later childhood and seems to be due to vasodilatation rather than due to an excess of
blood vessels.
Port wine stain

This is a common low-flow vascular malformation. The lesions contain many dilated blood vessels but
no other obvious histological abnormality.
Clinical features
The deep crimson color (of ‘port wine’) is distinctive and cosmetically very disfiguring, occurring most
commonly on the face (trigeminal nerve distribution) (Figure 12.32a) and scalp. Facial lesions may be
associated with mucosal and gingival involvement (Figure 12.32b).
The surface of the lesion becomes more thickened and rugose with age and even develops polypoid
outgrowths, adding to the grotesque appearance. When on a limb, deep vascular malformations may
also be present, which can cause limb hypertrophy. Over the ophthalmic region, the obvious skin
malformation of blood vessels may be associated with an underlying meningeal angiomatous
Benign tumors 181
TABLE 12.7
International Society for the Study of Vascular Anomalies (ISSVA) Classification of Vascular Anomalies
(©2018) (available at issva.org/classification)
Vascular anomalies
Vascular tumors Vascular malformations
SIMPLE COMBINED OF MAJOR NAMED ASSOCIATED WITH
VESSELS OTHER ANOMALIES
Benign Capillary CVM, CLM Affect Klippel–Trenaunay
malformations lymphatics syndrome
veins
arteries
Locally Lymphatic LVM, CLVM Anomalies of Parkes–Weber syndrome
aggressive or malformations origin
borderline course
number
length
diameter (aplasia,
hypoplasia, stenosis, ectasia/
aneurysm)
valves
communication (AVF)
persistence (of embryonal
vessel)
Malignant Venous CAVM Sturge–
malformations Weber syndrome
Arteriovenous CLAVM Maffucci syndrome
malformations
Microcephaly
Macrocephaly
Arteriovenous fistula CLOVES syndrome
Bannayan
Riley
Ruvalcaba
Proteus syndrome
malformation. When this combination of lesions is associated with epilepsy, the disorder is known as
the Sturge–Weber syndrome.
Lymphangioma circumscriptum
This lesion is a malformation of lymphatic channels, although there may also be an associated blood
vessel anomaly. The lesions usually have a deep component, which is almost impossible to eradicate
surgically.
Clinical features
The malformation is recognized as a diffuse skin swelling with what appears to be a cluster of tense
vesicles with clear or blood-stained fluid, with a frogspawn-like appearance. It can be found anywhere
but is common in lymphatic-rich areas (Figure 12.33).
FIGURE 12.33 Lymphangioma circumscriptum affecting

the abdomen.
Vascular tumors
Infantile haemangioma (‘strawberry
naevus’)
The lesions are not usually visible at birth but
develop in the first few weeks of life and undergo
spontaneous involution. It has been suggested that
they may represent an embolus of maternal pla
cental vascular endothelial cells, which begin to
proliferate in the child’s skin. They may be seg
mental or multifocal involving the viscera.
Clinical features
They are raised, purplish nodules and plaques
whose surface is often lobulated (supposedly like
a strawberry), and they show an enormous range
of sizes. The smaller lesions have little functional
significance and usually flatten or disappear
within a few years. The larger lesions may be very
deforming and destructive and may cover quite
a large area of skin (Figure 12.34). Periocular
hemangiomas may lead to visual problems
(Figure 12.35).
FIGURE 12.32 (a) Typical port wine stain in the dis The larger lesions, particularly, may ulcerate
tribution of trigeminal nerve and (b) mucosal involvement after minor trauma, presumably due to ischaemia
in the same patient. of the overlying superficial dermis and overlying
epidermis because of the shunting of blood be
tween the larger, deeper vessels of the angioma.
Any bleeding can be stopped with gentle pressure and the eroded area gradually heals with routine
care. One other rare complication only occurs with the largest of capillary angiomas. Blood platelets
Benign tumors 183
FIGURE 12.34 Large capillary naevus affecting the thigh and lower abdomen (from Marks and Motley, 18th edition).
become sequestered in the abnormal vascular

channels of the angioma, creating a consump
tion coagulopathy and uncontrolled bleeding
(Kasabach–Merritt syndrome).
Angiokeratoma
There are several types of angiokeratoma,
which all consist of a small, subepidermal
vascular malformation surmounted by a hy
perkeratotic epidermis.
Clinical features
They may occur as solitary red papules or, oc
casionally, as a crop of red spots over the
FIGURE 12.35 Periocular haemangioma which may lead to scrotum (Figure 12.36). When literally hun
visual disturbance. dreds of tiny red papules develop over the trunk
in young men (bathing trunk distribution), the
possibility of the very rare inherited metabolic abnormality known as angiokeratoma corporis diffusum
or Fabry’s disease must be considered.
Cysts
A cyst is an epithelium-lined cavity filled with fluid or semi-solid material. The distinguishing features
of the commonly encountered cysts of the skin are summarized in Table 12.8. Their treatment is briefed
in Table 12.9.
Epidermoid cysts
These lesions are lined by the epidermis and produce stratum corneum (keratin).
Clinical features
Firm, skin-colored papules or nodules containing
keratin that are surrounded by a tough, fibrous cap
sule, presumably stimulated by leakage of the cyst
contents. A keratin filled punctum may be present
(Figure 12.37). If the cyst contents find their way into
the dermis, considerable inflammation results. The
horny content may eventually degenerate, forming a
foul-smelling, semi-solid material. The fancied re
semblance of this to sebum has mistakenly led to the
term ‘sebaceous cysts’ for these lesions. Epidermoid
cysts may occur anywhere but are most common
over the head, neck, and upper trunk. Gardner syn
drome, an autosomal dominant disorder representing
familial adenomatous polyposis (FAP), is associated
with multiple epidermoid cysts.
Milia
They are tiny epidermoid cysts that occur sponta
neously over the upper cheeks and beneath the eyes
(Figure 12.38) and at the sites of subepidermal
blistering, as seen in porphyria cutanea tarda.
FIGURE 12.36 Angiokeratoma of the scrotum (from Clinical features

Marks and Motley, 18th edition).
They are small white papules usually no larger than a
pinhead. They contain tiny accretions of the horn.
Pilar cysts (tricholemmal cysts)

They are often genetically determined as an autosomal dominant trait. The lining epithelium of these cysts,
which are commonly seen on the scalp, is derived from a portion of the hair follicle neck and shows a
TABLE 12.8
Differential diagnosis of common skin cysts
Cyst type Body site Clinical features
Epidermoid Virtually anywhere Smooth-walled, firm lesions; may become
inflamed if they leak; common
Milium At sites of blistering, Pinhead-sized, white, hard lesions
spontaneously on upper cheeks
Pilar Scalp and scrotum May be inherited; often multiple; less common
than epidermoid cysts; smooth-walled but not
as firm as epidermoid cysts
Sebocystoma multiplex Anywhere, but especially the May be inherited; always multiple; usually small,
upper trunk smooth-walled; contents less firm than other
types; may become inflamed and develop acne-
like lesions; uncommon
Dermoid Face, particularly around the eyes Deep-set in skin; may be oval and less mobile
than other cyst types
Benign tumors 185
TABLE 12.9
Treatment of cysts
Cyst Treatment
Epidermoid cysts • Uninflamed cyst: dissected out
• Inflamed cyst: incised and drained followed by phenolization
Milia • Expressed by slitting the thin epidermis over them with a needle tip
Pilar cysts • Uncomplicated cysts: dissected out
• Proliferating cysts: excised with a margin
Sebocystoma multiplex • Due to their large number, surgical excision is impractical
Dermoid cysts • Surgical excision
FIGURE 12.37 Epidermal inclusion cyst.
quite characteristic type of keratinization in which

there is an abrupt formation of a glassy-appearing
type of horn without a granular cell layer.
Clinical features
Pilar cysts are solitary or multiple smooth, firm,
and rounded nodules. They occur on the scalp and
on the scrotum in particular. Inflammation can
cause tenderness.
Sebocystoma multiplex (steatocystoma

multiplex)
FIGURE 12.38 Milia. These cystic malformations are formed from se
baceous gland tissue and other hair follicle-derived
epithelium. They are inherited as an autosomal dominant trait. Their content is sometimes pure sebum.
The familial forms are associated with pachyonychia congenita type 2 (hypertrophic nail dystrophy, focal
keratoderma, multiple pilosebaceous cysts).
Clinical features
They are small cysts, always multiple, often in very large numbers, and distributed over the body,
particularly over the upper trunk and sternum. They usually have no punctum and comedones can be
present.
Dermoid cysts
Dermoid cysts are uncommon lesions that are present from birth but may only become apparent several
years later. They seem to contain embryonic epithelium capable of forming a wide spectrum of tissue
types.
Clinical features
These cysts may occur anywhere but are especially often found around the eyes as oval, firm, smooth-
walled swellings. They may extend deeply into the tissue and occasionally are associated with defects in
the underlying bone.
Follicular retention cysts

When large hair follicles develop a hard, immovable comedonal plug in the follicular neck or at the skin
surface, the follicle distends because of the continuing secretion of sebum and production of horny
material. Often, these cysts rupture, causing inflammation, but sometimes this does not happen and quite
large swellings are produced. This seems to occur particularly frequently over the back in the elderly
when they appear as giant comedones.
13
Malignant diseases of the skin
Yasmeen Jabeen Bhat

Anupam Das
Malignant diseases of the skin are becoming more common, the reason being increased cumulative
exposure to ultraviolet radiation (UVR), which is due to an increasingly elderly population, increased
outdoor activities, clothing styles, depletion of atmospheric ozone, and environmental pollutants.
Non-melanoma skin cancer

Non-melanoma skin cancers (NMSCs) are epithelial cancers that originate from the epidermal kerati
nocytes or adnexal structures.
Premalignant lesions
Various precancerous lesions include actinic keratosis, Bowen’s disease, HPV-induced intraepithelial
neoplasia, and bowenoid papulosis, arsenical keratosis, thermal keratosis, radiation keratosis, etc.
Actinic keratosis
Actinic or solar keratosis is common. It includes localized areas of rough scaling of the skin surface
caused by chronic solar exposure leading to dysplasia.
• Incidence: More common in white males beyond middle age. In the subtropical parts of Western
countries, solar keratosis has been found in more than 50% of the population over the age of 40 years.
However, dark-skinned subjects from Asia develop these, if they are excessively exposed to the sun.
• Pathogenesis: Chronic exposure to solar UVR is the most important cause, followed by chronic
heat damage, X-ray irradiation, and chemical carcinogens.
• Clinical features: Single or multiple discrete raised, rough, pink or grey, scaly, or warty hy
perkeratotic plaque are found for months to years on the exposed areas of the skin of elderly, fair-
skinned subjects who show other signs of solar damage (Figure 13.1). The lesions are better felt
than seen, and the scales are adherent.
• Investigations: Dermoscopy of the lesion helps in diagnosis.
• Pathology: Paraketatosis and hyperkeratosis surmount the variably thickened epidermis, mild to
moderate pleomorphism in the basal layer, heterogeneity of cell and nuclear size, shape, and
staining (epidermal dysplasia).
• Differential diagnosis: Seborrheic keratosis, flat warts, discoid lupus erythematosus, and su
perficial basal cell carcinoma.
• Course and complications: A small proportion of solar keratoses disappear spontaneously over
years, but a few can transform to squamous cell carcinoma (0.2%).
• Treatment: Sunscreen application on the exposed sites may prevent the occurrence.
187
FIGURE 13.1 Multiple actinic keratosis presenting as rough scaly lesions in an elderly woman.
• Topical therapy: Curretage or cryotherapy for single lesions; topical chemotherapy for multiple
lesions. Topical 5-fluorouracil 5% is applied as a single application daily for 2 weeks or on
alternate days for 2 months. Daily doses may cause erythema and erosions of the skin. Imiquimod
5% cream, an immune response-modifying agent, is applied three times per week for 16 weeks.
Topical diclofenac 3% gel appears to be quite effective and is applied twice daily for 3–4 months
to the affected skin with mild skin reactions. Topical retinoids have a prophylactic as well as a
therapeutic effect when used over long periods.
• Photodynamic therapy: Is effective and useful for large areas – such as the bald scalp. A topical
photosensitizer – methyl amino laevulinic acid – is applied to the skin for several hours and the
skin is exposed to an intense light – which activates the photosensitizer and destroys superficial
areas of keratosis. Laser therapy with erbium or carbon dioxide lasers may be helpful.
• Systemic therapy: Retinoids like acitretin or isotretinoin can be used for extensive lesions.
Bowen’s disease
Bowen’s disease or intraepidermal epithelioma or squamous cell carcinoma in situ (SCCIS) is a
localized area of epidermal neoplasia remaining within the confines of the epidermis.
• Incidence: Increasing.
• Pathogenesis: UVR, HPV, tar, chronic heat, chronic radiation.
• Clinical features: The most typical type of lesion of Bowen’s disease is a well-defined, raised,
red, scaling plaque, and lesions are often very psoriasiform in appearance. They are mostly
present on light-exposed areas of skin and are often seen on the legs of women who are more
commonly exposed to UV light or chronic heat (Figures 13.2 and 13.3). Single lesions are most
common, but multiple lesions also occur.
• Investigations: Dermoscopy shows glomerular capillaries with diffuse erythema (strawberry
appearance).
• Pathology: The histological appearance is as an exaggerated version of an actinic keratosis in
which there is marked thickening and marked heterogeneity of the epidermal cells in the form of
atypical keratinocytes, single-cell dyskeratosis, and increased mitotic rate (Figure 13.4).
• Differential diagnosis: Psoriasis, discoid eczema, superficial BCC, seborrheic keratosis.
• Course and complications: Untreated, it will progress to invasive SCC.
Malignant diseases of the skin 189
FIGURE 13.2 Psoriasiform patch of Bowen’s disease FIGURE 13.3 Pigmented Bowen’s disease on the leg of
on the abdomen of an elderly man. a patient with erythema ab igne.
• Treatment: Bowen’s disease may be treated with local destruction by curettage, cautery, and
cryotherapy, with topical agents such as 5-fluorouracil or imiquimod, or with photodynamic
therapy. Surgical excision should be done in lesions where invasion cannot be excluded by biopsy.
Erythroplasia of Queyrat
This is the term used for squamous cell carcinoma in situ affecting the glans penis and vulva. It presents
as a red, velvety patch that slowly progresses, eventually transforming into a squamous cell carcinoma if
left untreated. Surgical excision of the affected area is the best form of treatment. Anogenital HPV-
induced scc in situ is referred to as bowenoid papulosis.
Squamous cell carcinoma/Squamous cell epithelioma

Squamous cell carcinoma of the skin is a malignant tumor of keratinocytes.
• Incidence: In the United States, 12 males and 7 females per 100,000 white population. Organ
transplant recipients have a markedly high incidence of SCC, about 40–50 times that in the
general population.
• Pathogenesis: Chronic UVR damage from solar exposure, phototherapy, and tanning beds in
fair-skinned persons is the most important aetiological factor in SCC development with chronic
immunosuppression as a very significant disease-modifying factor. Other factors include irra
diation damage to the skin; persistent heat injury (as in erythema ab igne); chronic inflammatory
and scarring disorders of the skin, such as discoid lupus erythematosus, hypertrophic lichen
planus, and dystrophic epidermolysis bullosa; chronic wounds, ulcers, and burns; certain geno
dermatoses and localized congenital malformations such as xeroderma pigmentosum, epi
dermodysplasia verruciformis, and epidermal naevus; human papillomavirus infection – certain
oncogenic types (e.g. HPV types-5, -16, -18, -31, -33) seem particularly likely to cause malignant
FIGURE 13.4 Histopathology of Bowen’s disease showing occasional dyskeratotic cells.
transformation in immunosuppressed renal transplantation patients and those with HIV; exposure
to chemical carcinogens, such as industrial contact with tars and pitch or systemic administration
of arsenic.
• Clinical features: The majority of lesions of squamous cell carcinoma are asymptomatic warty
nodules or plaques that evolve gradually or, in some cases, rapidly enlarge to form exophytic
eroded nodules or ulcerated plaques. The lesion is in most cases solitary and occurs against a
background of solar damage with multiple solar keratosis in sun-exposed sites such as the scalp,
ears, lips, and dorsa of the hands. In differentiated SCC, indurated papule, plaque, or nodule with
adherent keratotic scale, central ulceration, and elevated margins can be seen (Figures 13.5a and
13.5b). In undifferentiated SCC, pap-illomatous, cauliflower-like growths occur with central
necrotic ulcerations and fleshy margins, bleeding easily on touch (Figure 13.6). Regional lym
phadenopathy due to metastasis is common.
Investigations
• Dermoscopy: A red starburst pattern may point to the aggressive growth of the tumor.
• Histopathology: There is marked epidermal thickening with cellular and nuclear heterogeneity
and atypia and evidence of abnormal mitotic activity. There is also evidence of focal and in
appropriate keratinisation so that so-called horn pearls are formed (Figure 13.7). There is usually
evidence of invasion of surrounding tissue by epithelial clumps and columns.
Several innovative optical imaging techniques, such as Raman spectroscopy, confocal microscopy, and
fluorescence imaging may help intraoperatively for margin assessment and tumor detection.
• Differential diagnosis: Squamous cell carcinoma has to be distinguished from the massive but
benign epidermal thickening known as pseudoepitheliomatous hyperplasia, which is seen in
hypertrophic lichen planus, prurigo nodularis, and lichen simplex chronicus. Keratoacanthoma
may be indistinguishable from well-differentiated SCC.
• Course and complications: Local tissue destruction and metastases occur if the primary lesions
are left untreated, spreading to local lymph nodes, and ultimately lungs, bone, and brain. Most
squamous cell carcinomas are removed before they metastasize, but patients who are
FIGURE 13.5 (a) Well-differentiated squamous cell carcinoma with raised margins and central ulceration; (b) Well-
differentiated SCC on the background of erythema ab igne due to Kangri (Kangri cancer).
immunosuppressed are at a much higher risk of developing a metastatic disease. SCCs that are
large, recurrent, and involve cutaneous nerves metastasize more.
Treatment
• Surgical: Excision – with an adequate margin to ensure inclusion of all neoplastic tissue and
some healthy tissue all around the lesion, with primary closure, skin flaps or grafting – is suf
ficient for cure in more than 95% of patients. Moh’s micrographic surgery can be done in difficult
sites. This involves taking a thin saucer-like layer of tissue from beneath the tumor and then
examining the undersurface of the tissue using frozen histological sections. Residual tumor is
identified and localized in the wound and the process is repeated until the wound is tumor-free.
For the very elderly with solitary, large, difficult to remove lesions, treatment by radiotherapy may be
more appropriate.
FIGURE 13.6 Undifferentiated SCC with fragile and necrotic tissue.
FIGURE 13.7 Histopathology of SCC demonstrating, atypia, and horn pearls.
For high-risk lesions involving deeper tissues, patient immunosuppression, location on ear and lip,
oral 5-fluorouracil, retinoids, and interferons are given.
Cetuximab, a monoclonal chimeric IgG1 antibody that binds and blocks the epidermal growth
factor receptor, acts in metastatic or unresectable squamous cell carcinoma when combined with
radiotherapy.
FIGURE 13.8 Keratoacanthoma on the upper lip presenting as a nodule with central crater.
Keratoacanthoma (molluscum sebaceum)

This term describes a rapidly growing epidermal tumor with many of the characteristics of a squamous
cell carcinoma, but which may resolve spontaneously after many months.
• Incidence: Seen in people above 50 years of age, twice as common in males as females.
• Pathogenesis: It seems to be provoked by the same stimuli that cause solar keratoses, but is much
less common. It has been suggested that keratoacanthomas develop from hair follicle epithelium.
• Clinical features: It usually appears within a week or two on light-exposed skin as a solitary
crateriform nodule (Figure 13.8). It then gradually enlarges for a few weeks and stays at that size
for a variable period before finally remitting after several months, leaving a crater-like scar.
Rarely, it may be multiple and eruptive. Multiple self-healing squamous epithelioma of Ferguson-
Smith (MSSE) is a rare autosomal dominantly inherited disease with recurrent, histologically
malignant tumors that undergo spontaneous regression.
• Investigations: The keratoacanthoma is diagnosed on clinical grounds. On histopathology,
keratoacanthoma has a characteristic, symmetrical, cup-shaped, or flask-shaped structure with
epidermis extending over the sides of the crater. There is a minor degree of epidermal dysplasia
and little evidence of tissue invasion.
• Differential diagnosis: SCC, hypertrophic actinic keratosis, verruca vulgaris.
• Course and complications: Spontaneous regression occurs in months. Untreated, these lesions
may often reach 2–3 cm in diameter and become offensive due to necrotic infected tissue.
Occasionally true squamous cell carcinomas may also arise rapidly and be indistinguishable.
• Treatment: Although spontaneous resolution may occur, this does not happen for many months –
and frequently leaves an unsightly scar. For these reasons, therapeutic intervention is usually
indicated. Surgical excision or curettage and cautery may be employed. Intralesional metho
trexate and prednisolone have also been reported to be effective. Systemic retinoids can be given
for multiple lesions.
Basal cell carcinoma (basal cell epithelioma)

Basal cell carcinoma is a locally invasive but rarely metastasizing malignant epithelial tumor of basaloid
cells without the tendency to differentiate into horny structures.
Incidence: Worldwide, BCC is the most common skin cancer with a higher incidence in countries
closer to the equator. As with squamous cell carcinoma and other forms of photodamage, basal cell
carcinoma appears to be increasing in incidence. In the United States, the rate of incidence is 500–1000
people per 100,000 white population.
Pathogenesis: Most lesions of basal cell carcinoma are due to chronic solar exposure and UVR
damage, as they occur on light-exposed sites in photodamaged subjects. However, a larger proportion
occurs in younger, non-light-exposed, non-photodamaged subjects than solar keratoses or other forms of
NMSC. The explanation for this is uncertain.
Clinical features: There are several clinical types.
Nodular. These are by far the most common variety. Translucent or skin-colored, dome-shaped
nodules (0.5–1.5 cm in diameter) slowly appear on the skin and remain static for long periods, often for
several years, before ulcerating (Figure 13.9). They often have a telangiectatic overlying skin and maybe
flecked with pigment. They usually occur as solitary lesions on the exposed areas of the skin of the head
and neck and are uncommon on the limbs. Some 20% occur on the trunk.
Ulcerative. The nodulocystic type eventually breaks down to form an ulcer with a raised, smooth,
pearly border (Figure 13.10). This type is known colloquially as ‘rodent ulcer’.
Pigmented. Brown to black, firm nodules with smooth, glistening surface, and surface telangiectasia
(Figure 13.11).
Morpheaform. These are often whitish, scar-like, depressed, firm plaques, and are so named because
of their supposed resemblance to localized scleroderma.
Superficial. These take the form of variably sized, thin, pink, scaling plaques with a well-defined,
fine, thread-like border and telangiectasia. They often occur on the trunk and limbs.
Fibroepithelioma of Pinkus. Resembling a skin tag, long strands of interwoven basiloma cells are
embedded in fibrous stroma.
Investigations Dermoscopy: Shows arborizing vessels, starburst pattern at periphery, and leaf-like
structures.
FIGURE 13.9 Nodular BCC presenting as an erythematous scaly nodule with telangiectasias.
FIGURE 13.10 Ulcerative BCC (rodent ulcer) near the medial canthus of the eye.
Histopathology: Clumps of small basophilic epidermal cells occupy the upper dermis with the
outermost cells often being more columnar and arranged in a palisaded pattern. Variable amounts of
mucinous stroma can be seen. Many mitotic figures may be seen among the mass of basal cells, as may
many degenerate cells. Laser-induced fluorescence spectroscopy is an emerging diagnostic technique
for the diagnosis and demarcation of BCC.
Differential diagnosis: Dermal melanocytic nevi, trichoepithelioma, dermatofibroma for nodular
type; SCC and painless firm ulcers for ulcerative type; superficial spreading and nodular melanoma for
pigmented type; morphea or superficial scar for morphoeic; Bowen’s disease for superficial type.
Course and complications: Basal cell carcinomas rarely metastasize, but untreated, they are pro
gressively and inexorably destructive to local tissues. As a majority of lesions occur on the head and
neck, especially the face, effective treatment of these lesions is essential to prevent unsightly and
unnecessary destruction of facial features. Untreated periocular basal cell carcinomas may spread to
involve the orbit and even extend into the brain.
FIGURE 13.11 Pigmented BCC presenting as a pigmented plaque with raised beaded margin.
Treatment Depends upon the anatomic location and histologic features.
• Surgical: For the majority of facial lesions with clinically well-defined margins, the treatment of
choice is surgical excision with a 3-mm margin around the tumor, which should be further
defined by curettage prior to excision.
Where the margins of the tumor are ill-defined, when the tumor has recurred after previous treatment
or where smaller surgical margins are desired for technical or aesthetic reasons, the tumor should be
removed and the margins should be examined using Mohs’ micrographic surgery, which has the highest
cure rates for all forms of basal cell carcinoma.
Curettage and cautery or electrodessication is a common and successful technique for treating basal
cell carcinomas on extremities and trunk and when tumor growth is non-aggressive. Cautery or elec
trodessication is used to obtain haemostasis and to destroy an additional layer of tissue.
Radiotherapy is an effective treatment but also depends on accurate identification of the clinical
margins of the tumor. It is rather time-consuming, expensive and leaves a wound, which is slow to heal
and with time becomes atrophic and unsightly. For these reasons, as the skills of dermatological sur
geons have increased, radiotherapy has become a less popular choice.
At non-critical (non-facial) sites, a variety of additional therapeutic options exist, including topical
chemo- or immunotherapy with 5-fluorouracil or imiquimod, cryotherapy with liquid nitrogen, or
photodynamic therapy.
For metastatic BCC, good results have been seen with chemotherapy with cisplatin and paclitaxel.
Vismodegib, a specific oncogene inhibitor, is a new drug approved for the treatment of advanced
BCC where radiation is contraindicated or lesions are inoperable.
Basal cell naevus syndrome (Gorlin’s syndrome)

This is a rare, autosomal, dominantly inherited condition in which multiple pigmented basal cell car
cinoma lesions develop as part of a multi-system disorder.
Incidence: Occurs mostly in whites but also occurs in people of color.
FIGURE 13.12 Basal cell naevus syndrome presenting as multiple BCCs on the face of an elderly man.
Pathogenesis: Mutations in the PTCH1 gene are responsible for Gorlin’s syndrome. The PTCH1 gene
is a tumor-suppressor gene, which prevents cells from proliferating too rapidly or in an uncontrolled way.
Clinical features: The three characteristic abnormalities are tumors like BCC, palmoplantar pits, and
odontogenic cysts of the jaw. Multiple basal cell carcinomas may start to develop in the second decade of
life and erupt in large numbers in succeeding years. Less severely affected individuals start to develop
them later in life and develop fewer lesions (Figure 13.12). The lesions are mostly pigmented and may
occur anywhere on the skin surface, to the inexperienced observer many of these basal cell carcinomas
have the appearance of small naevi. Small pits may be found on the palms (more easily seen if the hands
have been soaked in water for a few minutes beforehand), but otherwise, there are no skin abnormalities.
A series of skeletal anomalies are also present in the majority of patients, including mandibular cysts
and bifid ribs. In addition, patients have a high incidence of benign ovarian, central nervous system, and
spinal tumors.
Treatment: Individual lesions should be removed as necessary. In general, lesions on the face should
be excised – if necessary with Mohs micrographic surgery. At non-facial sites, a variety of other treat
ments may be more practical, particularly when there are very large numbers present and new lesions are
continuing to appear. Curettage and cautery, cryotherapy, photodynamic therapy, and topical che
motherapy – with products such as imiquimod – can be considered. Radiotherapy should be avoided – it
may lead to more tumors in the periphery of the irradiated field. The administration of systemic retinoids
will reduce the number of lesions and the rate of appearance of new basal cell carcinomas. Vismodegib is
effective for the treatment of keratocystic odontogenic tumors and basal cell carcinomas.
Xeroderma pigmentosum
Xeroderma pigmentosum is the name given to a group of rare, inherited disorders in which there is a
faulty repair of damaged DNA and the development of numerous skin cancers.
Incidence: It has been estimated that the incidence of xeroderma pigmentosum is 1 in 250,000 but in
some areas, such as parts of the Middle East, the condition is unusually common.
Pathogenesis
Clinical features: The phenotypic expression depends on the particular genetic abnormality responsible,
but in all types, pre-neoplastic and neoplastic lesions including actinic keratoses, squamous cell carci
nomas, basal cell carcinomas, and melanomas develop from childhood, and in the worst cases cause death
in late adolescence or early adult life. The development of skin cancers is accompanied by severe pho
todamage (Figure 13.13). In one severe recessive variety known as the de Sanctis–Caccione syndrome,
there are also crippling neurological defects, including cerebellar ataxia and intellectual impairment.
Treatment
Management is directed to genetic counselling, removal of neoplastic lesions as they occur, and pre
vention of further photodamage by advice and sunscreens. Addition of DNA repair enzymes (photolyase
and endonuclease) to traditional sunscreens may lessen UVR-induced molecular damage. The use of
systemic retinoids may reduce the rate of development of new cancers.
Melanoma skin cancer

Melanoma is a malignant tumor of melanocytes, affecting most commonly the photoexposed parts. It
accounts for less than 5% of all skin cancers diagnosed but the disease burden is significant as more than
50,000 deaths occur annually from it worldwide.
FIGURE 13.13 Multiple freckles, actinic keratosis and FIGURE 13.14 Lentigo maligna in a female presenting
keratoacanthoma in a girl with xeroderma pigmentosum. as a pigmented macule with variegated colors.
Lentigo maligna (Hutchinson’s freckle)

Incidence: Equal in males and females; older populations and outdoor workers are affected.
Clinical features: Lentigo maligna is a slowly progressive, pre-neoplastic disorder of melanocytes,
which develops insidiously on exposed areas of skin, particularly the skin of the face. The lesion itself is
a pigmented macule with a well-defined, rounded or polycylic edge, which may be up to 5 cm in
diameter or even larger (Figure 13.14). A characteristic feature is the varying shades of brown and black
contained within the lesion – a feature known as variegation.
Investigations: Dermoscopy and skin biopsy help in diagnosis. There are many abnormal, often
spindle-shaped, melanocytic clear cells at the base of the epidermis and clumps of melanin pigment in
the upper part of the dermis. As the disease progresses, clumps of abnormal melanocytes appear,
projecting into the dermis, and a dense infiltrate of mononuclear cells develops.
Differential diagnosis: Seborrhoeic wart, simple senile lentigo, and pigmented solar keratosis.
Course and complications: The disorder is usually slowly progressive over a period that may be in excess
of 20 years. If left untreated, a true malignant melanoma develops within the lentigo maligna, which then has
the characteristics of a typical malignant melanoma. Amelanotic melanoma may develop within lentigo ma
ligna and so any nodular component, whatever the color, should be treated with suspicion.
Treatment: This is dictated by the size and exact site of the lesions. Wherever possible, surgical
excision is the treatment of choice. However, they may be of a considerable size and alternative
treatments may be required. These include locally destructive measures, such as curettage and cautery,
and radiotherapy. Cryotherapy should be avoided because it may create non-functioning but viable
melanocytes, which may recur without pigmentation to indicate their return. Imiquimod cream has been
reported to be effective in some cases. Follow-up is advised after these non-excisional treatments in
order to detect recurrence of the lesion; even after surgical excision, it is not uncommon for further
lentigo maligna to develop in the vicinity of the original lesion or in other areas of skin. This can be
considered part of a ‘field effect’ of susceptibility to the lentiginous atypia.
Malignant melanoma
Melanoma is an invasive, neoplastic disorder of melanocytes in which the tendency is for invasion
either horizontally and upwards into the epidermis or vertically downwards. Different patterns are
described: superficial spreading malignant melanoma (SSMM), nodular malignant melanoma (NMM),
acral lentiginous malignant melanoma, and desmoplastic malignant melanoma.
Incidence: Malignant melanoma is rare before puberty but can occur at any age after that. It is
seen in all racial types, but is more common in fair-skinned, Caucasian types. The rates of melanoma
are 20 times more common in whites than in African-Americans with the overall lifetime risk of
getting it being about 2.4% for whites, 0.1% for blacks, and 0.5% for Hispanics. Acral lentiginous
melanoma seems most frequent in black-skinned individuals and subjects of Japanese or other Asian
descents.
Pathogenesis: Solar UVR is believed to be the single-most important causative factor, but, as up to 50%
of lesions of malignant melanoma occur on non-sun-exposed sites, other factors may play a role. The
propensity for patients with the dysplastic mole syndrome and large congenital melanocytic naevi to develop
this condition suggests that developmental factors may also be involved in some instances. Other risk factors
for the development of melanoma include melanocortin-1 receptor genotype, childhood cancer history,
immunosuppression, indoor tanning and Parkinson’s disease. Mutations in the Kit gene stimulate various
pathways like MAPK, PI3K, PTEN, and MITF in melanocyte proliferation.
Clinical features: Some 50% of lesions of malignant melanoma develop from a pre-existing
melanocytic naevus, and the other 50% develop de novo on any part of the skin surface. Any pig
mented lesion that suddenly develops or any change in the size, shape, or color of a pre-existing
pigmented lesion should be suspected of being a malignant melanoma. Particular signs that are va
luable in the recognition of these lesions are irregularity in the margin or in the degree of pigmen
tation, and erosion or crusting of the skin surface (Figures 13.15 and 13.16). Itchiness of the lesion is a
not uncommon symptom in malignant melanoma.
Melanoma can be classified as in Table 13.1. Late local signs are the development of satellite pig
mented (and non-pigmented) nodules and enlargement of the regional lymph nodes. Redness and other
signs of inflammation may be present, but benign compound moles may also become inflamed, and
inflammatory change by itself is not common in malignant melanoma.
The rate of progress of the disease seems largely determined by the inherent biology of the malignant
melanoma. When the lesion spreads horizontally (SSM), they tend to be noted and treated earlier than when
the predominant direction of growth is vertically downwards (nodular malignant melanoma – NMM). It is,
FIGURE 13.15 Melanoma with eroded surface developing in a previous mole.

FIGURE 13.16 Nodular melanoma developing on the trunk in a boy with giant congenital melanocytic naevus.
TABLE 13.1
Classification of melanoma
De novo melanoma Melanoma arising from precursors
Melanoma in situ (MIS) Dysplastic naevomelanocytic naevi
Lentigo maligna melanoma (LMM) Congenital nevomelanocytic naevi
Superficial spreading melanoma (SSM) Common nevomelanocytic naevi
Nodular melanoma (NM)
Acral-lentiginous melanoma (ALM)
Melanoma of the mucous membrane
Desmoplastic melanoma
therefore, not surprising that the overall prognosis is much better for SSM than for NMM. The single most
important determinant of prognosis appears to be the depth of invasion into the dermis, but this is really a
proxy measurement for the overall tumor mass. Thus, patients with small lesions of less than 1 mm invading
into the dermis have an expected 5-year survival rate of 95%. Because of the significance for the prognosis
of the depth of invasion into the dermis, various classifications based on microscope measurements have
been developed. The two most common are the Breslow thickness technique and the Clark staging method.
In the Breslow technique, the maximum depth of malignant melanocytes is measured from the granular cell
layer in the epidermis to the deepest cell in the dermis. Four categories are commonly described: <1 mm,
1–2 mm, 2.1–4 mm, and >4 mm. The Clark staging method recognizes five stages depending on where the
tumor reaches: stage 1 being confined to the epidermis, and stage 5 including infiltration of the subcutaneous
fat. Stages 2, 3, and 4 describe progressively deeper levels within the dermis.
Investigations: Melanomas can be detected early by the ABCDE rule (Table 13.2). Dermoscopy:
plays a very important role in the early detection of melanoma. Skin biopsy: on histopathological
examination, there are clumps of abnormal melanocytes at the dermoepidermal junction. In SSMM,
abnormal melanocytes tend to invade upward into the epidermis and horizontally along the epidermis. In
NMM, there are groups of abnormal cells invading vertically downwards (Figure 13.17). There is
usually some accompanying inflammatory cell infiltrate. Immunohistochemistry and fluorescent in situ
hybridization, utilizing various antibodies like S100, HMB-45, Melan-A, and MART-1 help in the
diagnosis of cutaneous melanoma.
Differential diagnosis: Melanocytic naevus, pigmented basal cell carcinoma, dermatofibroma, and
vascular malformation.
FIGURE 13.17 Clusters of melanin-producing tumor cells infiltrating the dermis in a melanoma. (H&E ×100).
Course and complications: Spread of malignant melanoma is local, regional, and distant. Distant
metastases occur by haematogenous spread. Haematogenous metastases may occur anywhere, but quite
commonly they develop in the lungs, liver, and brain. Regional spread is via the lymphatics to regional
lymph nodes. When regional lymph node metastases have been found, the 5-year survival rate is less
than 25%, and when distant metastases have occurred, the comparable figure is around 5%.
Secondary satellite lesions develop around the primary malignant melanoma in many instances. When
metastases are widespread, the production of melanin pigment and its subsequent release into the cir
culation may be sufficiently great to result in a generalized darkening of the skin and even excretion of
melanin in the urine (melaninuria), although this is quite rare. Occasionally, regression of part of the
lesion occurs and, rarely, the entire lesion and metastases may undergo spontaneous resolution.
Overall, men have a worse prognosis than women. Back lesions in men and leg lesions in women
have the least favorable prognoses.
Treatment: Melanoma development can be prevented by limiting exposure to UVR by using
sunscreens and protective clothing. Regular screening of the moles by ABCDE rule and dermoscopy is
advisable. Long-term use of aspirin may be associated with a reduced risk of melanoma.
Surgery: The definitive treatment is wide surgical excision with a generous margin of normal skin
(Table 13.3). Sentinel lymph node biopsy is an experimental technique in which a radioactive tracer is
injected at the site of the previous melanoma and then followed to the first ‘sentinel’ lymph node. This node
is excised and examined for evidence of melanoma. If present the other lymph nodes within the lymph node
basin are removed. It is proposed that early removal of the lymph nodes in patients in whom the sentinel
node is involved may be advantageous compared with later removal of clinically involved lymph nodes.
Immunotherapy: Various immunomodulators include phosphodiesterase-1 inhibitors (pem
brolizumab, nivolumab), cytokines (interferon-α, interleukin 2), BCG vaccine, and imiquimod cream.
Targeted therapy for melanoma by BRAF inhibitors (sorafenib), MEK inhibitors (trametinib), c-kit
inhibitors (imatinib), CTLA-4 inhibitors (ipilimumab) Chemotherapy by isolated limb perfusion and
radiotherapy have also been used.
TABLE 13.2
ABCDE rule for melanoma detection
A (asymmetry) One-half of the mole does not match the other
B (border) Borders are irregular, ragged, notched, or blurred
C (color) The color is not uniform, includes shades of brown and black
D (diameter) The spot is larger than 6 mm across
E (evolving) The mole is changing in size, shape, or color.
TABLE 13.3
Recommended margins for surgical excision
Tumor thickness Recommended margins
In situ 0.5 cm
1 mm 1 cm
1–2 mm 1–2 cm
2–4 mm 2 cm
Over 4 mm 2 cm
Neoplastic disorders of mesenchymal elements

Kaposi’s sarcoma
Kaposi’s sarcoma is a rare, multifocal, malignant vascular tumor of skin and other organs, which occurs
either as an endemic, slowly progressive disease or as a rapidly progressive disorder in the
immunosuppressed.
Incidence: The endemic type occurs predominantly in elderly males of either Jewish origin from
central Europe or of Italian origin. The rapidly progressive type occurs in patients with AIDS, parti
cularly male homosexuals, renal transplant patients, and in areas of Africa – notably Uganda.
Pathogenesis: Human herpesvirus 8, also known as Kaposi’s sarcoma-associated herpesvirus
(KSHV) is involved and causes proliferation of B cells and endothelial cells.
Clinical features: Mauve or purplish-red nodules and plaques and brownish macules develop over
the dorsa of the feet and the lower legs. These lesions are usually accompanied by swelling of the lower
legs. In AIDS patients, the clinical manifestations are similar to those of endemic Kaposi’s sarcoma, but
are much more extensive and much more rapidly progressive. Four clinical types are classic, endemic,
iatrogenic, and HIV-related.
Investigations: Histopathology: the lesions consist of abnormal, slit-like vascular channels lined with
spindle-shaped cells, a mixed inflammatory cell infiltrate, haemorrhage, and fibrosis.
Differential diagnosis: Vascular naevi, pyogenic granuloma.
Course and complications: They are slowly progressive and may not appear in other sites for many
years. It has been estimated that the mean survival time after the appearance of the first lesions is
approximately 12 years. Eventually, lesions disseminate to other parts of the skin and to the viscera.
Treatment: Wide excision, cryotherapy, radiotherapy and mTOR inhibitors like sirolimus or rapa
mycin have been used. In patients with HIV-associated Kaposi’s sarcoma, highly active antiretroviral
drugs appear to be effective at controlling the condition. Patients who are taking immunosuppressive
drugs may respond to chemotherapy with interferons, paclitaxel, doxorubicin, and etoposide.
Dermatofibrosarcoma
This is a slowly progressive neoplastic disorder of fibroblasts. It looks quite similar to a dermatofibroma
histologically and is an intracutaneous form of plaque clinically. These lesions often extend widely into
the skin and subcutaneous tissues and the clinical margins may be difficult to detect. Wide surgical
excision is necessary or Mohs’ microscopically controlled excision.
Lymphomas of skin (cutaneous T-cell lymphoma)

Mycosis fungoides
It is a multifocal, neoplastic disorder of T-lymphocytes that primarily affects the skin.
FIGURE 13.18 Infiltrated erythematous plaques on the leg in a patient with mycosis fungoides.
Incidence: Mycosis fungoides and Sezary syndrome together comprise 53% of primary cutaneous
lymphomas that occur in 1/100,000 people.
Pathogenesis: Various chemokines, cytokines, and adhesion molecules lead to lymphocyte extra
vasation and skin homing of malignant T cells.
Clinical features: This uncommon disorder starts off as a series of red macules and scaly patches
over the trunk and limbs, which gradually extend and become more prolific, but at first only cause
inconvenience because of their appearance and mild pruritus. The red patches persist, although they may
fluctuate in intensity, and eventually start to thicken and become plaques and, later still, eroded tumors
(Figure 13.18). The ringworm-like appearance of some of the early patches and the fungating plaques in
the late stages was presumably responsible for the term mycosis fungoides. In the later stages of the
disorder, lymph node enlargement, hepatosplenomegaly, and infiltration of other viscera occur.
Histopathology: Epidermotropism of the malignant lymphocytes containing cerebriform nuclei
(Pautrier’s microabscess) in the absence of spongiosis is diagnostic. Immunohistochemistry and flow
cytometry help in the identification of neoplastic T cells.
Differential diagnosis: Depends on the stage.
Course and complications: The disorder is inevitably fatal, although the rate of progress is quite
variable, with survival ranging from 2 or 3 years in some patients to 20 years in others.
Treatment: Depends on the stage. Topical steroids, nitrogen mustard, bexarotene, phototherapy,
interferons, and biologicals may be used.
Sézary syndrome
This is marked by an erythroderma that has a particularly intense erythematous color, a picture
sometimes referred to as l’homme rouge. It is accompanied by thickening of the tissues of the face,
neck, and palms. It is also characterized by the appearance of abnormal mononuclear cells circulating in
the peripheral blood. These cells, which are identified in the ‘buffy coat’, are large and have a large,
dense, reniform nucleus.
Other forms of T-cell lymphoma

i. Parapsoriasis
ii. Lymphomatoid papulosis
14
Skin problems in infancy and old age
Sumit Sethi
Rashmi Sarkar
Infancy
Functional differences
In the neonatal period and early infancy, the skin’s defences are not yet fully developed, and it is much
more vulnerable to chemical, physical, and microbial attack. The surface area–to–weight ratio is higher,
thus a greater hazard from increased absorption of topically applied medicaments. There is also a greater
rate of transepidermal water loss through intact, non-sweating skin in the newborn compared with the
adult, indicating immaturity of the skin’s barrier function.
During the early weeks of life, newborns possess the blood levels of hormones found in the mother at
birth. This may be of special significance for the sebaceous glands, which react to circulating androgenic
compounds by enlargement and increased sebum secretion.
Management problems in infancy

Medicaments are absorbed by infant skin far more easily and are more likely to cause systemic toxicity.
Topical agents that are well tolerated by adults may cause quite severe reactions in infancy because of
the lack of maturity of the skin barrier.
The ability to scratch does not seem to fully develop until around the age of 6 months, and when it
does, a rash may alter substantially because of the secondary lesions and the physical effects of
persistent scratching on the skin (lichenification) as well as the presence of infective lesions. The
inability of the infant to complain of discomfort and irritation leads to general irritability and per
sistent crying. When this continues for long periods, the parents cannot sleep and the intra-familial
emotional tension spirals upwards within the family home, necessitating attention to all those
involved.
Widespread rashes may rapidly lead to dehydration in infancy because of the greatly increased rate of
water loss through the abnormal skin. Hypothermia can develop very rapidly in young infants who have
a widespread inflammatory skin disorder. These two complications, dehydration and hypothermia, may
be prevented by anticipating and monitoring water loss with an evaporimeter and monitoring body
temperature by taking the rectal temperature. Nursing infants with severe widespread skin disease are
kept in an incubator for maintaining body temperature and hydration.
Napkin rash
This term is applied indiscriminately to any rash localizing in the napkin area. Several disorders focus
on this area, which is perhaps not surprising when we consider the physical assault provided by wearing
of napkins.
204
Skin problems in infancy and old age 205
FIGURE 14.1 Erosive napkin dermatitis; note sparing in the flexures (from Marks and Motley, 18th edition).
Erosive napkin dermatitis

This is the most common type of napkin dermatitis. Red, glazed, fissured and even eroded areas
develop on the skin at sites in contact with the napkin (Figure 14.1). The flexures are mostly spared,
because the skin in these sites is less exposed to the foul soup of urine and feces, with the convexities
commonly affected. There is often a strong ammoniacal smell when a soaked napkin is removed after
a long time. This is due to the release of ammonia as a result of the action of the urease in fecal
bacteria on the urea in the urine.
The condition responds to nursing without napkins for 2 or 3 days, but if this is not possible, more
frequent napkin changes, the use of soft muslin napkins and avoidance of abrasive towelling napkins
help, as do efficient disposables that maintain the skin surface dry. An emollient cleansing agent and a
moisturizer used two or three times per day also help. Topical 1% hydrocortisone ointment twice daily
could be used if the condition proves resistant.
This is less common than erosive napkin dermatitis. Scaling, red areas develop, mainly in the folds of
the skin, although the eruption ‘overflows’ on to other areas in the napkin area. When the condition is
severe’, other sites such as the scalp, face, and neck may be affected. The involved sites may also crack
and become exudative. The same kind of care of the napkin area as outlined earlier for erosive napkin
dermatitis should be advised. In addition, a weak topical corticosteroid in combination with broad-
spectrum antimicrobial compounds such as an imidazole (e.g. miconazole or clotrimazole) should be
used twice daily.
Napkin psoriasis
This is an uncommon, odd, psoriasis-like eruption that develops in the napkin area and may spread to
the skin outside – the flexural areas in particular. Treatment should once again be directed to better
hygiene. Weak topical corticosteroids and emollients used as indicated earlier usually improve the
condition quite quickly. The relationship with adult plaque-type psoriasis is uncertain.
Atopic dermatitis
The condition rarely starts before 4–6 weeks of age and usually begins between the ages of 2 and
3 months. It may first show itself on the face but spreads quite quickly to other areas, although the
napkin area is conspicuously spared – presumably as a result of the area being kept moist. The ability to
scratch develops after about 6 months of age and the appearance of the disorder alters accordingly, with
excoriations and lichenification. At this time, the predominantly flexural distribution of the disorder
begins, with thickened, red, scaly, and excoriated (and sometimes crusted and infected) areas in the
popliteal and antecubital fossae. The eyes are often affected, eye rubbing being the probable cause of
sparseness of eyebrows and eyelashes. It may also be the cause of corneal softening (keratomalacia) and
its deformity (keratoconus). Emollients are important in management and mothers should be carefully
instructed on their benefit and how to use them. Similarly, bathing should be in lukewarm water, with
patting dry, rather than long-lasting hot scrubs with vigorous towelling afterwards. Weak topical cor
ticosteroids only should be used – 1% hydrocortisone and 0.1% clobetasone butyrate are appropriate.
For more severely affected infants, topical tacrolimus (Protopic) or pimecrolimus (Elidel) has proved a
useful alternative to steroids.
Cradlecap
The newborn often develop a yellowish scale over the scalp with very little other abnormality apparent.
This has no special significance and usually disappears after a few weeks.
Infantile acne
It is not uncommon for infants a few months old to develop seborrhoea, comedones, superficial papules,
and pustules on the face (Figure 14.2). Deep inflammatory nodules or cysts are very uncommon but
occur rarely. These maternal androgens cause the infant’s sebaceous glands to enlarge and become more
active. When the disorder develops after infancy and is severe, the possibility of virilization due to an
endocrine tumor or adrenocortical hyperplasia has
to be considered. Other signs of androgen over
activity, such as precocious muscle development
and male distribution of facial and body hair, should
be sought as indicators of this much more serious
problem. Although the disorder usually subsides
within a few weeks, it can be unpleasantly
persistent.
Treatment with mild topical agents is usually
sufficient to control the problem, e.g. 0.25% tretinoin
gel or 2.5% benzoyl peroxide gel. Tetracyclines
should not be given as they can cause bone and tooth
dystrophy in childhood and adolescence.
Staphylococcal scalded skin syndrome

This affects infants in the first few weeks of life but
can occur in older children. There is a widespread
erythematous eruption with striking desquamation
of large areas of skin, as in a scald or burn. There
may be a slight fever and some systemic dis
turbance, but usually, the children are not severely
ill, although there is a 2–3% mortality rate. The
disorder is due to a particular phage-type of
Staphylococcus aureus (phage type II), which re
leases an erythematogenic exotoxin. This toxin can
FIGURE 14.2 Infantile acne showing numerous acne be shown experimentally to cause shedding of the
spots on the cheeks and forehead (from Marks and most superficial part of the epidermis and stratum
Motley, 18th edition). corneum in the skin of the newborn.
Treatment should be with an appropriate systemic antibiotic such as flucloxacillin. The skin should be
managed as for a burn, and concern over heat loss, dehydration, and severe infection is necessary.
Lip-licking cheilitis
Children aged 4–8 years sometimes develop an area around the mouth contiguous with the lips, which
becomes sore, red, scaly, and cracked (Figure 14.3). It is due to licking the lips and the skin around the
lips, which become irritated and dry and are then licked to moisten them, making the situation worse.
The treatment is to explain patiently the nature of the problem to mother and child and to use an
emollient on the affected area. It is often mistaken for perioral dermatitis.
Juvenile plantar dermatosis

This disorder has apparently become more common in recent years, predominantly affecting children
aged 6–16 years. It is a type of eczema that affects the soles of the forefeet and the toes. The affected
skin becomes ‘glazed’, red scaly, and cracked, and the condition tends to be very persistent. Treatment
with emollients, topical corticosteroids, and weak tar preparations is recommended, but the disorder
tends to resist treatment and eventually remits spontaneously. The exact cause of this odd skin disorder
is obscure but is been suspected to be due to the occlusive footwear (towards sports or training shoes).
Old age
There is a growing acreage of elderly skin because of the staggering increase in the proportion of the
population over the age of 60 years. The increase in longevity since the beginning of the twentieth
century is approximately equal to that seen in the human race in the previous 5000 years. We certainly
need to know more about the ageing process and its effects on the skin.
The ageing process

Generally, we distinguish between intrinsic ageing and extrinsic ageing. The latter is not true ageing, i.e.
the effects of the passage of time alone on the tissues, but the results of cumulated environmental
FIGURE 14.3 Lip-licking cheilitis.

trauma. As far as the skin is concerned, the most significant environmental trauma stems from solar
radiation in the form of ultraviolet radiation.
There are many hypotheses to account for intrinsic ageing, which range from a kind of built-in
obsolescence within the DNA molecule itself to the cumulated results of metabolic damage from the
inevitable generation of active oxygen species and free radicals. Another inexplicable aspect of
ageing is its variability. There are enormous variations in the rates at which different individuals age,
as well as major differences in the rates at which individual organs and systems age within one
individual.
Skin changes in the elderly

Structural changes
Both the epidermis and the dermis become thinner at non-light-exposed sites with the passing of the
years. The degree of thinning is variable, but, between the ages of 20 and 80, dermal thickness on the
flexor aspect of the forearm changes in men from a mean of 1.1 to 0.8 mm. The epidermis thins down
from four to five cells thick at age 20 to approximately three cells thick at age 80. The individual
keratinocytes also shrink with age, although the horn cells at the surface inexplicably increase in area.
Interestingly, the stratum corneum does not appear to change substantially in thickness during ageing
remaining approximately 15–20 µm. The papillary structure is gradually lost, and the dermoepidermal
junction flattens.
Blood vessels decrease in number with age, but thicken. Adnexal structures also decrease in size and
number with increasing age. This applies also to the hair but not always to the sebaceous glands, as on
the face they may, paradoxically, enlarge, which is sometimes clinically evident in the condition of
sebaceous gland hyperplasia.
The dermal connective tissue loses much of its proteoglycan ground substance and the collagen fibres
become mainly tough, insoluble, and heavily cross-linked biochemically. Pigment cells become fewer in
number and smaller, and Langerhans cells are also less in evidence in the skin of the elderly.
Functional changes
Wound healing is slower and may be less complete in the elderly. The aged also respond less vigorously
to chemical and physical trauma – the erythema and swelling are less marked and slower to develop.
However, it does not seem to apply to immediate hypersensitivity. Delayed hypersensitivity is depressed
and this also applies to other components of the immune response. Skin surface markings become less
prominent in the elderly and overall the surface flattens at non-exposed sites.
The activity of the pigment cells is depressed, and non-exposed areas of skin are in general paler in
the elderly than in young and mature subjects. On exposed areas of skin, melanocytes show irregular
increases in pigmentation. Sweat gland responses to heating decrease and the rate of sebum secretion
also decreases, although this is less marked than many other functions in the elderly. Sensory dis
crimination decreases in the elderly, but, unfortunately, not the sensations of itch or pain!
Skin disease in the elderly

There are very few skin disorders that are specific to the elderly. However, there are many disorders that
are more common in the aged, and others that have a different natural history and appearance.
Dry and itchy skin

As the skin ages, it becomes drier (i.e. tends to be scaly and rough) and tends to become itchier. This
tendency is heightened by:
• Low relative humidity

• Frequent hot bathing and vigorous towelling
• Low ambient temperature
The itchiness can be disabling and it is important to try to reduce the desiccating stimuli to which the
skin is exposed. The generous use of emollients as topical applications, as cleansing agents, and in bath
additives is mandatory.
Although itchiness due to dry skin in the elderly is quite common, it has to be remembered that
scabies and the other causes of generalized pruritus also occur in this age group and should be diligently
sought.
Eczema
Eczema is a common problem in one form or another in the elderly. In most cases, no cause is found for
the development of eczema, particularly in elderly people, in whom it can spread rapidly and become
extremely disabling.
• Atopic dermatitis is uncommon in the elderly.
• Discoid eczema is a form of constitutional eczema that is more common in the elderly, which
typically occurs as round coin-sized scaling patches.
• Eczema craquelée/Asteotic dermatitis is an eczematous disorder that is virtually specific to the
skin of the elderly, occurring against a background of generalized xerosis, or drying of the skin
surface.
• Photosensitive eczema is more common in elderly men and is often very persistent, causing great
difficulties in its management.
• Mild cases seborrhoeic dermatitis are very common in the elderly, and occasionally the disorder
can spread to become generalized.
Treatment
The treatment of eczema in the elderly is similar to that in other age groups but it can spread and become
generalized more quickly than in other age groups. However, emollients are even more important and
there should be greater readiness to use systemic remedies, including ciclosporin, azathioprine, and
corticosteroids.
Skin tumors
Skin tumors are a frequent reason for the elderly consulting a physician. Seborrhoeic warts are found in
virtually everyone over the age of 60 years and, although benign, often result in minor symptoms and
some cosmetic embarrassment. They can easily be removed by curettage and cautery, but when present
in large numbers, can present an insoluble problem. Although very few progress to squamous cell
cancer, they indicate that serious solar damage has occurred and that more significant lesions may
develop. They are uncommon below the age of 45 years and very common over the age of 60 years. As
with seborrhoeic warts, solar keratoses may also cause minor symptoms and some cosmetic problems.
Basal cell carcinomas are almost as common as solar keratoses. Because of their capacity for local
invasion and tissue destruction, they cause considerable morbidity. Squamous cell carcinomas are much less
common, but can metastasize as well as cause local tissue destruction. Squamous cell carcinomas of the
penis, lips, and ears have a bad reputation for metastasis. Malignant melanoma is slightly more common in
the elderly compared with young age groups, but lentigo maligna is virtually restricted to the elderly.
Management of skin disorders in the elderly

Through no fault of their own, the elderly are often physically, socially, and economically deprived.
Their housing, hygiene, nutrition, clothing, and means of heating may all be deficient, and this should be
taken into account when designing treatments. If they live alone, as is often the case, they may well be
unable to find anyone to help with the application of ointments to body parts they cannot reach
themselves or to assist with bandages because of lack of mobility.
Older patients suffer from pruritus more severely and more frequently than patients of younger age
groups. It must be remembered that the elderly may also have difficulty in hearing, understanding, and/
or remembering instructions, especially if these are complex and involve more than one medicament. If
possible, instructions on the medications should also be given to an accompanying relative or legibly
written out.
The previously mentioned potential difficulties need to be taken into account when trying to help an
elderly patient with a skin problem.
15
Disorders of keratinization and other
genodermatoses
Aparajita Ghosh
Anupam Das
Introduction
Epidermal differentiation
The epidermis is the outermost layer of the skin and is composed almost entirely of keratinocytes with a
few other cells, like melanocytes, Merkel cells, and Langerhans cells interspersed among them.
The keratinocytes transform from metabolically active, cuboidal basal cells (stratum basale) to
polyhedral cells of stratum spinosum to terminally differentiated, flattened, dehydrated, and dead cor
neocytes (stratum corneum) that are programmed to be shed off (desquamation). This complex and
finely regulated process of differentiation is called keratinization. A human keratinocyte takes about
14 days to transit from the basal layer to stratum corneum. During this transit, the cell progressively
loses its organelles and water content; there is polymerization and deposition of keratin filaments and
filaggrin in the cytoplasm just beneath the plasma membrane and dissolution of the nucleus in the
terminal stage. The end result, the stratum corneum, is a chemically and mechanically resistant barrier
composed of stacks of protein-rich, anucleate, dead cells in a continuous matrix of extracellular lipid.
Further, 14 days are required by these corneocytes to traverse the layers of stratum corneum and
subsequently desquamate (Figure 15.1). Desquamation normally leads to inconspicuous shedding of
individual corneocytes and is a controlled process involving degradation of corneodesmosomes by
various lytic enzymes.
“Scaling” is the result of abnormal desquamation leading to conspicuous, visible shedding of cor
neocytes which have failed to separate from each other.
The function of the epidermis

The epidermis, particularly the stratum corneum, acts a barrier to physical, chemical, and micro
biological insult. It prevents water loss from the underlying tissue, protects against solar injury, and
effectively prevents penetration by microbes. It provides partial protection against mechanical shearing
or stress.
Disability in disorders of keratinization

Epidermal differentiation and keratinization are complex processes, and various genetic mutations can
disrupt the usual course of maturation. The resultant altered epidermis is unable to perform its normal
functions or serve as an effective barrier. There is an increase in transepidermal water-loss, making the
skin dry and prone to irritation. Impaired immunity to microbial infections can result in frequent in
fections. The defective epidermis is also considerably less compliant and pliable compared to normal
211
FIGURE 15.1 Schematic diagram of keratinization.
epidermis, and this can often cause blistering over pressure points or limitation to movements ac
companied by pain and fissuring. However, the greatest impact of these disorders is possibly because of
the significant cosmetic disability that they cause. The skin is of primary importance in determining the
appearance of an individual, and abnormal skin can hamper the socio-economic and emotional aspects
of the life of the affected individual.
Xerosis
The term ‘xerosis’ refers to dryness of the skin, and as such does not signify any particular disease.
Xerosis often occurs or increases with age, and in the dry season. It may be worsened by repeated
washing with soaps. Xerotic skin is often more prone to pruritus and is sometimes associated with atopy.
Adequate use of emollients is helpful.
Ichthyosis
It is the name given to a heterogeneous group of non-inflammatory disorders of the skin presenting with
generalized scaling. The word is derived from the Greek word ichthys, meaning ‘fish’, and refers to the
similarity in appearance of the characteristic scales of the affected skin to the scales of a fish. The
various ichthyoses are listed in Table 15.1.
TABLE 15.1
Common ichthyoses with their mode of inheritance
Autosomal dominant ichthyoses Autosomal recessive ichthyoses X-linked ichthyoses
• Ichthyosis vulgaris • Lamellar ichthyosis • X-linked recessive ichthyosis (steroid

• Epidermolytic • Congenital ichthyosiform sulfatase deficiency)
hyperkeratosis erythroderma • Chondrodysplasia punctata
• Ichthyosis bullosa of • Harlequin ichthyosis
Siemens
Disorders of keratinization and other genodermatoses 213
Ichthyosis vulgaris (autosomal dominant ichthyosis)

This is the commonest form of ichthyosis and is inherited in an autosomal dominant fashion. The cause is a
mutation in the gene-encoding profilaggrin. The disease is more severe in individuals in whom both alleles
are affected (homozygotes or compound heterozygotes) than in those who have a single defective allele.
Clinical features
The disease is characterized by scaling, which is prominent over extensors, particularly over the shins
(Figure 15.2). The scales here are often dark-colored and polygonal in shape. A fine white scaling is
usually present over other areas of the body, like the trunk. The flexures are mostly spared. The affected
individuals often have hyperlinear palms, thickening of the skin (keratoderma) of palms and soles, and
keratosis pilaris (Figure 15.3). Asthma, atopic dermatitis, and other manifestations of atopy are fre
quently associated. Symptoms are worse during the winter when the climate is dry.
Pathology and aetiopathogenesis

Profilaggrin is a precursor of the protein filaggrin, which is important for aggregation of keratin fila
ments and retention of water in the keratinocytes. Filaggrin is a component of the keratohyaline
granules. Mutations in the profilaggrin gene lead to decreased synthesis of profilaggrin with a resultant
decrease or absence of filaggrin in the keratinocytes. Histopathology shows mild hyperkeratosis with a
diminished or absent granular layer. The keratohyalin granules are absent or are abnormal in shape and
small, as shown by electron microscopy.
Treatment
Emollients and humectants are the mainstays of treatment. Topical keratolytic agents like urea and
salicylic acid preparations increase desquamation and decrease the prominence of scales.
FIGURE 15.3 Keratosis pilaris with plugging of the

hair follicle.
FIGURE 15.2 Moderately severe scaling in

autosomal dominant ichthyosis (from Marks
and Motley, 18th edition, with permission).
X-linked recessive ichthyosis

This is a relatively uncommon form of ichthyosis caused by the deficiency of the enzyme steroid
sulfatase. Because of an X-linked recessive pattern of inheritance, a majority of the affected individuals
are males. Females act as carriers of the mutation.
Clinical features
The disease is usually more severe than ichthyosis vulgaris. Scales are larger and dark brown in color
and predominantly affect extensors. However, there might be significant involvement of the flexures in
many cases. The face and neck are often involved, leading to significant cosmetic impairment. Corneal
opacities, cryptorchidism, and increased incidence of testicular cancer are observed in affected males.
Pathology and aetiopathogenesis

The cause is a mutation in the steroid sulfatase gene located on Xp22 chromosome. This leads to a
decreased or absent activity of the enzyme steroid sulfatase in most tissues. In the epidermis, this results
in the accumulation of cholesterol sulfate, leading to abnormal desquamation. The fetal adrenal hor
mones are desulfated to estrogens by the steroid sulfatase present in the fetal placenta. Deficiency of the
enzyme in the fetal placenta leads to decreased levels of estrogen and failure or difficulty in initiation or
progress of labor in case of a male fetus.
Histopathology shows orthokeratotic hyperkeratosis. The granular layer is increased. The epidermis
shows acanthosis and papillomatosis.
Treatment
Emollients and keratolytics may be used in the management of milder cases. More severe cases can
benefit from the use of systemic retinoids.
Autosomal recessive congenital ichthyosis (ARCI)

It is a spectrum of disorders inherited in an autosomal recessive pattern. In the majority of the cases, the
disorder manifests at birth. The baby may be born encased in a taut, parchment-like membrane (col
lodion baby). Subsequently, the individual may develop large, plate-like scales without any redness of
skin (lamellar ichthyosis) or generalized fine white scaling with erythroderma (congenital ichthyosiform
erythroderma). However, many individuals develop features overlapping with both these entities.
The underlying genetic defect is not well-characterized, and several different genes encoding for
proteins involved in cornified envelope formation, membrane transport, etc., have been implicated. As
such, ARCI appears to be a genetically heterogeneous group.
Lamellar ichthyosis (LI)

The disorder is characterized by large dark plate-like scales with minimal erythema of the skin
(Figure 15.4). The scales are tightly adherent to the skin, and, in severe cases, cause scarring alopecia
with loss of scalp hair, ear deformity, and ectropion and eclabium due to traction on eyelids and lips.
Sweating may be impaired, leading to heat intolerance.
Histopathology shows mild to moderate acanthosis with orthokeratotic hyperkeratosis.
Treatment
Oral retinoids are the only effective modality of treatment and have to be given for long periods.
Emollients provide symptomatic relief. Patients with ectropion also require eyecare with lubricants and
artificial tears to prevent corneal ulcers.
FIGURE 15.4 Lamellar ichthyosis with large plate-like scales.
Congenital ichthyosiform erythroderma (CIE)

This condition presents with generalized redness of the skin with fine, white scales (Figure 15.5). Large,
plate-like scales, as seen in lamellar ichthyosis, are usually absent. Histopathology shows acanthosis and
hyperkeratosis with parakeratosis.
Epidermolytic hyperkeratosis (EHK)

This condition, earlier known as bullous ichthyosiform erythroderma, is inherited in an autosomal
dominant pattern. The cause is usually a mutation in genes encoding for keratin 1 or keratin 10.
The disease becomes apparent at birth with blistering, redness, and peeling of skin at sites of trauma.
With age, the blistering improves but hyperkeratosis develops. The hyperkeratosis is usually severe and
malodorous due to infection by mixed microbial flora and is more prominent over joints (Figure 15.6).
There are several clinical phenotypes of the disease. The disease may present in generalized, localized,
or nevoid forms. Palms and soles may be involved in certain clinical types.
Histopathology is classical. There is vacuolar degeneration (epidermolysis) of the suprabasal kera
tinocytes accompanied by severe hyperkeratosis.
Systemic retinoids are the only effective treatment, especially for the generalized or severe forms of
the disease.
The comparative features of various ichthyoses have been summarized in Table 15.2.
Collodion baby
This is a condition where the baby is born encased in a taut, parchment-like membrane. The similarity of
the membrane to ‘collodion’ lends the name to this condition. The membrane subsequently fissures and
peels off but leads to impaired barrier function, water loss, and improper temperature regulation. The
FIGURE 15.5 Non-bullous ichthyosiform FIGURE 15.6 Epidermolytic hyperker

erythroderma (from Marks and Motley, 18th atosis showing typical severe hyperkeratosis
edition, with permission). and scaling (from Marks and Motley, 18th
tightness of the membrane sometimes leads to restrictions in movement, respiration, and sucking. The
condition is classically associated with autosomal recessive ichthyosis but may be the presenting feature
in certain other keratodermas and Gaucher’s disease. Very rare cases of self-healing collodion baby
have been described wherein after peeling off the collodion membrane the skin develops normally. The
various conditions associated with collodion membrane at birth are listed in Table 15.3.
Treatment
Such babies need to be carefully monitored for any signs of dehydration, infection, and hypo- or
hyperthermia. They are preferably nursed in a warm and humidified environment. Bland emollients may
be used to keep the membrane soft and pliable and facilitate desquamation and healing.
Harlequin fetus
The child is born encased in thick plates of skin with deep fissures, which form a geometric pattern.
There is striking ectropion and eclabium and the ears are poorly developed. The condition is fatal and
most die within a few days after birth, though very rare cases of survival with oral retinoid therapy have
been reported.
Acquired ichthyosis
Ichthyosis may sometimes develop later in life, secondary to various systemic causes. The causes of
acquired ichthyosis are summarized in Table 15.4.
TABLE 15.2
Comparative features of certain common ichthyoses
Ichthyosis vulgaris X-linked recessive ARCI (lammellar Epidermolytic
ichthyosis ichthyosis and hyperkeratosis
congenital ichthyosiform
erythroderma)
Mode of Autosomal X-linked recessive Autosomal recessive Autosomal dominant
inheritance dominant
Mutation Filaggrin gene – Steroid sulfatase TGM1, ABCA12, Keratin 1,10
absence of ALOXE3, ALOX12B
filaggrin
Characteristics of Fine, white, flaky, Fine to large scales Large, thick, plate-like Brown verrucous
scales and larger on brown scale (LI) scales, may be
lower limbs fine, white, generalized porcupine-like
scales with (hystrix)
erythroderma (CIE)
Flexural Spared Involved Involved Predominantly
involvement involved
Onset Infancy or At birth or infancy At birth At birth
childhood
Collodion Absent Absent Present Absent
membrane
Associated Keratosis pilaris, Cryptorchidism, comma Scarring alopecia, Blistering at birth,
features hyperlinear palms shaped corneal ectropion, eclabium, frequent infections
and soles, atopy opacity, h/o prolonged heat intolerance (LE), leading to bad odor
labor decreased sweating and
heat intolerance (CIE)
Other disorders of keratinization

Keratosis pilaris
It is characterized by plugging of hair follicles, sometimes with perifollicular erythema, predominantly
affecting the extensor aspect of upper arms, thighs, and buttocks. It is common in children and ado
lescents, and in a majority of cases, it is physiological. Keratosis pilaris is often associated with ich
thyosis vulgaris and atopic dermatitis. Rarely, a variant of keratosis pilaris followed by atrophy is seen
to involve eyebrows, scalp, and cheeks.
TABLE 15.3
Disorders presenting with collodion membrane at birth
Autosomal recessive congenital ichthyosis
X-linked hypohidrotic ectodermal dysplasia
AEC (Ankyloblepharon – Ectodermal defect – Cleft lip and palate) syndrome
Chondrodysplasia punctata
Loricrin keratoderma
Trichothiodystrophy
Neutral lipid storage disorders
Gaucher’s disease
Self-healing collodion baby
TABLE 15.4
Causes of acquired ichthyosis
Physiological – old age
Malignancies – Hodgkin’s lymphoma; non-Hodgkin’s lymphoma; mycosis fungoides; carcinoma of breast, lungs, cervix
Acquired immunodeficiency syndrome
Autoimmune disease – SLE, dermatomyositis, mixed connective tissue disorder
Endocrine causes – hypothyroidism, diabetes mellitus
Bone marrow transplant
Sarcoidosis
Drugs – lipid-lowering agents, clofazimine, butyrophenone, allopurinol, hydroxyurea
Nutritional deficiency, malnutrition, malabsorption states
Treatment
Topical retinoids and keratolytics like salicylic acid and urea can improve the condition.
Darier’s disease (keratosis follicularis)

It is an autosomal dominant disorder, though sporadic cases are common. The causative mutation lies in
the ATP2A2 gene, which codes for SERCA 2, a calcium transporter.
Clinical features
The disease starts around puberty and is characterized by the eruption of dirty looking, greasy, keratotic
papules over face, scalp, ears, neck, upper chest, and back (Figure 15.7). The papules may coalesce to
form plaques and may become infected and malodorous. The condition usually worsens in summers.
Palms and soles show pitting and nails show characteristic red and white longitudinal stripes with a
v-shaped indentation at the free edge.
Histopathology
Histopathology is characteristic and shows suprabasal clefting due to acantholysis. There is abnormal
keratinization of individual keratinocytes (dyskeratosis), leading to eosinophilic bodies called corps
ronds and grains.
Treatment
Avoidance of sunlight and heat may help in reducing exacerbation of the disease. For limited lesions,
topical retinoids like tazarotene and keratolytics like urea are helpful. Oral retinoids are effective in case
of widespread disease.
Hailey Hailey disease (benign familial pemphigus)

This is an autosomal dominant disorder due to mutation in the ATP2C1 gene. It is clinically char
acterized by vesicles, hypertrophic vegetating plaques, and painful erosions over flexures (Figure 15.8).
The disease worsens due to heat and sweating. It usually appears in the third to fourth decade of life and
as such shows a waxing and waning course. Histopathology shows acantholysis of keratinocytes giving
rise to a ‘dilapidated brick wall’ appearance. Dyskeratosis is usually not very prominent.
FIGURE 15.7 Brown keratotic papules on the trunk in Darier’s disease (from Marks and Motley, 18th edition, with
permission).
Palmo-plantar keratoderma (tylosis)

This group of disorders, which are clinically and genetically heterogeneous, is characterized by ab
normal thickening of the skin of palms and soles. The thickening may involve the whole of palms and
soles (diffuse) or may be focal or punctate. It may occur alone or may be accompanied by skin lesions
elsewhere or involvement of other organs of the body.
Pachyonychia congenita types I and II

These are rare autosomal dominant disorders that show plantar keratoderma at pressure points, with
occasional blistering and subungual hyperkeratosis. Hair and teeth anomalies may be present. The
mutation lies in genes encoding for Keratin 6 (a & b), 16, and 17.
Other genodermatoses
Tuberous sclerosis
It is an autosomal dominant disorder caused by mutations in TSC1 or TSC2 gene encoding for the
proteins ‘hamartin’ and ‘tuberin’, respectively. The disease is characterized by hamartomatous tumors
involving the skin, brain, eyes, kidneys, heart, lungs, and other organs of the body. Cortical tubers and
subependymal nodules are often found in the brain. Patients may present with epilepsy, mental re
tardation, or behavioral changes. Skin lesions are often diagnostic and include multiple ‘ash leaf’ hy
popigmented macules, facial angiofibromas, fibrous plaques on the forehead, and shagreen patch over
the lower back or buttocks. Nail involvement is common and is in the form of subungual and periungual
FIGURE 15.8 Hailey Hailey disease showing vegetating plaques and painful erosions affecting the axilla.
fibromas (Koenen’s tumors) with resultant longitudinal grooving of the nail plate. Gingival fibromas and
hyperplasia with dental pitting are frequently seen.
Neurofibromatoses
These are a group of autosomal dominant disorders, of which NF1 (von Recklinghausen’s disease) and
NF2 are the commonest. Rarely, segmental NF1 and familial café-au-lait macules without neurofi
bromas have been reported.
NF1 is caused by decreased levels of neurofibromin, due to mutation of the NF1 gene. The presence
of multiple brown macules (café-au-lait macules), axillary and intertriginous freckling, and neurofi
bromas, which are benign nerve sheath tumors are characteristic of this disorder. Neurofibromas arising
from peripheral cutaneous nerves appear as soft, skin-colored, pedunculated masses protruding from the
FIGURE 15.9 Neurofibromas: soft, skin-colored, pedunculated masses protruding from the skin surface in a case of NF1.
skin surface and result in significant cosmetic disability (Figure 15.9). Lisch nodules in the iris are
diagnostic. Optic nerve tumors and bony lesions like hypoplasia of the sphenoid wing, pseudoarthrosis
of the long bones, and scoliosis due to vertebral involvement are common causes of morbidity. These
patients are also at an increased risk of developing a variety of neoplasms like pheochromocytoma,
rhabdomyosarcoma, chronic myelomonocytic leukaemia, etc.
NF2 is less common and is caused by mutations in the gene which codes for a protein “merlin”. This
condition is characterized by vestibular schwannomas and a variety of central nervous system tumors.
Anhidrotic/Hypohidrotic ectodermal dysplasia

This rare condition is inherited as an X-linked recessive disorder. The affected males present with sparse
and fine scalp hair, frontal bossing, saddle deformity of nose, and peg-shaped or abnormal teeth. The
eccrine sweat glands are absent, leading to absent or severely reduced sweating with resultant heat
intolerance.
16
Metabolic disorders and
reticulohistiocytic proliferative
disorders
Soumya Jagadeesan
Porphyrias
Porphyrias are rare disorders caused by defects in haemobiosynthesis. Most of them are inherited and
many of them have specific cutaneous manifestations due to the phototoxic effects of porphyrins (haem
precursors), which accumulate in these disorders. Traditionally, these disorders are classified into he
patic and erythropoietic forms, depending upon the sites where the defective enzymes are expressed.
However, from a clinician’s point of view, it is more appropriate to classify them as acute and non-acute
forms, depending on the presence or absence of acute neurological attacks. The important porphyrias are
summarized in Table 16.1.
Porphyria cutanea tarda

Porphyria cutanea tarda (PCT) is the most common of all porphyrias and results from the deficiency of
uroporphyrinogen decarboxylase (UROD) enzyme, the fifth enzyme in the haem biosynthesis pathway.
(A schematic diagram representing haemosynthesis and the enzymes involved is given in Figure 16.1.)
This results in the accumulation of haem precursors, called uroporphyrins and coproporphyrins, in the
blood, stool, and urine. These substances are responsible for photosensitization. This enzyme defect is
acquired/sporadic and is seen only in the hepatocytes in the majority of the cases; however, inherited
forms where the enzyme defect is present in all tissues also do occur. A wide variety of factors,
especially hepatotoxins, are known to trigger the clinical features of PCT, including alcohol, estrogens,
iron, polychlorinated hydrocarbons, and viral infections, like hepatitis C and HIV.
Clinical features
The disease onset is usually in the third or fourth decade of life, though it may present earlier in the
familial forms. The characteristic features are seen in the light-exposed areas. In the early stages of the
disease, blistering and fragility of the skin on the face and backs of the hands are noted (Figure 16.2).
The affected areas also develop an odd pigmented and mauve, suffused appearance. Later, increased
hair growth occurs on the involved skin and a sclerodermiform thickening of the skin develops.
Erosions, crusting, and scarring are also seen in the affected areas. The patients often experience
worsening in summer but may not correlate the skin changes with sun exposure as the burning sensation
accompanied by severe photosensitivity seen in erythropoietic porphyrias is not seen here.
222
Metabolic disorders and reticulohistiocytic proliferative disorders 223
TABLE 16.1
Summary of the important porphyrias
Disease Inheritance Incidence Age of onset Clinical features
Porphyrias with cutaneous disease alone
Porpyhria cutanea AD, sometimes Commonest type Third–fourth Moderate–severe photosensitivity,
tarda acquired decade vesicles, and bullae, milia,
hypertrichosis, scarring in the
sun-exposed areas
Congenital AR Rare Infancy or the Severe–very severe
erythropoietic first decade photosensitivity, vesicles,
porpyria of life bullae, hyperpigmentation,
hypertrichosis, mutilation, and
scarring
Erythropoietic AD, XLD, AR Second most common Early childhood Pain following sun exposure,
protoporphyria among cutaneous urticaria, erythema, oedema,
porphyrias sometimes blistering
Cutaneous disease with acute attacks
Hereditary AD Very rare Any age Photosensitivity is rare, blistering
coproporphyria can occur
Variegate porphyria AD Common in South 15–30 years Cutaneous manifestations are
Africa indistinguishable from Porphyria
cutanea tarda. Acute attacks as
in AIP
Acute attacks only
Acute Intermittent AD More common in 10–40 years No skin manifestations. Acute
porphyria Scandinavian attacks ranging from mild
countries abdominal pain to very severe
attacks with bulbar palsy and
respiratory paralysis
AD – Autosomal dominant; AD- Autosomal recessive; XLD – X-linked dominant; AIP – Acute intermittent porphyria.
Investigations
The diagnosis is made by finding increased uroporphyrins and coproporphyrins in the urine and stool. A
plasma spectrophotometry peak is seen at 615–620 nm. Iron overload is also a frequent, accompanying
feature. Histologically, the blistering is subepidermal with festooning of the dermal papillae and, in the
long-standing cases, fibrosis develops and deposits of immunoglobulin are found perivascularly.
Other porphyrias like variegate porphyria, hereditary coproporphyria, milder forms of congenital ery
thropoietic or hepatoerythropoietic porphyrias and pseudoporphyrias may mimick PCT. But a careful
examination of urine, stool, and plasma porphyrins is helpful in identifying PCT.
Treatment
The objective is to reduce the circulating levels of porphyrins. This is achieved by regular venesection –
removing a pint of blood at a time – every 2 or 3 weeks, or by the use of low doses of the antimalarial
drug chloroquine orally, resulting in the secretion of large amounts of porphyrins in the urine.
Photoprotection plays an important role in controlling the symptoms before specific therapies take
effect. Regular monitoring of liver function and regular ultrasounds and alpha-fetoprotein levels is
essential to detect hepatic carcinoma at a treatable stage.
FIGURE 16.1 Schematic diagram representing haemo-synthesis and the enzymes involved. Haemo-synthesis pathway
illustrating the enzyme defects in the various porphyrias. ALA, Aminolevulinic acid; AIP, Acute intermittent porphyria;
CEP, Congenital erythropoietic porphyria; PCT, Porphyria cutanea tarda; HC, Hereditary coproporphyria; VP, Variegate
porphyria; EPP, Erythropoietic protoporphyria.
FIGURE 16.2 Porphyria cutanea tarda; note the eroded areas in the light-exposed skin of the backs of the hands (from
Marks and Motley, 18th edition).
Congenital erythropoietic porphyria

(Gunther’s disease)
This is a very rare porphyria, causing severe muti
lating photosensitivity and haematological disease. It
is inherited as an autosomal recessive disorder due
to the deficiency of the enzyme uroporphyrinogen
III cosynthase. This enzyme is required to form the
biologically useful type III porphyrin isomers, and
the defect in this enzyme causes accumulation of
type 1 isomers (which cannot participate in haem
formation) in the erythroid precursor cells, which
later leak into the plasma.
FIGURE 16.3 Congenital erythropoietic porphyria with
erosions and scars in the face and hands (courtesy of
Dr MS Sadeep, Govt Medical College, Kottayam). Clinical features
The onset is usually in infancy itself, but a late-
onset, milder variant has also been described. Affected individuals are extremely photosensitive and
shun the light. They develop dreadful facial scarring with hypertrichosis (Figure 16.3). This combi
nation of clinical features has suggested to some that these patients provoked the fable of ‘werewolves’.
The eyes and internal organs are also frequently involved. The teeth are almost always stained brown
and fluoresce under Wood’s lamp (Figure 16.4). There may be osteopenia, pathological fractures,
vertebral collapse and resorption of the bones of the digits. The high concentration of porphyrins in
erythrocytes results in haemolytic anaemia and marrow hyperplasia. Earlier, the affected individuals
used to die by the age of 40, but now, the mortality rates have come down with the improved man
agement of complications. Haematological complications may still be fatal.
Investigations
Red cells and urine contain large amounts of type 1 isomers of uro- and coproporphyrins and feces
contain increased concentrations of type 1 isomers of coproporphyrin. Due to the presence of por
phyrins, urine shows bright pink-red fluorescence.
FIGURE 16.4 Erythrodontia in congenital erythropoietic porphyria, reddish fluorescence under Wood’s lamp (courtesy of
Dr MS Sadeep, Govt Medical College, Kottayam).
Treatment
Management involves strict photoprotection, treatment of haemolytic anaemia by hypertransfusion and
prompt treatment of secondary infections. Allogenic bone marrow transplantation from a tissue-matched
donor may be considered in the severely affected cases, as it offers a chance of long-term cure.
Erythropoietic protoporphyria
Erythropoietic protoporphyria (EPP) is a very rare, autosomal dominant disorder in which excess
protoporphyrins are produced. These protoporphyrins are detectable in the blood, and this forms the
basis of diagnostic tests. Clinically, the disorder often presents in childhood as episodes of skin soreness
and extreme pain and discomfort when exposed to the sun, unlike other cutaneous porphyrias. Physical
signs may be minimal with subtle oedema and minimal erythema. Later, fine pitted scarring is found on
exposed sites. Pigment gallstones may develop.
Porphyria variegata
This is a very rare combination of PCT and acute intermittent porphyria (AIP). Cutaneous changes
mimic a milder form of PCT and acute attacks ranging from mild abdominal pain to very severe attacks
with bulbar palsy and respiratory paralysis, as seen in AIP, may occur. The latter is caused by a
deficiency of delta-aminolaevulinic acid synthetase and is precipitated by certain drugs and anaesthesia,
among other things.
Pseudoporphyria
It is a non-porphyric dermatosis that clinically and histopathologically mimics PCT, but has normal por
phyrin levels in the urine, feces, and blood. The most common causes are photosensitizing drugs, especially
non-steroidal anti-inflammatory drugs like naproxen and nabumetone, UVA tanning beds, and hemodialysis.
Haemochromatosis (bronzed diabetes)

There are primary and symptomatic forms of this disorder. In the primary form, there is excessive gas
trointestinal absorption of iron, resulting in iron deposition in the liver, testes, skin, and pancreas.
Involvement of the skin causes a brown–grey pigmentation due to both the iron and increased melanin in
the skin. Diabetes is caused by deposition of iron in the pancreas, and cirrhosis due to liver involvement.
The condition seems to be inherited as a recessive characteristic but is much more common in men.
Secondary forms are found in conditions necessitating repeated blood transfusion and in conditions in
which there is chronic haemolysis (e.g. sickle cell disease).
Amyloidosis
‘Amyloidosis’ is the term used for a group of disorders in which an abnormal protein is deposited
extracellularly in tissues. Amyloidosis can involve the skin alone, as localized cutaneous amyloidosis or
as cutaneous manifestations of systemic amyloidosis. Systemic amyloidosis is divided into primary and
secondary forms. The latter develops after long-standing inflammatory disease, including infections
such as chronic tuberculosis and chronic osteomyelitis. It may also occur in patients with long-standing
severe rheumatoid arthritis. Skin manifestations are rare in secondary systemic amyloidosis. A classi
fication of the amyloidosis affecting the skin is given in Table 16.2.
In primary systemic amyloidosis, the abnormal protein components are synthesized by clones of
abnormal plasma cells and the condition is sometimes associated with multiple myeloma. In primary
amyloid disease, amyloid material is deposited in various organs as well as in the skin. In the skin, it is
deposited in and around the dermal capillary blood vessels, which become fragile and leaky. Swollen
TABLE 16.2
Classification of amyloidosis
Localized cutaneous amyloidosis
Primary localized cutaneous amyloidosis
Papular primary localized cutaneous amyloidosis
Macular primary localized cutaneous amyloidosis
Nodular primary localized cutaneous amyloidosis
Secondary localized cutaneous amyloidosis
Cutaneous amyloidosis due to systemic disease

Non-hereditary systemic amyloidosis with cutaneous involvement
Primary systemic or myeloma-associated amyloidosis
Secondary systemic amyloidosis associated with inflammation or tumor
Hereditary systemic amyloidosis with cutaneous involvement
Familial amyloid polyneuropathy
Hereditary systemic disease with secondary cutaneous amyloidoses
Muckle–Wells syndrome
TNF-receptor 1 associated periodic fever syndrome
mauve–purple areas develop around the eyes and around the flexures, especially after trivial trauma.
Hemorrhagic blisters, macroglossia and dystrophic nail changes may also be seen.
There are also ‘amyloid’ disorders that are restricted to the skin, called localized cutaneous amy
loidosis. In the type called macular amyloidosis, itchy, ‘rippled’, brown macular areas appear over the
trunk (Figure 16.5). It seems to be more common in women and in patients of Asian origin. Friction
and sun exposure seem to play an important role in
the development of the lesions. Lichen or papular
amyloidosis is another localized cutaneous form of
amyloidosis in which brown or pink, firm popular
or nodular lesions occur, especially over the shins
(Figure 16.6). Histologically, the deposits of ma
cular and papular amyloidosis are seen in the
papillary dermis.
Amyloid can be detected in tissue using var
ious histochemical tests. It appears as amorphous
FIGURE 16.6 Papular lesions on the shin in lichen

FIGURE 16.5 Pigmented area on the back in macular amyloidosis (courtesy of Dr Ashique KT, KIMS Alshifa
amyloid. Note the rippled pattern. Hospital, Perinthalmanna, Kerala).
eosinophilic deposits in routine Hematoxylin

and Eosin staining. Using Congo red stain,
amyloid deposits exhibit the typical ‘apple
green’ birefringence, when viewed under po
larized light. They also exhibit fluorescence
with thioflavine T and can also be demon
strated by immunohistochemical tests.
Xanthomata
Xanthomata are deposits of lipid in histiocytes
FIGURE 16.7 Yellowish plaques on the eyelids in in the skin and may be associated with normal
xanthelasma (from Marks and Motley, 18th edition). levels of lipids in the blood (normolipaemia) or
with elevated levels of serum lipids (hyperlipi
daemia). The lipidized histiocytes have a char
acteristic ‘foamy’ appearance.
Xanthelasma
Xanthelasma is a common form of xanthoma in which lesions appear as arcuate or linear yellowish soft
plaques around the eyes (Figure 16.7). The condition is not associated with hyperlipidemia in 60–70%
of patients. The lesions can be removed by surgical excision, electrocautery, or by topical treatment with
trichloroacetic acid, if the patient finds them to be a cosmetic nuisance. However, they may often recur
after treatment.
Xanthoma tuberosum
The lesions of xanthoma tuberosum are large nodules containing lipidized histiocytes and giant cells.
The nodules develop around the tendons and extensor aspects of the joints in familial hyperlipidaemia,
particularly over the Achilles tendon, the knees, and the elbows (Figure 16.8).
FIGURE 16.8 Xanthoma tuberosum affecting the elbows.

FIGURE 16.9 A typical lesion of granuloma annulare over the dorsum of the hand.
Eruptive xanthomata
These mostly develop in diabetes and any diseases associated with hypertriglyceridemia. Large numbers
of yellowish-pink papules develop rapidly over the skin, especially over the extensor surfaces of elbows,
knees, and buttocks.
Treatment
The treatment of these xanthomatous disorders is based on the treatment of any underlying disease, diet,
and the use of lipid-lowering agents.
Necrobiotic disorders
The term ‘necrobiosis’ is applied to a particular histological change in which there are foci of damage
making the dermal structure ‘blurred’ and more eosinophilic than usual. The foci are surrounded by
inflammatory cells – lymphocytes, histiocytes, and occasional giant cells.
Granuloma annulare
This is not an uncommon inflammatory disorder, often seen in children and young adults, characterized
by papules and plaques that adopt a ring-like pattern (Figure 16.9). Lesions develop on the extensor
aspects of the fingers, dorsae of the feet, hands, and wrists. Granuloma annulare (GA) tends to last for a
few months and then disappears as mysteriously as it came. Treatment is generally not indicated.
There are different types, including disseminated, papular, perforating, subcutaneous, and patch GA.
Diabetes is more common in this group of patients.
Necrobiosis lipoidica diabeticorum

This condition is seen in 0.3% of diabetics and is strongly associated with the diabetic state. It occurs
mainly on the lower legs as yellowish-pink plaques, which persist and become atrophic. It is char
acterized by necrobiotic foci histologically.
FIGURE 16.10 Seborrheic dermatitis-like

lesions with purpura in Langerhans cell
histiocytosis (courtesy of Dr Shobhana
Kumari, Government Medical College,
Kottayam).
FIGURE 16.11 Seborrheic dermatitis-like lesions in

Langerhans cell histiocytosis.
Reticulohistiocytic proliferative disorders

This is a group of poorly understood disorders that includes the proliferation of the cells of the
mononuclear-phagocyte system, including the dendritic cells. The major types include Letterer–Siwe
disease (LSD), Hand–Schüller–Christian disease (HSCD), eosinophilic granuloma (EG), xanthoma
disseminatum (XD), and juvenile xanthogranuloma (JXG).
LSD, HSCD, and EG seem to belong to the same ‘family of diseases’ in which there appears to be a
reactive proliferation of Langerhans cells, grouped together as Langerhans cell histiocytosis (LCH) and
the other entities belong to non-Langerhans cell histiocytosis (non-LCH). The revised classification of
Langerhans cell histiocytosis by the Writing Group of the Histiocyte Society is shown in Table 16.3.
TABLE 16.3
Classification of Langerhans cell histiocytoses
Single system disease
Localized Mono-ostotic bone involvement/isolated skin involvement/solitary lymph node involvement
Multiple sites Polyostotic bone involvement/multifocal bone disease/multiple lymph node involvement
Multisystem disease
Low-risk group Disseminated disease with involvement of pituitary/skin/lymph node/bone
High-risk group Disseminated disease with involvement of haemopoietic system/lung/liver/spleen
FIGURE 16.13 Yellowish lesions in juvenile

xanthogranuloma.
FIGURE 16.12 Hepatosplenomegaly in acute dis

seminated Langerhans cell histiocytosis (courtesy of Dr
Shobhana Kumari, Government Medical College,
Kottayam).
LSD is an uncommon disorder of infants and young children, characterized by a papular and scaling
eruption of flexures, trunk and scalp, with some resemblance to seborrhoeic dermatitis. Purpuric lesions
may also be seen (Figures 16.10 and 16.11). There is a dense infiltrate of cells having the ultrastructural
and immunocytochemical characteristics of Langerhans cells. There may be severe malaise and hepa
tosplenomegaly and some patients succumb (Figure 16.12). Treatment with corticosteroids and cyto
toxic agents is required.
In HSCD, abnormal Langerhans cell deposits occur mostly in the lung, pituitary, bone and orbit. In
EG, the deposits are, for the most part, limited to the bony skeleton.
Historically, LCH has been described under the names as described earlier: LSD being the prototype
of the acute, disseminated, multisystemic form that appears in infancy with an often fatal course
and HSCD being the chronic, progressive, multifocal form, usually presenting in childhood and
eosinophilic granuloma, the localized, benign form; now this classification is maintained only for
didactic purposes and LCH is mainly classified into single-system disease, multisystem disease, and
self-healing variants.
XD and JXG do not belong to the same ‘Langerhans cell’ group of disorders but are characterized by
the proliferation of the histiocytes other than Langerhans cells. JXG is the prototype of the non-LCH
group of disorders, characterized by isolated or limited numbers of yellowish-pink nodules occur in
young infants, which eventually disappear, usually by 5 years of age (Figure 16.13). Solitary, popular,
nodular, and plaque forms have been described. Systemic manifestations like ocular and visceral
involvement, bony changes and diabetes insipidus are rare in JXG, though not unknown. In XD, many
papular lesions develop on the skin, and sometimes mucosae, which often persist for long periods. The
lesions may be persistent, self-healing, or progressive. There is an association with paraproteinemias
and internal organ involvement may also be seen.
Cutaneous mucinoses
Cutaneous mucinoses are a class of disorders characterized by the deposition of mucin in the skin. They
are primarily divided into two groups: (i) primary cutaneous mucinoses, in which mucin deposition is the
main histopathological feature; and (ii) secondary mucinoses, in which mucin deposition is secondary only
an additional finding. A classification of cutaneous mucinoses is given in Table 16.4. Lichen myx
oedematosus/scleromyxedema is a prototype of idiopathic cutaneous mucinoses and is discussed next.
Scleromyxedema
Idiopathic disorders are characterized clinically by a generalized papular eruption and induration of skin
(sclerodermoid appearance) and histopathologically by the triad of mucin deposition, increased fibro
blast proliferation, and fibrosis. The exact pathogenesis is unknown; it may be associated with a
monoclonal gammopathy and has systemic implications. The age of onset is between 30 and 80 years.
There is no ethnic or sexual predilection. Scleromyxedema should be differentiated from other localized
forms of lichen myxedematosus, where the skin is the sole site of involvement. Treatment is usually
targeted against the gammopathy and can often be disappointing.
TABLE 16.4
Classification of cutaneous mucinoses
Primary mucinoses
Dermal mucinoses
Lichen myxedematosus
Scleredema
Reticular erythematous mucinoses
Myxedema in thyroid disease
Self-healing mucinoses
Papular mucinoses in connective tissue diseases
Cutaneous focal mucinoses
Digital myxoid cyst
Follicular mucinoses
Alopecia mucinosa
Urticaria like follicular mucinosis
Secondary mucinoses
Epidermal
Dermal
Follicular
17
Hair and nail disorders
Sumit Sethi
Both hair and nails are epidermal structures that originate from invaginations of the epidermis into the
skin (Figure 17.1). Hair and nails may develop signs of disorder, such as psoriasis or lichen planus, in
the absence of an obvious skin disease. In addition, there are disorders that are confined to either the hair
or the nails.
Disorders of hair (Table 17.1)
Hair loss (alopecia)

Hair loss may be diffuse over the scalp or localized to one or several sites on the scalp. The process may
be destructive and may be scarring or non-scarring in nature.
Congenital alopecia
Congenital alopecia may occur in isolation or with other congenital disorders.
Rarely, scalp hair growth is very slow and hair shaft density is low (congenital hypotrichosis).
Androgenetic (pattern) alopecia

Definition
This is a common, dominantly inherited, progressive form of alopecia, which is seen mostly in men. It
develops symmetrically at certain specific sites on the scalp and eventually causes almost complete
scalp hair loss in some patients.
Clinical features
The loss of hair starts in both temporal regions. Shortly after this bitemporal recession, thinning of the
hair and then alopecia develop over the vertex. The bald area over the vertex expands to meet
the triangular temporal bald areas until almost complete loss of hair results. There is almost always
preservation of hair growth in the small area of the occipital scalp. A general reduction in the density of
hair follicles also occurs and this may be the main feature of the disorder in women, in whom bitemporal
recession and some vertical thinning occur less commonly than in men. The condition may start as early
as in the late teens but generally presents in the third decade. Its rate of progress varies and seems
uninfluenced by environmental factors.
Pattern alopecia causes an enormous amount of psychological distress and patients will go to ex
traordinary lengths to attempt to arrest and reverse the process and/or to disguise its presence. The
233
FIGURE 17.1 Diagram of a hair follicle showing the relationship between the hair shaft, follicular epithelium, and
sebaceous glands.
TABLE 17.1
Overview of hair disorders
Hair loss Non-scarring Diffuse Ageing

Telogen effluvium
Drug-induced
Localized Male pattern baldness
alopecia areata
Mechanical causes
Scarring Trauma
Lupus erythematosus
Lichen planus
Increased hair growth (hirsuties) Constitutional
Androgenization
Drug-induced
condition is firmly embedded in popular mythology with regard to its supposed causes, which range
from dietary deficiencies to sexual excesses.

The hair follicles in the affected areas become smaller, sparser, and eventually disappear. Finally, true
atrophy of the skin occurs at the involved sites. The disorder is dominantly inherited but requires
androgenic stimulus in the form of testosterone and the passing of the years for full phenotypic ex
pression. The disorder can be precipitated by administering testosterone to female patients and is also a
sign of virilization in patients with a testosterone secreting tumor.
Hair and nail disorders 235
Treatment
The drug finasteride has been used to treat androgenetic alopecia in men with good results. Its effect is
limited to the specific testosterone receptor, which is found only in the hair follicle and prostate gland (the
drug was originally developed to treat prostatic hypertrophy). It is well tolerated and its side effects are
just higher than placebo; however, a statistically non-significant increase in the incidence of male breast
cancer has been reported in men taking the drug. The progress of pattern alopecia in men is halted by
castration, but there are few patients who would undergo the operation for this purpose. In women, the use
of an anti-androgen–prostagen combination (cyproterone acetate and ethinylestradiol – DianetteR) has
been tried and some reduction in the rate of hair loss has been claimed. The antihypertensive vasodilator
minoxidil has also been used topically, as increased hair growth was noted as a side effect from its oral
use. Although the drug may increase hair growth in 20–30% of patients, hair is lost again when treatment
stops, and the extent to which hair regrowth occurs is modest. Finasteride is contraindicated in women at
risk of pregnancy – because it would cause feminization of a male fetus and variable results have been
reported from studies in which it has been given to women with female pattern hair loss alopecia.
Hair transplantation utilizes hairs from the occipital scalp, which are harvested and reimplanted in
other areas. The best results are achieved with transplantation of single or small numbers of follicular
units, but typically 2000–3000 units have to be transplanted to achieve a reasonable outcome.
Pattern hair loss in men may be disguised in a number of ways, including:
• Wigs and toupes and hair weaving, in which the remaining hair is woven to cover the defect
• Surgical procedures such as ‘scalp reduction’, in which an area of bald scalp is excised, or hair
transplantation, in which follicles harvested from hair-containing skin in the occipital scalp are
transplanted to holes made in the bald area or advancing flaps of hair-bearing skin over bald areas
Alopecia areata
Definition
Alopecia areata is an autoimmune disorder of hair follicles causing loss of hair in sharply defined areas of skin.
Clinical features
Alopecia areata often starts quite suddenly as one or more rounded patches from which the hair is lost
(Figure 17.2). The hair loss continues for days or weeks until all the hair from the affected sites has
fallen. The individual areas vary in size from 1 cm2 to the entire scalp (alopecia totalis); rarely, the
eyelashes and eyebrows and all body hair are lost as well (alopecia universalis). Affected areas may
extend outwards and disease activity can be recognized by the appearance of so-called exclamation
mark hairs at the margin of the lesions. The condition occurs over a wide age range but seems
particularly common between the ages of 15 and 30 years.

The disorder can be associated with autoimmune disorders, such as vitiligo and thyrotoxicosis, and it
has been assumed that an immune attack is launched against components of the hair follicle. When
biopsies are taken from an actively extending patch, a dense, ‘bee swarm’–like cluster of lymphocytes
can be seen around the follicles.
Patches of baldness due to hair pulling (trichotillomania) are bizarrely shaped, not as well-demarcated as
alopecia areata, and have no exclamation mark hairs at the edge. Tinea capitis is marked by broken hairs
FIGURE 17.2 Multifocal alopecia areata.
and by a degree of redness and scaling of the scalp skin. Disorders that inflame the skin and destroy hair
follicles can usually be easily differentiated by the scarring they cause.
Treatment
Patients with a solitary patch or few patches usually do not need treatment. When the patches coalesce
to become a problem cosmetically or when there is alopecia totalis, treatment is often required by
patients. Intradermal injections of potent corticosteroids (typically 10 mg/mL triamcinolone) are the
most effective therapy, although overuse may lead to skin atrophy. It is reasonable to inject the affected
skin at 1 cm intervals, and, if necessary, repeat after a period of 3 weeks. Other less effective treatments
include potent topical steroids or systemic steroids; photochemotherapy with longwave ultraviolet ir
radiation (PUVA); dithranol; and allergic sensitization with diphencyprone. Even topical minoxidil has
been claimed to be partially successful. All of the preceding have inconvenient side effects and usually
work only while they are being given. Allergic sensitization with 1% diphencyprone causes an ecze
matous response and ‘kicks’ the follicles back to life in about half the patients. Some patients, having
experienced the side effects and frustration of the lack of efficacy of the treatments, decide to cut their
losses and disguise their disability with a wig. Sympathy and support are the most useful tools for this
depressing disorder.
Diffuse hair loss

This is predominantly a problem for middle-aged and elderly women. It is not a single entity, and its
causes include patterned hair loss, hypothyroidism, systemic illness such as systemic lupus er
ythematosus, and drug administration (particularly the anticancer drugs and the systemic retinoids).
Diffuse hair loss is also caused by telogen effluvium (see the following discussion). Ageing results in a
lower density of hair follicles, which is more obvious in some subjects than in others.
Having considered the previously mentioned possible causes, there are still some patients with ob
vious diffuse hair loss for whom there is no adequate explanation. Various deficiency states (particularly
iron) have been incriminated, but in the majority of instances, the supposed deficiency appears to have
no other sequel, and attempts at its rectification fail to improve the clinical state.
If there is no obvious cause for diffuse hair loss, the only medical treatment available is topical
minoxidil, but this is unlikely to give a substantial benefit.
Telogen effluvium
The human hair cycle (Figure 17.3) is asynchronous but can be precipitated into synchrony by childbirth
or a sudden severe systemic illness, such as pneumonia or massive blood loss. The stimulus causes all
the scalp hair follicles to revert to the telogen, or resting, phase. There is a sudden and significant loss of
terminal scalp hair some 3 months after the precipitating event, which continues for a few weeks but
then spontaneously stops. Hair regrowth gradually restores the scalp hair to its original state.
Traction alopecia
Repeated tugging and pulling on the hair shaft may produce loss of hair in the affected areas, such as that
which occurs when hair rollers are used or if the hair is tied back tightly from the forehead (Figure 17.4). The
hair is repeatedly damaged and this may lead to permanent hair loss. Hair loss can also develop in young
children due to friction when they continually rub their scalp on their pillow. Youngsters sometimes tug out
their hair, producing hair loss in a bizarre distribution over the scalp (trichotillomania, Figure 17.5). The
motivation for this strange behavior usually remains obscure; it is an impulse control disorder requiring
psychiatric treatment. The main differential diagnosis is alopecia areata and tinea capitis.
Scarring alopecia
Any inflammatory process on the scalp sufficient to cause loss of follicles and scar formation will result in
permanent loss of hair in the affected area. Mechanical trauma, burns, bacterial infections, and severe
inflammatory ringworm of the scalp can produce sufficient damage to cause scarring and permanent hair
loss. In discoid lupus erythematosus and lichen planus, the scalp skin may be characteristically affected by
the dermatosis concerned, but it may be difficult to distinguish these two conditions, even after biopsy.
Usually, the affected area is scarred and there is loss of follicular orifices – the few remaining being distorted
FIGURE 17.3 Diagram showing the various stages of the human hair cycle.
FIGURE 17.4 Traction alopecia due to the tight braids.
FIGURE 17.5 Trichotillomania: a bizarre pattern of hair loss from the scalp due to constant tugging of the hair (from
Marks and Motley, 18th edition, with permission).
and dilated and containing tufts of hair. An odd and unexplained type of scalp scarring known as pseu
dopelade is characterized by small, rounded patches of scarring alopecia without any inflammation and
presumably represents the remnants of a disease process which has spontaneously resolved.
Hair shaft disorders

Hair shaft abnormalities may be either congenital or acquired. Acquired abnormalities are more often
seen. All long hairs tend to become ‘weathered’ at their ends due to climatic exposure and the usual
washing and combing routines.
FIGURE 17.6 Thimble pitting of the fingernail in psoriasis. There is also an area of onycholysis (from Marks and Motley, 18th
Twisting hairs between the fingers, and other obsessive manipulation of hair, results in a specific type of
damage to the hair shafts known as trichorrhexis nodosa, in which expansions of the shaft (nodes) can be
seen by routine light microscopy and scanning electron microscopy. These nodes rupture and leave frayed,
‘paintbrush’-like ends. This deformity leads to broken hairs and even to the complaint of loss of hair.
Isolated congenital hair shaft disorders include the condition of monilethrix, in which there are spindle-like
expansions of the hair shaft at regular intervals, causing weakness and breaking of the scalp hair.
Hirsuties
This is the name given to the complaint of excessive terminal hair growth in women. When hirsuitism is
accompanied by acne, early pattern alopecia, and menstrual irregularities, tests for masculinization and
polycystic ovary syndrome should be performed. Removal of facial hair is usually by depilatories,
waxing, electrolysis, or with intense pulse light, alexandrite, or diode laser systems.
Disorders of the nails

Psoriasis, lichen planus, and eczema may all affect the nails, causing characteristic clinical appearances.
Psoriasis characteristically causes ‘thimble pitting’ of the fingernails (Figure 17.6). Psoriasis causes ir
regular, deep, and random pitting of nail plates along with onycholysis and subungual hyperkeratosis
(Figure 17.7). The nail plates may be thickened, with a yellowish-brown discoloration and subungual
debris often making it difficult to distinguish from onychomycosis of the nails. In lichen planus, the nail
plate may develop longitudinal ridging and pterygium formation (Figure 17.8). The process may even
destroy the nail matrix and cause permanent loss of the nail. Eczema, affecting the fingers, may cause
irregular deformities of the fingernails and even marked horizontal ridging.
Paronychia
This term is applied to the inflammation of the periungual tissue at the sides of the nail. In the common
form of chronic paronychia, the paronychial skin is thickened and reddened. It is often tender, and pus
may be expressed from the space between the nail fold and the nail plate. The eponychium disappears
and the nail plate is often discolored and deformed (Figure 17.9) and may demonstrate onycholysis
(see the following discussion). There is a deep recess between the nail fold and the nail plate, containing
FIGURE 17.7 Fingernails in psoriasis showing onychol- FIGURE 17.8 Pterygium in lichen planus.
ysis, subungual hyperkeratosis, and orange–red discolora
tion of the nail plate.
debris and microorganisms, which is difficult to keep dry. The condition mostly occurs in women whose
occupation involves frequent hand washing or other ‘wet’ activities (e.g. cooks, cleaners, barmaids), and
it seems likely that the inability of this group of individuals to keep their hands dry contributes sub
stantially to the condition’s chronicity. Candida microorganisms may contribute to the recurrent in
flammation to which the affected fingers are subject, but they are not the cause of the disorder. The
cause is compounded by mechanical trauma and overhydration, resulting in microbial overgrowth.
Treatment
The major goals in management are keeping the fingers completely dry and avoiding wet work. Potent
steroids combined with antifungal lotions are useful. Acute exacerbations may need to be treated with
systemic antibiotics. Provided the advice is taken and the treatment used, patients usually gradually improve.
Onycholysis
Onycholysis is a physical sign in which the terminal nail plate separates from the underlying nail bed. It
is observed in psoriasis, eczema, chronic paronychia, the ‘yellow nail syndrome’ (see the following
discussion), thyrotoxicosis, as a result of repeated mechanical trauma and idiopathicity.
FIGURE 17.9 Irregular, discolored nail plate seen in chronic paronychia.

Brittle nails and onychorrhexis

In older women, the nails may break easily and separate into horizontal strata (onychorrhexis). Probably
the single-most important factor causing this problem is repeated hydration and drying, as in housework,
as well as mechanical and chemical trauma.
The nails in systemic disease

Onycholysis due to thyrotoxicosis has already been mentioned. In hypoalbuminaemia (as in severe liver
disease), the lunulae may be lost and the nail plate turns a milky white. Beau’s lines are horizontal ridges
due to a sudden severe illness, trauma, and/or blood loss and presumably have the same significance as
telogen effluvium. They grow outwards and are eventually lost.
Brown–black pigmentation
Pigmented linear bands along the length of the nail may be due to a nevus or, may be caused by
malignant melanoma. Brown–black areas may be due to melanin or haemosiderin from trauma, and the
two may be very difficult to tell apart. Uncommonly, Pseudomonas infection of the nail plate produces a
diffuse black or black–green pigmentation. A yellow–green discoloration is also seen in the yellow nail
syndrome (Figure 17.10). In this rare disease, nail growth is greatly slowed and the nails are yellowish-
green, thickened, and show increased curvature. In addition, ankle and facial oedema, sinusitis, and
pleural effusion often accompany this condition, the cause of which is unknown.
Ringworm of the nails (Tinea unguium)

Ringworm of the toenails is quite common, but much less common in the fingernails due to their faster
growth. The affected nails are thickened and crumbly and are discolored yellow or yellowish-white or
black (Figure 17.11). Subungual debris is often present. The differential diagnosis includes psoriasis and
paronychia as well as the rare yellow nail syndrome.
Treatment
Treatment is dealt with on pages 26–27.
FIGURE 17.10 Nails in yellow nail syndrome. The

nails are discolored a yellowish-green and show
increased curvature. There is also loss of eponychium FIGURE 17.11 Discoloration and subungual debris in
(from Marks and Motley, 18th edition, with permission). thumbnail due to ringworm infection (tinea unguium).
18
Systemic disease and the skin
Anupam Das
Skin markers of malignant disease

Some skin disorders are precipitated by an underlying malignancy and almost always indicate a visceral
neoplasm. Early recognition may assist in the detection of the underlying neoplastic disease. There are
certain disorders that have a strong association with malignancies, while some have a moderate or poor
association. However, the importance of recognition of the dermatosis cannot be overemphasized, as
this can lead to urgent systemic workup and diagnosis of the underlying malignancy.
BOX 18.1 STRONG ASSOCIATION WITH MALIGNANCY

Acquired hypertrichosis lanuginosa
Acrokeratosis paraneoplastica of Bazex
Erythema gyratum repens
Necrolytic migratory erythema
Paraneoplastic pemphigus
Sign of Leser-Trélat
Tripe palms
Trosseau syndrome
Moderate association with malignancy

Acanthosis nigricans
Dermatomyositis
Neutrophilic dermatoses (Sweet syndrome, pyoderma gangrenosum)
Weak association with malignancy

Acquired ichthyosis
Amyloidosis, primary systemic
Bullous pemphigoid
Juvenile xanthogranulomas
Multicentric reticulohistiocytosis
Necrobiotic xanthogranuloma
Progressive systemic sclerosis
Scleromyxedema
242
Systemic disease and the skin 243
Disorders with a strong association with the underlying malignancy

Acrokeratosis paraneoplastica of Bazex
It presents with erythematous to violaceous psoiasiform lesions distributed on the ears, nose,
cheeks, hands, feet, and knees, along with palmoplantar keratoderma and nail dystrophy, mostly
associated with squamous cell carcinoma of the upper aerodigestive tract. Histology shows hy
perkeratosis, parakeratosis, lymphohistiocytic infiltrate, basal layer degeneration, and dermal
melanophages.
Necrolytic migratory erythema

Clinically, it is characterized by erythematous scaly lesions with centrifugal growth over the groin,
perineum, buttocks, lower abdomen, perioral areas, and distal limbs. This is usually caused by pan
creatic neuroendocrine tumors (PNETs) secreting glucagons. The skin disorder responds to the removal
of the underlying tumor, but usually, a complete removal is not possible.
Histology shows epidermal necrosis, neutrophilic infiltrate, bulla (acute lesion), and psoriasiform
lesions (chronic lesion). Blood tests reveal increased circulating glucagon, hyperglycemia, and
hypoaminoacidaemia.
Paraneoplastic pemphigus
This unique entity is characterized by intractable painful stomatitis and a polymorphous cutaneous
eruption (pemphigus vulgaris-like, bullous pemphigoid-like, erythema multiforme-like, and lichen
planus-like), associated with non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, Castleman’s
disease, retroperitoneal sarcoma, etc.
Acquired hypertrichosis lanuginosa

This is typified by the growth of silky and non-pigmented hair around the eyebrows, forehead, ears, and
nose. It has a strong association with the underlying adenocarcinoma of the gastrointestinal tract, lung,
breast, uterus, etc.
Tripe palms
Clinically, as the name suggests, it presents with thickened velvety palms. In patients with only tripe
palms, the most common malignancy is lung carcinoma. However, in patients with both tripe palms and
acanthosis nigricans, gastric carcinoma is the most common.
Acanthosis nigricans
Clinically, it presents as a sudden onset of symmetric hyperpigmented, hyperkeratotic, verrucous, and
velvety plaques on the intertriginous skin and mucosae and is associated with tripe palms, most
commonly with a background of gastric malignancy. Histology shows hyperkeratosis, papillomatosis,
and minimal acanthosis.
Acquired ichthyosis
It is associated with lymphomas and leukemias. Other causes of acquired ichthyosis include acquired
immune deficiency syndrome (AIDS), sarcoidosis, and leprosy, but if these can be excluded, a
neoplastic cause is the most likely explanation.
Sign of Leser Trelat

This is characterized by a sudden onset of multiple itchy seborrheic keratotic lesions, mostly associated
with adenocarcinomas of the gastrointestinal tract.
Dermatomyositis
A sudden onset of classical lesions of dermatomyositis is associated with malignancies of the geni
tourinary tract, mostly ovarian cancer.
Erythema gyratum repens

Clinically, it presents as extremely itchy serpiginous bands in concentric red swirls, referred to as a
‘wood-grained’ appearance, along with rapid migration of rings, commonly associated with malig
nancies of lung, oesophagus, breast, etc.
Sweet syndrome
It is clinically characterized by painful, edematous, and erythematous papulo-nodules and plaques over
the head, neck, and upper extremities; if associated with malignancies, acute myelogenous leukaemias
are the most common.
Pyoderma gangrenosum
Acute myelogenous leukaemias and multiple myeloma are the most common malignancies.
Skin metastases
Carcinomas of the breast, bronchus, stomach, kidney, and prostate are the most common visceral
neoplasms to metastasize to the skin. Secondary deposits on the skin may be the first sign of the
underlying visceral cancer. The lesions themselves are usually smooth nodules, which are pink or skin-
colored but may be pigmented in deposits of melanoma.
Bullous pemphigoid
This subepidermal blistering disorder occurs mainly in those over 60 years of age, who are anyway
more likely to be affected by a neoplasm. Nonetheless, there are a few patients with pemphigoid in
whom the skin disorder is provoked by the malignancy and remits after the neoplasm has been removed.
Trousseau syndrome
It is an acquired coagulopathy presenting as migratory thrombophlebitis, mostly associated with cancers
of the lung and pancreas.
Endocrine disease, diabetes, and the skin

Thyroid disease
Cutaneous manifestations of hyperthyroidism are varied. Skin, hairs, and nails have some important
clinical pointers, which can readily serve as clues to diagnose the underlying hyperthyroidism. The skin is
soft, smooth, and velvety, along with increased temperature and sweating. Besides, palmar erythema and
facial flushing may be seen due to hyperdynamic circulation. Other associations include
hyperpigmentation, pretibial myxedema, vitiligo,

goiter, urticaria, palmoplantar pustulosis, melano
derma, and melasma. Nails typically have a fast
growth rate. Besides, soft nails, koilonychias,
Plummer’s nails thyroid acropachy may be found.
Hairs are fine and thin. Diffuse alopecia and alopecia
areata have also been documented.
In hypothyroidism, the skin is pale, cold, scaly,
wrinkled, and ivory-yellow colored. Palmoplantar
keratoderma is frequently seen. Other findings are
puffy oedema of hands, eyelids, face; punctate tel
angiectasias on arms and fingertips; delayed wound
healing; xanthomatosis; cutis marmorata; and livedo
reticularis. Nails are brittle and striated, with a very
slow rate of growth. Hairs are coarse and scalpe.
Loss of lateral eyebrows may be found (Hertoghe’s
sign). Interesting associations include macroglossia,
gingival swelling, and oral candidiasis.
Pretibial myxoedema is characterized by red
dened, elevated plaques, often with a peau d’orange
appearance on the surface (Figure 18.1).
FIGURE 18.1 Plaque of pretibial myxoedema (from
Histologically, there is a cellular connective tissue
Marks and Motley, 18th edition, with permission). with deposition of mucinous material. The serum
from such patients contains substances that stimu
late the growth and activity of fibroblasts in vitro.
The condition is almost always a sign of Rebreak thyro-toxicosis and is accompanied by exoph
thalmos. It occurs in 5% of patients with thyrotoxicosis. It is persistent and difficult to treat, although
treatment with PUVA is sometimes successful. Rarely, there is diffuse infiltration with the similar
mucinous connective tissue of the hands and feet and finger clubbing in the condition of thyroid ac
ropachy. Patients with thyrotoxicosis have warm, sweaty skin, and some complain of pruritus. There is a
diffuse loss of scalp hair in some patients.
In myxoedema, the skin often feels dry and rough and may have a yellowish-orange tint, as car
otenaemia may accompany the disorder. In addition, there may be coarsening of the scalp hair, hair loss,
loss of the outer third of the eyebrows, pinkish cheeks, but a yellowish background color – the so-called
peaches and cream complexion.
Skin manifestations of diabetes

The manifestations may be classified as under:
1. Dermatological lesions associated with diabetes: pruritus, granuloma annulare, necrobiosis li
poidica, diabetic dermopathy, diabetic thick skin, acanthosis nigricans, diabetic bulla, perforating
dermatoses, lichen planus, vitiligo, bullous pemphigoid, skin tags, eruptive xanthoma, dermatitis
herpetiformis, psoriasis, xerosis, keratosis pilaris
2. Cutaneous infections in diabetes: candidiasis, dermatophytosis, rhinocerebral mucormycosis, fur
uncle, carbuncle, necrotizing fasciitis, malignant otitis externa, intertrigo, erythrasma, gas gangrene
3. Cutaneous lesions due to vascular abnormalities: distal ischemic changes, with shiny, atrophic
skin, hair loss, nail dystrophy, cold toes, and ischemic ulcers, pigmented purpura, erysipelas-like
erythema, periungual telangiectasia, splinter nail hemorrhages, pterygium inversus unguis, dia
betic rubeosis, wet gangrene of foot, diabetic dermopathy, etc.
4. Changes due to diabetic neuropathy: diabetic foot ulcer
5. Dermatologic complications of diabetic treatment:

• Due to oral hypoglycemic agents: pruritus, maculopapular rash, phototoxic rash, erythema
nodosum, exacerbation of porphyria cutanea tarda
• Due to insulin: pruritic nodule, localized induration, ulceration, abscess and scar formation,
keloid, lipoatrophy, lipohypertrophy, insulin oedema
6. Miscellaneous: chronic fluctuating dermatoses, annular figurate erythema, erosion, and bulla
Necrobiosis lipoidica
More than 50% of individuals who present with this disorder will already have insulin-dependent
diabetes. Many of those who do not have diabetes when they present will develop diabetes or have a
first-degree relative with diabetes. It starts as a firm dull-red papule and progresses to develop into
yellowish, atrophic irregular plaques with a glazed porcelain appearance and comedo-like plugs on the
lower legs and around the ankles (Figure 18.2). Uncommonly, lesions may occur elsewhere and there
may be areas of atrophy, telangiectasia, hypohidrosis, hypoesthesia, and ulceration. These plaques are
persistent and quite resistant to treatment.
Histologically, there is a central area of altered and damaged collagen in the mid-dermis, surrounded
by inflammatory cells, including giant cells.
Granuloma annulare
This disorder has some superficial resemblance to necrobiosis lipoidica, both clinically and histologi
cally, but in its common form, has no association with diabetes. However, there is a rare, generalized,
and ‘diffuse’ form that is strongly related to diabetes. The lesions in this diffuse generalized form are not
annular and not raised and plaque-like.
Ulceration of the skin in diabetes

The neuropathy of diabetes can result in neuro
pathic ulceration due to the failure of the so-
called nociceptive reflex, in which the limb is
rapidly withdrawn from a painful stimulus. Deep
‘perforating ulcers’ may develop on the soles
and elsewhere around the feet.
Atherosclerotic vascular disease is more
common in people with diabetes and the re
sulting ischaemia may also contribute sub
stantially to the ulceration of the feet or legs.
There is also a depressed ability to cope with
infections, and infection of the ulcerated area
usually complicates such lesions in diabetic
people. The resulting ulcerating areas tend to be
moist, contain slough, and be purulent. Wounds
in people with diabetes also tend to heal more
slowly, turning any minor injury of the foot into
a serious health risk.
Diabetic dermopathy
It is characterized by asymptomatic multiple,
FIGURE 18.2 Necrobiosis lipoidica on the ankle (from bilateral, annular/irregular, erythematous papules
Marks and Motley, 18th edition, with permission). and plaques, and atrophic hyperpigmented
macules, which clear within 1–2 years with residual atrophy, mostly on pretibial areas, thighs, and
forearms.
Xanthomata
Xanthomata is due to deposits of lipid within dermal histiocytes. Their clinical appearance and lipid
composition depend on the type of lipid abnormality. In diabetes, there is usually mixed hyperlipi
daemia in which both cholesterol and triglycerides are elevated. When the lipid levels are very ele
vated, eruptive xanthomata may develop in which numerous small, yellow–pink papules appear
anywhere, especially on extensor surfaces (Figure 18.3).
Skin infections and pruritus

As mentioned earlier, people with diabetes appear particularly susceptible to skin infections. Monilial
infection is a particular problem and monilial vulvovaginitis and balanoposthitis are common. These are
‘itchy disorders,’ and it may be that this is how it came to be believed that diabetic patients can develop
the generalized itch. In fact, there is little evidence that diabetes is responsible for generalized itch.
Cushing’s syndrome
The cutaneous signs of Cushing’s syndrome are the same regardless of whether they are caused by an
adrenal tumor, hyperplasia, or the administration of corticoids.
Clinical features
The most consistent clinical feature is skin thinning. The underlying veins can be easily seen and the
skin has a ‘transparent’ quality (Figure 18.4). The thinning is due to the suppressive action of gluco
corticoids on the growth and synthetic activity of dermal fibroblasts and the epidermis.
The dermal thinning also results in rupture of the dermal elastic fibres and the formation of striae
distensae. These are band-like atrophic areas that develop in areas of maximal stress on the skin. A
certain number is found on the upper arm, the anterior axillary fold, the lower and mid-back, and
occasionally elsewhere in normal adolescents. They also occur in most pregnant women on the thighs,
breasts, anterior axillary folds, and lower abdomen. It is thought that both tissue tension and the level of
circulating glucocorticoids are important in the production of striae.
FIGURE 18.3 Numerous yellow–pink papules due to eruptive xanthoma in a patient with diabetes (from Marks and
Acne papules occur on the chest, back, and face

in most patients with Cushing’s syndrome. Steroid
acne lesions are more uniform in appearance than
adolescent acne and consist predominantly of small
papules with few comedones. This type of acne is
more resistant to treatment than ordinary acne.
Skin infections are also more common and more
severe in patients with Cushing’s syndrome.
Pityriasis versicolor is often present and often very
extensive.
Addison’s disease
This disorder, due to the destruction of the adrenal
cortex from autoimmune influences, tuberculosis,
and amyloidosis or metastatic neoplastic disease,
results in weakness, hypotension, and generalized
hyperpigmentation (Figure 18.5). The increased
pigmentation may be particularly evident in the
major flexures and on the buccal mucosa and in the
palmar creases.
Androgenization (virilization)
This disorder of women may be due to androgen-
FIGURE 18.4 Skin thinning in Cushing’s syndrome secreting tumors of the ovaries or the adrenal
(from Marks and Motley, 18th edition, with permission).
cortex, but it is usually due to polycystic ovaries in
which there is an abnormality of steroid metabo
lism, leading to an accumulation of androgens. Patients present with acne and increased greasiness of
the skin, or hirsutism. Increased hair growth is also a major complaint of patients with androgenization.
Vellus hair on forearms, thighs, and trunk is transformed to pigmented, thick, terminal hairs. A mas
culine distribution of body and limb hair develops.
The appearance of beard hair is usually the reason for patients attending the clinic. In clinical practice, the
most common problem is to distinguish hirsuties due to androgenization from hirsuties due to non-endocrine
causes. It is not generally recognized that the presence of some terminal hair on the face or limbs of some
otherwise healthy women is normal. This is particularly the case in dark-complexioned women of Arab,
Asian, or Mediterranean descent. The tendency for ‘excess hair’ is also familial. Thinning of the scalp hair
and pattern alopecia are also quite common and very distressing to women with virilization.
In authentic virilization, the following features help distinguish the condition from ‘non-endrocrine’
hirsuties: the excess hair growth is recent in onset and progressively becoming more noticeable, the
hirsuties is accompanied by other physical signs including acne and seborrhea and there is a significant
menstrual disturbance.
In most cases, extensive investigation is not appropriate and plasma testosterone and abdominal
ultrasound are all that is required.
Nutrition and the skin

Marasmus
It is characterized by dry, thin, lax, purpuric, and wrinkled skin; monkey facies; baggy pants; and
diminished axillary fat. Hairs are thin and brittle with excessive lanugo hair. Nails show impaired
growth.
FIGURE 18.5 Hyperpigmentation of facial skin in Addison’s syndrome (from Marks and Motley, 18th edition, with permission).
Kwashiorkor
This is referred to as ‘wet’ protein-energy malnutrition leading to a sugar baby appearance. Important
findings include generalized dermatitis, flaking enamel paint appearance, etc. Hairs show alternate
bands of normal pigmentation and reduced pigmentation, known as Flag sign. Mucosa is characterized
by cheilosis and angular stomatitis. Systemic findings are anasarca, bloated abdomen, hepatomegaly,
and irritable child.
Essential fatty acid deficiency

The skin is dry, scaly, leathery, and erythematous along with intertriginous erosions. Besides, alopecia is
an important finding.
Vitamin A (retinol)
Retinol is a vital, lipid-soluble vitamin found in dairy produce and liver, and is also obtainable in the
form of beta-carotene from carrots, tomatoes, and other vegetables. It is essential for growth and
development, resistance to infection, reproduction, and visual function. In deficiency states, it causes
follicular hyperkeratosis and roughening of the skin (phrynoderma). When excessive amounts are
ingested, pruritus, widespread erythema and peeling of the palms and soles, and liver damage occur.
These symptoms and signs are similar to those of retinoid toxicity.
Nicotinic acid
This is a water-soluble B vitamin found in grains and vegetables. Its deficiency causes the condition
of pellagra, resulting in diarrhoea, dementia, and photosensitivity dermatitis. The photosensitivity
dermatitis develops a characteristic post-inflammatory hyperpigmentation and is often very marked
around the neck.
Vitamin C (ascorbic acid)

Vitamin C is a water-soluble vitamin found in fruit and vegetables. Deficiency results in scurvy, which
causes a clotting defect and poor wound healing. A characteristic rash seen in patients with scurvy
consists of numerous tiny haemorrhages around hair follicles.
Zinc
The inherited form of zinc deficiency is known as acrodermatitis enteropathica. Clinically it presents
with acrally and periorificially distributed pustular and bullous dermatitis. There are patchy red dry
scales with exudation and crusting over the face, flexors, and groin along with angular cheilitis. Chronic
lesions acquire a psoriasiform pattern. Alopecia and thinning of nails are also seen.
Selenium
Deficiency leads to leuconychia and Terry’s-like nails along with hypopigmentation of skin and hair
(pseudoalbinism).
Iron
Deficiency leads to aphthous stomatitis, angular stomatitis, glossodynia, and atrophied tongue papillae.
Nails show thinning, flattening, and koilonychias. Hairs are lusterless, brittle, and dry.
Senile osteoporosis
In this disorder of faulty bone mineralization due to vitamin D deficiency, bone thinning, and multiple
fractures, the skin becomes ‘thinner’ and is almost transparent, with the veins being abnormally pro
minent. The thinning can be demonstrated by ultrasound – using a simple pulsed A scan device.
The skin and the gastrointestinal tract

There are numerous interrelationships between the skin and the gastrointestinal tract, and only the more
important ones fall within the scope of a book of this size.
Buccal mucosa
Erythema multiforme is a widespread inflammatory disorder accompanied by severe mouth ulcers.
Behçet’s syndrome causes marked orogenital ulceration, ocular inflammation, and other problems,
including arthropathy.
This itchy, blistering disorder is strongly associated with an absorptive defect of the small bowel. Small-
bowel mucosal biopsy using a Crosby capsule or endoscope demonstrates partial villous atrophy in
some 70–80% of patients with dermatitis herpetiformis. There are also some functional absorptive
abnormalities in most patients, which can result in serious clinical consequences such as anaemia or
osteoporosis. This gut disorder is, in fact, a form of gluten enteropathy (as is coeliac disease) and can be
improved by a gluten-free diet.
Peutz–Jeghers syndrome
This is a rare, autosomal dominant disorder in which perioral and labial pigmented macules occur in
association with jejunal polyps. Pigmented macules also occur over the fingers.
Gardner’s syndrome
In this autosomal dominant disorder, epidermoid cysts and benign epidermal tumors occur in association
with colonic polyposis.
Hepatic disease
In severe chronic hepatocellular liver failure, hypoalbuminaemia occurs, which results in the curious
sign of whitening of the fingernails (Figure 18.6). Severe liver failure may also cause multiple spider
naevi to develop over the arms, upper trunk, and face. These vascular anomalies consist of a central
‘feeding’ blood vessel (‘the body’) with numerous fine radiating ‘legs’. Their cause is uncertain, but
they may be related to the plasma levels of unconjugated oestrogens.
In biliary cirrhosis, severe pruritus develops, resulting in excoriations and prurigo papules. In addi
tion, Jaundice and a generalized dusky pigmentation are seen.
In hemochromatosis, the findings include greyish pigmentation, black keratin cysts, black stasis
dermatitis, and porphyria cutanea tarda.
Wilson’s disease is characterized by blue lunulae and pretibial hyperpigmentation.
Cutaneous manifestations of hepatitis B virus infections are urticaria, serum sickness, angioedema,
erythema nodosum, erythema multiforme, polyarteritis nodosa, etc.
Cutaneous manifestations of hepatitis C virus
infections are mixed cryoglobulinemia, porphyria
cutanea tarda, polyarteritis nodosa, nec-rolytic acral
erythema, urticarial vasculitis, lichen planus, etc.
Systemic causes of pruritus

End-stage renal failure (uraemia) often causes a
persistent, severe itch. The itch is accompanied by a
dusky, grey–brown pigmentation.
Obstructive jaundice from any cause results in
intolerable itching.
Thyrotoxicosis sometimes causes itching, but this
does not seem to be due to the sweatiness or in
creased warmth of the skin experienced by such
patients.
Itching is sometimes a complaint of patients with
hyperparathyroidism and other disturbances of cal
FIGURE 18.6 White fingernails due to liver disease cium metabolism.
(from Marks and Motley, 18th edition, with permission).
The symptom of an itch is occasionally a sign of Hodgkin’s disease or, less often, of another type of
lymphoma. Rarely, the itch is a presenting symptom of the neoplasm.
Itch is a well-known disabling complaint of patients with polycythaemia rubra vera. For some curious
reason, the itch may be a particular problem when these patients have a bath.
It has often been claimed that patients with diabetes have pruritus, but if this is the case, it must be
extremely rare. People with diabetes are prone to candidiasis, which causes perigenital itch, and it is
possible that this is how the idea began.
19
Disorders of pigmentation
Rashmi Sarkar
Anupam Das
Melanin pigment is produced in melanocytes in the basal layer of the epidermis. The degree of racial
pigmentation does not depend on the number of melanocytes present, but on their metabolic activity and
the size and shape of their melanin-producing organelles – the melanosomes. Melanocytes account for
5–10% of the cells in the basal layer of the epidermis. They are dendritic but appear as ‘clear cells’ in
formalin-fixed sections.
Melanin synthesis is controlled by melanocyte-stimulating hormones and is influenced by oestrogens
and androgens. Melanocytes are also stimulated by ultraviolet radiation (UVR) and by other irritative
stimuli. Melanin is a complex, black–brown polymer synthesized from the amino acid dihydroxy-
phenylalanine (L-DOPA). Two forms of melanin exist: ‘ordinary’ melanin, known as eumelanin, and a
reddish melanin synthesized from cysteinyl DOPA, known as phaeomelanin.
Melanin synthesis is initially catalyzed by a copper-containing enzyme known as tyrosinase, which
also catalyzes the transformation of L-DOPA to tyrosine. Melanin is produced in melanocytes, but
‘donated’ via their dendrites to neighboring keratinocytes. The melanin granules then ascend through
the epidermis in the keratinocytes. Melanosomes go through several stages of melanin synthesis during
their melaninization (stages I–IV). Mature melanosomes aggregate into melanin granules and it is these
granular particles within keratinocytes that give protection against damage from UVR.
Melanin in keratinocytes is black and absorbs all visible light, UVR, and infrared radiation. It is also a
powerful electron acceptor and may have other uncharacterized protective functions.
Excessive pigmentation is known as hyperpigmentation and decreased pigmentation is known as hypo
pigmentation. Both may be localized or generalized. Non-melanin pigments may also cause skin darkening.
Hypopigmentation
The etiology of hypopigmentation is diverse and can be broadly summarized as in Table 19.1.
Generalized hypopigmentation
Oculocutaneous albinism
There are several varieties of genetically determined defects in melanin synthesis, the most common of
which is recessively inherited oculocutaneous albinism. Affected individuals have a very pale or even
pinkish complexion with flaxen, white, or slightly yellowish hair, and very light-blue or even pink eyes.
Albinos are also subject to nystagmus, either horizontal or rotatory. In addition, they are photophobic
and often have serious refractive errors. They are extremely sensitive to the harmful effects of solar
irradiation and in sunny climates often develop skin cancers.
Albinos have a normal number of melanocytes in the basal layer of the epidermis, but lack tyrosinase
and are unable to synthesize melanin. If the hair is plucked and incubated in a medium containing
L-DOPA, the hair bulb does not turn black, as it does normally.
253
TABLE 19.1
Classification of hypopigmentation
• Genetic and nevoid: oculocutaneous albinism, Hermansky–Pudlak syndrome, Chédiak–Higashi syndrome,

Piebaldism, Waardenburg syndrome, phyenylketonuria, vitiligo, tuberous sclerosis, incontinentia pigmenti,
hypomelanosis of Ito, naevus depigmentosus
• Disruption of melanoblast migration to target tissues during development: Waardenburg syndrome, piebaldism, Cross
syndrome
• Disruption of melanin synthesis: oculocutaneous albinism
• Disruption of melanosome formation: Hermansky–Pudlak syndrome, Chediak–Higashi syndrome
• Disruption of melanosome transport: Griscelli syndrome
• Post-inflammatory and infections: pityriasis versicolor, leprosy, post kala-azar dermal leishmaniasis, pinta,
syphilitic leucomelanoderma, onchocerciasis
• Endocrine: hypothyroidism, hypopituitarism, hypogonadism
• Chemical factors: monobenzylether of hydroquinone (rubber factories), monomethylether of hydroquinone, p-tertiary-
butylphenol, p-tertiary amylphenol, chloroquine and hydroxychloroquine, topical steroids, arsenic
• Physical factors: heat, freezing, X-ray, ionizing radiation, UV radiation, laser light
• Nutritional: Kwashiorkor, selenium deficiency, copper deficiency
• Neoplasms: melanoma-associated leukoderma, halo nevus
• Hypopigmentation with vascular cause: Bier spots, Woronoff ring, cutaneous edema, anemia
• Miscellaneous: pityriasis alba, mycosis fungoides, sarcoidosis, lupus erythematosus, scleroderma, idiopathic guttate
hypomelanosis, lichen sclerosus et atrophicus
Mutation in the TYR gene, P gene, TYRP1 gene, and MATP gene leads to OCA-1,2,3 and 4, re
spectively. Ocular albinism is a distinct variant wherein only ocular symptoms are present without any
cutaneous lesions.
Management
Albino patients must learn to protect themselves against UVR with sunscreens and avoid sun wherever
possible. Regular checks to detect early changes in skin cancer is also important.
There are several other types of albinism, most of which are recessive. In the Hermanski–Pudlak
syndrome, there is an associated clotting defect due to a platelet abnormality. Patients have a bleeding
tendency, interstitial pulmonary fibrosis, and granulomatous colitis. This is ‘tyrosinase positive’ and hair
bulbs turn black after they are incubated with L-DOPA. Chediak–Higashi syndrome is characterized by
severe immunodeficiency and silvery-white hair, and the histology is classical, showing giant mela
nosomes within melanocytes. Griscelli syndrome, on the other hand, is a severe immunological disorder
with hemophagocytic syndrome in addition to having silvery-white hairs and pigmentary dilution of
skin. Waardenburg syndrome is a distinct entity manifesting as achromia of skin, hairs, and eyes,
heterochromia iridis, congenital deafness, broad nasal root, and dystopia canthorum. The hallmark
finding in piebaldism is white forelock and the presence of normal skin within the depigmented patches.
Vitiligo
Definition
This is a common skin disorder in which there is focal failure of pigmentation due to the destruction of
melanocytes that is thought to be mediated by immunological mechanisms.
Clinical features
Sharply defined areas of depigmentation appear (Figure 19.1). The depigmented patches are often
symmetrical, especially when they are over the limbs and face. Nascent patches of vitiligo are more
Disorders of pigmentation 255
FIGURE 19.1 Vitiligo in a dark-skinned patient (from Marks and Motley, 18th edition).
easily identified if the skin is examined with UV light illumination. UV light may also enhance the
appearance of follicular pigmentation within patches of vitiligo. The melanocytes associated with
follicles are often unaffected and act as the reservoir from which repigmentation may occur.
In some patients, vitiligo shows a propensity to develop at sites of skin trauma (the Koebner phe
nomenon). Based on distribution, vitiligo can be focal, segmental, acrofacial, generalized, universal, and
mucosal. Vitiligo may occasionally be associated with regression of pigmentation in malignant mela
noma and it is wise to examine the entire skin surface of patients presenting with the condition. In halo
naevus (Sutton’s naevus, Figure 19.2), the depigmentation of vitiligo begins around one or a few
compound naevi. This may also be associated with a regressing malignant melanoma – although it is
usually a benign phenomenon in children and teenagers. Clinical variants include trichrome, quad
richrome, pentachrome, and confetti type.
Vitiligo is more noticeable in summer when the surrounding skin is tanned. It is a serious cosmetic
problem for darkly pigmented people.
The condition often starts in childhood and may

spread, ultimately causing total depigmentation, or
persist, with irregular remissions and relapses.
Pathogenesis and epidemiology

Vitiligo occurs in 1–2% of the population and is
more common when it has already occurred in other
members of the family. It is also more common in
hyperthyroidism, hypothyroidism, pernicious an
emia, Addison’s disease, alopecia areata, and dia
betes, and appears to be due to an autoimmune
attack on melanocytes.
Treatment
Treatments with topical corticosteroids – 0.3% ta
crolimus – or photochemotherapy with long-wave
ultraviolet irradiation (PUVA) is sometimes effec
tive in stimulating repigmentation, but the response
is irregular. Reassurance and cosmetic camouflage
are helpful in many patients. Where the vitiligo is
stable, of limited extent, and in a cosmetically
sensitive area – such as the face or dorsa of the
FIGURE 19.2 Halo naevus (from Marks and hands, it may be possible to transplant autologous
Motley, 18th edition). melanocytes using epidermal skin grafts from un
affected skin. The epidermis is removed from the
area of vitiligo – either by dermabrasion or laser
ablation – and a thin epidermal skin graft is raised from an area of pigmented skin – either by creating a
large blister in the skin – and taking the roof of the blister or by the use of a mechanical dermatome. In
some circumstances, areas of vitiligo may be camouflaged by tattooing the skin; however, the normal
skin may alter in color in response to sun exposure and the tattooed skin then becomes conspicuous
again due to its different pigmentation.
Other causes of localized depigmentation of skin

In many countries, the fear of leprosy makes the differential diagnosis of a ‘white patch’ an urgent and
vitally important issue. The classical lesion of leprosy is a hypopigmented hypoesthetic patch along with
peripheral nerve thickening. Examination in long-wave UVR enhances loss of epidermal pigment (as in
vitiligo) and helps identify areas of developing depigmentation. It may also detect a yellow–green
fluorescence in some cases of pityriasis versicolor, which is otherwise clinically seen as round-to-oval,
centrally coalescent hypopigmented macules with furfuraceous scales.
Tuberous sclerosis is characterized by the presence of 1–100 hypopigmented macules, present since
birth or early neonatal period over the posterior trunk. The pigmentation can be polygonal, confetti-type,
segmental, or thumbprint-like. Hypomelanosis of Ito is identified by the typical whorled patches of
hypopigmentation along the lines of Blaschko. Nevus depigmentosus manifests as a circumscribed area
of depigmentation on the posterior trunk.
Pityriasis alba manifests as a hypopigmented patch with powdery white scales on the head and neck
region of pre-adolescent children.
Hyperpigmentation
Hyperpigmentation, similarly, has a wide range of causes and they have been tabulated as follows:
Congenital
Circumscribed
• Nevus of Ota
• Nevus of Ito
• Mongolian spot
• Dermal melanocytic hamartoma
• Lentiginosis (generalized, zosteriform, eruptive, centrofacial)
• Café-au-lait macules
Diffuse
• Incontinentia pigmentii
• Linear and whorled nevoid hypermelanosis
• Dyskeratosis congenita
• X-linked reticular pigmentary disorder
• Naegeli–Franceshetti–Jadassohn syndrome
• Dermatopathia pigmentosa reticularis
• Dyschromatosis hereditaria universalis
• Reticulate acropigmentation of Dohi
• Reticulate acropigmentation of Kitamura
• Dowling–Degos disease
• Familial progressive hypermelanosis
Acquired
Circumscribed
• Freckles
• Fixed drug rash
• Post-inflammatory hyperpigmentation
• Becker’s nevus
• Nevus of Hori
• Riehl’s melanosis
• Erythema dyschromicum perstans
• Flagellate pigmentation
Diffuse
• Endocrine: Addison’s disease, Cushing’s syndrome, Melasma, pregnancy, diabetes, acan
thosis nigricans
• Nutritional: Kwashiorkor, pellagra, vitamin B12 deficiency
• Metabolic: prophyria, cutanea tarda, hemochromatosis
• Physical: radiation, trauma
• Drug induced: clofazimine, amiodarone, zidovudine, antimalarials, minocycline
TABLE 19.2
Non-melanin causes of brown–black discoloration
Haemosiderin – from broken haem pigment in extravasated blood
Homogentisic acid – deposited in cartilage, in particular, in the inherited metabolic defect known as alkaptonuria
Unknown pigment in thickened stratum corneum – severe disorders of keratinization such as lamellar ichthyosis
Drugs and heavy metal toxicity – dark pigmentation of the skin and mucosae seen in silver, gold, mercury, and arsenic
poisoning; amiodarone and phenothiazines cause slate-grey, dusky skin pigmentation in exposed sites; minocycline may
cause patchy pigmentation in exposed or other sites
• Toxin mediated: arsenic

• Neoplastic: mast cell disorders, melanoma
• Miscellaneous: onchocerciasis, erythema ab igne, prurigo pigmentosa
It has to be determined whether the pigmentation is due to melanin or some other pigment (Table 19.2).
Generalized melanin hyperpigmentation is seen in Addison’s disease due to destruction of the adrenal
cortex from tuberculosis, autoimmune influences, metastases, or amyloidosis. Pigmentation is marked in
the flexures, sites of trauma, scars, and sun-exposed areas, but the mucosae and nails are also hy
perpigmented. The pigmentation is mediated via activation of the melanocortin-1 receptor. The diagnosis
is supported by hypotension, hyponatraemia, and extreme weakness. The hyperpigmentation is due to an
excess of pituitary peptides resulting from the lack of adrenal steroids. After bilateral adrenalectomy,
pigmentation may be extreme (Nelson’s syndrome). This is associated with an enlarged pituitary gland,
elevated fasting plasma ACTH level, and neurologic symptoms. Pheochromocytoma is characterized by
Addisonian pigmentation due to ectopic ACTH and MSH production. Carcinoid syndrome manifests with
diffuse hyperpigmentation due to an MSH-secreting tumor; along with pellagroid dermatitis.
Generalized hyperpigmentation may be part of Acanthosis nigricans (see p. 254), which is much more
marked in the flexures and is accompanied by exaggerated skin markings and skin tags.
A ‘bronzed appearance’ is seen in primary haemochromatosis (bronzed diabetes), in which iron is
deposited in the viscera, including the pancreas (giving rise to diabetes) and the liver (causing cirrhosis).
The increased pigmentation is caused by both iron and excess melaninization in the skin. The pig
mentation is more pronounced over sun-exposed areas, genitalia, and scars. Increased pigmentation is
also evident in secondary haemosiderosis. Generalized hyperpigmentation is also seen in cirrhosis,
particularly primary biliary cirrhosis, chronic renal failure, glycogen storage disease, and Gaucher’s
disease. Biliary cirrhosis and renal failure are usually accompanied by severe pruritus.
Drugs can cause generalized diffuse hyperpigmentation, patchy generalized, or localized hy
perpigmentation. Classic examples are due to the rare heavy metal intoxications. Arsenic ingestion
causes a generalized ‘raindrop’ pattern of hyperpigmentation, and topical silver preparations cause
‘argyria’, producing a dusky, greyish discoloration of the skin and mucosae.
Modern drugs can also produce darkening. Minocycline (Minocin®) can cause darkening of the scars
of acne; it can also produce dark patches on exposed areas. The pigment is a complex of iron, the drug,
and melanin, and the condition is only partially reversible but can be successfully treated with Q-
switched frequency-doubled Nd:YAG and ruby lasers. Amiodarone, an antiarrhythmic drug, causes a
characteristic greyish color on exposed sites. Phenothiazines, in high doses over long periods, produce a
purplish discoloration in the exposed areas due to the deposition of a drug–melanin complex in the skin.
Chlorpromazine is particularly prone to doing this.
Carotenaemia produces an orange–yellow, golden hue due to the deposition of beta-carotene in the
skin. It is seen in food faddists who eat large amounts of carrots and other red vegetables. Beta-carotene
is also given for the condition of erythropoietic protoporphyria (see p. 235). Systemic sclerosis can also
lead to diffuse hyperpigmentation, without elevated MSH.
Canthexanthin is another carotenoid that produces a similar skin color and was sold for this purpose to
simulate a ‘bronzed’ suntan. Pigment crystals were found in the retina of patients taking the drug and it
has been withdrawn for this reason.
Transient skin discoloration is seen in methaemoglobinaemia and sulfhaemoglobinaemia due to

dapsone administration.
Localized hyperpigmentation
Mongolian spots, the naevus of Ota, and the naevus of Ito are large, flat, grey–brown patches and can be
confused with bruising and other conditions (Figure 19.3). The bluish color is attributed to the Tyndall
effect. Hori’s nevus, otherwise known as ABNOM (acquired bilateral nevus of Ota like macules), café-
au-lait patches are part of neurofibromatosis (von Recklinghausen’s disease, see Chapter 12). Numerous
flat, light-brown macules, which vary from 0.5–4 cm2, are present all over the skin surface – and
characteristically in the axillae alongside the neurofibromata (Figure 19.4).
Not dissimilar brown macules are found on the lips and around the mouth and on the fingers in
Peutz–Jeghers syndrome, accompanied by small bowel polyps, and in Albright’s syndrome, in which
there are associated bone abnormalities.
A very common type of localized hyperpigmentation is chloasma or melasma. This facial pigmen
tation may be part of the increased pigmentation of pregnancy or may occur independently. The cheeks,
FIGURE 19.3 Macular grey–brown pigmentation in naevus of Ota (from Marks and Motley, 18th edition).
FIGURE 19.5 Diffuse brown pigmentation of the cheek

FIGURE 19.4 Axillary freckling in a patient with von in chloasma (from Marks and Motley, 18th edition).
Recklinghausen’s disease (from Marks and Motley, 18th
edition).
periocular regions, forehead, and neck may be affected in this so-called mask of pregnancy
(Figure 19.5). Riehl’s melanosis (pigmented cosmetic dermatitis) is frequently seen over the forehead.
Post-inflammatory hyperpigmentation may be due to melanocytic hyperplasia occurring as part of
epidermal thickening in chronic eczema, particularly atopic eczema. This is transient and of no real
consequence.
It may also be due to the shedding of melanin from the damaged epidermis into the dermis, where it is
engulfed by macrophages. This ‘tattooing’ may last many months. It is seen in lichen planus and in fixed
drug eruption.
Index
Note: Italicized page numbers refer to figures, bold page numbers refer to tables.
A diagnosis, 110; epidemiology, 109–10; natural history,

109–10; pathogenesis, 111; pathology, 111;
ABNOM (acquired bilateral nevus of Ota-like macules), 259 treatment, 111
acanthosis nigricans, 243, 258 alopecia; androgenetic (pattern), 233–5; areata, 235–6, 236;
ACE inhibitors, 66 congenital, 233; diffuse, 236–7; scarring, 237–8;
aciclovir, 90 traction, 237
acitretin, 65, 130 amiodarone, 258
acne, 134–43; aetiology, 140–1; chloracne, 138; clinical amoxicillin-clavulanate, 31, 32
course, 137–8; clinical features, 134–6; conglobata, amyloidosis, 226–8, 227, 227. see also metabolic disorders
138; cosmetica, 138; cystic, 134, 135; definition, 134; anagen, 7
drug-induced, 138, 139; epidemiology, 138; androgenetic (pattern) alopecia, 233–5; clinical features,
excoriated, 139; infantile, 139; mechanica, 139; 233–4; definition, 233; pathogenesis, 234; pathology,
neonatal, 139; nodulocystic, 134; occupational, 138; 234; treatment, 235
pathogenesis, 140–1; pathology, 140–1; prevalence, androgenization (virilization), 248
134; rate variants, 139–40; sites affected, 137; special androgens, 138
types, 138–9; treatment, 141–4, 144; antibiotics, 143; angioedema. see also immunologically mediated skin
antimicrobials, 142, 143; basic principles, 141; disorders; angioneurotic, 57; in drug eruptions, 75;
hormonal therapy, 144; isotretinoin, 143–4; drug-induced, 57; hereditary, 58; idiopathic, 57; without
macrolides, 143; systematic, 142; tetracyclines, 143; wheals, 57–8
topical, 142; tropical, 138 angiokeratoma, 172, 183
acne conglobata, 88, 90 angioneurotic angioedema, 57
acne fulminans, 134 angiotensin (AT) II antagonists, 119
acquired bilateral nevus of Ota-like macules angiotensin-converting enzyme (ACE) inhibitors, 119
(ABNOM), 259 anhidrotic/hypohidrotic ectodermal dysplasia, 221.
acquired hypertrichosis lanuginosa, 243 see also keratinization disorders
acquired ichthyosis, 216, 218, 243. see also ichthyosis; animal scabies, 48
keratinization disorders annular erythemas, 61–2, 62
acquired immune deficiency syndrome (AIDS). see HIV/AIDS anogenital warts, 41
acrodermatitis continua, 122 anthrax, 34
acrodermatitis enteropathica, 249 anti-p200 pemphigoid, 80, 81. see also blistering skin
acrokeratosis paraneoplastica of Bazex, 243 disorders
actinic keratosis, 187–8, 188. see also non-melanoma skin antibiotics, 61, 143
cancers antigen, 111
acute generalized exanthematous pustulosis (AGEP), 75 antihistamines, 59
acute intermittent porphyria, 223, 226. see also porphyrias antimicrobials, 102, 142, 143
acyclovir, 60 antiretroviral drugs, 91
Addison’s disease, 15, 248, 249, 258 apocrine hidrocystoma, 160, 166, 166, 166. see also tumors,
adenoma sebaceum, 172, 179 benign
adipocytic tumors, 158 apocrine sweat glands, 8
adnexal structures, 6 aquagenic urticaria, 57. see also urticaria
AIDS. see HIV/AIDS argyria, 258
albinos, 253–4 arterial ulcers, 153
Albright’s syndrome, 259 arthritis, psoriatic, 121, 122
alitretinoin, 102, 130 arthritis mutilans, 121, 122
alkaptonuria, 15 asteatotic eczema, 105–6, 106
allergic contact dermatitis, 97, 109–11. see also dermatitis ataxia telangiectasia, 93
(eczema); clinical features, 109; definition, 109; atopic dermatitis, 96–102, 97; aetiopathogenesis, 100;
261
262 Index
associated disorders, 98–9; clinical features, 96–8; Borrelia recurrentis, 50

clinical variants, 98; complications, 99–100; definition, Bowen’s disease, 122, 188, 189, 190. see also
96; in elderly, 209; epidemiology, 100; incidence, 1; non-melanoma skin cancers
in infants, 205–6; laboratory findings, 100; management, boxcar scars, 134, 137
100–2; alitretinoin, 102; antimicrobial agents, 102; coal bronzed diabetes (haemochromatosis), 226, 258
tar, 101; dupilumab, 102; moisturizers, 101; systemic Brooke’s tumor, 168
agents, 101–2; topical corticosteroids, 101; topical brown pigmentation, 15
phosphodiesterase inhibitors, 101; natural history, 100; brown-black pigmentation, 15–6, 258
popliteal fossa in, 14; signs and symptoms, 96–8 bubonic plague, 51
atypical mole syndrome, 175–6 buccal mucosa, 250
Auspitz’s sign, 113 Buckley syndrome, 93
autoimmune disorders, 62–3 bulla, 9, 12
autosomal recessive congenital ichthyosis, 214. bullous (senile) pemphigoid, 77, 78, 79, 80, 244.
see also ichthyosis; keratinization disorders see also blistering skin disorders
azathioprine, 64, 83, 101 bullous impetigo, 30, 30, 31
azelaic acid, 142, 148 burrows, 11
azidothymidine, 90
azithromycin, 92, 143 C
café au lait macules and patches, 10, 163, 164, 220, 259
B
calcifying epithelioma of Malherbe, 168
B cell lymphoma, 11 Campbell De Morgan spot, 160–1
bacillary angiomatosis, 87 candidiasis, 27–8; causative organism, 27; cutaneous, 27; in
bacterial infections, 29–38; anthrax, 34; bullous diabetic patients, 252; diagnosis, 27; predisposing factors,
impetigo, 30, 30, 31; carbuncles, 32–3; causative 27; satellite lesions, 28; systemic therapy, 28; treatment, 28
organism, 29; cellulitis, 32–3; direct infection, 29; canine scabies, 47
ecthyma, 30–1; erysipelas (St. Anthony’s fire), 31, canthaxanthin, 258
31–2; folliculitis, 32, 32–3; furuncles (boils), 32–3; capillaritis, 73–4
impetigo contagiosa, 29–30, 30; leishmaniasis, 37, capillary aneurysm, 161
38; leprosy (Hansen’s disease), 36–7; lupus vulgaris, carbuncles, 32–3
34; Lyme disease, 37; scrofuloderma, 35, 35; cardiovascular diseases (CVDs), 121
swimming pool granuloma, 35; treatment of, 35; carotenaemia, 258
tuberculosis, 34, 34; tuberculosis verrucosa cutis catagen, 7
(warty tuberculosis), 34 ceftriaxone, 92
Bannayan’s syndrome, 158 cellular blue naevus, 174
basal cell carcinoma (basal cell epithelioma), 193–6, 194, cellular naevus, 170–1
195. see also non-melanoma skin cancers cellulitis, 32
basal cell naevus syndrome (Gorlin’s syndrome), 196, cephalexin, 31, 32
196–7. see also non-melanoma skin cancers ceruminous glands, 8
basal cell papillomas, 164–5 cetirizine, 59
Beau’s lines, 241 chancroid, 92
Becker’s naevus, 172, 176–7, 177. see also naevi Chediak Higashi syndrome, 254
bedbugs (Cimex lectularius), 53 cherry angioma, 160–1
bees, 53 chicken pox, 40–1
Behçet’s syndrome, 250 Chiclero’s ulcer, 38
benign familial pemphigus (Hailey Hailey disease), 218, 220 chloasma, 259, 260
benign tumors. see tumors, benign chloracne, 138. see also acne
benzyl benzoate, 48 chlorpromazine, 5, 258
beta-carotene, 258 cholinergic urticaria, 56–7. see also urticaria
bexarotene, 90 chronic bullous disease of childhood, 79, 80
bilirubin, 5 chronic venous hypertension, 16
black pigment, 5 chymotrypsin, 3
blistering skin disorders, 77–83; anti-p200 pemphigoid, 80, ciclosporin, 59, 64
81–2; bullous pemphigoid (senile pemphigoid), 77, 78, ciprofloxacin, 92
79, 80; dermatitis herpetiformis, 78–9, 79, 80; circumscribed neurodermatitis (lichen simplex chronicus),
epidermolysis bullosa, 79–81, 81; epidermolysis bullosa 106–7, 107
acquisita, 80, 81; intraepidermal, 78, 82; linear IgA clear cell acanthoma (degos acanthoma), 169, 170
disease, 79, 80; mucous membrane pemphigoid, 77–8, clindamycin, 31, 142, 143
80; pemphigus, 82–3, 83; subepidermal, 78, 80 clofazimine, 37
body lice, 50 clotrimazole, 205
boils (furuncles), 32–3 coal tar, 101
Index 263
cold urticaria, 57. see also urticaria dendrites, 3

collagen, 6 Denny Morgan folds, 98
collodion baby, 215–6, 217. see also ichthyosis; depression, and psoriasis, 121
keratinization disorders dermal (blue) naevi, 174. see also naevi
comedones, 11, 14, 134, 135; cosmetica, 139 dermal cellular naevi, 171–4. see also naevi
congenital erythropoietic porphyria (Gunther’s disease), dermal vasculature, 6
223, 225, 225–6. see also metabolic disorders dermatitis (eczema), 96–112; allergic contact dermatitis,
congenital ichthyosiform erythroderma, 215, 216. 109–11; atopic, 96–102; atopic dermatitis, 96–102;
see also ichthyosis; keratinization disorders common types, 97; contact dermatitis, 107; discoid
congenital immunodeficiencies, 92 (nummular) eczema, 104–5, 105; eczema craquelée
connective tissue naevi, 178–9 (asteatotic eczema), 105–6, 106; lichen simplex
contact dermatitis, 107 chronicus (circumscribed neurodermatitis), 106–7, 107;
contact urticaria, 57. see also urticaria perioral, 148–9; photosensitivity, 250; primary irritant
coproporphyrins, 222 dermatitis, 107–9; seborrhoeic dermatitis, 102–4; stasis
corneocytes, 3, 211 dermatitis, 111–2; venous (gravitational) eczema, 111–2
corneo-desmosomes, 3 dermatitis herpetiformis, 47, 78–9, 80, 251.
cornifin, 5 see also blistering skin disorders
corticosteroids, 59, 69, 72, 101, 133 dermatofibroma, 158–9, 160, 161. see also tumors,
cotrimoxazole, 31, 87 benign
Cowden’s disease, 158 dermatofibrosarcoma, 202
crab lice, 50–1 dermatomyositis, 14, 16, 68–70.
cradle cap, 206 see also immunologically mediated skin disorders;
cradle crap, 103 childhood, 70; clinical features, 68–9; course and
CREST syndrome, 66 complications, 69; differential diagnosis, 69;
crisaborole, 101 incidence, 68; investigations, 69; and malignancies,
crusted (Norwegian) scabies, 47–8, 87–8 244; pathogenesis, 68; treatment, 69
crusts, 11 dermatophytosis, 25
cryotherapy, 188 dermatosis, 82
cryptococcosis, 29 dermatosis papulosa nigra, 165
Cushing’s syndrome, 247, 247–8, 248 dermis, 6
cutaneous adverse drug reactions (CADRs), 88 dermoid cysts, 186. see also cysts
cutaneous B cell lymphoma, 11 desquamation, 5, 211
cutaneous candidiasis, 27–8 diabetes; pruritus in, 247; skin infections, 247; skin
cutaneous larva migrans, 54–5, 55 manifestations of, 245–6; ulceration of skin in, 246
cutaneous mucinoses, 232, 232. see also metabolic disorders diabetic dermopathy, 246–7
cutaneous small-vessel vasculitis (CSVV), 70 diclofenac, 188
cutaneous tuberculosis, 34; in AIDS, 87; classification of, dicloxacillin, 31, 32
34; forms of, 35; treatment of, 35 differentiation, 3
cycloheximide, 26 diffuse cutaneous systemic sclerosis (dSSc), 65, 67
cyclophosphamide, 59, 64, 66, 83 dimethicone, 50
cyclosporine, 101–2, 127–8, 130 discoid (nummular) eczema, 97, 104–5, 105, 122.
cylindroma, 160, 165–6, 166. see also tumors, benign see also eczema (dermatitis)
cystic acne, 134, 135 discoid lupus erythematosus, 64–5.
cysts, 183–6; dermoid, 186; differential diagnosis, 184; see also immunologically mediated skin disorders
epidermoid, 183–4; follicular retention, 186; pilar, dolutegravir, 90
184–5; sebocystoma multiplex (steatocystoma doxycycline, 31, 37, 77, 148
multiplex), 185–6; treatment of, 185 drug eruptions, 74–6; clinical features, 74–6; course and
complications, 76; differential diagnosis, 76; fixed, 75;
incidence, 74; investigations, 76; lichenoid, 76;
D
pathogenesis, 74; treatment, 76
danazol, 59 drug hypersensitivity syndrome, 75
dapsone, 37, 77, 78–9, 143 drug rash with eosinophilia and systemic symptoms
Darier’s disease (keratosis follicularis), 218, 219, 219. (DRESS syndrome), 75
see also keratinization disorders drug-induced angioedema, 57
decubitus ulcer, 154. see also ulcers dupilumab, 102
deep fungus infections, 28–9 dyes, 109
degos acanthoma, 169 dysplastic naevus syndrome (atypical mole syndrome),
delayed pressure urticaria, 57 175–6. see also naevi
demographism, 57 dystrophic epidermolysis bullosa, 81
264 Index
E erythromycin, 31, 92, 95, 143, 148

eccrine hidrocystoma, 160, 168 erythroplasia of Queyrat, 188–9. see also non-melanoma
eccrine poroma, 160, 166, 168. see also tumors, benign skin cancers
eccrine spiradenoma, 166 erythropoietic protoporphyria, 223, 226. see also metabolic
eccrine sweat glands, 8 disorders; porphyrias
ecthyma, 30–1 essential fatty acids, 249
eczema (dermatitis), 96–112; allergic contact dermatitis, eumelanin, 253
109–11; atopic dermatitis, 96–102; common types, 97; exanthematic (maculopapular) reactions, 74
contact dermatitis, 107; discoid (nummular), 104–5, excoriated acne, 139. see also acne
105; eczema craquelée (asteatotic eczema), 105–6, excoriation, 11
106; in elderly, 209; lichen simplex chronicus
(circumscribed neurodermatitis), 106–7, 107; primary F
irritant dermatitis, 107–9; seborrhoeic dermatitis,
fat naevi, 179, 180. see also naevi
102–4; venous (gravitational), 111–2; in venous favus, 24
ulcers, 152
fexofenadine, 59
eczema craquelée (asteatotic eczema), 97, 105–6, 106, 209 fibrohistiocytic tumors, 158–9
elderly skin problems, 207–10; ageing process, 207–8; dry
fibrous histiocytoma, 158–9
and itchy skin, 208–9; eczema, 209; functional skin
filaggrin, 4, 211
changes, 208; management, 210; skin tumors, 209; filiform warts, 41
structural skin changes, 208
fissures, 11
Elidel, 206 flexural/inverse psoriasis, 118, 119
endemic pemphigus, 82
fluconazole, 28, 90; antiretroviral drugs, 91
endocrine disease, 244–5
5-fluorouracil, 187, 188
endothrix, 23 foliaceus, 82
enfuviritide, 90
follicular retention cysts, 186. see also cysts
entry inhibitor, 91 folliculitis, 32, 32–3, 86
eosinophilic granuloma (EG), 230–1. foscarnet, 90
see also reticulohistiocytic proliferative disorders
fungal infections, 19–29; candidiasis, 27–8; deep fungus
epidermal naevus, 166, 176, 177 infections, 28–9; pityriasis versicolor, 19–21;
epidermis, 3–5; defined, 211; differentiation, 211; function
subcutaneous, 28; superficial mycoses, 19–21; tinea
of, 211
(ringworm) infections, 21–6
epidermoid cysts, 183–4. see also cysts furuncles (boils), 32–3
epidermolysis bullosa, 79–81, 81. see also blistering skin
fusidic acid, 31
disorders fusion inhibitors, 90, 91
epidermolysis bullosa acquisita, 80, 81. see also blistering
skin disorders
epidermolysis bullosa simplex, 81
G
epidermolytic hyperkeratosis, 215, 216. see also ichthyosis; ganciclovir, 90
keratinization disorders Gardner’s syndrome, 251
epiloia, 179 gastrointestinal tract and skin, 250–1
epinephrine, 59 generalized pustular psoriasis, 120
epithelioid, 170 genodermatoses, 219–21; anhidrotic/hypohidrotic
Epstein-Barr virus (EBV), 86 ectodermal dysplasia, 221; neurofibromatoses, 220,
erosion, 11 220–1; tuberous sclerosis (epiloia), 219–20
erosive napkin dermatitis, 205 gentamycin, 26
eruptive xanthomata, 229. see also metabolic disorders Gentian violet, 31
erysipelas (St. Anthony’s fire), 31, 31–2 giant cell arteritis, 73
erythema, 14, 18 glomangioma, 159–60
erythema gyratum repens, 244 glomus cell tumor, 159–60, 160
erythema induratum, 35 glucocorticoids, 138
erythema migrans, 53 Golgi-Mazzoni corpuscles, 6
erythema multiforme, 59–60, 60, 250. gonorrhoea, 92
see also immunologically mediated skin disorders; in Gottron’s papules, 71
drug eruptions, 75 Gram-positive bacteria, 29
erythema nodosum, 60–1. see also immunologically granuloma annulare, 229, 229, 246. see also metabolic
mediated skin disorders disorders
erythemato-telangiectatic, 148 gravitational eczema, 111–2
erythrodermic psoriasis, 3, 118 Griscelli syndrome, 254
erythrodontia, 225 guttate psoriasis, 116, 117
Index 265
H immune reconstitution inflammatory syndrome, 89–90;

H2 antihistamines, 59 mucosal lesions, 88; nail changes, 88; pruritus, 88;
haemochromatosis (bronzed diabetes), 226, 258. psoriasis, 88; Reiter’s syndrome, 88; seborrhoeic
see also metabolic disorders dermatitis, 88; skin cancers, 88; treatment of, 90;
Haemophilus ducreyi, 92 xerosis, 88; drug-induced immunodeficiency, 91;
haemosiderin, 15, 258 epidemiology, 84; fungal infections, 86; infectious
haemosynthesis, 222, 224 conditions, 85–6; parasitic infections, 87–8;
Hailey Hailey disease (benign familial pemphigus), 218, pathogenesis, 84–5; treatment of, 90; treatment of
220. see also keratinization disorders cutaneous conditions, 90–1; viral infections, 86
hair cycle, 7, 238 Hodgkin’s disease, 252
hair disorders, 233–4, 233–9; alopecia areata, 235–6, 236; homogentisic acid, 258
androgenetic (pattern) alopecia, 233–5; congenital hormonal therapy, 143
alopecia, 233; diffuse hair loss, 236–7; hair loss horny layer (stratum corneum), 3
(alopecia), 233; overview, 234; scarring alopecia, 237–8; housewives’ dermatitis, 109
telogen effluvium, 237; traction alopecia, 237 human hair cycle, 238
hair follicles, 6–8, 7, 234 human papillomavirus, 41
hair loss (alopecia); alopecia areata, 235–6, 236; humectants, 101
androgenetic (pattern), 233–5; congenital, 233; diffuse, hydrocortisone, 205
236–7; scarring, 237–8; traction, 237 hyper-IgE syndrome (HIES), 93
hair matrix, 7 hyperkeratosis, 187
hair shaft disorders, 238–9 hyperparathyroidism, 251
halo naevus, 255, 256 hyperpigmentation, 257–60; acquired, 257; brown-black
hamartin, 219 pigmentation, 258; circumscribed, 257; congenital, 257;
Hand–Schüller–Christian disease (HSCD), 230–1. diffuse, 257; localized, 259; post-inflammatory, 260
see also reticulohistiocytic proliferative disorders hyperthyroidism, 244–5
Hansen’s disease (leprosy), 36–7; causative organism, 36; hypertrophic lichen planus, 132
clinical features, 36–7; skin depigmentation in, 256; hypoalbuminaemia, 241
transmission, 36; treatment, 37 hypohidrotic ectodermal dysplasia, 221
Harlequin fetus, 216. see also ichthyosis; keratinization hypopigmentation, 253–6; classification of, 254;
disorders generalized, 253–4; management of, 254;
head lice, 49–50 oculocutaneous albinism, 253–4; vitiligo, 254–6
heat urticaria, 57. see also urticaria hypothyroidism, 245
heavy metals, 258
helminthic infestations, 54 I
hemosiderin, 16
Henoch Schönlein purpura (HSP), 72–3. ice pick scars, 134, 136
see also immunologically mediated skin disorders ichthyosis, 97. see also keratinization disorders; acquired,
hepatic disease, 251 216, 218, 243; autosomal recessive congenital, 214;
hepatosplenomegaly, 231 collodion baby, 215–6, 217; comparative features, 217;
hepatotoxins, 222 congenital ichthyosiform erythroderma, 215, 216;
hereditary angioedema, 58 epidermolytic hyperkeratosis, 215, 216; Harlequin fetus,
hereditary coproporphyria, 223 216; lamellar, 214; mode of inheritance, 212; vulgaris
herpes genitalis, 39 (autosomal dominant), 213, 213; X-linked recessive, 214
herpes gladiatorum, 39 idiopathic angioedema, 57
herpes labialis, 12 imiquimod, 188
herpes simplex, 39–40, 86; causative organism, 39; clinical immune reconstitution inflammatory syndrome
features, 39; diagnosis, 39; precipitating factors for (IRIS), 89–90
recurrence, 39; transmission, 39; treatment, 40 immunodeficiency disorders, 93
herpes viruses, 38 immunoglobulins, 83
herpes zoster (shingles), 41, 42 immunologically mediated skin disorders, 56–87; annular
herpetic gingivostomatitis, 39 erythemas, 61–2, 62; autoimmune disorders, 62–3;
Hertoghe’s sign, 245 dermatomyositis, 68–70; discoid lupus erythematosus,
highly active antiretroviral therapy (HAART), 86 64–5; drug eruptions, 74–6; erythema multiforme,
hirsuties, 239 59–60, 60; erythema nodosum, 60–1; Henoch Schönlein
histiocytoma, 158–9 purpura (HSP), 72–3; morphoea, 66–8; polyarteritis
histoplasmosis, 29 nodosa, 73–4; systemic lupus erythematosus, 63–4;
HIV/AIDS, 29; bacterial infections, 86–7; congenital systemic sclerosis, 65–6; urticaria, 56–9; vasculitis, 70–1
immunodeficiencies, 92; defined, 84; dermatological immunosuppresants, 65, 69
manifestations, 85; acne conglobata, 88, 90; cutaneous impetigo contagiosa, 29–30, 30
adverse drug reactions (CADRs), 88; hair changes, 88; impetigo herpetiformis, 122
266 Index
infant skin problems, 204–7; atopic dermatitis, 224; cradle 219–21; Hailey Hailey disease (benign familial pemphigus),
cap, 206; erosive napkin dermatitis, 205; functional 218, 220; Harlequin fetus, 216; ichthyosis, 212, 212–6;
differences, 204; infantile acne, 206, 206; juvenile keratosis pilaris, 213, 217–8; lamellar ichthyosis, 214;
plantar dermatosis, 207; lip-licking cheilitis, 207, 207; neurofibromatoses, 220, 220–1; pachyonychia congenita
management problems, 204; napkin psoriasis, 205; type i and, ii, 219; palmo-plantar keratoderma (tylosis), 219;
napkin rash, 204; seborrhoeic dermatitis, 205; tuberous sclerosis (epiloia), 219–20; xerosis, 212; X-linked
staphylococcal scalded skin syndrome, 206–7 recessive ichthyosis, 214
infantile acne, 139, 139, 206, 206. see also acne keratinocytes, 3, 211
infantile haemangioma (‘strawberry naevus’), 172, 182–3. keratitis, 147
see also naevi keratoacanthoma (molluscum sebaceum), 191–3, 193.
infantile/X-linked agammaglobulinaemia, 93 see also non-melanoma skin cancers
infestation; animal scabies, 48; helminthic, 54; pediculosis keratosis follicularis (Darier’s disease), 218, 219
capitis (head lice), 49; pediculosis corporis (body lice), keratosis pilaris, 213, 217–8
50; pediculosis pubis (public lice), 50–1; scabies, 45–8 kerion, 23
insect bites and stings, 51–4; bedbugs (Cimex lectularius), ketoconazole, 90
53; bees, 53; diagnosis, 53; diseases caused by, 51; fleas, Kindler syndrome, 81
51–2; methods of injury to skin, 51; mites, 52, 53; Koebner’s phenomenon, 114
mosquitoes, 51, 52; papular urticaria, 53; ticks, 52, 52; Krause end bulbs, 6
treatment, 54; wasps, 53 Kwashiorkor, 249
integrase inhibitors, 90, 91
intercellular IgA dermatosis, 82 L
interferons, 190
intermediate filaments, 4 lamellar ichthyosis, 214. see also ichthyosis; keratinization
intraepidermal blistering skin disorders, 78, 82 disorders
intraepidermal epithelioma, 188 Langerhans cell histiocytoses, 230.
intraepidermal epithelioma or squamous cell carcinoma in see also reticulohistiocytic proliferative disorders
situ (SCCI), 188 Langerhans cells, 3, 5
inverse psoriasis, 118, 119 lanolin, 109
involucrin, 5 lasers, 129
L-DOPA, 253
IRIS (immune reconstitution inflammatory
syndrome), 89–90 leg ulcers; decubitus, 154; diagnosis, 156; investigations,
iron, 250 157; ischemic, 153; neuropathic, 154–5; pressure, 154;
ischemic ulceration, 153 pyoderma gangrenosum, 155, 156; vasculitic, 156–7;
isotretinoin, 130, 143–4, 148 venous, 150–3
itching, 16–7 leiomyoma, 160
itraconazole, 28, 90 leishmaniasis, 37, 51; cutaneous, 37–8, 38, 55;
ivermectin, 48, 148 mucocutaneous, 38
lentigo maligna (Hutchinson’s freckle), 197–8, 198, 209
leprosy (Hansen’s disease), 36–7; causative organism, 36;
J clinical features, 36–7; skin depigmentation in, 256;
Jarisch–Herxheimer reaction, 95 transmission, 36; treatment, 37
Job syndrome, 93 Letterer–Siwe disease (LSD), 230–1. see also reticulohistiocytic
junctional epidermolysis bullosa, 81 proliferative disorders
junctional zone, 4, 5–6 leuconychia, 249
juvenile melanoma, 176 levocetirizine, 59
juvenile plantar dermatosis, 207 lichen nitidus, 10, 132
juvenile xanthogranuloma (JXG), 230–2, 231. lichen planopilaris, 132
see also reticulohistiocytic proliferative disorders lichen planus, 14, 130–3; aetiology, 130–1; atophic, 132;
epidemiology, 130; histopathology, 132–3; hypertrophic,
132, 133; lesions, 131; treatment, 133; variants, 132
K lichen sclerosus et atrophicus (LSA), 68, 69
Kaposi’s sarcoma, 88, 201–2 lichen scrofulosorum, 35, 36
keratin, 211; soft, 3; tonofilaments, 4 lichen simplex chronicus (circumscribed neurodermatitis),
keratinization, 3, 5, 211, 212 97, 106–7, 107, 122
keratinization disorders, 211–2; acquired ichthyosis, 216, 218; lichenification, 13
anhidrotic/hypohidrotic ectodermal dysplasia, 221; limited cutaneous systemic sclerosis (lSSc), 65
autosomal recessive congenital ichthyosis, 214; collodion linear IgA disease, 79, 80
baby, 215–6, 217; congenital ichthyosiform erythroderma, linezolid, 31
216; congenital ichthyosiform erythroderma, ichthyosis, lip-licking cheilitis, 207, 207
215; Darier’s disease (keratosis follicularis), 218, 219; lipodermatosclerosis, 152
epidermolytic hyperkeratosis, 215, 216; genodermatoses, lipoma, 158, 160, 161. see also tumors, benign
Index 267
lipomatosis, 158 pseudoporphyria, 226; xanthelasma, 228; xanthoma

loratadine, 59 tuberosum, 228, 228; xanthomata, 227
loricrin, 5 methotrexate, 59, 64, 101, 127, 127, 130
lunulae, 241 methyl amino laevulinic acid, 188
lupus erythematosus; discoid, 64–5; systemic, 63–4 metronidazole, 148
lupus vulgaris, 10, 34 miconazole, 205
Lyme disease, 37, 62 milia, 183–4
lymphangioma circumscriptum, 172, 181 miliaria pustulosa, 12
lymphocytoid, 170 military tuberculosis, 87
lymphoedema, 147 milium, 13
minocycline, 5, 15, 31, 148, 258
M mites (Sarcoptes scabiei var. homini), 45, 52, 53
moisturizers, 101
macrolides, 143 mole, 170–1
macules, 9, 10 Moll’s glands, 8
Madura foot, 28, 29 molluscum contagium, 43, 43
malaria, 51 molluscum sebaceum (keratoacanthoma) this term describes
malathion, 50 a rapidly growing epidermal tumor, 191–3, 193
Malessezia ovalis, 102, 103 Mongolian spot, 174
malignant diseases of the skin, 187–203; melanoma skin Mongolian spots, 259
cancer, 197–201; neoplastic disorders of mesenchymal monilethrix, 239
elements, 201–2; non-melanoma skin cancers, 187–97; morphoea, 66–8; clinical features, 67; course and
T-cell lymphoma, 202–3 complications, 67–8; differential diagnosis, 67;
malignant diseases, skin markers of; acanthosis nigricans, generalized, 67; incidence, 66; lichen sclerosus et
243; acquired hypertrichosis lanuginosa, 243; acquired atrophicus (LSA), 68, 69; pathogenesis, 66; pathology, 67
ichthyosis, 243; acrokeratosis paraneoplastica of Bazex, mosquitoes, 52
243; association with malignancy, 242; bullous mucocutaneous end organs, 6
pemphigoid, 244; dermatomyositis, 244; erythema mucous membrane pemphigoid, 77–8, 80.
gyratum repens, 244; necrolytic migratory erythema, see also blistering skin disorders
243; paraneoplastic pemphigus, 243; pyoderma mupirocin, 31
gangrenosum, 244; sign of Leser Trelat, 244; skin muscle tumors, 164. see also tumors, benign
metastases, 244; Sweet syndrome, 244; tripe palms, 243 Mycobacterium leprae, 36
malignant melanoma, 198–201; classification of, 200; clinical Mycobacterium marinum infection, 35, 36
features, 199; course and complications, 200–1; differential mycophenolate mofetil, 64, 83
diagnosis, 200; in elderly, 209; incidence, 198; mycosis fungoides, 122, 202–3
investigations, 200; nodular, 199, 200; pathogenesis, 199;
rate of progress, 199; treatment, 201
N
Malpighian layer, 4
mammary glands, 8 nadifloxacin, 142
marasmus, 248 naevi, 170–83; acquired, 170–1, 172, 173; adenoma
mask of pregnancy, 260 sebaceum, 172, 179; angiokeratoma, 183; Becker’s
Meissner’s corpuscle, 6 naevus, 176–7, 177; compound, 171; congenital, 170,
melanin, 5, 253 172; connective tissue, 178–9; defined, 170–1;
melanocytes, 3, 5 degenerative changes in, 174; dermal (blue), 174; dermal
melanocytic naevi, 171, 173 cellular, 171–4; dysplastic naevus syndrome (atypical
melanoma skin cancer, 197–201; lentigo maligna mole syndrome), 175–6; epidermal, 176, 177; fat, 172,
(Hutchinson’s freckle), 197–8, 198; malignant 179, 180; infantile haemangioma (‘strawberry naevus’),
melanoma, 198–201 182–3; junctional, 171; melanocytic, 171, 173; naevus of
melanosomes, 253 Ito, 175, 259; naevus of Ota, 172, 174, 175, 259;
melasma, 259 sebaceous, 172, 177–8, 178; Shagreen patch, 172, 178,
membrane-coating granules of lamellar bodies, 4 178; Spitz naevus (juvenile melanoma), 172, 176;
mercaptobenzthiazole, 109 treatment of, 172; tuberous sclerosis (epiloia), 179;
Merkel cells, 5 vascular, 180–3; vascular tumors, 182
metabolic disorders, 222–9; amyloidosis, 226–8, 227, 227; naevocytic naevus, 170–1
congenital erythropoietic porphyria (Gunther’s disease), naevus araneus, 162
225, 225–6; eruptive xanthomata, 229; erythropoietic naevus lipomatodes cutaneus superficialis, 172, 179, 180
protoporphyria, 226; haemochromatosis (bronzed nail disorders, 239–41; Beau’s lines, 241; brittle nails, 241;
diabetes), 226; porphyria cutanea tarda, 222–3, 224; brown–black pigmentation, 241; onycholysis, 113, 240;
porphyria variegata, 226; porphyrias, 222–6, 223; onychorrhexis, 241; paronychia, 239–40, 240; ringworm
268 Index
of the nails (tinea unguium), 241; in systemic orf (contagious pustular dermatitis of sheep), 44
disease, 241 Osler’s sign, 15
napkin psoriasis, 205 osteoporosis, senile, 250
napkin rash, 204
necrobiosis lipoidica, 246, 246 P
necrobiosis lipoidica diabeticorum, 229. see also metabolic
disorders pachyonychia congenita types I and II, 219.
necrobiotic disorders, 229 see also keratinization disorders
necrolytic migratory erythema, 243 Pacinian corpuscles, 6
Nelson’s syndrome, 258 palmo-plantar keratoderma (tylosis), 219.
neonatal acne, 139 see also keratinization disorders
nerve structures, 6 palmoplantar warts, 41
neural tumors, 162–4; neurilemmoma, 164; neurofibroma, PAPA syndrome, 140
162–4, 163; neuroma, 68; von Recklinghausen’s disease, papular pruritic eruption, 88
162–4, 163 papules, 9, 10, 13
neurilemmoma, 160, 164 papulonecrotic tuberculide, 35
neurofibroma, 160, 162–4, 163 papulopustular rosacea, 148
neurofibromatoses, 10, 220, 220–1. see also keratinization parakeratosis, 187
disorders paraneoplastic pemphigus, 82, 243
neuropathic ulcers, 154–5. see also ulcers paronychia, 239–40, 240
nicotinamide, 77 patches, 9, 10
nicotinic acid, 250 pattern (androgenetic) alopecia, 233–5; clinical features,
nodules, 9, 11 233–4; definition, 233; pathogenesis, 234; pathology,
nodulocystic acne, 134. see also acne 234; treatment, 235
non-melanoma skin cancers (NMSCs), 187–97; actinic pediculosis, 47, 48–51; capitis (head lice), 49; corporis
keratosis, 187–8, 188; basal cell carcinoma (basal cell (body lice), 50; pubis (public lice, crab lice), 50–1;
epithelioma), 193–6, 194, 195; basal cell naevus treatments for, 50
syndrome (Gorlin’s syndrome), 196, 196–7; Bowen’s Pediculus humanus capitis (head louse), 48–9
disease, 188, 189, 190; erythroplasia of Queyrat, 188–9; Pediculus humanus humanus (body or clothing louse), 48
keratoacanthoma (molluscum sebaceum), 191–3, 193; pellagra, 250
premalignant lesions, 187–9; squamous cell carcinoma/ pemphigoid gestationis, 80
squamous cell epithelioma, 189–91, 191, 192; pemphigus, 82–3, 83. see also blistering skin disorders
xeroderma pigmentosum, 197 pemphigus foliaceus, 82
non-nucleoside reverse transcriptase inhibitors (NNRTI), 91 pemphigus vegetans, 82
Norwegian scabies, 47–8, 87–8 pemphigus vulgaris, 82
nuchal stain, 180 penicillamine, 66
nucleoside reverse transcriptase inhibitors (NRTI), 91 penicillin V, 32
nucleotide reverse transcriptase inhibitors, 91 pericytic (perivascular) tumors, 159–60. see also tumors,
nummular eczema, 104–5 benign
nutritional deficiency, 249–50; essential fatty acids, 249; perioral dermatitis, 148–9
iron, 250; Kwashiorkor, 249; marasmus, 248; nicotinic periungual warts, 41
acid, 250; selenium, 250; vitamin A (retinol), 249–50; perivascular tumors, 159–60
vitamin C (ascorbic acid), 250; zinc, 250 permethrin, 48, 50
Peutz–Jeghers syndrome, 251, 259
O phaeomelanin, 253
phemphigoid; anti-p200, 80, 81–2; bullous (senile), 77, 78,
occupational acne, 138 79, 80, 243; mucous membrane, 77–8, 80
occupational dermatitis, 109 phenothiazines, 258
ocular rosacea, 148 phosphodiesterase inhibitors, 101
oculocutaneous albinism, 253–4. photodynamic therapy, 188
see also hypopigmentation photosensitive eczema, 209
old age, 207–10; ageing process, 207–8; dry and itchy skin, photosensitivity dermatitis, 97, 250
208–9; eczema in, 209; functional skin changes in, 208; phototoxic dermatitis, 75
management of skin disorders in, 210; skin tumors, 209; phrynoderma, 249
structural skin changes in, 208 Phthirus pubis, 48, 50
omalizumab, 59 physical urticaria, 56–7. see also urticaria
onchocerciasis, 51, 54, 55 pigmentation, drug-induced, 75
one hand-two feet syndrome, 23 pigmentation disorders, 253–60; hyperpigmentation,
onycholysis, 113, 240 257–60; hypopigmentation, 253–6; vitiligo, 254–6
onychomycosis, 26 pigment-producing cells, 5
onychorrhexis, 241
Index 269
pilar cysts, 184–5. see also cysts 113–4; Auspitz’s sign, 113; Koebner’s phenomenon/
pilomatrixoma, 160, 168 isomorphic response, 114, 116; nails, 113, 115;
pimecrolimus, 101, 206 Woronoff’s ring, 113; prevalence rates, 113; pustular,
pityriasis rubra pilaris, 122 119, 119–22, 120; rupioid type, 118; thimble pitting of
pityriasis versicolor, 19–21; causative organism, 86; nails in, 239; treatment, 122–9; biological, 128–9;
clinical features, 20; differential diagnosis, 20; cyclosporin, 127–8; factors in, 123; lasers, 129;
furfuraceous scaling in, 13; investigations, 20; methotrexate, 127, 127; options, 124–5; topical
pathogenesis, 19; risk factors, 20; skin depigmentation therapy, 123–6; ultraviolet radiation, 128; uncommon
in, 256; treatment of, 20, 21 types, 118
Pityrosporum ovale, 86, 103 psoriatic plaques, 14, 15
plaque psoriasis, 116 pubic lice, 50–1
plaques, 9, 10, 15 pustular psoriasis, 119–22; acrodermatitis continua, 122;
plasmapheresis, 83 generalized, 120; impetigo herpetiformis, 122; palmoplantar
Pnemocystis jiroveci, 87 pustulosis, 119, 119–20, 120; in pregnancy, 121
pock scars, 134, 136 pustule, 9
poikiloderma, 13 pyoderma, 87
poison ivy, 109 pyoderma gangrenosum, 155, 156, 244. see also ulcers
polyarteritis nodosa, 73–4 pyrogenic granuloma, 160
popliteal fossa, 14
porphyrias, 222–6, 223. see also metabolic disorders; acute Q
intermittent, 226; acute intermittent porphyria, 223;
quinolones, 143
congenital erythropoietic porphyria, 223; congenital
erythropoietic porphyria (Gunther’s disease), 225,
225–6; erythropoietic protoporphyria, 223, 226;
R
hereditary coproporphyria, 223; porphyria cutanea tarda, raltegravir, 90
222–3, 223, 224; porphyria variegata, 226; ranitidine, 59
pseudoporphyria, 226; variegate porphyria, 223 Raynaud’s phenomenon, 65
port wine stain, 172, 180 Reiter's syndrome, 88, 92
prednisolone, 59, 60, 69, 76 relapsing fever, 50
premalignant lesions, 187–9 retapamulin, 31
pressure ulcers, 154 reticulohistiocytic proliferative disorders, 230–2.
pretibial myxoedema, 245 see also metabolic disorders
primary irritant contact dermatitis, 97 retinoic acid, 143–4
primary irritant dermatitis, 107–9. see also dermatitis retinoids, 90, 102, 126, 127, 130, 133, 142, 148, 188, 190,
(eczema); clinical features, 107–8; definition, 107; 197, 214, 215, 216, 218
differential diagnosis, 108; epidemiology, 108–9; natural retinol, 127
history, 108; prevention and management, 109 rhinophyma, 147
primary lesions, 9 rhinophymatous rosacea, 148
procaine penicillin, 95 Rickettsia prowazekii, 50
Propionibacterium acnes, 140–1 Riehl’s melanosis, 260
protease inhibitors, 91 rifampicin, 32, 37
Proteus syndrome, 158 ringworm (tinea) infections, 21–6; causative organism, 21;
Protopic, 206 clinical features, 21–3; diagnosis, 25–6; lesion
prurigo, 13 morphology, 21, 22; tinea capitis, 23–4, 24, 27; tinea
pruritus, 16–7, 247; in AIDS, 88; in diabetes, 247; scabies, corporis, 21, 27; tinea cruris, 23, 27; tinea incognito, 25;
45; systemic causes of, 251–2 tinea manuum, 23; tinea pedis, 23, 25; tinea unguium,
pseudokoebnerization, 114 24–5, 25, 27, 241, 241; treatment, 26, 27
pseudoporphyria, 226 rituximab, 83
psoriasis, 88, 113–29; acrodermatitis continua, 122; age rolling scars, 134, 136
groups, 113; associations, 121; defined, 113; rosacea, 144–8; aetiology, 145; classification, 144; clinical
differential diagnosis, 122; drug-aggravated/drug- features, 145–6; complications, 147; lymphoedema, 147;
induced, 118, 119; elephantine type, 118; ocular, 147; rhinophyma, 147; definition, 144;
erythrodermic, 118; flexural/inverse, 118, 119; differential diagnosis, 146, 147; epidemiology, 145;
generalized pustular psoriasis, 120; genetics, 115; erythemato-telangiectatic, 148; general management,
guttate, 116, 117; impetigo herpetiformis, 122; 148; lesions, 145; natural history, 146; ocular rosacea,
Koebnerized type, 118; lichenified type, 118; 148; papulopustular rosacea, 148; pathogenesis, 145;
morphological classification, 116–8; palmoplantar pathology, 146; rhinophymatous rosacea, 148; sites
pustulosis, 119, 119–20, 120; pathogenesis, 115–6; affected, 145, 146; treatment, 148
photosensitive type, 118; plaque, 116; presentation, Ruffini corpuscles, 6
270 Index
S skin diseases, 1; disabilities from, 17–8; painful, 17; signs

SAHA syndrome, 140 and symptoms, 9–18; color alteration, 13; primary
salicylic acid, 142 lesions, 9; secondary lesions, 11; special lesions, 11–3;
salmon patch, 180 symptoms of, 16–8
SAPHO syndrome, 140 skin infections, 19–44; bacterial, 29–38; in diabetes, 247;
Sarcoptes scabiei var. homini (mites), 45, 52, 53 fungal diseases, 19–29; viral, 38–44
scabies, 45–8; aetiology, 45; in AIDS, 87; animal, 48; skin metastases, 244
clinical features, 45–6; community outbreaks, 47–8; soft keratin, 3
community treatment, 48; crusted (Norwegian), 47–8, solar keratosis, 166, 209
87–8; diagnosis, 46–7; differential diagnosis, 47; solar urticaria, 57. see also urticaria
epidemiology, 45; treatment, 47; treatment of, 48 sores, 17
scales, 11, 13; ringworm, 22 special lesions, signs and symptoms, special lesions, 11–3
scaling, 211 spider angioma, 162
scalp psoriasis, 114 spider naevus, 160, 162, 162
Schamberg’s disease, 74, 74 spider telangiectases, 162
schwannoma, 164 Spiegler’s tumor, 165–6
scleromyxedema, 232. see also metabolic disorders spinosad, 50
sclerosing haemangioma, 158–9 Spitz naevus (juvenile melanoma), 172, 176
scrofuloderma, 35, 35, 87 sporotrichosis, 28
sebaceous follicles, 7 squamous cell carcinoma in situ (SCCIS), 188
sebaceous gland hyperplasia, 160, 169 squamous cell carcinoma/squamous cell epithelioma,
sebocystoma multiplex (steatocystoma multiplex), 185–6. 189–91, 191, 192, 209. see also non-melanoma skin
see also cysts cancers
seborrhoeic dermatitis, 97, 102–4, 205. see also dermatitis stanazolol, 59
(eczema); aetiopathogenesis, 103–4; in AIDS, 88, 89; staphylococcal scalded skin syndrome, 206–7
clinical features, 102–3; cradle crap, 103; definition, staphylococci, 29
102; differential diagnosis, 103, 104, 122; in elderly, Staphylococcus aureus, 46
209; epidemiology, 104; natural history, 104; signs and stasis dermatitis, 111–2
symptoms, 102–3; treatment, 104 steatocystoma, 11
seborrhoeic keratoses, 160, 164–5, 166 steatocystoma multiplex (sebocystoma multiplex), 185–6
seborrhoeic warts, 164–5, 166 stereotyping as terrorists, cosmetica, 139
sebum, 7–8 steroid acne, 139
secondary lesions, 11 steroids, 61, 65
selenium, 250 Stevens–Johnson syndrome, 75
senile (bullous) pemphigoid, 77, 78, 79, 80, 244. stork mark, 180
see also blistering skin disorders stratum basale, 211
senile angioma, 160, 160–1 stratum corneum (horny layer), 3, 211
senile comedones, 14, 140 streptococci, 29
senile osteoporosis, 250 Streptococcus pyogenes, 46
severe combined immunodeficiency (SCID), 93 Sturge–Weber syndrome, 181
Sézary syndrome, 203 subepidermal blistering skin disorders, 78, 80
Shagreen patch, 172, 178, 178 sulfacetamide, 148
shingles, 41, 42, 86 sulfonamides, 143
sign of Leser Trelat, 244 sulphur (6%) in petrolatum ointment, 48
skin; functions, 1–8, 4; overview, 1; structure, 1–8, 2; superficial basal cell carcinoma, 122
surface, 1–3; surface area, 1 superficial mycoses, 19
skin cancers, 88; actinic keratosis, 187–8, 188; basal cell sweat glands, 8
carcinoma (basal cell epithelioma), 193–6, 194, 195; basal Sweet syndrome, 244
cell naevus syndrome (Gorlin’s syndrome), 196, 196–7; swimming pool granuloma, 35, 36
Bowen’s disease, 188, 189, 190; dermatofibrosarcoma, syphilis, 87, 93–5; causative organism, 93; clinical features,
202; erythroplasia of Queyrat, 188–9; Kaposi’s sarcoma, 93; diagnosis, 94; treatment, 95
201–2; keratoacanthoma (molluscum sebaceum) this term syringocystadenoma papilliferum, 166
describes a rapidly growing epidermal tumor, 191–3, 193; syringoma, 160
lentigo maligna (Hutchinson’s freckle), 197–8, 198; syringoma (syringocystoma), 165, 166, 166
malignant melanoma, 198–201; melanoma, 197–201; systemic agents, 101–2
mycosis fungoides, 202–3; non-melanoma, 187–97; systemic lupus erythematosus, 63–4, 80.
premalignant lesions, 187–9; Sézary syndrome, 203; see also immunologically mediated skin disorders
squamous cell carcinoma/squamous cell epithelioma, systemic sclerosis, 65–6. see also immunologically
189–91, 191, 192; xeroderma pigmentosum, 197 mediated skin disorders
Index 271
T leiomyoma, 164; lipoma, 158, 161; naevi, 170–83; neural

tacrolimus, 62, 67, 101, 206 tumors, 162–4; neurilemmoma, 164; neurofibroma, 162–4,
tar preparations, 101 163; neuroma, 68; pericytic (perivascular) tumors, 159–60;
Targretin, 90 pilomatrixoma, 168; sebaceous gland hyperplasia, 169;
T-cell lymphoma, 202–3 seborrhoeic keratoses, 164–5; senile angioma, 160–1; spider
telangiectasia, 11, 145 naevus, 162, 162; of sweat gland origin, 165–8, 166;
telogen, 7 syringoma (syringocystoma), 165, 166; treatment for, 160;
tetracycline, 148 trichoepithelioma (Brooke’s tumor), 168; tumors of
tetracyclines, 143 epidermal origin, 164–5, 165, 166; tumors, benign, 164;
T-helper lymphocytes, 100 vascular tumors, 160–2; von Recklinghausen’s disease,
theques, 170 162–4, 163
thiouram, 109 turban tumor, 165–6
thrombophlebitis, 244 tylosis (palmo-plantar keratoderma), 219
thyroid acropachy, 245 Tyndal effect, 174
thyroid disease, 244–5 typhus, 50
thyrotoxicosis, 240, 251
ticks, 52, 52 U
tinea (ringworm) infections, 21–6; causative organism, 21; ulcers, 11; chronic, 17; decubitus, 154; diagnosis, 156;
clinical features, 21–3; diagnosis, 25–6; lesion investigations, 157; ischemic, 153; neuropathic, 154–5;
morphology, 21, 22; tinea capitis, 23–4, 24, 27; tinea pressure, 154; pyoderma gangrenosum, 155, 156;
corporis, 21, 27; tinea cruris, 23, 27; tinea incognito, 25; vasculitic, 156–7; venous, 150–3
tinea manuum, 23; tinea pedis, 23, 25; tinea unguium, ulesfia, 50
24–5, 25, 27, 241, 241; treatment, 26, 27 ultraviolet radiation, 128
tinea capitis, 23–4, 24, 27 uroporphyrinogen decarboxylase (UROD), 222
tinea corporis, 27 uroporphyrins, 222
tinea cruris, 23, 27 urticaria, 56–9. see also immunologically mediated skin
tinea incognito, 25 disorders; aquagenic, 57; cholinergic, 56–7; clinical
tinea manuum, 23, 27 features, 56–8; cold, 57; complications, 59; contact, 57;
tinea pedis, 23, 25 course, 59; delayed pressure, 57; demographism, 57;
tinea unguium, 24–5, 25, 27, 241, 241 differential diagnosis, 58; in drug eruptions, 75; heat, 57;
topical corticosteroids, 100–2 incidence, 56; investigations, 58; ordinary, 56;
toxic epidermal necrolysis, 75 pathogenesis, 56; physical, 56–7; solar, 57; treatment,
toxic pustuloderma, 75 59; vasculitis, 57; vibratory, 57
trench fever, 50
Treponema pallidum, 93
V
tretinoin, 142
trichoepithelioma (Brooke’s tumor), 160, 168 varicella, 40–1
tricholemmal cysts, 184–5 variegate porphyria, 223
trichomatricoma, 168 vascular naevi, 180–3
trichorrhexis nodosa, 239 vascular tumors, 160–2, 182
tripe palms, 243 vasculitic ulcer, 156–7. see also ulcers
tropical acne, 138 vasculitis, 70–1, 94. see also immunologically mediated
Trousseau syndrome, 244 skin disorders
trypanosomiasis (sleeping sickness), 51 vasodilators, 66
tuberculosis, 34, 34 Venereal Disease Reference Laboratory (VDRL) test, 94–5
tuberculosis verrucosa cutis (warty tuberculosis), 34 venereal diseases; chancroid, 92; dermatological aspects of,
tuberculous chancre, 35 92–5; gonorrhoea, 92; Reiter’s syndrome, 92;
tuberin, 219 syphilis, 93–5
tuberous sclerosis (epiloia), 179, 219–20, 256. venous (gravitational) eczema, 111–2
see also keratinization disorders venous eczema, 97
tumor necrosis factor (TNF)-alpha, 128 venous ulcer, 150–3. see also ulcers; bleeding, 152; clinical
tumors, 9; benign, 158–86; of epidermal origin, 164–5, 165, features, 151–2; common causes of leg ulcer, 152;
166; soft-tissue, 159 complications, 152; epidemiology, 150; pathogenesis,
tumors, benign, 158–86; adipocytic tumors, 158; apocrine 150–1; treatment, 152–3; venous drainage, 153; wound
hidrocystoma, 166, 166; capillary aneurysm, 161; care, 152–3
classification, 159; clear cell acanthoma (degos acanthoma), verruca plana, 41
169, 170; cylindroma, 165–6; cysts, 183–6; dermatofibroma, verruca vulgaris, 41, 43
158–9, 161; eccrine hidrocystoma, 168; eccrine poroma, verrucous epidermal naevus, 172
168; fibrohistiocytic tumors, 158–9; glomangioma, 159–60; vesicles, 9, 12
glomus cell tumor, 159–60; of hair follicle origin, 168–9; vibratory urticaria, 57
272 Index
viral infections, 38–44, 43; chicken pox, 40–1; herpes Wiskott–Aldrich syndrome, 93
simplex, 39–40; herpes zoster (shingles), 41, 42; Wood’s lamp examination, 27
molluscum contagium, 43, 43; orf (contagious pustular Woronoff’s ring, 113
dermatitis of sheep), 44; viral warts, 41–2 wound healing; factors in, 150; principles of, 150, 151
viral warts, 41–2, 166; causative organism, 41; course, 42;
histopathology, 41; treatment, 42–3
X
virilization (androgenization), 248
vismodegib, 197 xanthelasma, 228. see also metabolic disorders
vitamin A (retinol), 127, 249–50 xanthoma disseminatum (XD), 230–2
vitamin C (ascorbic acid), 250 xanthoma tuberosum, 228, 228. see also metabolic disorders
vitiligo, 254–6. see also hypopigmentation; clinical xanthomata, 227, 247. see also metabolic disorders
features, 254–6; definition, 254; epidemiology, 256; xeroderma pigmentosum, 197. see also non-melanoma skin
macules in, 10; pathogenesis, 256; treatment, 256 cancers
von Recklinghausen’s disease, 162–4, 163, 220, 259, 260 xerosis, 88. see also keratinization disorders
Von Zumbusch’s disease, 120 X-linked recessive ichthyosis, 214. see also ichthyosis;
keratinization disorders
W
Y
Waardenburg syndrome, 254
warty tuberculosis, 34 yellow nail syndrome, 240, 241
wasps, 53
Wassermann reaction (WR), 94–5 Z
wheal, 9
white dermatographism, 98 zidovudine, 90
Wilson’s disease, 251 zinc, 250

Concise Dermatology

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Concise Dermatology

Uploaded by

Copyright:

Available Formats

Concise Dermatology

CRC Press is an imprint of Taylor & Francis Group, LLC

Library of Congress Cataloging-in-Publication Data

ISBN: 978-0-367-53365-6 (hbk)

Typeset in Times New Roman

1. An introduction to skin and skin disease .................................................................................. 1

2. Signs and symptoms of skin disease........................................................................................... 9

3. Skin infections ............................................................................................................................. 19

4. Infestations, insect bites, and stings ......................................................................................... 45

5. Immunologically mediated skin disorders............................................................................... 56

6. Blistering skin disorders ............................................................................................................ 77

7. Skin disorders in AIDS, immunodeficiency, and venereal disease....................................... 84

9. Psoriasis and lichen planus...................................................................................................... 113

10. Acne, rosacea, and similar disorders ..................................................................................... 134

11. Wound healing and ulcers ....................................................................................................... 150

12. Benign tumors ........................................................................................................................... 158

13. Malignant diseases of the skin ................................................................................................ 187

14. Skin problems in infancy and old age ................................................................................... 204

15. Disorders of keratinization and other genodermatoses ....................................................... 211

16. Metabolic disorders and reticulohistiocytic proliferative disorders................................... 222

17. Hair and nail disorders............................................................................................................ 233

18. Systemic disease and the skin ................................................................................................. 242

19. Disorders of pigmentation ....................................................................................................... 253

Index ...................................................................................................................................................... 261

Skin structure and function

The skin surface

ESG D (1–2 mm)

The stratum corneum

• Permeability barrier to water and electrolytes

• Mechanoreceptors (touch, vibration, pressure)

The junctional zone

The dermal vasculature

The adnexal structures

FIGURE 1.4 The hair cycle.

Eccrine sweat glands

Apocrine sweat glands

• Scale: visible exfoliation of the skin,

FIGURE 2.6 Tumor in cutaneous B cell lymphoma.

FIGURE 2.9 Pustules in miliaria pustulosa.

FIGURE 2.10 Furfuraceous scaling in pityriasis versicolor.

Alterations in skin color

• Psoriatic plaques: dark red (Figure 2.15)

FIGURE 2.12 Painful fissures in popliteal fossa in

• Brown pigmentation: caused by a break­

Symptoms of skin disease

FIGURE 2.17 Lower legs of a patient with chronic

Painful skin disorders

Disabilities from skin disease

many skin disorders were caused by neurotic traits,

Fungal diseases of the skin

• Morphology: lesions are characterized by discrete or confluent, scaly, discolored, or depigmented

• Non-pharmacologic therapy: Sunlight accelerates pigmentation of residual hypopigmented areas

FIGURE 3.1 Hypopigmented macules with furfuraceous scaling in pityriasis versicolor.

Tinea (Ringworm) infections/Dermatophytic infections

• Anthropophilic – e.g., Epidermophyton floccosum, Trichophyton mentagrophytes var. Interdigitale,

Morphology of typical lesions

Clinical features of ringworm infection

Differential diagnosis: Discoid eczema, psoriasis

PICTORIAL REPRE SENTATION OF

Ringworm infection of the feet may be

• Dermatophytic infection of the palmar aspect of the hand

FIGURE 3.6 Tinea unguium and pedis.

a. Skin: with scalpel blades from the ac­

FIGURE 3.8 KOH hair mount showing branching fungal hyphae.

• Brown pigmentation: caused by a break

a. Skin: with scalpel blades from the ac

or lower limbs (Figure 3.13). The inflamma

• Lichen scrofulosorum: lichenoid eruptions of papules predominantly in children often peri