C Handbook. Varna - Rev

DERMATOLOGY AND VENEREOLOGY
HANDBOOK FOR MEDICAL, DENTAL AND PHARMACY STUDENTS
FIRST EDITION
Sonya Márina, MD, PhD

Professor of Dermatology and Venereology
Department of Infectious Diseases, Parasitology and Dermatovenereology
Medical University of Varna
Valentina Broshtilova, MD, PhD

Associated Professor of Dermatology and Venereology
Filka Georgieva, MD, PhD

Assistant Professor of Dermatology and Venereology
Zhenya Dimitrova, MD, PhD

Assistant Professor of Dermatology and Venereology
Editors
Sonya Márina, MD, PhD
Valentina Broshtilova, MD, PhD
Reviewer
Jana Kazandjieva, MD, PhD
Associated Professor of Dermatology and Venereology
Department of Dermatology and Venereology
Medical Faculty, Medical University of Sofia
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Preface
This handbook is a humble contribution and modest attemp to provide a comprehensive

teaching guide in dermatology and venereology to English-educated medical, dental and
pharmacy students in Bulgaria.
Ultimately, it may be a useful tool for all Board-preparatory specializing dermatologists.
The every-day practice highly relevant topics can serve as updated reference for both
-expertised dermatologists and other specialists. We hope to meet all educational needs.
Comments from readers for any ommissions or errors would be highly apprecuated.
Authors
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CONTENTS
GENERAL DERMAROLOGY
SKIN EMBRYOLOGY V. Broshtilova
SKIN ANATOMY V. Broshtilova
Epidermis
Dermis
Hypodermis
Skin Vasculature
Appendageal Glands
Hairs
Nails
MUCOUS MEMBRANES V. Broshtilova
SKIN FUNCTIONS V. Broshtilova
DIAGNOSTIC APPROACH TO SKIN DISEASES V. Broshtilova
THERAPY
Systemic Therapy S. Marina, F. Georgieva
Topical Therapy F. Georgieva
Basic Topical Preparations
Topical Preparations According to Mechanism of Action
Physiotherapy
Phototherapy. Lasers F. Georgieva, S. Marina
Cryosurgery. Electrosurgery. Curettage F. Georgieva
Climatotherapy. Thalassotherapy. Balneotherapy F. Georgieva
SPECIAL DERMATOLOGY
DERMATOSES FROM PHYSICAL FACTORS
Dermatoses Caused by Environmental Factors F. Georgieva
Photodermatoses V. Broshtilova, F. Georgieva
ECZEMA/DERMATITIS
Contact Dermatitis F. Georgieva, V. Broshtilova
Atopic Dermatitis V. Broshtilova, F. Georgieva
Seborrheic Dermatitis S. Marina, F. Georgieva
URTICARIA. STROPHULUS V. Broshtilova, F. Georgieva
ADVERSE CUTANEOUS DRUG REACTIONS S. Marina, V. Broshtilova, F.
Georgieva
Fixed Drug Eruption
Drug-induced Urticaria, Angioedema, and Anaphylaxis
Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)
PIGMENTARY DISORDERS S. Marina
Vitiligo
Oculocutaneous Albinism
Melasma
Pigmentary Changes Following Inflammation of the Skin
ERYTHEMATOUS DISEASES S. Marina
Erythema Nodosum
Erythema Multiforme
PAPULOSQUAMOUS, LICHENOID AND ECZEMATOUS DERMATOSESS. Marina
Psoriasis. Parapsoriasis
Lichen Planus
Pityriasis Rosea
IMMUNOBULLOUS DISEASES S. Marina
Pemphigus
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Pemphigoid
Dermatitis Herpetiformis
CONNECTIVE TISSUE DISEASES S. Marina
Lupus Erythematosus
Dermatomyositis
Scleroderma
VASCULITIDES AND VASO-OCCLUSIVE DISEASES S. Marina
Vasculitis
Henoch-Schönlein Purpura
Polyarteritis Nodosa
Urticarial Vasculitis
Chronic Venous Insufficiency
SKIN APPENDICES DISEASES S. Marina
Disorders of Hairs
Non-scarring Alopecias
Alopecia Areata
Androgenetic Alopecia
Diseases of Pilosebaceous Unit
Acne Vulgaris
Rosacea
Perioral Dermatitis
DISEASES OF THE MOUTH S. Marina
MUCOSAL DISEASES S. Marina
Chronic Benign Aphthosis
Behçet’s Disease
BENIGN NEOPLASMS AND HYPERPLASIAS S. Marina
PRECANCEROUS DERMATOSES S. Marina
MALIGNANT SKIN TUMORS
Basal Cell Carcinoma
Squamous Cell Carcinoma
Cutaneous Melanoma. Lentigo Maligna
INFECTIOUS DISEASES S. Marina
Viral Infections
Human Herpesviruses Diseases
Herpes Simplex
Herpes Zoster
Human Papillomavirus Infections
Common, Plantar, and Flat Warts
Condyloma Acuminata
Poxvirus Diseases
Molluscum Contagiosum
Orf
Bacterial Infections
Pyococcal Infections
Staphylococcal Infections
Streptococcal Infections
Mycobacterial Infections
Tuberculosis
Leprosy
Spirochetal Infection
Lyme Disease
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Fungal Infections
Tinea Versicolor
Dermatophytosis
Candidiasis
Ectoparasitic Diseases
Scabies
Pediculosis
VENEREOLOGY Zh. Dimitrova
SEXUALLY TRANSMITTED INFECTIONS (STIs)
Classification, Epidemiology, Diagnosis, Treatment, Patient Education, Prophylaxis,
Public Health Considerations
SYPHILIS
Epidemiology, Etiology, Classification
Pathogenesis, Immunity, Allergy, Superinfection and Reinfection
` Primary Syphilis
Secondary Syphilis
Tertiary Syphilis
Congenital Syphilis
Early Congenital Syphilis
Late Congenital Syphilis
Serologic Diagnosis of Syphilis
Therapy of Syphilis. Endotoxine Shock (Jarisch-Herxheimer)
GONORRHEA
Epidemiology, Etiology, Pathogenesis
Gonorrhea in Men
Gonorrhea in Women
Disseminated Gonococcal Infection
Gonorrhea in Children
Diagnosis and Therapy
URETHRITIS
Classification of Urethritides. Epidemiology
Sexually-transmitted Urethritis
Not – sexually Transmitted Urethritis
HIV INFECTION AND AIDS
Epidemiology, Etiology, Pathogenesis, Clinical Classification
Cutaneous and Mucosal Manifestations of HIV Infection
Diagnostic Approach. Diagnosis of HIV
Therapeutic Principles. Therapeutic Approach
Prevention of HIV
BALANITIS AND BALANOPOSTHITIS
VULVITIS AND VULVOVAGINITIS
CHLAMYDIAL GENITAL INFECTIONS
TRICHOMONIASIS
5
GENERAL DERMATOLOGY
Definition
Dermatology is a medical specialty with a focus on the diagnosis and treatment of skin
disorders (Greek, derma – skin, logos – science). Skin (integumentum) is the largest organ of
the body in surface area and weight, which consists of different tissues that are joined to
perform a specific function (hair, nails, sweat and sebaceous glands, mucous membranes).
Skin Embryology
Ectoderm starts to form the skin as a single layer during the 3rd week of gestation. At the 6th
week it differentiates towards outer flattened periderm and inner, cuboidal (germinal) layer,
from which the entire epidermis evaluates. The fetal basal membrane appears in the 7th week,
together with the primordial tooth. The epidermal stratification begins in the 8th week and is
totally completed till the end of the second trimester. The other cytological components of the
epidermis - melanocytes, Langerhans cells and Merkell cells populate it till the 12th week.
Dermal-subcutaneous boundary district appears from 8th to 12th week. The full differentiation
of dermal-epidermal junction with the formation of anchoring filaments and
hemidesmosomes ends in the beginning of the second trimester. At that time the primordial
hairs and nails appear. Nail bed starts to keratinize between the 12-14th week, together with
the formation of collagen type III, parallel ectodermal ridges, eccrine and sebaceous
primordia. Till the end of the 14th week fibroblasts begin to actively synthesize collagen and
elastin. Melanin production starts till the 16th week, while the melanosome transfer begins at
the 20th week. The full differentiation of hair follicle completes till the 24th week, at which
time the epidermis matures and starts normal keratinization. Last, the adipocytes appear.
Skin Anatomy
The integumentum is a flat, tight complex and highly-specified organ that cover the whole
body surface. Its area is 1.5-2 m²; the depth varies from 0.1 mm at the eyelid to 4 mm at the
palmar-plantar zones. The subcutaneous fat is most pronounced on the abdomen and back (up
to 4 cm). The total skin weight is 3.5 kg, which is 5-7% of the whole body weight. The skin
surface is figurated by linear and rhomboidal fine lines named: “sulci interpapillaris et
intercristales”, as those on the fingertips are individually specific and served as a clue of
personification (dermatoglyphs).
Histologically, skin is divided into three layers: epidermis, dermis and hypodermis (subcutis).
Epidermis
The epidermis is the mechanical and antimicrobial barrier which prevents the trans-epidermal
water loss and provides immunological protection. Its thickness varies from 0.04 mm of the
eyelid to 1.5 mm on palmo-plantar zones. Histologically, it is divided into four layers:
stratum basale (germinativum) – presented by cuboidal actively mitotic stem cells; stratum
spinosum – polygonal cells, attached with desmosomes; stratum granulosum – flattened cells
with deteriorating organelles and cytoplasm, full of lamellated granules of released lipids and
keratohyalin; and stratum corneum – dead cells represented by flat membranous sacs filled
with keratin and glycolipids in the extracellular space.
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Basement Membrane Zone
The dermal-epidermal junction is a selective barrier that allows interaction between the two
areas and provides anchoring of the epidermis towards the dermis. It contains four distinct
zones on electron microscopy: inferior portion of basal keratinocytes, lamina lucida, lamina
densa and sublamina densa. The first area is represented by the hemidesmosomal
macromolecules – BPAG1 (230 kDa), BPAG2 (180kDa), α 6-β 4 integrin and plectin. Lamina
lucida is the electron-lucid space under hemidesmosomes and is the most fragile and weakest
link in basement membrane zone. It contains anchoring filaments, perpendicularly stretching
from the plasma membrane to lamina densa, represented by laminin 1, fibronectin, uncein,
and entactin. Lamina densa is the major component of basement membrane zone, presented
by cross-linked sheet-like collagen IV fibers and laminin-5, providing high flexibility and
elasticity. The anchoring fibrils in sublamina densa contain collagen VII and fibrillin. They
interact with banded collagen fibrils of papillary dermis to form fan-shaped clumps.
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Melanocytes
These are pigment-producing dendritic cells, derived from neural crests to reside in the basal
layer of the epidermis, hair, uveal tract of eye, leptomeninges, and inner ear. The process of
migration and survival of melanoblasts depends on specific interactions, mainly c-kit
activation. Normally, one melanocyte rates ten basal keratinocytes and distributes
melanosomes to 36 keratinocytes (epidermal-melanin unit).
Langerhans Cells
Langerhans cells are bone-marrow-derived dendritic cells with monocyte-macrophage
lineage, found in stratum spinosum. They constitute 3-5% of all epidermal cells, to which
they connect via E-cadherin receptors. Histochemically, feature actin and vimectin. Their
function is critical in recognizing and presenting foreign antigen to specific T lymphocytes.
On electron microscope, Langerhans cell contain Birbeck granules – rod-shaped or tennis
racquet-like organelles with striated appearance. UV exposure depletes these cells and
decreases their ability to present antigens.
Merkel Cells
Neural crest or ectoderm-derived cells functioning as mechanoreceptors found among the
basal keratinocytes, staining positive for S-100. They have greater density on areas of high
tactile sensitivity such as lips, fingers, hair outer root sheath, and oral mucosa. A battery of
neuropeptides and neurotransmitter-like substances – neuron-specific enolase (NSE),
vasoactive intestinal peptide (VIP), calcitonine gene-related peptide (CGRP), chromographin
A, synaptophysin, etc. - are presented in their cytoplasm. Immunohistochemically, they are
identified by cytokeratin 20.
Dermis
Dermis is the mesodermal-derived component of skin, divided into superficial (papillary) and
deep (reticular) compartment, containing larger collagen bundles and mature branching
elastic fibers. The major dermal constituents are a family of fibrous collagen proteins with
more than twenty genetically distinct types identified up to now, which provide structural
stability. They account for 70-80 % of dry dermis weight. Collagen is a triple-helix
configuration, composed of glycin, proline and hydroxylysine or hydroxyproline. It is
degraded by a group of interstitial collagenases – metaloproteinases. Collagen synthesis is
stimulated by retinoic acid and inhibited by IL-1, glucocorticosteroids, D-penicillamine, UV
radiation, TNF-α. Elastic tissue is a continuous network spanning from lamina densa. It
represents 4% of dry dermis weight and provides skin elasticity. The elastin-specific amino
acids are desmosine and isodesmosine. They are produced and cross-linked via the
copper-dependent enzyme - lysyl oxidase. Elastic fibers are represented by two complex
structures: oxytalan – running perpendicular in the papillary dermis and eulanin – parallel
thicker fibers in the reticular dermis. UV radiation damages elastic tissue, thus dermal
elastosis is the hallmark of photo-aging. The amorphic gel-like medium, embedding the
connective tissue fibers, is called ground substance. It is primarily composed of
proteoglycans – core protein, attached to peripheral glycosoaminoglycans such as hyaluronic
acid, dermatan sulfate, heparin sulfate, chondroitin sulfate. It functions as water reservoir and
lubrication between collagen and elastic fibers. With aging hyaluronic acid and dermatan
sulfate contain decrease, while chondroitin sulfate becomes more. Deficiency in lysosomal
hydrolases that normally cleave the glycosaminoglycans results in pathological accumulation
of acid mucopolysaccharidoses. In the dermis of distal extremities, modified smooth muscle
cells that allow shunting of blood from arterioles to venules without going through the
capillaries are presented – the so-called: “glomus cells”.
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Hypodermis
A subcutaneous layer of loose connective tissue, the hypodermis (subcutis) is the skin
interaction to the underlying structures. The hypodermis is the microscopically lightest layer
visible and consists mainly of adipose tissue. Dense connective tissue strands extend from the
dermis to form the septal hypodermal component that divides islands of adipocytes, grouped
into lobules (lobular hypodermal component). Remarkably, the central part of the adipose
lobule contains an arteriole, while the venous, lymph vessel and nerve retain in the peripheral
septal part.
Skin Vasculature
Three distinct horizontal plexuses exist in the skin: subpapillary, dermal-hypodermal and
hypodermal. The subpapillary plexus is the most superficial one. It lies between the papillary
and reticular dermis, forming ascending nutritional arterioles toward the epidermis. The
second plexus lies close to the dermal-hypodermal junction. It provides arteries to the sweat
glands and hair follicles. The deepest plexus extends into the hypodermis. Vertical vascular
arcades provide constant interaction between all three plexuses.
Appendageal Glands
Eccrine Sweat Glands
Eccrine sweat glands are universally distributed all over the body surface with the exception
of clitoris, glans penis, labia minora, external auditory canal and lips. Their total number is
2-5 mln. Histologically, they are presented by a secretory coil at the border of the deep dermis
and subcutaneous fat that consists of glycogen-rich pale cells and smaller darker cells, fitting
together in one layer, and myoepithelial cells; a straight duct stretches within the dermis,
consisting of double layer-cuboidal epithelium, lined by eosinophilic cuticle and upper most
acrosyringium – intraepidermal spiral duct - which opens to the skin surface. Eccrine glands
possess cholinergic innervation, stimulated by acetylcholine.
Apocrine Sweat Glands
A part of the pilo-sebaceous unit, they are genetically confined to axillae, breast, ano-genital
region, external auditory canal (ceruminous gland) and eyelids (Moll's glands). They secrete
via decapitation and respond mainly to sympathetic adrenergic stimuli.
Sebaceous Glands
Formed initially as outgrowth from upper portion of hair follicle, they contain lobules of
pale-staining cells, characterized by lipid vacuoles. Their secretion is holocrine with
distention of sebocytes into the excretory canal lumen. Almost all sebaceous glands open into
the common pilo-sebaceous ostium. Free openings on skin surface feature the sebaceous
gland on the following locations: eyelid margins – Zeis glands; tarsal plate of eyelid –
Meibomiam glands; nipple and areola – Montgomery tubercle; external fold of prepuce –
Tyson's glands; vermilion border of the lips and buccal mucosa – Fordyce spots. The
sebaceous glands are under adrenergic control and enlarge due to androgenes at puberty. The
lipid composition of sebum contains 57% triglycerides, 25% wax esters, 15% squalene, less
than 3% cholesterol and cholesterol esters.
Hairs
Pilo-sebaceous unit is a complex, ectodermal structure in close interaction with dermal
mesenchymal papilla. It is positioned at an angle, typically within the subcutaneous fat. Each
hair consists of modified keratin and is divided into the hair shaft (a keratinized tube) and
hair bulb (actively dividing cells, and melanocytes which give pigment to the hair).
The average number of hairs on the scalp is 100 000. New follicles cannot develop in adult
skin. Normally, up to 100 hairs are lost every day. There are 3 main types of hair: lanugo hair
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(fine long hair in fetus); vellus hair (fine short hair on all body surfaces, non-medullated and
non-pigmented); and terminal hair (coarse long hair on the scalp, eyebrows, eyelashes and
pubic areas). They are medullated and pigmented. The shape of follicle defines the
appearance of hair – round follicle results in straight hair, while oval follicles form curly
hairs.
Longitudinally, the hair is presented by infundibulum – the upper portion of follicle
extending from the surface of the epidermis to the sebaceous gland opening; isthmus –
middle portion extending from the sebaceous gland opening to the insertion of arrector pili
muscle, where the bulge zone of hair follicle stem cells is located; and inferior segment or
lower hair follicle extending from base of isthmus to hair bulb, consisting of matrix cells,
inner root sheath that envelop the protruded into the hair bulb mesenchymal dermal papilla,
non-keratinizing outer root sheath, and bulb melanocytes to provide melanosomes for hair
color.
The cross-section anatomy of hair follicle includes seven concentric layers, which are
(outside-to-inside): glassy membrane (dermal root sheath); outer root sheath (external
epithelial root sheath); Henle's inner root sheath (outer layer of the internal epithelial root
sheath); Huxley's inner root sheath (middle layer of the internal epithelial root sheath); cuticle
inner root sheath (inner layer of the internal epithelial root sheath); hair shaft cuticle; cortex
and medulla.
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Physiologically, each hair goes through three different growth cycles. Anagen is the hair
growth phase, which usually lasts 3-6 years for the scalp hairs and its duration determinates
the hair length. Usually a scalp hair grows 0.4 mm/day. Eighty five percent of hairs
demonstrate this cycle at any one time. The transitional phase of bulb regression and loss of
inner root sheath is called catagen. Up to 5% of the hairs demonstrate this cycle at one time.
Its duration is 2-4 weeks for the scalp hairs. Telogen is the resting phase of hair follicle,
which at that time is club-shaped. In the scalp it lasts 3 months and involves up to 15% of
hairs. The hair shaft is stabilized through disulfide bonds formed by the sulfur-containing hair
keratins. Melanocytes in matrix area of hair follicle couple only in anagen. No pigment is
produced during the catagen and telogen phase.
Nails
Nail apparatus is composed of nail plate, nail bed, nail matrix, lateral and proximal nail folds
and hyponychium. Nail matrix contains the germinative cells of nail apparatus, which are
analogous to the keratinocytes of basal epidermal layer. It is a wedge-shaped area, divided
into proximal and distal portion. The hemispheric paler zone, called lunula, represents the
distal compartment of nail matrix. Melanocytes also reside in the nail matrix, mainly in its
distal portion. Nail plate consists of fully cornified cells – onychocytes – created by the nail
matrix epithelium. Proximal nail matrix synthesizes the dorsal aspect of the nail plate, while
the distal nail matrix creates the ventral surface of the nail plate. Nail plate is firmly attached
to the underlying nail bed. The pink color of the nail plate is due to the longitudinally situated
subungual capillaries. The proximal nail fold is closely attached to the nail bed via the
eponychium or cuticle. The growth rate of fingernails is 2-3 mm/month, and of toenails – 1
mm/month. Complete replacement of nail requires 6 months for fingernail and 18 months for
toenail. Pathology of the nail may involve: abnormalities of the nail matrix e.g. pits and
ridges; abnormalities of the nail bed e.g. splinter hemorrhage; and abnormalities of the nail
plate e.g. discolored or thickened nails.
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Mucous Membranes
The oral and genital mucosa consists of stratified squamous epithelium and an underlying
connective tissue termed lamina propria. Keratinized stratified squamous epithelium can be
found on the dorsum of the tongue, hard palate and attached gingiva, labia minora et majora,
prepuce and clitoris. Non-keratinized stratified squamous epithelium covers the soft palate,
inner lips (labial mucosa), inner cheeks (buccal mucosa), the floor of the mouth (alveolar
mucosa), the ventral surface of the tongue and the vagina.
The dorsal surface of the tongue is lined by specialized mucosa that contains nerve endings
for general sensory reception and taste perception. Anatomic landmarks of the tongue, four
types of papillae exist: filiform are regularly distributed in its anterior part, intermingling
with fungiform papillae. The posterior compartment consists of laterally spread foliate
papillae and central V-line of circumvallate papillae.
Readily transformation of non-keratinized to keratinized type of epithelium may occur upon
frictional or chemical trauma. This process of hyperkeratinization usually affects buccal
mucosa with the formation of a horizontal linear plaque called linea alba. Higher risk of
hyperkeratinization is associated with bruxism, HPV infections, alcohol and tobacco use.
Lamina propria is a connective-tissue proper that features two layers: papillary and dense in
full analogy with their dermal equivalents. The higher amount of plasma cells and nerve
tissue is distinguishable feature of the superficial layer of the lamina propria. The submucosa
is transiently seen depending on the oral cavity region. It overlies bone or muscle structures
and contains loose connective or adipose tissue, and salivary glands. Misplaced sebaceous
glands (Fordyce spots) in the submucosa may be seen in a variable number throughout the
non-keratinized epithelium.
Skin Functions
Protective Barrier against Environmental Insults
Keratopoesis is the process involved in formation of the skin barrier. Keratinocytes comprise
80-85% of the epidermal cells. Epidermal self-renewal termed: “turn-over time”, maintained
by stem cells in the interfollicular epithelium and bulge region of the hair follicle, lasts 45-60
days as keratinocytes migrate from basal to corneal layer for 30-50 days and desquamate 15
days later. During this time, the keratinocytes complete the process of keratinization to
produce intermediate filaments which form the cytoskeletal network to provide integumental
resilience and structural integrity. The final result is the formation of highly cross-linked
lipid-rich flexible structure, enveloping the corneocytes and serving as insoluble exosceleton
and rigid scaffold for internal keratin filaments.
Melanin Synthesis
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Melanogenesis is the process of melanin pigment synthesis and its subsequent transfer to
keratinocytes, providing absorption and protection from UV radiation. Melanin is synthesized
in a specialized type of lysosome named “melanosome” that passes through four stages of
maturation before being transferred to keratinocytes via phagocytosis of melanocyte tips.
Melanin synthesis starts from the protein tyrosine by the copper-dependent enzyme
tyrosinase through DOPA and DOPA quinone to form two types of melanin – eumelanin
(brown to black, stored in oval melanosomes) and pheomelanin (yellow to red,
sulfur-containing melanin, stored in round lamellar melanosomes). Melanogenesis is
stimulated by melanocyte-stimulating hormone (MSH), which is derived from larger
precursor propiomelanocortin (POMC), from which adrenocorticotropic hormone (ACTH) is
also produced. Loss of function mutation in melanocortin-1 receptor (MC1R) results in
over-expression of pheomelanin with fair skin, which is more prone to UV damage and with
higher melanoma risk. The follicular melanocytes rate one to five keratinocytes and the
gradual decrease in their function results in graying of hair. Chronic sun exposure causes
formation of larger melanosomes. All races have same melanocyte density. The dark-skinned
people have larger melanosomes, quicker melanization and less melanosome degradation.
They transfer their melanosomes as individual organelles in contrast with light-skinned
individuals who has smaller melanosomes and transfer them in membrane-bound clusters.
Sensation
Sensory receptors are evenly distributed throughout the whole body surface area. They are
divided into corpuscular (which contain nervous and non-nervous components) and free
nerve endings. Immunohistochemically, they are identified by S-100 and neurofilaments
staining. Free nerve endings are rapidly adapting receptors of non-myelinated C-type fibers
and a few myelinated A-δ-type fibers. They terminate into the epidermis or superficial
papillary dermis and detect touch, pressure and pain. The corpuscular receptors are divided
into nonencapsulated – Merkel cells (found in the basal layer in close contact with sensory
nerve terminal, detectors of touch) and encapsulated – Vater-Pacini corpuscle (rapidly
adapting mechanoreceptor of deep pressure and vibration resembling an onion, found on
dermis/subcutis with greater density on palms, soles, nipples and ano-genital region);
Meissner's corpuscle (elongated mechanoreceptor for light touch, located just below the
dermal-epidermal junction with highest density in palmo-plantar skin); Ruffini corpuscle
(thin fluid-filled slow adapting receptor for continuous pressure, located in the deep dermis);
and Krause end bulbs (mucocutaneous receptors on vermillion border, perianal region, glans
penis, clitoris, and labia minora).
Temperature Regulation and Secretory Function

Skin prevents from hyper- or hypothermia through coordination of blood vasculature and
eccrine sweat glands function. Vasoconstriction and vasodilation regulate the
thermo-convection and conduction. The perspiration can increase to 12 l per day during
extreme physical exertion and high external temperature. Sweat contains 98% water, 1%
sodium chloride, and 1% organic compounds such as urea, uric acid, ammonium, and lactic
acid. The toxic substances (mercury, arsenic, carbohydrate, cyanohydrate, etc.), halogenic
substances, and medications are excreted through the sweat.
Vitamin D Synthesis
Vitamin D is a fat-soluble steroid prohormone with endocrine, paracrine and autocrine
functions. The endocrine effects of vitamin D are mainly involved in control the levels of
calcium found in the bloodstream by constantly allowing calcium and phosphate absorption
from the intestine or taking calcium from bones. The paracrine and autocrine effects of
vitamin D depend on genetic transcription, unique to the type of cell expressing nuclear
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vitamin D receptors, which inhibit cell proliferation, promote cell differentiation, and
apoptosis. Vitamin D precursor 7-dehydrocholesterol in the plasma membranes of both
epidermal basal and suprabasal keratinocytes and dermal fibroblasts is converted to
previtamin D3 through exposure to UV light with the spectral range (255–330 nm) and a
maximum effect at 295 nm. A whole body exposure to UVB radiation for 15-20 min is able
to induce the production of up to 250 μg vitamin D (10 000 IU). Extended photoexposure
results in conversion of previtamin D3 to the inactive photoproducts - lumisterol and
tachysterol - which balances the cutaneous biosynthesis of vitamin D3 as a feedback loop.
Immunosurveillance
The skin provides the first defense line against a broad array of microbial pathogens and
mechanical triggers via a versatile complex of active mechanisms. The unique interaction
between skin innate and adaptive immune factors serves as a model for immune function at
epithelial-cell interfaces with the environment. The skin innate immunity acts as rapid but
less specific first line defense with no memory function that recognizes non-specific
pathogens by unspecific receptors.
The specificity of immune reaction is a function of adaptive immunity. It is presented with a
delayed initial but more specific response due to individual antigen-induced gene
rearrangement, utilized by T- , B- lymphocytes and Langerhans cells under the control of
IL-2, IL-4, IL-5, IFN-γ, TGF-β and classical complement. Keratinocytes are also a major
source of cytokines, including the proinflammatory TNF-α, IL-1, IL-6, IL-18, the neutrophil
chemotaxis-induced IL-8, and anti-inflammatory IL-10.
Langerhans cells, together with dendritic cells, are the main antigen presenting cells in the
skin. Derived from bone marrow, they host in the epidermis, watchfully capture specific
antigens, bind them to major histocompatibility complex (MHC) molecule and thus present
them to the T cells in the regional lymph nodes. Th1 mediate delayed-type contact
hypersensitivity reactions, enhance cell-mediate immunity, activate macrophages and produce
high levels of IL-2, IL-12, IFN-γ, and TNF-α. Diseases with Th1 prototype are allergic
contact dermatitis, tuberculoid leprosy, cutaneous leishmaniasis, psoriasis, erythema
nodosum. Th2 cells upregulate humoral immunity by producing IL-4, IL-5, activate
eosinophils, induce IgG4 and IgE, and downregulate Th1 response via IL-10. Th2 provides
optimal protection against viruses, extracellular bacteria and parasites. Diseases with Th2
profile are atopic dermatitis, lepromatous leprosy, Sezary syndrome, and parasitic
infestations.
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Cosmetic Appearance
The physical appearance is of great social impact. Cosmetology is a branch of dermatology
that deals with the problems of aging. It investigates the physiological aging process and its
concomitant pre-matured phenomena, e.g. photoaging.
Diagnostic Approach to Skin Diseases

Dermatological History
The standard structure of history taking is followed; however, some specific details are taken
into consideration. Presenting complaints are discussed according to their nature, localization
and duration. The subjective symptoms, particularly itch and pain, together with aggravating
and relieving symptoms have to be identified. Previous and current treatment modalities,
recent contacts, travel, and stressful events are specified. History of sunburn and/or use of
tanning machines are confronted to skin type. Personal and family past medical history and
history of atopy – asthma, allergic rhinitis, and eczema, together with occupational and social
details, are taken. Medications that are regularly or recently used and allergies have to be
identified. Impact on quality of life due to skin conditions is also assessed.
Physical Examination
Four important principles are strictly implemented – inspect, describe, palpate and make a
systemic check. The general observation requires description of the location and number of
lesions, pattern of distribution and configuration. The lesions can be generalized
(erythroderma - involving more than 90% of the body surface area), widespread, extensive,
localized to certain body area (flexural – at the body folds; extensoral – on knees, elbows,
shins; on pressure areas); with typical distribution – zosteriform (affecting the dermatomes),
photosensitive (on photoexposed areas), Blaschko lines (following the embriological
ectodermal compartments). Configuration of lesions refers the pattern or shape of grouped
lesions – discrete, separated from one another, confluent, linear, annular (circular), discoid
(round-shaped), nummular (as a coin), targetoid (in a dartboard-like fashion). The individual
lesion is always specified according to the SCAM algorhytm: Size, Shape, Colour,
Associated secondary change and Margins. Upon palpation the surface, consistency, mobility,
tenderness and temperature are assessed. The specific dermatological evaluation also includes
nails, scalp, hair and mucous membranes.
From a deductive point of view, skin lesions are divided into seven groups according to their
specific morphology and pathogenicity.
Macular Skin Lesions
Lesions due to change in skin colour. They divide in 6 subgroups:
1. Macula hyperemica - hyperemic macules (formed through active or passive hyperemia) –
flat, erythematous patches that fades in vitropressure. According to size, there are: roseola (a
small one); erythema (up to the size of a palm) and erythroderma (extended to more than
90% of the body surface area).
2. Macula anemica - anemic patch due to lack of blood vasculature or blood spasm.
3. Macula hyperchromica - hyperchromic (hyperpigmented) patch due to melanocytic
proliferation, evaluated via the ABCD rule - Asymmetry, Borders, Color, and Diameter (>
6mm) or impared melanin function (postinflammatory hyperpigmentation).
4. Macula achromica – hypopigmented patch due to congenital defect of melanin production
(albinism) or acquired melanin dysfunction (vitiligo, postlesional hypopigmentation).
5. Macula teleangiectatica – a spider-like dilation of capillary loops, either congenital (naevus
araneus) or inflammatory (rosacea, lupus erythematosus).
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6. Hemorrhagic macules - due to interstitial erythrocytic extravasation. Never fades upon
vitropressure. According to size, there are: petechia (pinpoint lesions), ecchymosis (larger
lesions) and suffusion (deeper lesions).
An erythematous macule on the mucosal membranes is called enanthema.
Papular Skin Lesions
These are skin lesions that are infiltrated and slightly elevated above the skin surface. Papules
have a diameter up to 1 cm. According to their size, there are: miliar (as a grain); lenticular
(as a lens); gutate (as a drop) and nummular (as a coin). Confluence of papules leads to the
development of plaques, have a larger than 2 cm diameter. Nodules are deeply localized and
firmer on palpation. Tumors are solid, firm and when lobulated as cauliflower termed:
vegetation. The wheal is well-defined, erythematous papule or plaque that lasts less than 24
hours and is caused by transient dermal edema. Lichenification is well-defined roughening of
skin with accentuation of skin markings.
Exudative Skin Lesions
Vesicule is an intra- or subepidermal lesion, which contains serous exudate and has a
diameter up to 1 cm. Larger lesions are termed – bullas (blisters). If the exudate is pustular,
the lesion is called pustule. A cavity with a pre-existing lining, filled with serous exudate, is
called cyst; and if the exudate is pustular – abscess.
Disrupted Skin Lesions
These lesions appear upon skin surface damage. If the defect does not penetrate the
dermal-epidermal junction, erosion appears. Deeper defects lead to formation of ulcer.
Rhagada is an epidermal crack often due to excess dryness, usually affecting the
palmar-plantar skin. Fissure is a linear epidermal defect which appears at the orificial sites.
An excoriation is a loss of epidermis following mechanical friction, usually due to scratching.
It serves as an objective evidence of itch.
A mucous ulcer with fibrous coating and erythematous border is called aphthae.
Discard Skin Lesions
Scales are dry, exfoliating flakes on the surface of a papular lesion. Rough surface consisting
of dried serum, blood, bacteria and cellular debris that has exuded through an eroded
epidermis is a crust. Solid, firm keratotic material into the follicular orificium is called
comedon. Eschara is a well-demarcated dry necrosis of the skin.
Skin Lesions Due to Change in Structure and Volume of Skin Elements
A scar (cicatrix) is a new fibrous tissue which occurs post-wound healing, and may be
atrophic (thinning), hypertrophic (hyperproliferation within wound boundary), or keloidal
(hyperproliferation beyond wound boundary). Atrophy refers to adiminution of some or all
layers of the skin. Epidermal atrophy as cigarette paper-like wrinkling, dermal with loss of
connective tissue and depression. Striae are linear areas which progress from purple to pink
and white, with the histopathological appearance of a scar. Poikiloderma is skin atrophy
presented with hypo- or hyperpigmentations and teleangiectasias.
Lesions that appear de novo as an initial manifestation of a skin disorder are primary. These
are: macule, papule, nodule, tumor, wheal, lichenification, vesicule, bulla, pustule and
abscess. Secondary lesions are those evolving upon primary: erosion, ulcer, scale, crust, scar
and atrophy.
Skin Histopathology Changes

The evaluation of epidermal and dermal histopathological phenomena verifies specific
dermatological dysfunction and confirms the clinical diagnosis. Specific changes have been
described in all skin compartments. The epidermal changes encompass: hyperkeratosis –
thickened corneal layer due to elongated turn-over time; hypergranulosis – thickened granular
cell layer; hypogranulosis or agranulosis – thinning or absence of granular cells due to
shortened turn-over time; acanthosis – thickening of the epidermis due to increased number
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of spindle keratinocytes; spongiosis – intercellular edema; inflammatory cell extravasation –
migration of inflammatory cells into the epidermis – either neutrophils – in infections or
sterile pustular dermatoses, or lymphocytes – in eczemas; epidermotropism – invasion of
atypical lymphoid cells in primary T-cell lymphomas; reticular degeneration – profound
spongiosis which leads to loss of desmosomal contacts as seen in acute eczemas; balloon
degeneration – viral invasion of keratinocytes leading to intracellular edema and subsequent
osmotic cell degeneration; suprabasal acantholysis – loss of desmosomal contacts above the
basal keratinocytic layer with the formation of “tomb stones”, typical in pemphigus vulgaris;
superficial acantholysis – loss of desmosomal contacts at the granular cell layer, typical for
pemphigus foliaceus; epidermal atrophy – thinning of the epidermis with flattening of the
dermal-epidermal junction; vacuolar degeneration – hydropic degeneration of basal
keratinocytes due to lymphocytic infiltration that obscures the dermal-epidermal junction.
Dermal changes include: perivascular inflammation – inflammatory lympho-plasmocytic or
polymorphonuclear cells around the blood vessels; interstitial inflammation – inflammatory
cells in the interstitial zones; lichenoid infiltration – dense, band-like infiltration that fills in
the papillary dermis (lichen planus); hyalinization – deposit of thick eosinophilic material
along the dermal-epidermal junction or around the vascular spaces; amyloidosis – amorphic
eosinophilic material on the tips of dermal papillas and homogenously along the
dermal-epidermal junction; sclerodermic degeneration – thickening and condensation of
collagen bundles in parallel arrangement throughout the whole dermis; granuloma formation
– granulomatous inflammation of specific pattern – tuberculoid, sarcoid, palisading (around
necrobiotic dermal changes) and foreign body granuloma; elastolysis – degeneration of
elastic fibers.
Subcutaneous changes are presented by thickening and fibrotic proliferation of septal
components (septal panniculitis), and necrotic or proliferative inflammation of adipocytes
(lobular panniculitis).
Apart from the individual histopathological phenomenona, the methodological
clinico-pathological approach requires utilization of a checklist of sequential steps with
specific pattern analysis. The first important step is the differentiation of the lesion as
inflammatory, malformative, or neoplastic. If the lesion is neoplastic it should be verified as
benign or malignant due to its architectural pattern, size, symmetry, circumscription and
cytology. The inflammatory infiltrates are additionally sub-classified into eight major
categories, according to the pattern of change in the epidermis and dermis as well as the
predominate cell type: 1. perivascular dermatitis (superficial as well as superficial and deep
perivascular); 2. nodular and diffuse dermatitis; 3. vasculitis; 4. vesicular dermatitis
(intraepidermal vesicular and/or subepidermal vesicular); 5. pustular dermatitis
(intraepidermal and infundibular epidermal pustular dermatitis); 6. peri-infundibulitis and
perifolliculitis; 7. fibrosing dermatitis; 8. panniculitis (predominantly septal or predominantly
lobular).
Immunofluorescence Studies
Immunofluorescence pattern studies are very helpful in differentiation of the immunological
disorders. They are used for mapping the location of the dermal-epidermal split in the
autoimmune bullous dermatoses and hereditary bullous disorders. Four main approaches
exist: 1. direct iimmunofluorescence (DIF); 2. indirect immunofluorescence (IIF); 3. IIF
utilizing salt-split skin (SSS); 4. immunoblotting (IB) to determine molecular weight of
antigens. DIF method uses fluorescein-labeled antibodies (IgG, IgA, IgM) to recognize and
attach to immunoglobulins or complement that is deposited in the basal membrane zone area
in patient's skin. Thus, DIF is always needed to verify the specific diagnosis in autoimmune
blistering diseases. IIF uses fluorescein-labeled antibodies to immunoglobulins to test if
patient's serum contains circulating antibodies that will bind to the basal membrane zone
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molecules in normal skin, e.g. IIF is a method for monitoring the immunological activity of
an already diagnosed autoimmune blistering disorder. SSS method utilizes normal or patient's
skin treated with 1M NaCl to separate epidermis and dermis among the anchoring filaments
in the lamina lucida compartment. Labeled antibodies determine if antigens are on the
epidermal or dermal side of the artificial split. Hemidesmosomes are the target antigens in
bullous pemphigoid and gestational pemphigoid. Mucous membrane pemphigoid is
heterogenous with most individuals showing immunoreactants on the epidermal side and
those with laminin-5 antigen – on the dermal side. Linear IgA dermatosis features versatile
antibodies, which bind a variety of antigens above and below the lamina lucida. Collagen
VII/anchoring fibrils target epidermolysis acquisita and bullous lupus erythematosus
antibodies of dermal side of the split.
Skin Allergic Tests

Prick Test
Skin prick testing (SPT) is a reliable method to diagnose IgE-mediated allergic disease in
patients with rhinoconjunctivitis, asthma, urticaria, anapylaxis, atopic eczema and suspected
food and drug allergy. It is minimally invasive approach, which provides evidence for
sensitization and confirms a suspected type I allergy. The identified sensitivity recognizes
inhalant, food, drug and occupational allergens. The clinical history should always be
considered in the light of appropriate avoidance measures to be given and, as necessary,
correct specific immunotherapy to be prescribed. SPT is also used to screen for atopic
predisposition, which can be done with a limited number of allergens, or to identify all
sensitized subjects in a certain population. Epidemiologic studies, which determine trends in
sensitization rates or regional differences, are also relying on SPT. Adults and children from
birth onwards can be tested. Repeated analysis may be necessary in order to detect new
sensitizations, especially in children, when symptoms change, or if new environmental
allergens are suspected.
Patch Testing
The patch test procedure is a simple, direct biological assay that can be used to identify and
often confirm the cause of allergic contact dermatitis – a prototype of delayed
hyper-reactivity allergic reaction type IV. The patient is exposed to suspected chemicals for
48 hours. Readings are usually taken at 48hr, 72hr, 96hr and at 1w. Weak positive reaction is
presented by non-vesicular erythema and papules. Edematous, vesicular eruption appears in
strongly positive individuals. Bullous and ulcerative lesions appear in extremely sensitized
patients. False negative early readings are expected at 34% rate, while false positive results
are due to misinterpretation of irritant reactions. The late readings are most important for
picking up delayed positive reactions to neomycin and some organic dyes which would be
otherwise missed. To date, over 2 800 allergens have been identified, with a core group of
about 100 that account for most reactions, including metals, perfumes, conservatives,
medications, etc. A clear correlation between the positive result and a patient's environmental
exposure should be identified. Experienced, well-read, tenacious investigator should be able
to link the sensitization to a certain exogenous trigger.
Wood Lamp Examination

Wood lamp emits black light with a wavelength 320-450 nm (peak 365 nm). The method
works on the principle of fluorescence - a coloured glow seen when certain substances
(collagen or porphyrin) absorb black light and emit it at a wavelength of the visible spectrum.
Under Wood light normal skin is slightly blue, the hyperkeratotic zones are white, the oily
skin is yellow, and the dehydrated skin - purple. Hypopigmented skin has sharper borders
under black light, therefore, Wood lamp is used to identify acquired hypopigmentation
diseases (vitiligo, hypomelanosis of Ito, etc.); differentiate epidermal (enhanced) from dermal
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(unchanged) pigmentation; verify some infectious diseases such as pityriasis versicolor
(glowing yellow-to-orange); malassezia folliculitis (bluish-white); Microsporum infection
(blue-green); Trychophyton Schoenleinii infection (dull blue); erythrasma (coral-pink);
Pseudomonas in hot-tube folliculitis and wound infections (green); porphyria cutanea tarda
(red-pink).
Mycology Tests
Fungal infections are detected and confirmed by examination of skin, hair and nail tissue.
The diagnostic approaches encompassed Wood’s examination, direct microscopy of skin
scrapping and nail clipping, mycology culture identification, blood tests for systemic mycotic
infections, molecular biology techniques. Potassium hydroxide (KOH) 10-30% is used to
identify dermatophytes by the presence of fungal hyphae, forming a mycelium, arthrospores,
arthroconidia, endotrix or ectothrix invasion. A yeast infection is recognized via
pseudohyphae making up a pseudomycelium and budding. Growing the fungus in culture
usually takes 3-4 weeks. Sabouraud’s dextrose agar with cycloheximide and chloramphenicol
is most commonly used. The culture identifies the exact pathological agent and selects the
most appropriate treatment.
Serology Tests
Syphilis is a sexually-transmitted infection caused by Treponema pallidum, which is usually
diagnosed confronting clinical findings and serological tests. The appropriate use and
interpretation of diagnostic testing are important for optimal patient management. Two
different types of serologic tests exist – treponemal and non-treponemal. Non-treponemal
tests detect antibodies directed against lipoidal antigens, damaged host cells, and possibly
from treponemes. Most commonly rapid plasma reagin (RPR) and venereal disease research
laboratory (VDRL) tests are used. Seroconversion occurs between 3-6 week. The results are
semiquantitative and reflect infection activity. Under appropriate treatment, they usually
become negative. The treponemal tests identify specific bacterial components. Their
positivity implies infection but does not determine its duration and therapeutic
implementations. Therefore, the diagnostic paradigm requires the use of treponemal test to
strictly identify the Treponema pallidum nature of the disease, and non-treponemal tests to
rule out active infection or therapeutic resistance.
THERAPY
Systemic Therapy
Antibacterial Drugs
Penicillins (PCNs)
Inhibit bacterial cell wall synthesis by inactivates bacterial enzymes (PCN-binding proteins)
involved in peptidoglycan synthesis.
Contains β-lactam ring; drug excretion via kidneys.
Specific types of PCNs:
PCNs with β-lactamase inhibitor: amoxicillin and clavulanate (Augmentin).
Penicillinase-resistant PCNs: dicloxacillin, methicillin, oxacillin, cloxacillin.
Spectrum: Gram-positive (GP) bacteria, spirochetes, Neisseria gonorroeae, actinomycetes.
Treatment: erysipelas, erysipeloid, anthrax, strep/staph infections, cat/dog/human bites,
syphilis, gonorrhea.
Side effects (SEs): morbilliform eruption, angioedema, anaphylaxis, hemolytic anemia,
interstitial nephritis, acute generalized exanthematous pustulosis (AGEP), toxic epidermal
necrolysis (TEN).
Contraindication (CI): hypersensitivity to any β-lactam antibiotic.
Cephalosporins
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Contains β-lactam ring with same mechanism as PCNs; 10% cross-reactivity with PCNs.
Spectrum of bacterial coverage based upon generation of cephalosporin:
First generation: GP > Gram-negative (GN); second generation: GP = GN; third generation:
GP < GN; fourth generation: GP, GN (little activity against β-lactamase).
Treatment: severe skin, soft tissue and other infections.
SEs: AGEP, morbilliform eruption (serum sickness associated with cefaclor).
CIs: same as with PCNs.
Vancomycin
Glycopeptide antibiotic.
Inhibits bacterial cell wall synthesis; only given intravenously.
Spectrum: aerobic and anaerobic GP bacteria and coagulase-negative microorganisms.
Treatment: severe skin, soft tissue and other infections caused by microorganisms resistant to
other antibiotics and for patients allergic to β-lactam antibiotics.
SEs: red man syndrome, anaphylaxis, TEN, oto- and renal toxicity, phlebitis at i.v. site, ↓
blood pressure.
CIs: hypersensitivity to drug, renal and hearing impairment, elderly pts, severe intestinal
inflammation.
Zyvox (Zyvoxid)
Reversible non-selective monoamineoxidase inhibitor (MAOI). Contains linezolid, which is a
synthetic antibacterial agent of the oxazolidinone class. Given p.o. and i.v. → equal
bioavailability.
Treatment: complicated skin, soft tissue and other infections caused by GP bacteria and
MRSA.
SEs: headache, nausea, vomiting, diarrhea, bone marrow suppression.
CIs: accept inhibitors MAO, uncontrolled hypertension, thyrotoxicosis, bipolar depression,
schizoaffective disorders, coadministration of adrenergic or seritonergic medications.
Aminoglycosides
Inhibit bacterial protein synthesis targeting 30S ribosomal subunit.
Spectrum: aerobic GN bacteria.
SEs (oral): ototoxicity, nephrotoxicity, vestibular problems, neuromuscular disorders, chronic
liver disease, chronic renal failure or deteriorating renal function.
CIs: hearing and vestibular problems, neuromuscular disorders, chronic liver and renal
diseases, deteriorating renal function.
Tetracyclines
Spectrum: GP/GN bacteria, Chlamydia, Mycoplasma, rickettsia, spirochetes (syphilis, Lyme
disease), certain mycobacteria (leprosy), acne vulgaris, rosacea.
SE: photosensitivity.
Contraindicated in patients <9 years old due to brown discoloration of gingival third of teeth
and photosensitivity.
Clindamycin
Spectrum: GP and anaerobic bacteria.
SE: pseudomembranous colitis (oral form).
CIs: Myastenia gravis, Crohn΄s disease, ulcerated colon, severe liver disease, severe renal
impairment, allergies to lincosamines.
Macrolides
Spectrum: GP/GN bacteria, spirochetes, Neisseria gonorroeae, Chlamydia, atypical
mycobacteria; alternative for PCN-allergic patients.
SEs: cholestatic hepatitis (estolate form of erythromycin), nausea, dyspepsia, diarrhea,
20
pseudomembranous colitis.
Contraindicated in patients receiving terfenadine therapy who have preexisting cardiac
abnormalities.
Fluoroquinolones
Inhibits bacterial DNA gyrase.
Spectrum: GN bacteria, strep/staph, certain mycobacteria.
SEs: tendon rupture, cartilage damage in joints, ↑ LFTs, nephrotoxicity.
CIs: pregnancy and children (due to deposition of drug in cartilage).
Rifampin (Rifampicin)
Inhibits RNA synthesis by inhibiting DNA-dependent RNA polymerase.
Spectrum: mycobacteria (tuberculosis and leprosy), GP/GN bacteria.
SEs: orange-red discoloration of urine/tears, ↓ OCP efficacy, nausea, fatigue, vomiting,
diarrhea, flu-like symptoms.
CIs: hypersensitivity to drug, liver disorder, alcoholism, caution if diabetes mellitus, hepatic
impairment and colitis.
Sulfonamides
Sulfamethoxazole and sulfasalazine; interferes with bacterial folic acid synthesis (needed for
nucleic acid synthesis) by inhibiting dihydropteroate synthetase.
Spectrum: GP/GN bacteria, Chlamydia, Nocardia.
SEs: hemolytic anemia [especially if glucoso 6 Phosphat Dehydrogenase-deficient
(G6PD-deficient)], nephrotoxicity, hepatotoxicity, TEN, Stevens–Johnson syndrome (SJS),
AGEP, photosensitivity.
CIs: hypersensitivity to drug, pregnancy (third trimester).
Dapsone
Antibacterial and anti-inflammatory (mainly toward neutrophils by inhibition of
myeloperoxidase); sulfone family (related to sulfonamides).
Spectrum: mycobacteria.
Treatment: leprosy, autoimmune blistering diseases, Behçet’s disease.
SEs: hemolytic anemia (especially if G6PD-deficient), cholestatic jaundice,
methemoglobinemia, agranulocytosis, motor peripheral neuropathy, acute psychosis, dapsone
hypersensitivity syndrome, photosensitivity.
CIs: hypersensitivity to drug, G6PD deficiency, severe anemia, methemoglobinemia, renal
and hepatic impairment, impaired cardiovascular fxn.
Metronidazole (Flagyl)
Forms toxic metabolites in bacteria, which inhibits bacterial DNA synthesis and prevents the
replication of bacteria.
Spectrum: anaerobes and protozoa.
Treatment: anaerobic infections, trichomoniasis, rosacea.
SEs: hypersensitivity, glossitis, disulfiram-like reaction (with alcohol).
CIs: hypersensitivity to drug, pregnancy, alcohol use, caution if CNS disorder, blood
dyscrasia and hepatic impairment.
Clofazamine (Lamprene)
Unclear mechanism; used for leprosy, erythema nodosum leprosum, DLE.
SEs: abdominal sx, severe, hepatitis, jaundice, intestinal obstruction, GI bleeding, splenic
infarction, thromboembolism, QT prolongation, torsades de pointes.
CIs: hypersensitivity to drug, caution if electrolyte abnormalities, caution if heart disorders.
Antifungals
Triazoles
Itraconazole (Sporanox)
Blocks ergosterol synthesis by inhibiting 14 α-demethylase.
21
Fungistatic, lipophilic, needs acidic milieu for absorption.
Treatment: dimorphic fungi, aspergillosis, candidiasis, superficial dermatophytes,
onychomycosis, sporotrichosis.
SEs: ↑ LFTs, ↓ WBC, ↑ TG, nephrotoxicity, CHF worsening.
CIs: pregnancy, peripheral neuropathy, hearing loss, liver dysfxn, caution in elderly pts,
caution if renal/hepatic impairment and cardiovascular dz.
Fluconazole (Diflucan)
Inhibits cyt p450.
Fungistatic, crosses blood–brain barrier.
Treatment: candidiasis, pityriasis versicolor (PV), cryptococcosis, histoplasmosis, superficial
dermatophytes, coccidioidomycosis.
SEs: vomiting, diarrhea, rash, increased liver enzymes/liver problem.
CIs: pregnancy, breastfeeding, caution if renal/hepatic impairment, electrolyte abnommalities
and heart dz.
Imidazoles
Ketoconazole (Nizoral)
Inhibits 14 α–demethylase and cytochrome p450.
Fungistatic, lipophilic, needs acidic milieu for absorption, ↑ absorption with food.
Treatment: dermatophytes, candidiasis, dimorphic fungi, PV.
SEs: fulminant hepatitis (rare), ↑ LFTs (15%), gynecomastia.
CIs: pregnancy, breastfeeding, alcohol use, hepatic dz, caution if concurrent hepatotoxic
agent use.
Allylamines
Terbinafine (Lamisil)
Inhibits squalene epoxidase (first step of ergosterol synthesis).
Fungicidal, biotransformed in liver.
Treatment: onychomycosis, tinea corporis, tinea pedis.
SEs: nausea, metallic taste, liver damage, drug-induced LE.
CIs: CrCi <50, hepatic dz, caution if hepatic impairment, immunodeficiency, SLE and
psoriasis.
Polyenes
Amphotericin B
Binds ergosterol and forms membrane pores; i.v. administration.
Treatment: moulds and yeasts, including dimorphic pathogens such as Coccidioides immitis,
Histoplasma capsulatum, Blastomyces dermatitidis, and Paracoccidioides brasiliensis, etc.
SEs: phlebitis at the infusion site, acute reaction after infusion (fever, chills, nausea,
tachypnea), nephrotoxicity, agranulocytosis, seizures, arrhythmias.
CIs: pregnancy, renal disease, electrolyte imbalance, caution in hematological disease.
Others
Caspofungin
Inhibits synthesis of glucan (fungal cell wall); i.v. administration.
Treatment: candidiasis and aspergillosis
SEs: hypersensitivity rxn, anaphylaxis, erythema multiforme, Stevens-Johnson syndrome,
toxic epidermal necrolysis, septic shock, respiratory failure, pleural effusion, nephrotoxicity,
hepatotoxicity, pancreatitis, anemia.
CIs: hypersensitivity to drug, caution if hepatic impairment.
Griseofulvin
Disrupts microtubule function.
Fungistatic, ↑ absorption w/fatty meal, induces cytochrome p450, resistance seen in T.
rubrum.
Treatment: dermatophytes (NOT yeast or bacteria).
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SEs: nausea, fatigue, vomiting, diarrhea, headache, paresthesias, photosensitivity, skin rashes
hypersensitivity type, drug-induced LE, worsens acute intermittent porphyria.
CIs: pregnancy, breastfeeding, hepatocellular failure, porphyria.
Nystatin
Antibiotic containing mycosamine.
Treatment: diseases caused by yeast-like fungi of the genus Candida (oropharyngeal,
esophageal, gastrointestinal candidiasis).
Rare SEs: nausea, vomiting, diarrhea, stomach pain, allergic skin reactions.
CI: hypersensitivity to drug.
Antiviral drugs,????/ Pregnancy Category Miscellaneous

Most of them are purine or pyrimidine analogs and act as antimetabolites. They must be
activated through phosphorylation of viral or cellular enzymes. Antiviral agents target
specific viral proteins, usually an enzyme involved in viral multiplication therefore they
inhibits active replication but do not eliminate non-replicating or latent virus.
Acyclovir (Zovirax)
Phosphorylated by viral thymidine kinase to acyclovir monophosphate, which blocks viral
DNA polymerase → stops viral DNA synthesis.
Treatment: herpes simplex virus (HSV), varicella-zoster virus (VZV).
Regimen: acute herpes labialis or genitalis 5 X 200 mg orally; chronic herpes labialis or
genitalis 3 X 200 mg orally; herpes zoster 5 X 800 mg orally, 5-7 days. In
immunocompromised patients – 30 mg/kg/d i.v. in 3 divided doses.
SEs: i.v. infusion associated with reversible obstructive nephropathy, rarely may cause severe
CNS.
CIs: caution if renal and hepatic impairment, electrolyte abnormalities, neurologic dz, caution
in elderly pts.
Valacyclovir (Valtrex)
Prodrug of acyclovir, same mechanism of action (viral thymidine kinase-dependent activity);
better bioavailability than acyclovir.
Treatment: HSV, VZV, cytomegalovirus (CMV).
SE: Thrombotic thrombocytopenic purpura/ hemolytic uremic syndrome (TTP/HUS) seen in
advanced HIV disease and transplant patients taking high doses.
CIs: renal disorder, elderly pts, pregnancy, breastfeeding.
Famciclovir
Phosphorylated by viral thymidine kinase (similar mechanism to acyclovir).
Treatment: HSV, VZV.
SEs: neutropenia, thrombocytopenia, cholestatic jaundice, anaphylaxis, hallucinations.
CIs: hypersensitivity to drug, caution if renal impairment
Foscarnet
Noncompetitive inhibition of viral DNA polymerases. Does not require phosphorylation so
active against acyclovir-resistant viruses. Only i.v. form.
Treatment: CMV (retinitis), resistant HSV, resistant VZV.
SEs: penile ulcerations or erosions, nephrotoxicity.
CIs: hypersensitivity to foscarnet sodium, caution if renal impairment.
Antiretroviral Drugs
Treatment: HIV infection and AIDSMechanism of Action Characteristics
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors
Zidovudine (AZT)
Thymidine analogue, inhibits HIV reverse transcriptase (RT).
SEs: melanonychia, mucocutaneous pigmentation, bone marrow suppression, lipodystrophy.
23
Didanosine (ddI)
Pyrimidine analogue, similar to AZT.
SEs: pancreatitis, optic neuritis, peripheral neuropathy, lactic acidosis.
Abacavir (ABC)
Nucleoside RT inhibitor.
SE: hypersensitivity reaction (can be fatal upon rechallenge).
Tenofovir
Nucleotide analogue, inhibits RT.
SEs: Peripheral wasting, cushingoid appearance.
Protease inhibitors
Indinavir, Ritonavir, Lopinavir
Block HIV-1 protease enzymes.
SEs: lipodystrophy (buffalo hump), gynecomastia, periungual pyogenic granulomas,
paronychia, hepatotoxicity.
Antiparasitic Drugs
Include anthelmintics, scabicides, pediculicides, and insecticides.
Ivermectin
Blocks glutamate-gated chloride channels → paralysis, death of parasite.
Treatment: head lice (pediculosis capitis), Norwegian scabies
SEs: abdominal pain, asthenia, hypotension, dizziness, headache, etc.
CIs: hypersensitivity to drug, loiasis co-infection, caution if hyperreactive onchodermatitis,
caution if asthma.
Metronidazole (Flagyl) (see Antibacterial Drugs)
Antihistamines
Act by competitive inhibition of H1 and H2 receptor sites on target cells. Competition is
possible because most antihistamins have substituted ethylamine grouping, which are also
present in histamines. All H1 blockers have anticholinergic and central nervous system
effects as well as antihistaminic effects.
Treatment: urticaria, angioedema, eczema/dermatitis, lichen planus, etc.
H1 blockers are subclassified into 2 groups:
First generation or classical antihistamines (lipophilic):
Diphenhydramine, promethazine, cyproheptadine, chlorpheniramine, hydroxyzine.
Cyproheptadine: treatment of choice for cold urticaria.
Chlorpheniramine: safest in pregnancy.
Hydroxyzine: side effects include EKG changes, arrhythmias.
SEs: prominent sedation effect and decreased attention, increased sleep duration and changes
in EEG patterns, drowsiness and anticholinergic symptoms (blurry vision, urinary retention,
dry mouth, constipation).
CIs: benign prostatic hypertrophy, glaucoma, pyloric stenosis.
Second generation or “non-sedating” antihistamines, depending on chemical structure.
Fexofenadine, loratidine, cetirizine, levocetirizine.
Fexofenadine: few sedative effects, few to no anticholinergic symptoms.
Loratidine: long-acting, minimally sedating.
Cetirizine: low sedation, metabolite of hydroxyzine, ± anticholinergic effect.
SEs: drowsiness and anticholinergic symptoms.
CIs: childhood and pregnancy.
H2 blockers (cimetidine, ranitidine) are used primarily as inhibitors of gastric acid secretion.
Indications: Mostly for the symptomatic treatment for chronic urticaria, pruritus, allergic drug
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reactions, psychocutaneous reactions and a number of other histamine-related diseases.
SEs: Cimetidine - gynecomastia, impotence, loss of libido.
Contraindications and precautions. Alcohol and barbiturates enhance the central nervous
system effects of antihistamines so their use should be avoided.
Others
Doxepin: tricyclic antidepressant, H1/H2 antihistamine, inhibits histamine and
acetylcholine, anticholinergic, cardiotoxic (may prolong QT interval ); side effects:
conduction disturbances, seizure disorder, urinary retention.
Amitriptyline: tricyclic antidepressant with some H1 blocking activity; side effects
include anticholinergic symptoms and risk of cardiac arrhythmias.
Cromolyn sodium: blocks mast cell degranulation.
Montelukast, zafirlukast: leukotriene receptor antagonist.
Zileuton: inhibitor of 5-lipoxygenase, which subsequently inhibits leukotriene
formation.
Immunosuppressants drugs
Glucocorticoids
Steroids are synthetic derivatives of the natural steroid, cortisol, produced by the adrenal
glands.
Anti-inflammatory, antimitotic, immunosuppressive, and vasoconstrictive properties; forms
complex with intracellular receptors and modulates transcription of certain genes.
Effects: ↓ circulating lymphocytes/eosinophils/monocytes, ↓ macrophage response to
lymphokines, ↓ Ab production, ↓ synthesis of proinflammatory molecules, ↓ fibroblast
production of collagen; ↑ neutrophils, ↑ blood glucose (stimulates gluconeogenesis), ↑ protein
catabolism, ↑ plasma fatty acids/ketone body formation, ↑ acid/pepsin secretion in stomach.
Short-acting glucocorticoids: cortisone and hydrocortisone. Greatest mineralocorticoid
activity; lowest glucocorticoid activity.
Intermediate and long-acting glucocorticoids: methylprednisolone, triamcinolone,
dexamethasone, betamethasone. Virtually no mineralocorticoid activity;
dexamethasone/betamethasone with highest glucocorticoid activity.
Treatment: anaphylaxis, urticaria, angioedema, SJS, TEN, autoimmune bullous diseases,
connective tissue diseases, eczema/dermatitis, erythema multiforme, lichen planus,
vasculitides, lymphomas, etc.
Administered orally, intramuscular, intravenously and intralesional.
Single morning dose ↓ risk of HPA suppression.
Divided daily dosing may ↑ anti-inflammatory efficacy but also ↑ systemic toxicity.
Alternate day dosing reduces all complications except osteoporosis and cataracts.
Regimen. Usually the treatment is started with a higher dose of prednisone, such as 40–60
mg/d, to gain control of the skin condition. In 2–4 weeks, the dose is reduced. Steroid dose
should be: low dose < 10 mg/d of prednisone; medium dose 10–20 mg/d of prednisone and
high dose > 20 mg/d of prednisone, rarely more than 100 mg/day.
Methylprednisolone pulse therapy 500 mg to 1 g over 2-4 hours for 3-5 days.
Intralesional injections → inflammatory lesions or keloids, triamcinolone acetonide
suspension 2.5-40 mg/ml.
SEs: Cutaneous - atrophy, telangiectasias, striae, poor wound healing.
Other - ↑ appetite, peptic ulcers, pancreatitis, osteoporosis, Cushing’s syndrome,
hyperglycemia, hypertriglyceridemia, sodium retention, cataracts, glaucoma, ↑ risk of
infection, hypertension, hirsutism, HPA axis suppression, failure to thrive, aseptic necrosis of
femoral head, muscle weakness, psychosis, pseudotumor cerebri.
CIs: active infection, bleeding disorders, hypertension with CCF, psychosis, peptic ulcer,
diabetes mellitus, osteoporosis, glaucoma, pregnancy.
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Cytotoxic and Antineoplastic Drugs
Treatment: autoimmune bullous dermatoses, connective tissue diseases, severe forms of
psoriasis, severe vasculitides, severe atopic dermatitis, lymphomas, etc.
Azathioprine (Imuran)
Purine analogue which blocks purine synthesis (S-phase-specific).
Excreted by kidneys.
Check thiopurine methyltransferase levels before starting medication.
SEs: bone marrow suppression, hypersensitivity syndrome, teratogenicity,
lymphoproliferative malignancies.
CIs: hypersensitivity to drug, caution if renal impairment, caution if prior alkylating agents.
Methotrexate
Antimetabolite and antifolate drug.
Renal excretion; liver biopsy at cumulative dose of 1.5 g; caution in patients with ↑ alcohol
intake, diabetes, or renal failure.
SEs: hepatotoxicity, pancytopenia, teratogenicity, radiation recall, acral erythema, ±
lymphoma.
CIs: hypersensitivity to drug, pregnancy, neonates, bone marrow suppression, infections,
pulmonary disease, renal disease, GI disease, hepatic disease, alcoholism, sunlight (UV)
exposure.
Mycophenolate Mofetil (Cellcept)
Inhibits de novo purine synthesis; T- and B-cells particularly affected.
Renal excretion.
SEs: nausea, vomiting, reversible dose-related bone marrow toxicity, progressive multifocal
leukoencephalopathy, pure red cell aplasia.
Caution in peptic ulcer disease; of note, not hepatotoxic or nephrotoxic.
CIs: hypersensitivity to drug, pregnancy.
Cyclophosphamide (Cytoxan)
Nitrogen mustard derivative
SEs: teratogenicity, ↑ lymphoma risk, ↑ leukemia risk, ↑ bladder cancer risk, ↑ SCC risk,
bone marrow suppression, hemorrhagic cystitis, azoospermia, pulmonary eural fibrosis,
alopecia, hyperpigmentation of skin/nails.
CIs: hypersensitivity to drug, pregnancy, breastfeeding, urinary obstruction, ANC <1500, Plt
<50,000, caution if high dose tx, prior or concurrent cardiotoxic tx, prior XRT, hepatic, renal,
and heart impairment, severe infection, wound healing, caution in elderly pts.
Cyclosporine (CsA)
Inhibits T-cell activity by binding to cyclophilin, which subsequently blocks cyclophilin’s
ability to activate calcineurin; calcineurin regulates NFAT and IL-12, which results in overall
inability to produce/release IL-12.
SEs: nephrotoxicity, reversible hypertension (HTN), gingival hyperplasia, hyperlipidemia, ↑
K and ↓ Mg , ↑ uric acid, paresthesias, hypertrichosis, lymphoma.
Check BP regularly; if renal creatinine above 30% of baseline, dose should be reduced.
CIs: hypersensitivity to Sandimmune® (cyclosporine), abnormal renal function, uncontrolled
hypertension, uncontrolled infections and malignancy.
Hydroxyurea
Inhibits ribonucleotidase reductase (inhibits DNA synthesis).
SEs: hematologic toxicity, photosensitivity, mucosal ulceration, anemia, hepatitis, renal
toxicity, poikiloderma of hands/feet, diffuse hyperpigmentation, leg ulcers, radiation recall.
CIs: hypersensitivity to drug, pregnancy, breastfeeding, myelosuppression, anemia, severe,
leg ulcers, caution if interferon use, long-term use, CrCl <60, and myeloproliferative disorder.
Thalidomide
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Inhibits TNF-α but exact mechanism unknown.
Treatment: erythema nodosum leprosum, HIV associated mucosal ulceration, recalcitrant
DLE or SCLE.
SEs: fetal anomalies, peripheral neuropathy (proximal muscle weakness, painful paresthesias
of extremities), somnolence, TEN, hypersensitivity reaction, leukopenia.
CIs: hypersensitivity to drug, pregnancy, children, HIV infection.
Chemotherapy Drugs
Treatment: i.l. or i.v. monotherapy or in the combined therapeutic regimens for advanced
BCC, AK, SCC, primary cutaneous lymphomas, MM.
Chlorambucil
Alkylating agent derived from nitrogen mustard.
SEs: bone marrow suppression, urticaria, mucositis.
5-Flourouracil (5-FU)
Cell cycle–specific pyrimidine antagonist, blocks DNA/RNA synthesis.
SEs: extravasation reaction (infusion), chemotherapy recall, inflammation of AKs.
Bleomycin
M- and G2- phase-specific → damages DNA by direct binding.
SEs: Raynaud’s phenomenon, pulmonary toxicity, flagellate hyperpigmentation.
Doxorubicin (Adriamycin)
Cytotoxic antibiotic → DNA/RNA transcription.
SEs: cardiac toxicity, mucositis, chemotherapy recall, radiation recall.
Dactinomycin (Actinomycin)
Cytotoxic antibiotic → blocks DNA/RNA/protein synthesis.
SE: radiation recall.
Vinblastine
Periwinkle plant extract, cell-cycle-specific (arrests in metaphase).
Vincristine analogue of vinblastine.
SE: extravasation reaction (vincristine).
Cytarabine
Blocks DNA synthesis in S phase.
SEs: acral erythema, neutrophilic eccrine hidradenitis, eccrine squamous syringometaplasia,
inflammation of SKs.
Immunomodulators
Treatment: autoimmune bullous dermatoses, connective tissue diseases, severe forms of
psoriasis, severe vasculitides, BCC, MM, skin lymphomas, etc.
Interferon
Antiviral and antiproliferative properties.
SEs: flu-like symptoms, leukopenia, hepatotoxicity.
CIs: hypersensitivity to drug, pregnancy, neonatal-period, heart disease, cirrhosis,
autoimmune diseases, severe depression or psychosis, some forms of eye disease, organ
transplant (except liver transplant).
Biologically Engineered Immunomodulators
TNF-α Inhibitors
Etanercept (Enbrel) → subcutaneous TNF-α inhibitor. Avoid live vaccines.
SEs: multiple sclerosis, + ANA and LE symptoms, worsening of CHF, serious infections, TB
reactivation, malignancies.
Infliximab (Remicade) → intravenous TNF-α inhibitor. Avoid live vaccines.
SEs: infusion reaction, other side effects similar to etanercept.
Adalimumab (Humira) → subcutaneous TNF-α inhibitor.
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SEs: same as other TNF-α inhibitors.
Golimumab (Simponi) → subcutaneous TNF-α inhibitor.
Certolizumab Pegol (Cimzia) → subcutaneous TNF-α inhibitor.
IL-12/IL-23 Inhibitor
Ustekinumab (Stelara) → subcutaneous IL-12/IL-23 inhibitor.
SEs: comparable to TNF-α inhibitors.
IL-17A Inhibitor
Cosentyx (Secukinumab) → subcutaneous IL-17A inhibitor.
SEs: cold symptoms, diarrhea, upper respiratory infections, allergic reactions.
Antimalarials
Anti-inflammatory and immunosuppressive agents.
The antimalarial agents have the 4-aminoquinoline radicals as their basic chemical structure.
They have profound effects on the acid vesicle system because it increases the pH inside the
intracellular.
Treatment: DLE, SLE, dermatomyositis, photosensitivity dermatoses (i.e., polymorphous
light eruption), sarcoidosis.
Regimen. Most commonly used antimalarial agents are chloroquine (Aralen) and
hydroxychloroquine (Plaquenil). Quinacrine (Atabrine) and amodiaquine (Camoquin) also
could be administrated. Chloroquine 250 mg is equivalent to hydroxychloroquine 400 mg;
quinacrine 100 mg or amodiaquine 200 mg. Pretreatment assessment include a complete
ophthalmologic examination and laboratory studies (complete blood count, blood urea
nitrogen, creatinine and liver function tests).
Lupus erythematosus initial treatment should be hydroxychloroquine 400 mg/d for 3 months.
After the positive response is observed the dosage is gradually reduced to alternative-day
therapy.
Polymorphous light eruption. The drugs are used for prophylaxis or for short periods.
SEs: accumulates in melanin-rich tissue (i.e., choroid); ocular toxicity can manifest as
retinopathy (potentially irreversible), mucocutaneous and nail blue-gray pigmentation,
hemolysis (mainly in G6PD deficiency), mental changes, headaches, convulsions,
leucopenia, bleaching of hair roots, alopecia. Quinacrine (Atabrine) - side effects
similar to other antimalarials, but no risk of retinopathy.
Contraindications and precautions. The drug should be avoided in children and the dosage
not exceed 5-7 mg/kg/d → risk of teratogenecy. Antimalarics can provoke or exacerbate
psoriasis.
Other drugs
Retinoids
Class of natural and synthetic compounds chemically related to vitamin A.
Retinoids classified into three generations:
First generation (nonaromatic) - tretinoin (all-trans retinoic acid), isotretinoin (13-cis retinoic
acid - Roacutane), alitretinoin (9-cis retinoic acid);
Second generation (monoaromatic) - etretinate (Tigason), acitretin (Neotigason);
Third generation (polyaromatic) - adapalene, tazarotene, bexarotene.
Function. Normalizes keratinization (allowing for decrease in follicular occlusion).
Isotretinoin + atrophy of sebaceous glands, reduction in sebum (up to 90%) so P. acnes
unable to thrive.
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Treatment. Disorders of keratinization → psoriasis, ichthyosis, keratoderma palmo-plantaris,
Darier disease, etc. Severe acne → nodulocystic acne, recalcitrant inflammatory acne, acne
fulminans. Bexarotene → cutaneous T-cell lymphoma (CTCL).
Regimen. Severe psoriasis → etretinate (Tigason), acitretin (Neotigason), 0,5 – 1 mg/kg/d,
for several weeks before increasing to maintain dose. Severe acne → isotretinoin
(Roacutane), 0,5 – 1 mg/kg/d taken 4-6 months to obtain remission.
SEs: teratogenicity, skin and mucosal dryness, cheilitis, alopecia, skin fragility, photophobia,
reduced night vision, headache, musculoskeletal problems, hepatotoxity, hyperlipidaemia,
elevated triglycerides, pseudotumor cerebri, etc.
Females must avoid pregnancy during and after treatment.
CIs: hypersensitivity to drug, pregnancy, breastfeeding, hepatic and renal insufficiency,
hypervitaminosis A, excessively elevated blood lipid values, taking tetracyclines.
Vitamins for Systemic Treatment

Vitamin A (Retinol)
Used in dermatoses with disturbed keratopoesis - psoriasis, keratodermiae, keratotic
follicular papules, xerosis, ichthyosis, acne, alopecia, night blindness, keratomalacia.
Vitamin B1 (Thiamine)
Used in inflammatory processes of the peripheral nerves - herpes zoster, glossitis, peripheral
neuropathy, pellagra, pruritus, eczema/dermatitis.
Vitamin B2 (Riboflavin)
Used in ariboflavinosis + cheilitis, stomatitis, glossitis, balanitis, vulvovaginitis, rosacea,
photophobia, conjunctivitis.
Vitamin B3 (Niacin or nicotinic acid)
Has a vasodilating and photoprotective action. Useful in pellagra, photodermatoses, cheilitis,
stomatitis, perianal dermatitis, acrocyanosis.
Vitamin B5 (Pantothenic acid)
Administrated in alopecia, vitiligo, wound healing, sun burns.
Vitamin B6 (Pyridoxine)
Participate in the regulation of proteins and lipid metabolism. Administrate in
eczema/dermatitis, seborrheic dermatitis-like periorificial eruption, acne, cheilitis, glossitis,
conjunctivitis, aphthosis, peripheral neuropathy.
Vitamin B7 (Biotin, Vitamin H)
Used in seborrheic dermatiris, xeroderma, cheilitis, glossitis, stomatitis, periorificial eruption,
conjunctivitis, paresthesias, alopecia, seizures.
Vitamin B9 (Folic Acid)
Stimulates erythropoiesis and leucopoiesis. Used in psoriasis, photodermatoses, cheilitis,
stomatitis, glossitis, aphthosis, diffuse hyperpigmentation (patchy), megaloblastic anemia.
Vitamin B12 (Cobalamin)
Participates in maturation of erythrocytes, epithelization and regeneration. Used in psoriasis,
erythroderma, herpes zoster, generalized hyperpigmentation, megaloblastic anemia, glossitis,
paresthesias, peripheral neuropathy.
Vitamin C (Ac. Ascorbinicum)
Has an anti-inflammatory, capillary-tonic effects. Takes part in the processes of hemostasis
and regeneration. Used in scurvy, follicular hyperkatosis, corkscrew hairs, perifollicular
hemorrhage, petechiae, epistaxis, gingivitis, stomatitis, delayed wound healing, haemorrhagic
dermatoses, allergic reactions, erythroderma, melanoderma.
Vitamin D
Has immunomodulatory effect, participate in differentiating and modulate antiproliferative
activities of normal and cancer cells. Vitamin D2 useful in tuberculosis cutis luposa, acne
conglobata, alopecia; vitamin D3 in psoriasis.
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Vitamin E (α-, β-, γ-, and δ-Tocopherols and Their Related Corresponding Tocotrienols)
Fat-soluble antioxidant. Acts as a free-radical scavenger protecting the skin from solar
radiation. Used in atopic dermatitis, psoriasis, cutaneous ulcers, wound healing, keloides,
melasma, acne, scleroderma, etc.
Vitamin K (vit K1=phytomenadione; vit K3=menadione)
Participates in blood clotting as an anti-haemorrhagic factor. Useful in purpura, ecchymoses,
hemorrhage.
Photosensitization and Photoprotective Drugs

Photosensibilizators: 8-methoxypsoralen (Meladinine, Oxoralen, Psoralen, Methoxalen,
Puvalen, etc.).
Treatment: psoriasis, vitiligo, atopic dermatitis, alopecia areata, parapsoriasis placata, etc.
Administered orally, 0.5 mg/kg/d 2 hours before UVA phototherapy [PUVA therapy (Psoralen
+ UVA phototherapy)].
SEs: itching, vesicles, nausea, malaise, general malaise, hepatic and renal impairment,
cataract, BCC, SCC, MM.
CIs: hypersensitivity to drug, photosensitivity, melanoma or squamous cell carcinomas,
aphakia (risk of retinal damage due to the absence of lenses).
Photoprotectors: carotenoids – β-carotene (Carotaben).
Treatment: photodermatoses.
SE: orange discoloration of skin.
CI: pregnancy.
Vasodilators and Vasotonic Drugs

Peripheral vasodilators: Vasolat, Dilminal, Padutin, Trental, Ac. Nicotinicum, Dusodril,
Cinnarizin.
Treatment. Acrocianosis, perniones, Morbus Raynaud, systemic scleroderma,
post-thrombophlebital ulcuses, etc.
Venotonic: Glyvenol, Troxevasin (Venoruton), Detralex, Dioket, Entan, etc.
Treatment. Varices, trombophlebites, venous ulcers of the legs, haemorrhoides.
Capillarotonic: Rutascorbin, Peflavit C, etc.
Treatment. Purpura, allergic vasculitis, drug-induced capillaropathies, etc.
Neurotropic Drugs
Psychotropic agents are administrated in cases of highly pruritic or painful dermatoses, as
well as in processes causing cosmetic skin defects, that act traumatically on patients' psyche,
obsessive compulsive skin manipulation, delusions of parasitosis, and post-herpetic
neuralgia. These are different groups of medications that include: sedatives, neuroleptics,
tranquilizers, antidepressants, psychostimulating and toning agents. All of them interact with
central or peripheral neuronal receptors.
Neuroleptics have sedative, antipsychotic and tranquilizing action. They eliminate mental
tension and potentiate the effect of sedative and anti-anxiety drags. The most useful is
Clonazepam (Klonopin). It binds receptors at several sites within the CNS, including the
limbic system and reticular formation. Its effects may be mediated through the GABA
receptor system. Major side effects are confusion, difficulty with sleeping, excessive
dreaming, lack of feeling or emotion, muscle tension or tightness, nightmares, skin rash and
others.
Tranquilizers reduce fear, anxiety and stress, as well as they increased excitability and bias in
the emotional sphere. In this group are: benzothiazine derivatives (Disepin, Rudotel) and also
Neurolax, Tranquilan, Lonetil.
30
Antidepressants (Amitriptyline, Psychoforin, and Insidon) are used in dermatoses
accompanied by anxiety-depressive conditions.
SEs: allergic reactions, dry mouth, ↓ libido, dyspeptic disorders, constipation, drowsiness,
fatigue.
CIs: pregnancy, glaucoma, prostate hypertrophy, etc.
Topical Therapy
Basic Topical Preparations - Fluids, Oils, Greases, Powders
The topical active ingredients should be applied into specific carriers (vehicles), which
provide resorption and enough skin bioavailabitity. Throughout the vehicle, the active
substance is diluted, distributed over the skin's surface, retained or released and penetrated
the skin.
Monophasic Vehicles
Liquids (Liquors).
The most commonly used liquids are aqua distillate, spiritus vini, glycerol, ether, acetone,
propylene glycol and others. Indications: cleaning, washing, bases for solutions and mixtures.
Oils (Olea).
Depending on their origin, they are mineral (Oleum Paraffini), animal (Oleum jecoris Aselli)
and plants-derived. The last are divided into drying (Ol. Heliathi, Ol. Lini, Ol. Arachidi) and
non-drying (Ol. Olivarum, Ol. Ricini, Ol. Amigdalarum). They are used to clean and
smoothen the skin, to enable desquamation and repair and reinforce the skin barrier.
Greases.
The oily substances are of mineral, animal and plant origin. Mineral products are vaseline
(vaselinum album et flavum - chemically neutral vehicle, which does not penetrate skin) and
paraffin (Paraffinum solidum). The greases from animal origin are lard, which is convenient
for use in the hair parts; lanolin - dense fat extracted from sheep's wool and whale fat. Waxes
are used mainly in cosmetics. Fat-like substances are used for ointments, creams and other
complex formulations. Cocoa butter is a representative of fats of vegetable origin.
Powders (pulvers).
Depending on their origin the powders are inorganic (mineral or synthetic) and organic
(plant). Powders of mineral origin are coarser but more stable - zincum oxydatum, talcum
venetum, Bolus Alba. Synthetic powders are sulfonamides, antibiotics, antiseptics, and
others. The plant powders are different types of starches. They reduce friction and have good
covering properties.
Complex topical preparations consist of two or more basic forms.
Solutions.
Powders dissolved in liquids. The most common solvents are water and alcohol. Used for
wet dressings, compresses, and healing baths in acute wetting processes. Used for rinsing and
gargling in oral pathology. Liquid phase evaporates, leaving a therapeutic film to cool and dry
the damaged skin. Most useful in exudative stages of the diseases.
Powder can be used alone or mixed with each other. Finer powders with smaller particles
are more effective. The powders are used to dry the wet and oily areas of the skin. Depending
on their composition, the powders are indifferent, antiseptic, antiseborrhoic, photoprotective
and others.
Mixtures consist of powders and liquids. Have anti-inflammatory and protective effects.
Should be shaken before use.
Emulsions/liniments are dispersed systems consisting of two non-intermixing liquids.
Emulsions the outer fluid dispersed the internal phase. Depending on which liquid is the
external phase, there are two types of emulsions: water/oil (the outer phase is oil) and
oil/water. They are used for burns, acute bullous dermatoses and others.
Creams are two-phase oil-water emulsion systems composed of fats and liquids. Creams are
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easy to wash off and leave no oily gloss. The oil ingredient is twice less than the liquid
medium. They are applied in acute inflammatory processes.
Ointments are lipid-containing dispersed systems with an active ingredient less than 30%.
Fats, waxes and oils are used as vehicles due to their high plastic properties. They form a thin
layer on the skin, preventing evaporation, moisturizing stratum corneum and providing
maximal penetration of the active ingredient. Ointments are used in chronic inflammatory
dermatosis with infiltration.
Gels are hydrophilic colloids that have a soft semisolid consistency. Applied to the skin they
form an easily washable, thin and greaseless film.
Aerosols/sprays are two-phase dispersion systems, containing powdered or liquid
components and pressurized gas stored in special, durable packages.
The golden rules for choosing the proper topical preparation are: “wet on wet” (which means
that wet topical preparation should be applied on oozing skin) and “dry on dry” (which
means that ointment topical preparation should be applied on infiltrative dry lesions).
Topical Preparations According to Mechanism of Action

Local Antiseptics
Antiseptics mostly used are iodine and its organic compounds iodoform, vioform; oxidizers -
hydrogen peroxide 1%, potassium permanganate and phenol derivatives - resorcinol, ditranol;
dyes - Fuchsine, Pyoctanin, Gentianviolet and others. They quickly dry and hold without
dressing on the skin. Used in bacterial, viral, and fungal skin infections.
Chlorhexidine (Hibiclens) → Broad antimicrobial spectrum (bacterial, viral, fungal).
SEs: ocular irritation and ototoxicity.
Hexachlorophene (pHisoHex) → Gram+ cocci.
SEs: teratogenic, skin absorption can cause neurotoxic effects.
Povidone-Iodine (Betadine) → Broad antimicrobial spectrum including fungi.
Effective only if dry, inactivated by blood or sputum.
SEs: skin irritant, contact dermatitis.
Benzalkonium chloride (Zephiran) → Gram+ bacteria, Gram– bacteria.
Nonirritating; inactivated by anionic compounds such as soap.
Isopropyl alcohol → Gram+ bacteria.
Flammable in setting of cautery, skin irritant.
Silver sulfadiazine (Silvadene) → broad spectrum.
SEs: argyria (local), leukopenia.
CIs: sulfonamide hypersensitivity; caution if renal or liver disease or G6PD deficiency.
Hydrogen peroxide → bacteria, fungi (at ↑ H2O2 concentration).
Corrosive to normal skin, bleaching action. May cross-react with radiopaque iodine or
iodides in medications.
Topical Antibiotics
Used in pyodermas, impetiginized dermatoses, papulous forms of acne and rosacea,
post-thrombophlebitis ulcers and others.
Erythromycin is a bacteriostatic macrolide antibiotic produced from Streptomyces erythreus.
Used for prophylaxis or treatment of superficial pyogenic skin infections and acne. Available
in 1.5% or 2% as a pledget, gel, solution or ointment.
Clindamycin phosphate is a lincosamide, which suppresses bacterial protein synthesis. Used
in acne, perioral dermatitis, superficial skin infections, folliculitis, hidradenitis suppurativa,
etc. Available in solution, lotion, and gel forms.
SEs: skin dryness, itching, redness, swelling, Gram-negative folliculitis.
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Gentamicin is a bactericidal aminoglycoside that inhibits bacterial protein synthesis. Used for
minor bacterial infections and secondary infected skin lesions. Available as a 0.1% cream or
ointment. Excessive use may result in emergency of resistant bacteria and fungi.
Mupirocin is derived from Pseudomonas fluorescents. Bacteriostatic at low concentrations
and bactericidal at higher concentrations. Effective against staphylococci and streptococci.
Indicated for treatment of impetigo and for prophylaxis of nasal St. aureus carriage. Available
as a 2% ointment (Bactroban).
Metronidazole has antibacterial and anti-inflammatory effects in treatment of rosacea.
Available as 0.75% gel or 1% cream.
SEs: transient redness, dryness, burning and irritation.
Bacitracin, Neomycin, Polymyxin B
Bacitracin is a polypeptide bactericidal antibiotic. Effective against Gram-positive cocci and
bacilli.
Neomycin sulfate is a bactericidal aminoglycoside. Effective against Gram-negative
organisms.
Polymyxin B is a cyclic polypeptide. Effective against Gram-negative organisms.
Compound preparations are indicated for minor skin wound infections.
Topical Antifungal Preparations
Dyes and iodine, besides antiseptic, are also classic antifungal agents. Salicylic acid 5-10%,
benzoic acid 10%, resorcinol and their derivatives act as fungistatic and fungicidal agents.
Acids act keratolytically, and thus mechanically remove dermatophytes by desquamation of
stratum corneum.
Imidazoles (Clotrimazol 1%, Miconazole 2%, Ketoconazole 2% and Econazol) have
broad-spectrum fungicidal action against dermatophytes, yeast, molds and Gram-positive
bacteria. Ketoconazole shampoo is used to treat tinea capitis as well as seborrhoeic dermatitis
and scalp psoriasis.
Polyenes (Nystatin, Amphotericin B) have fungicidal action against Candida.
Whitfield's ointment (benzoic acid) is an old-fashioned antifungal agent, limited today. Acts
as a keratolytic agent but also has mild antifungal properties. Contains benzoic and salicylic
acid in ointment base. The main indication is chronic hyperkeratotic form of tinea pedis.
SE: irritation.
Ciclopirox olamine 1% is a synthetic broad-spectrum fungistatic agent that inhibits fungal

growth.
Allylamines (Naftifine, Terbinafine) are fungicidal against dermatophytes but fungistatic
against Candida species.
Topical Antiparasitic Preparations
Applied locally they kill mites, lice and other causative infestation agents.
Benzylum benzoicum 30% for adults and 10-15% in children is used for scabies and lice
treatment.
Lindan 1% cream or lotion used for scabies and lice treatment. Applied on the entire body for
6-12 hours in scabies. Not used in pregnant women and babies under 1 year → risk of central
nervous system toxicity. Shampoo for head lice.
Crotamition 10% cream or lotion is applied as Lindan, not as effective but less toxic.
Sulfur praecipitatum 30% in petrolatum is applied for 3 consecutive nights.
Permethrin 1% for head lice used as cream and shampoo.
Vitamins for Topical Therapy
Vitamin A (Retinol) is used in precancerous tumors. Vitamin A acid derivatives (Retin A,
Eudina) - in hyperkeratotic dermatoses.
Vitamin D (calcipotriol) is used in the treatment of psoriasis. A major improvement is
obtained at a concentration of 50 mg of vehicle administered twice daily, with a maximum
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effect observed after 6-8 weeks. High doses of local vitamin D can lead to impaired calcium
metabolism.
Vitamin B5 (Pantothenic acid). Dexpanthenol is an alcohol corresponding to pantothenic
acid. Applied in burns, ulcers and other skin integrity disorders.
Vitamin C is available in the form of creams, serum and transdermal patches. Used to prevent
and treat antioxidant changes associated with photoaging and hyperpigmentation.
Vitamin E is used in burns, wounds, surgical scars. 0.1% vitamin E in combination with other
vitamins reduces hemostatic skin changes. It is an important component of antiaging
cosmetics.
Topical Antipruritic Preparations
Act on the skin free nerve endings suppressing the itch. Main indications are pruritus caused
by insect bites, fungal infections, psoriasis, eczema, sunburn. Carbolic acid 1%, citric acid
2%, tartaric acid 3%, menthol 0.5-2%, and thymol show such properties. Topical antipyrine,
anesthesin and procaine also have an anti-pruritic effect. These drugs are available in the
form of creams, lotions and sprays. Baking soda dissolved in water, relieves fungal itch.
Topical corticosteroids, Calamine lotion (contain zinc oxide and iron oxide), curcumin and
papain-based topical creams show anti-pruritic properties, too.
Topical Corticosteroids. Indications and Contraindications. Side Effects
All topical corticosteroids show strong anti-inflammatory, antiproliferative, vasoconstrictive,
immunosuppressive, and local anesthetic effects. According to their chemical structure, three
groups of topical corticosteroids are distinguished: non-fluorinated (hydrocortisone,
prednisolone), monofluorinated (dexamethasone, betamenazone and triamcinolone) and
double fluorinated (fluacenolone acetonide, flumetasone pivalate). The non-fluorinated
corticosteroids are considered less potent, the double-fluorinated show moderate
anti-inflammatory property, betamethasone valerate belongs to the group of high potency
topical corticosteroids, and Clobethasol – to the ultra high potency corticosteroids.
Indications: all types of dermatitis/eczema, acute or chronic inflammatory dermatoses. After
prolonged use and sudden stopping, a rebound phenomenon occurs.
SEs: acne, rosacea, pyoderma activation, delayed epithelialization of wounds, skin atrophy,
hypertrichosis, increased capillary breakability, steroid acne, stretch marks, purpura.
CIs: pyoderma, dermatovirosis, dermatomycosis, tuberculosis.
Calcineurin Inhibitors
Calcineurin inhibitors are modulators of T-cell immune response. They have
anti-inflammatory and anti-proliferating properties. Topical calcineurin inhibitors are
pimecrolimus (Elidel) and tacrolimus (Protopic 0.03% and 0.1%). Used in atopic dermatitis,
psoriasis, seborrhoeic eczema, lichen planus, lichen sclerosus, vitiligo, lupus erythematosus
and pityriasis alba.
SEs: local skin irritation, burning, pruritus.
Keratolytic preparations. Agents enhancing skin desquamation
All these substances dissolve corneocytes intercellular contacts, enhancing desquamation and
microbacterial eradication. Therefore, they show antiseptic, antiparasitic and antimycotic
properties. The most common ingredients are: salicylic acid over 5%, benzoic acid 5-10%,
urea over 5%, trichloracetic acid over 15%, vitamin A acid preparations, Resorcinum,
Betanaphtolum and others. Depilatory agents such as barium sulfuricum, and thioglycols also
exert keratolytic effect.
Indications: keratoderma, clavi, seborrhea, and psoriasis vulgaris.
Keratoplastic Agents. Agents Enhancing Skin Epithelization .
Salicyic acid up to 5%, urea up to 5%, benzoic acid up to 5% exert epithelization properties.
The skin cracks, fissures, erosions and ulcers may be treated with 1-10% silver nitrate
solution, vitamin A oleosum, Peruvian balm, ointments containing 10% eucalyptol and
ready-made formulations such as Madecassol, Deflamol, Cruresil and others.
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Local Astringents
Astringents are chemical ingredients that coagulated superficial skin proteins thus reducing
skin water contain. They affect only the superficial layer, reduce cellular permeability, make
the surface mechanically stronger, decrease exudation, protect from external irritation and
have mild pain relieving action. Divided into: vegetable astringents (tannic acid, gallic acid),
metallic astringents (aluminium salts – alum, aluminium chloride, aluminium acetate), zinc
salts (zinc chloride, zinc sulfate), ferric chloride, silver nitrate, copper sulfate and others. The
use of astringents is to cause mild coagulation of skin proteins, dry, harden, and protect the
skin, cleaning the face and preventing acne breakouts and stopping bleeding.
Reductive Agents - Tars. Dithranol
The use of tars in dermatology is based on their antipruritic, anti-inflammatory and
antiproliferative properties.
Most commonly used in psoriasis vulgaris, either alone or in combination with UVB
radiation (Goeckerman regimen).
Fototar (cream, stick) and others. Shampoos - Denorex, Doak tar, Sebuton and others. Tar can
be also combined with keratolytics and topical corticosteroids.
Tar bath oils are added to the bathwater. Tar lotion, paste, cream, and stick are applied
directly to the psoriatic lesions. The tar preparations should be left on the skin for at least 2
hours before rinsed.
SEs: non-melanoma skin cancer, folliculitis, irritation.
Dithranol is a synthetic compound, a yellow powder, produced from anthracene. Dithranol is
indicated for mild-to-moderate psoriasis, applied alone or in combination with phototherapy
(method of Ingram) or with UV and corticosteroid ointment (Ferber’s method).
Chemical Destructors – Wart and Calluses Preparations
Applied as pure substances many topical agents have caustic effect - potassium
permanganate, β-naphthol, all keratolytic agents, silver nitrate, acetic and trichloroacetic acid,
nitric acid. Some cytostatics such as podophylline (20-35%), colchicine, and fluorouracil
(Flurorex 1% or Efudex 2% or 5% cream) also destroy hyperkeratotic lesions, which makes
them suitable for treating anogenital and multiple flat warts. Podophylline is teratogenic and
shouldn’t be used during pregnancy.
Depigmenting Preparations
Inhibition of melanogenesis or regulation of melanosomes synthesis and transfer.
Used in melasma, post inflammatory hyperpigmentation, ephelides, age relating
hyperpigmentations.
Pharmacological depigmenting agents: Hydroquinone targets tyrosinase activity, but although
it is highly effective, its safety is still controversial. Rare side effects are exogenous
ochronosis and permanent depigmentation.
Tretinoin (0.025% to 0.1%) is a topical retinoid, which acts by inhibiting the activity of
tyrosinase.
SEs: erythema and irritation.
Cosmetic depigmenting agents: Perhydrol 2-10% and iontophoresis with vitamin C can also
be used as depigmented agents. Keratolytic agents, such as arbutin, azelaic acid, Kojic acid
and others in increasing concentrations, achieve the so called chemical dermabrasion.
Photoprotective Agents. Photosensitizing Agents
Photoprotective Agents
Photo-filters are chemical and physical compounds. According to the spectrum of
photo-protection they are divided into UVA and UVB sunscreens. The most commonly used
chemical substances are: p-Aminobenzoic acid, oxybenzone homosalate, octrocrylene,
sulfobenzone, titanium dioxide, zinc oxide. The evaluation of the photo-protective agents is
quantified on their sun protection factor - SPF. This is the ratio between the minimal
erythema dose of the skin treated with and without a photo-protective preparation. The choice
35
of photo-protective agent depends on skin phototype, duration and intensity of sun exposure
and patients age.
Photosensitizing Agents (Psoralens)
Derivatives of coumarin and furocoumarin. Used to enhance UVA skin absorption
[Psoralen+UVA (PUVA) Therapy].
Physiotherapy
Phototherapy
Includes UVB (narrowband or broadband) and UVA (UVA1 or UVA2 ± psoralen).
Possible mechanism of action: ↓ cellular proliferation, apoptosis of T cells, suppression of
Langerhans cells.
Used in psoriasis, atopic dermatitis, pityriasis rosea, parapsoriasis, cutaneous T-cell
lymphoma, etc.
Regimen. At least 3 times weekly to every day. Patient’s skin type and disease severity
should be judged prior treatment.
Can be used in pregnant women and children.
Adjunctive therapies include topical use of coal tar (Goeckerman regimen), anthralin (Ingram
regimen) or combination with methotrexate or retinoids.
SEs: phototoxicity, photoallergy, photoaging, cutaneous carcinomas, accelerating skin aging.
CIs: photosensitizing medication (i.e., thiazides) and photosensitive disorders (i.e., lupus).
Broadband UVB (290–320 nm): emits light in broad range.
Narrowband UVB (NBUVB) (311–313 nm): narrower spectrum relates to better therapeutic
effect than broadband.
Broadband UVA: UVA2 (320–340 nm, similar to UVB) and UVA1 (340–400 nm, penetrates
deeper).
PUVA (typically peaks at 352 nm): UVA + psoralen (type of furocoumarin, topical or oral).
Oral psoralen (i.e., methoxalen): peak concentration occurs 1.5 h after ingestion.
↓ cellular proliferation, results in apoptosis of T cells, and suppresses Langerhans cells.
Used in psoriasis, vitiligo, atopic dermatitis, lichen planus, parapsoriasis, T cell skin
lymphomas, pruritus, alopecia.
Regimen. Psoralen may be given orally as 10 mg capsules 2 hours before UVA or applied
topically as a 0,1% or 0,01% ethanol-based solution 30 minutes before irradiation is
administered.
SEs: nausea, vomiting, stinging, pruritus, headache, phototoxic reaction, hyperpigmentation,
lentigines, photoaging, carcinogenesis.
Precautions. Hepatotoxity → psoralens are metabolized by the liver so hepatic dysfunctions
demands observation. Ocular toxity → patients must have ophthalmologic examination
before therapy; cataract is a contraindication. May detect psoralen in lens for up to 12 h after
ingestion; patients should avoid sun exposure for 24 h after PUVA treatment.
CIs: autoimmune disorders, photosensitivity, severe liver, kidney, cardiovascular and nervous
system diseases, etc.
Excimer Laser (308 nm): targeted phototherapy for recalcitrant psoriatic lesions and vitiligo.
Extracorporeal Photochemotherapy (ECP): extracorporeal UVA irradiation of WBCs after
8-MOP added, then returned back to patient; used in treatment of erythrodermic CTCL.
Photodynamic Therapy (PDT): Therapeutic wavelength between 400 and 800 nm but
typically blue light (near 400 nm). Topical 5-aminolevulinic acid (ALA) or methyl
aminolevulinate (MAL) transformed into protoporphyrin IX (higher amounts found in
tumors) → selectively destroys premalignant and malignant cells.
Used in premalignant and malignant lesions.
Lasers (Light Amplification by Stimulated Emission of Radiation)

36
The laser is a monochromatic stimulated light in the area of ultraviolet, visible or infrared
rays. There are low- and high-intensity lasers. Low-intensity lasers (helium-neon;
helium-cadmium) have an anti-inflammatory and biostimulating effect on trophic ulcers.
High-intensity lasers (CO2, Argon, Alexandrine, Ruby, Dye Nd:Yag) cause skin thermal
damage through photocoagulation and photoevaporation to treat hemangiomas, verrucae
vulgares, condylomata acuminate, pigmentary dermatoses, BCC, etc.
Laser light: monochromatic (single, discrete wavelength), spatially coherent (light in phase),
collimated (light in parallel fashion).
Laser treatment based on principle of selective thermolysis → destroyed targeted lesion.
Chromophores: components in skin which absorb laser light → endogenous: hemoglobin,
melanin, water; exogenous: tattoo ink.
Laser characteristics: wavelength, pulse duration, spot size, fluence (J/cm²), power (J/s).
Laser medium determines wavelength of light → liquid (dye lasers), gas (argon, CO2,
helium-neon), solid (Nd:Yag, ruby).
Pulse duration (exposure time of laser) → determines confinement of heat and extent of
thermal injury in tissue.
Spot size → larger spot size allows for deeper energy penetration (less scattering).
Q-switched or “quality-switched” → allows accumulation of excessive energy in laser cavity
prior to emission; extremely short pulses of very high power (nanosecond range); used
mainly for removal of tattoo pigment and superficial pigmented lesions.
Hair removal → target thought to be bulge of hair follicle as well as dermal papilla.
Cryosurgery. Electrosurgery. Curettage

Cryosurgery
Targeted tissue destruction via necrosis induced by subzero temperature with liquid nitrogen.
Direct cellular damage due to ice crystal formation.
Indirect damage: cold-induced damage to capillaries causing local ischemic necrosis.
Used in benign lesions such as actinic keratosis, seborrheic keratosis, lentigo solaris, verruca,
sebaceous hyperplasia, haemangiomas, telangiectasias, molluscum contagiosum, initial BCC.
Cryogens. Liquid nitrogen (temperature of -196C). Applied with a cotton-tipped swab,
hand-held spray unit or cryoprobe.
SEs: pain, edema, bullae, hypopigmentation, scarring, neural damage.
Contraindications and precautions. Any abnormal reaction to cold as cryoglobulinemia, cold
urticaria and Raynaud’s disease.
Electrosurgery
Use of high-frequency alternating current to create thermal tissue destruction (includes
electrosection, electrocoagulation, electrofulguration, electrodesiccation).
Used in benign lesions such as fibroma, pyogenic granuloma, cellular nevus; initial BCC;
verruca vulgaris, condylomata acuminata; punctiforme haemangioma, stellatum
hemangioma.
Curettage
Simple technique for removing benign superficial lesions with curettes. No anesthesia
needed.
Used in molluscum contagiosum, seborrheic keratosis, and actinic keratosis.
Climatotherapy. Thalassotherapy. Balneotherapy

The impact of various climatic factors (air, sun, seawater, mineral water, air ionization, wind,
moisture, etc.,) has a beneficial effect on various dermatoses.
High Mountain Climatotherapy (above 1600-2000 m sea level)
Pathogenetic mechanism is unclear. Total hyposensibilization and stimulation of adrenal
gland function is supposed.
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Used in atopic dermatitis, chronic urticaria, immunobullous dermatoses, etc.
Thalassotherapy
Sea-based therapy → complex thermal, chemical and physical UV radiation and seawater
effects lead to improvement of keratopoesis, vasodilatation, activation of pigmentation, and ↓
mast cell synthesis.
Used in psoriasis, vitiligo, skin tuberculosis, acne vulgaris, chronic urticaria, scleroderma,
ichthyosis, etc.
Balneotherapy
Used the beneficial effect of sulphide waters, hydrogen sulphide baths and mud treatment.
The water with different mineral content is applied in the form of baths, compresses, water
for drinking. Greater effect has the external application → acts by mechanical, thermal,
chemical and electrical factors on skin receptors and impact on the immune system.
Used in psoriasis, atopic dermatitis, chronic urticaria, ichthyosis, idiopathic pruritus, lichen
planus, scleroderma.
SPECIAL DERMATOLOGY
DERMATOSES FROM PHYSICAL FACTORS
Dermatoses Caused by Environmental - Mechanical, Thermal and Ionizing – Factors
Skin changes under the influence of environmental factors.
Pathogenetic Mechanisms: allergic/non-allergic.
Dermatoses from Mechanical Factors
Etiology.
Arise as a result of acute or chronic mechanical injury.
Causes → household, occupational/accidental traumas. Clinical picture depends on
repeatability, affected site and skin adaptation properties.
Dermatitis Traumatica Bullosa (Friction Blister)
At the site of mild, repetitive or acute trauma. One or more bullas on the site of trauma + pain
or burning. Self-limited changes after the mechanical trauma stopps.
Traumatic Hemorrhages
Calcaneal Petechiae (Black Heel)
Punctual skin hemorrhages in the most stressed places. Result of recurrent foot trauma during
an active sporting activity or walking. Due to cappilary vulnerability.
Adaptive Skin Reactions
Callositas
Localized hyperkeratosis on the site of recurrent traumas. Often represent occupational
stigmas - shoemakers, mechanics, violinists and others. Thickened stratum corneum with a
yellowish-brown color, ± painful rhagadas.
Clavus (Helos)
Localized hyperkeratosis of the more protruding areas of the palms and feet ± secondary
manifestation of skeletal deformations. Causes pain under pressure.
Treatment.
Keratolytic agents, cryotherapy and surgical removal.
Atrophy of the Skin Due to Mechanical Factors
Striae Cutis Distensae Atrophicae
Multiple symmetrically linear stretch marks in pregnancy, weight change, rapid growth.
Etiology.
Genetic predisposition. Adverse effects of topical corticosteroids.
Pathophysiology.
Skin distension → damage of collagen and elastin fibers.
Dermatoses Caused by Normal Skin Reactivity to Cold
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Congelatio (Frostbite)
Etiology.
After long periods of cold exposure with subsequent thermoregulatory mechanisms
decompensation.
Pathogenesis.
Extracellularly/intracellularly small icy crystalline → mast cells degranulation → histamine
release → swelling and hyperemia. Erythrocytes aggregation and necrosis of affected tissue.
Clinical Picture.
White and insensitive skin in exposed parts of the body - fingers, nose, and ears. First-degree
frostbite (frostnip), affects only the surface of the skin → dermatitis irritate a frigore.
Second-degree frostbite cause the skin to freeze and become hardened; does not affect the
deep tissues. Purple-colored blisters with thick walls usually appear in 2 days ± nerve damage
→ numbness, pain to total loss of feeling. Loss of heat and cold sensation may be permanent.
Third- and fourth-degree frostbite → deep tissue injury with necrosis and eschars.
Dermatoses Caused by Abnormal Skin Reactivity to Cold
Perniones (Chilblains)
Mostly young women. Recurs during the cold and wet months.
Red nodular changes on distal sites of fingers, wrists, feet, ears, etc. + burning and pain.
Treatment.
Vasodilators.
Acrocyanosis
May be transient after cold exposure but frequently persist during winter and even in summer.
Coolness and blue or cyanotic discolorations of hands and less frequently of feet.
Thermal Injury of the Skin
Combustio
Etiology.
Skin burning after contact with hot objects, liquids or electrical current.
Pathogenesis.
Damage of the skin's integrity → protein coagulation and capillary destruction → locally↑
capillary permeability → loss of tissue fluid → ↓ blood in the blood circulation → the heat
balance changes.
Clinical Picture.
Three-degree severity depending on skin damage depth: first degree - erythema and swelling.
Pain varies in intensity, changes take place for a few days and recover with or without
desquamation; second degree -↑redness, ↑swelling + painful, tense, bright blisters resorted or
ruptured with formation of erosions. Healing lasts for several weeks and skin heals without
scars; third degree - hypodermal necrosis → demarcation of the necrotic zone → ulcer with a
slow tendency to granulation and epithelization. Very severe pain. Heals with hypertrophic
scars and keloids.
Treatment.
Surgical treatment in second and third degree burns. Anti-shock therapy. Monitoring of renal
and cardiac function. General and local antiseptics.
Dermatoses Caused by Ionizing Rays
Etiology.
Skin damage from ionizing radiation (emitions of α, β and γ particles and X-rays). Mainly
occupational, observed in radiologists, dentists, laboratory workers and others.
Acute Radiodermatitis
Four stages depending on ionizing radiation dose. First stage - moderate erythema and
edema. The hair fell. Swelling and temporary hyperpigmentation. Second stage after 10 days
- significant erythema and edema + burning and pain, permanent alopecia. Third stage -
39
exudative lesions → erosions without epithelization. Four stage with ulceration
(radiodermatitis ulcerosa).
Chronic Radiodermatitis
Irradiation of the skin with 12-15 Gray or repeated cumulative irradiation with a smaller dose
→ chronic radiodermatitis after more than 2 years of exposure. The skin is atrophic +
telangiectasias + hyper- and hypopigmentation (poikiloderma). Necrotic ulcerations may
occur, especially in moist areas.
Photodermatoses
Dermatoses of increased photosensitivity.
Acute and chronic.
Classification:
I. Genodermatoses – xeroderma pigmentosum, Bloom syndrome, porphyrias, etc.;
II. Metabolic diseases – pellagra, porphyria cutanea tarda, etc;
III. Connective-tissue diseases – lupus erythematosus, dermatomyositis, etc;
IV. Inflammatory skin diseases with concomitant photosensitivity – acne, rosacea,
seborrheic dermatitis;
V. Reaction due to combination of light (typically UVA) and photosensitizing chemicals
– phototoxic and photoallergic contact dermatitis;
VI. Idiopathic photodermatoses – polymorphous light eruption, juvenile spring eruption,
actinic prurigo, hydroa vacciniforme, solar urticaria, chronic actinic dermatitis.
Phototoxic Dermatitis
Etiology.
Common reaction resembling sunburn with rapid onset (minutes to hours) due to
photosensitizer, which enhances sunlight destructive effect on keratinocytes.
Clinical Picture.
Typically occurs only on sun-exposed sites. Erythema and oedema, postinflammatory
hyperpigmentation, onycholysis.
Treatment.
Photoprotection and removal of photosensitizer.
Photoallergic Dermatitis
Etiology.
Delayed-type allergic contact dermatitis due to an allergen taken via systemic or topical route
always prior photoexposition.
Clinical Picture.
Erythematous papules and plaques, sometimes exudative lesions, which may cause
lichenification in chronic stages.
Treatment.
Allergen avoidance and photoprotection.
Phytophotodermatitis
Etiology.
Dermatitis due to UV-exposure after contact with plants, containing phototoxic chemicals
(especially furocoumarins) or photoallergens (parsley).
Clinical Picture.
Vesicules and blisters on sites of UV exposure in acute phase, erosions, covered with crusts
and prurigo papules in subacute phases, and lichenification – in chronic phases.
Treatment.
Avoidance of photosensitizers, topical corticosteroid.
Polymorphous Light Eruption (PMLE)
Etiology.
40
Most common form of idiopathic photodermatosis. Acquired photo-induced disease with an
onset in second or third decade; exacerbates in spring or early summer; delayed
hypersensitivity reaction to endogenous photo-induced antigen of obscured origin.
Clinical Picture.
Polymorphous eruption of patchy erythematous papules, plaques or vesicles on sun-exposed
areas; appear hours to days after UV exposure; improves in the course of summer (natural
‘hardening’ phenomenon).
Juvenile Spring Eruption
Clinical Picture.
Typically involves the ears (helices) in boys or young men; pruritic erythematous papules and
wheals.
Treatment.
Restriction of UV exposure, desensitization therapy with low-dose NB-UVB or PUVA,
topical or oral corticosteroids, antimalarials.
Actinic Prurigo
Seen mainly in native Americans. Worse in spring and summer, starts in the first decade and
improves in adolescence.
Clinical picture.
Erythematous and edematous plaques with hemorrhagic crusts, linear excoriations; atrophic
pitted scars left after lesion resorption; cheilitis and conjunctivitis can occur simultaneously.
Treatment.
Photoprotection and topical corticosteroids.
Hydroa Vacciniforme
Rare sun-provoked scarring disorder with onset in early childhood; worsens in spring and
summer; sometimes associated with EBV infection.
Clinical Picture.
Erythematous papules and plaques, evolving in blisters with subsequent crusts and erosions,
resulting in varioliform scars.
Treatment.
Refractory to treatment, photoprotection.
Solar Urticaria
Wheals, which appear immediately after sun exposure.
Clinical Picture.
Burning and erythema followed by wheal formation on sun-exposed areas; anaphylactic-type
response possible.
Treatment.
Photoprotection, antihistamines and sometimes topical corticosteroids, UV desensitization.
Chronic Actinic Dermatitis (Actinic Reticuloid: Severe Clinical Variant)
Persistent UV-provoked eczematous reaction on photoexposed areas, exacerbates during
summer period; affects older men.
Clinical Picture.
Pruritic erythematous papules and plaques, lichenification and infiltration on sun-exposed
areas.
Treatment.
Photoprotection, topical corticosteroids, NB- UVB or PUVA desensitization, azathioprine,
cyclosporine.
ECZEMA/DERMATITIS
Contact Dermatitis (CD)
Acute or chronic inflammatory reaction to a substance in contact with the skin; two main
types: irritant and allergic CD
41
Irritant Contact Dermatitis (ICD)
Accounts for 80% of occupational CD.
Pathogenecity: direct local cytotoxic effect of irritant on the skin.
Acute ICD: acute exposure to toxic agent; presents with pruritus and sharply localized
erythema with vesicles, edematous papules or hemorrhagic blisters, ± scaling or crusting; no
distant spread.
Chronic ICD: repeated exposure to mild irritants (low-grade irritation); presents with diffuse
or localized but ill-defined scaly patches and plaques.
Allergic contact dermatitis (ACD)
Accounts for 20% of all CD.
Etiology.
Most common triggers – nickel, fragrances and preservatives.
Pathogenesis.
Type IV delayed hypersensitivity to contact allergen that has been in prior contact with skin;
delayed onset (24–96 h after exposure).
Clinical Picture.
Acute CD – pruritic vesicles, weeping and erythematous macules ± dissemination of the
lesions. Subacute CD - eczematous scaly plaques and prurigo-papules on areas of contact or
dissemination due to autosensitization (secondary eruption). Chronic CD – lichenification
and hyperkeratosis.
Patch testing is the gold standard for diagnosing ACD.
Treatment.
Avoidance of the irritants/allergens, topical corticosteroids, if severe - antihistamines and
short-term systemic corticosteroid course.
Atopic Dermatitis (AD)

Pruritic chronic-relapsing eczema with specific age-related clinical picture
Occurs in 10–15% people, onset - often at 2–3 months of age.
Pathogenesis.
Multifactorial pathogenesis but includes ↑ secretion of TH 2 cytokines (IL-4, IL-5), filaggrin
mutations, epidermal barrier dysfunction. The disease can be induced or exacerbated by
Staphylococcus aureus or Malassezia yeast.
Atopy triad: AD, allergic rhinitis, asthma.
Atopic diathesis: personal or family history (asthma, allergic rhinitis and or conjunctivitis,
and atopic dermatitis), and predisposition to overproduction of immunoglobulin E (IgE)
antibodies.
Unspecific hyperreactivity, a few patients show allergy to specific foods (eggs, milk,
soybeans, fish, wheat, peanuts).
Presents with eczematous lesions, xerosis, and lichenification.
Age-related distribution of skin lesions:
Infants - face, scalp, and extensor sites of extremities.
Children - antecubital/popliteal fossae, neck, wrists, ankles.
Adults - typically hands (chronic hand eczema), pityriasis alba - hypopigmented patches with
minimal scale, flexural lichenification.
Complications:
keratoconus (conical deformity of cornea), eyelid dermatitis,↑ risk of infection (impetigo,
eczema herpeticum, molluscum contagiosum), Kaposi’s varicelliform eruption.
Diagnosis.
Usually the diagnostic criteria of Hanifin & Rajika are used:
42
Must have three or more basic features:
1. Pruritus.
2. Typical morphology and distribution - flexural lichenification in adults and facial and
extensor eruptions in infants and children.
3. Chronic or chronically relapsing dermatitis.
4. Personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis).
Must have three or more following minor features:
1. Xerosis.
2. Ichthyosis (palmar hyperlinearity, keratosis pilaris).
3. Immediate (type I) skin test reaction.
4. Elevated serum IgE.
5. Early age of onset.
6. Tendency toward cutaneous infections (especially S. aureus and Herpes simplex), impaired
cell-mediated immunity.
7. Tendency toward non-specific hand or foot dermatitis.
8. Nipple eczema.
9. Cheilitis.
10. Recurrent conjunctivitis.
11. Dennie-Morgan infraorbital fold.
12. Keratoconus.
13. Anterior subcapsular cataracts.
14. Orbital darkening.
15. Facial pallor, facial erythema.
16. Pityriasis alba.
17. Anterior neck folds.
18. Itch when sweating.
19. Intolereance to wool and lipid solvent.
20. Perifollicular accentuation.
21. Food intolerance.
22. Course influenced by environmental and emotional factors.
23. White dermographism, delayed blanch.
DD.
Contact dermatitis, seborrheic dermatitis, prurigo simplex, scabies, miliaria, ichthyosis,
xerotic eczema, hand dermatitis (non-atopic).
Prophilactic.
Education of the patients to understand the chronic nature of the disease, to avoid rubbing
and scratching. Removal the irritants from environment (wool or synthetic fibres, detergents,
dust, sand, animal fur, flowers, pollens and etc.). Elimination of certain food. Bathing and
emollients.
Treatment.
Topical corticosteroids, topical calcineurin inhibitors, oral antihistamines, oral corticosteroids
(short course), phototherapy, thalassotherapy, immunosupressants
Seborrheic Dermatitis
Chronic eczema characterized by yellowish, oily, scaly red patches, occurring in regions
where the sebaceous glands are most active, such as face, scalp, presternal area, and body
folds (sebaceous areas). Mild scalp SD causes flaking, i.e., “dandruff” in adults or "cradle
cap" in infants.
Onset: In infancy (within the first months), puberty, between 20 and 50 years or older.
Sex: More common in males.
Etiology, Pathogenesis, Predisposing, and Aggravating Factors
43
Genetic Predisposition.
It is sometimes associated with psoriasis (seborrhiasis). The yeast Malassezia plays a
pathogenic role. Increased incidence in Parkinson disease and in immunosuppresed patients
(HIV/AIDS).
Clinical Picture
SD follows a chronic recurrent course, with exacerbations and remissions. Flares during
periods of stress and cold weather. Exposure to sunlight frequently is associated with
remissions. In infants, the disease resolves after a few months.
Skin Symptoms.
Pruritus is variable, often increased by perspiration.
Skin Lesions.
Orange-red or gray-white scales, macules, papules or patches, rather sharply marginated.
Affects the scalp, ears, nasolabial folds, and eyebrows. Severe cases extend to the central
chest, back, umbilicus, and intertriginous areas. Marked scaling present on scalp
(“dandruff“); sometimes - diffuse involvment. Nummular, polycyclic, and even annular
patches/plaques on the trunk.
Clinical Variants
In Infants:
”Cradle cap“ - erythema and yellow-orange scales and crusts on the scalp in infants.
„Napkin dermatitis” - chronic recurrent diaper dermatitis.
In Adults:
Face – salmon-pink plaques in nasolabial folds, eyebrows, and glabella.
Forehead - “corona seborrhoica“.
Ears - sticky crusts and fissures retroauricular and in meatus.
Pityriasis simplex faciei - an annual hypopigmented scaling eruption on the face and neck.
Medallion-type - multiple large, oval, yellowish-brown scaling patches on the chest and
back.
Seborrheic blepharitis - erythema, scaling, and crusting on the eyelid margins.
Body folds - diffuse, exudative, sharply marginated, brightly erythematous eruption; erosions
and fissures are common.
Genitalia - yellow crusts and psoriasiform lesions.
Diagnosis.
Occasionally there is an overlap clinically with psoriasis (sebopsoriasis), making the
diagnosis difficult without skin biopsy.
DD.
Psoriasis, impetigo, dermatophytosis, pityriasis versicolor, intertriginous candidiasis, etc.
Treatment
Scalp: Shampoos containing selenium sulfide, zinc pyrithione, salicylic acid, sulfur,
chloroxine or tar. Lower-potency glucocorticoid solution, lotion, or gels following a
medicated shampoo (ketoconazole or tar) are prescribed in more severe cases. Pimecrolimus,
1% cream, is very beneficial.
Body: Mild-potency topical corticosteroid creams and lotions, 2% ketoconazole cream, 1%
pimecrolimus cream, and 0.03% or 0.1% tacrolimus ointment.
Intertriginous areas: Combined treatment with antifungal and mild corticosteroid creams.
Systemic Treatment
In milder cases, itraconazole 100 mg twice daily.
In severe cases, 13-cis-retinoic acid orally.
URTICARIA. STROPHULUS
Urticaria
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Discrete erythematous areas of swelling (wheals) involving either superficial skin or mucosa
with associated pruritus; lesions last < 24 h, ± associated angioedema.
Acute urticaria < 6 weeks, chronic > 6 weeks.
Pathophysiology:
subsequent release of histamin from mast cell storage granules: newly formed mediators:
prostaglandin D2, leukotriene C4/D4/E4, platelet-activating factor.
Causes:
idiopathic, immunologic, non-immunologic
Immunologic
IgE-mediated type I hypersensitivity (allergic)
Immune complex deposition (serum sickness disease)
Complement-dependent
Autoantibodies: anti-IgE or anti-FcєRI antibodies (autoimmune urticaria, often
chronic)
Non-immunologic (direct/indirect degranulation)
Drugs (opiates, radiocontrast dye, polymyxin B, aspirin, NSAID),
contact-induced (i.e. nettle stings), certain foods
Histology:
papillary oedema of various degree, scant-to-moderate perivascular infiltrate of eosinophils,
lymphocytes or neutrophils (in secondary urticaria, usually associated with connective-tissue
diseases).
Clinical Variants:
Dermographism - urticarial lesions resulting from light scratching
Delayed pressure urticaria - deep swelling with overlying erythema at sites of sustained
pressure occurring with a delay of up to 12 h
Cholinergic urticaria - small erythematous papules appearing within 15 min of
sweat-inducing stimulus (i.e. physical exercise)
Solar urticaria - occurs typically within minutes of exposure to sun (UV or visible light), lasts
for <1 h, may have be accompanied by headache and syncope
Aquagenic urticaria - eruption after contact with water, typically lasts for <1 h
Cold urticaria - in cold-exposed areas occurs upon rewarming
Contact urticaria - at site of contact (i.e., nettle stings, latex)
Work-up for chronic urticaria: CBC, ESR, ANA, anti-IgE/FcєRI antibodies, anti-thyroid
antibodies, stool ova/parasite.
Treatment.
Trigger avoidance, antihistamines (H1, sometimes in combination with H2), short course of
oral corticosteroids only in acute urticaria, leukotriene antagonists, sedative drugs.
Angioedema (Without Urticaria)
Etiology
Idiopathic, drug-related (NSAID, ACEI) or abnormality of C1inhibitor (C1-INH).
C1-INH → serine protease inhibitor, prevents spontaneous activation of complement system.
Clinical Picture
Deep form of urticaria with localized non-pitting edema and
episodes of painful deep subcutaneous tissue swelling (periorbital and lips), GI tract
(abdominal pain) and upper respiratory tract (laryngeal edema), lasts usually few days.
Hereditary Angioedema (HAE)
Etiology
Autosomal dominance; C1-INH deficiency - Type 1: ↓ C1-INH level and Type 2: normal/↑
C1-INH level, but dysfunctional.
Clinical Picture.
45
Presents in 1st or 2nd decade. Characterized by extensive areas of deep, nonpitting
erythematous edema involving the skin/mucous membranes. Potentially life-threating.
Work-up: ↓ C4, ↓ C1-INH (level and/or function); C1q normal.
Treatment.
C1-INH concentrate during acute attack (antihistamines, epinephrine, and corticosteroids are
usually not effective), fresh-frozen plasma (FFP) before surgery, prophylactic treatment with
attenuated androgens like danazol and stanazolol.
Acquired C1 Inhibitor Deficiency (AAE)
Etiology.
Onset after fourth decade, no family history, due to destruction of C1-INH function through
either immune complexes or autoantibodies.
Clinical Types.
Type 1 → associated with lymphoproliferative disorders (i.e. B cell lymphoma, multiple
myeloma, non-Hodgkin’s lymphoma) with immune complexes consuming C1q; Type II →
associated with autoantibodies to C1-INH molecule.
Work-up: ↓ C1q, ↓ C4/C2.
Treatment.
Much higher amounts of C1-INH concentrate than in HAE required during acute attack.
Strophulus - Urticaria Papulosа Infantum
Chronically-relapsing, extremely pruritic dermatosis of childhood, presented by extended
erythematous papules, usually on acral sites.
Etiology and Pathophysiology.
Insect bites or food allergens (cocoa, milk, eggs, etc.) → sensitization to a presumptive toxin
→ pruritic erythematous papular rash → severe itching.
Clinical Picture.
Small sized, erythematous papular lesions. Rarely, vesicular-bullous lesions.
Treatment.
Topical corticosteroids, oral antihistamines, repelent usage and proper desinfection of linen
and clothing, dietary restrictions.
ADVERSE CUTANEOUS DRUG REACTIONS (ACDRs)

ACDRs are two types: mild and severe. The mild ACDRs are accompanied by pruritus, and
resolve promptly after the offending drug is discontinued. Severe ACDRs are life-threatening
and unpredictable. Drug eruptions can mimic virtually all the morphologic patterns in
dermatology and must be the first consideration in the differential diagnosis of suddenly
appearing eruption.
Etiology.
Most causative drugs: antibiotics, sulfonamides, other sulfa drugs (antidiabetic, diuretic),
quinidine, isoniazid, immunoglobulins, sulfamethoxazole, anticonvulsants, allopurinol,
nonsteroidal anti-inflammatory drugs (NSAIDs), ACE inhibitors, β-blockers, analgesics, oral
contraceptives, quinine (including quinine in tonic water), quinidine, etc.
Pathogenecity.
Immunologic – types I, II, III, IV or nonimmunologic, provoked by systemic or topical
administration of a drug.
Clinical Types of Adverse Cutaneous Drug Reactions:
exanthematous reactions; fixed drug eruptions; urticaria/angioedema; anaphylaxis and
anaphylactoid reactions; serum sickness disease; mimicking other dermatoses (erythema
multiforme, SJS, TEN, erythema nodosum, lupus erythematosus, bullous dermatoses, lichen
planus, dermatomyositis, scleroderma, psoriasis, pityriasis rosea, vasculitis, etc.).
46
Fixed Drug Eruption (FDE)
FDE is an adverse cutaneous reaction to an ingested drug, characterized by the formation of a
solitary erythematous patch. If the patient is rechallenged with the offending drug, the FDE
occurs repeatedly at the identical skin site (i. e., fixed) within hours of ingestion.
Skin Symptoms.
Usually asymptomatic. May be pruritic, painful, or burning. Time to onset of lesion: occur
from 30 min to 8 h after ingestion of drug in previously sensitized individual.
Duration of Lesion:
lesion persist if drug is continued or resolve days to few weeks after drug is discontinued.
Skin Lesions.
A sharply demarcated macule, round or oval in shape. Initially, erythema, then dusky red to
violaceous color. Most commonly, lesions are solitary and can spread to become quite large,
but they may be multiple with random distribution. Lesions may evolve to bullous and
erosive. Eroded lesions, especially on genitals or oral mucosa, are quite painful. After
healing, dark brown or violet postinflammatory hyperpigmentation appears. Genital skin is
frequently involved, but any site may be implicate (perioral, periorbital).
Treatment.
Stop the offending drug. Noneroded lesions → potent topical glucocorticoid ointments;
eroded lesions → antimicrobial ointments; widespread, generalized, and highly painful
mucosal lesions → oral prednisolone 1 mg/kg body weight tapered over a course of 2 weeks.
Drug-Induced Acute Urticaria, Angioedema, Edema and Anaphylaxis
Drug-induced urticaria and angioedema occur due to a variety of mechanism (see
”Urticaria“) and are characterized clinically by transient wheals and angioedema. In some
cases, urticaria/angioedema is associated with systemic anaphylaxis, which is manifested by
respiratory distress, vascular collapse, and/or shock. Urticaria/angioedema ACDRs are
classified as immune-mediated.
Skin Symptoms.
Pruritus, burning of palms and soles.
Skin Lesions.
Urticaria - large wheals. Angioedema - extensive tissue swelling with involvement of deep
dermal and subcutaneous tissues. Often pronounced on face or mucous membranes.
Constitutional Symptoms.
IgE-mediated - flushing, sudden fatigue, yawning, headache, weakness, dizziness; numbness
of tongue, sneezing, bronchospasm, substernal pressure, palpitations; nausea, vomiting,
crampy abdominal pain, diarrhea, ± arthralgia.
Treatment.
Identify and withdraw offending drugs. H1 or H2 blockers or combination. Intravenous
systemic glucocorticoids - hydrocortisone or methylprednisolone for severe symptoms. Oral -
prednisone, 70 mg, tapering by 10 or 5 mg daily over 1-2 weeks.
In acute severe urticaria/anaphylaxis epinephrine 0.3-0.5 mL of a 1:1000 dilution
subcutaneously, repeated in 15-20 min. Maintain airway. Intravenous access.
Avoid use of contrast media known to have caused prior reaction. If not possible, pretreat
patient with antihistamine and prednisolone (1 mg/kg) 30-60 min before contrast media
exposure.
Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)
SJS and TEN are acute life-threatening mucocutaneous reactions, characterized by extensive
necrosis and detachment of the epidermis. They are variants of the same disease and differ
47
only in the percentage of body surface involved: SJS < 10%; SJS/TEN overlap - 10 - 30%;
TEN > 30%.
Etiology.
Drugs: antibiotics (PCNs), sulfonamides, allopurinol, anticonvulsants (carbamazepine,
lamotrigine, phenytoin), barbiturates, NSAIDs, antiretrovirals.
Pathogenesis.
Cytotoxic immune reaction leading to destruction of the keratinocytes expressing foreign
(drug-related) antigens. Epidermal injury is based on the induction of apoptosis.
Clinical Manifestation.
Time from first drug exposure to onset of symptoms - 1-3 weeks.
Prodromes - fever, malaise, arthralgias 1-3 days prior eruption. Mild to moderate skin
tenderness, conjunctival burning or itching, then skin pain, burning sensation, tenderness,
paresthesia. Mouth lesions are painful, tender. Impaired alimentation, photophobia, painful
micturition, anxiety. Both can start with macular and target-like lesions, with/without
purpura; however, about 50% of TEN cases the condition evolves from diffuse erythema to
immediate necrosis and epidermal detachment resembling a second-degree thermal burn.
Raised flaccid blisters, ± Nikolsky sign (dermal-epidermal cleavage with tangential pressure
on normal appearing skin), ± Asboe-Hansen sign (bullae extend laterally with pressure).
Erythema with painful mucosal erosions/ulcerations involving genital, buccal, and ocular
mucosa seen in most cases; ± scalp, nails and palmoplantar involvement.
General Findings.
Fever usually higher in TEN than in SJS. Pulse may be >120 beats/min.
Acute renal failure, tubular necrosis may occur.
Respiratory and GI Epithelial Involvement:
sloughing of epithelium with erosions.
Course and Prognosis.
Average duration of progression is <4 days. Prognosis related to extent of skin necrosis.
Prerenal azotemia is common. Bacterial colonization is common and associated with sepsis.
Other complications include hypermetabolic state and diffuse interstitial pneumonitis.
Mortality rate for TEN is 25–50% and much less for SJS. If the patient survives the first
episode of SJS/TEN, re-exposure to the causative drug may be followed by recurrence within
hours to days, more severe than the initial episode.
Histology.
Full-thickness epidermal necrosis and detachment with subepidermal split above basement
membrane. Sparse lymphocytic infiltrate in dermis.
DD.
Exanthematous drug eruptions, EM major, phototoxic reactions, autoimmune bullous
diseases, staphylococcal scalded-skin syndrome
Treatment.
Early diagnosis and withdrawal of suspected drug(s). Treatment is symptomatic.
Systemic treatment with glucocorticoids and high-dose intravenous immunoglobulins is
advocated by some but still controversial. Supportive treatment (electrolyte replacement,
wound care, nutritional support, hydration) typically in intensive care unit or burn unit.
Diagnose and treat complicating infections, including sepsis.
Prevention.
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The patient must be aware of the likely offending drug and that other drugs of the same class
can cross-react. These drugs must never be re-administered. Patient should wear a medical
alert bracelet.
PIGMENTARY DISORDERS (Vitiligo; Oculocutaneous Albinism; Melasma;

Pigmentary Changes Following Inflammation of the Skin)
Hypomelanosis is a decrease of melanin in the epidermis. Two types of changes: a decrease
of the production of melanin → melanopenic hypomelanosis (albinism); a decrease in the
number of melanocytes in the epidermis → melanocytopenic hypomelanosis (vitiligo).
Hypomelanosis is due to genetic anomalies (albinism), autoimmune processes (vitiligo), or
other inflammatory conditions (postinflammatory leukoderma).
Vitiligo
Acquired pigmentary disorder of skin and mucous membranes with multifactorial etiology
(genetic and non-genetic), likely due to autoimmune destruction of melanocytes in affected
skin.
Inheritance.
Vitiligo has a genetic background → polygenic transmission with variable expression.
Pathogenesis.
Three theories about the mechanism of melanocytes destruction: autoimmune theory;
neurogenic hypothesis; self-destruct hypothesis.
Clinical Picture
Depigmented macules or patches surrounded by normal skin. Macules, 5 mm to 5 cm or more
in diameter. “Chalk” or pale white, sharply marginated. The disease progresses by gradual
enlargement of the old macules or by development of new ones. Margins are convex.
Trichrome vitiligo (three colors: white, light brown, dark brown) represents the different
stages in the evolution of the disease.
Distribution.
Predilection for periorifical facial areas, bony prominences and sites prone to trauma. Two
general patterns: 1. focal type - characterized by one or several macules in a single site; 2.
generalized vitiligo - widespread distribution of depigmented macules, often in a remarkable
symmetry. The “lip-tip” pattern involves the skin around the mouth as well as on distal
fingers and toes ± nipples, genitalia, and anus. Vitiligo universalis - near complete to
complete depigmentation. Segmental vitiligo - usually develops in one unilateral region.
Associated Cutaneous Findings.
White hair and prematurely gray hair. Circumscribed areas of white hair (poliosis). Alopecia
areata and halo nevi.
Isomorphic (Koebner) phenomenon - depigmentation at sites of injury.
Psychological problem - difficulties in social adjustment.
General Examination.
Rarely associated with systemic autoimmune and/or endocrine disease (Hashimoto
thyroiditis, diabetes mellitus, etc.).
Laboratory Examination
Wood lamp examination: differentiates depigmentation from hypopigmentation.
Histology. Normal skin except absence of melanocytes.
Course and Prognosis
Chronic disease. The course is highly variable, but rapid onset followed by a period of
stability or slow progression is most characteristic. Some spontaneous repigmentation may be
49
observed - particularly areas that are exposed to the sun. Rapidly progressive or “galloping”
vitiligo may quickly lead to extensive depigmentation with a total loss of pigment in skin and
hair. The treatment of vitiligo-associated disease (i.e., thyroid disease) has no impact on the
course of vitiligo.
Treatment.
Cosmetic coverage with make up.
Localized macules: topical glucocorticoids; topical calcineurin inhibitors (tacrolimus and
pimecrolimus); topical photochemotherapy [8-methoxypsoralen (8-MOP) and UVA]; 308 nm
- excimer laser.
Generalized vitiligo: systemic photochemotherapy [oral 8-methoxypsoralen (8-MOP) and
UVA]; narrow-band UVB, 311 nm (treatment of choice in children <6 years of age).
Minigrafting (graft transplantation of autologous melanocytes).
Depigmentation - ”one” skin color in patients with extensive vitiligo. Bleaching of normally
pigmented skin with monobenzylether of hydroquinone 20% (MEH) cream. .
Oculocutaneous Albinism
Mutations in the tyrosinase gene → deficient tyrosinase activity in melanocytes.
Present at birth.
Skin varied depending on type. “snow white”, creamy white, light tan.
Hair: white (tyrosinase negative); yellow, cream, light brown (tyrosinase positive).
Eyes: nystagmus, reduction of visual activity, iris translucency, decreased retinal pigment,
foveal hyperplasia, strabismus.
Histology:
melanocytes are present but tyrosinase reduced depending on type.
Significance: reduction of visual activity; development of dermatoheliosis, and skin cancer
without sun protection.
Treatment.
No treatment available. Albinos should be under care of an ophthalmologist (vision
problems) and a dermatologist (sun protection and detection of skin cancer).
Melasma (Chloasma)
Acquired hyperpigmentation in sun-exposed areas, most often on the face, primarily seen in
women (90%) and darker skin types.
No increase of melanocytes, increase production of melanin only → melanotic
hypermelanosis (melasma).
Associated with pregnancy, contraceptive hormones, extended sun-exposure, drugs
(diphenylhydantoin), or idiopathic.
Macular hyperpigmentation - tan to dark brown, or brown-gray, irregular patches, mostly
sharply defined in the malar and frontal areas of the face. Usually uniform but also blotchy.
Topical Treatment:
hydroquinone, azelaic acid, tretinoin, combination of tretinoin/topical
corticosteroid/hydroquinone, combination of hydroquinone/tretinoin or glycolic acid,
chemical peels.
Prevention:
sun protection.
Pigmentary Changes Following Inflammation of the Skin
Hyperpigmentation
Post-Inflammatory Epidermal Melanin Hyperpigmentation.
50
Develops in acne, psoriasis, cutaneous lupus erythematosus, lichen planus, atopic dermatitis,
contact dermatitis, drug intake, or after any type of trauma to the skin. Lesions are limited to
the site of preceding inflammation.
Riel Melanosis (Melanodermatitis Toxica) -
due to contact sensitivity or photocontact sensitivity to chemicals, particularly fragrance in
cosmetics; on the face and neck.
Clinical forms:
Berloque Dermatitis
(phototoxic reactions induced by furocoumarin)
Phytophotodermatitis (
phototoxic or photoallergic reaction induced by plants or fruits like
meadow grass, celery, lime)
Nonmelanin-Based Hyperpigmentation
due to drugs: antiarrhythmic (amiodarone); antimalarial (chloroquine, hydroxychloroquine,
quinacrine, quinine); antimicrobial (minocycline, clofazimine, zidovudine); antiseizure
(hydantoins); cytostatic (bleomycin, cyclophosphamide, doxorubicin, daunorubicin,
busulfan, 5-fluorouracil, dactinomycin); metals (silver, gold, iron); hormones (ACTH
estrogen/progesterone); psychiatric (chlorpromazine); dietary (β-carotene).
Hypopigmentation
Post-inflammatory hypomelanosis is related to loss of melanin → pityriasis versicolor,
atopic dermatitis, psoriasis, guttate parapsoriasis, cutaneous lupus erythematosus, seborrheic
dermatitis, leprosy, etc.
Depending on the associated disorder, post-inflammatory hypomelanosis may respond to
phototherapy or photochemotherapy.
ERYTHEMATOUS DISEASES (Erythema Nodosum; Erythema Multiforme)

Erythema Nodosum (EN)
EN is an acute inflammatory/immunologic reaction pattern of the subcutaneous fat to a
variety of stimuli.
Etiology.
Idiopathic. F > M. Infections (bacterial – streptococcal infections, tuberculosis, yersiniosis;
fungal - dermatophytosis; viral – hepatitis B, herpes simplex, etc.), drugs (sulfonamides, oral
contraceptives, minocycline, gold salts, penicillin, salicylates); Systemic diseases - mainly
sarcoidosis (Syndroma Löfgren).
Clinical Manifestation
Indurated, not sharply circumscribed, deep-seated nodules in the subcutaneous fat, bilateral
but not symmetric. The color is bright to deep-red. Painful on palpation. Commonly over
pretibial areas, also on knees and arms, rarely on the face and neck. Lesions continue to
appear for 1-2 weeks and leave bruise-like discolouration as they resolve (Erythema
contusiforme).
Skin lesions accompanied by fever, malaise, and arthralgia.
Laboratory Examinations
Hematology. Leucocytosis; elevated ESR and C-reactive protein.
Histology. Septal panniculitis.
Course.
Spontaneous resolution in 6 weeks. Course depends on the etiology. Lesions do not ulcerate
and resolve without atrophy or scarring.
Treatment
Treatment should focus on the underlying cause.
Anti-inflammatory treatment - salicylates, NSAID. Colchicine, potassium iodide (KI).
51
Systemic glucocorticoids – response is rapid, but their use is indicated only when the
etiology is known and infectious agents are excluded. Often relapse!
Bed rest, wet dressings.
Erythema Multiforme (EM)

Acute, often self-limited skin condition, associated with infection, drug intake and rarely
with systemic disease.
Etiology.
Idiopathic. M > F. Infections (mainly herpes simplex). Drugs (sulfonamides, phenytoin,
barbiturates, phenylbutazone, penicillin, allopurinol).
Sites of predilection. Typically involves the extremities (especially dorsal hands, palms and
soles) and the mucous membranes. Bilateral and often symmetric.
Skin lesions. Abrupt onset but lesions may develop over ≥ 10 days. Macule → papule (1-2
cm) → vesicles and bullae in the center of the papule → typical iris or target-like lesions.
Mucous membranes: lips, nasal, conjunctival, oropharynx, larynx, genital, anal. Erosions
with fibrin membranes; occasionally ulcerations. Eyes: conjunctivitis; keratitis with corneal
ulcers; anterior uveitis.
Two types: EM minor and EM major. EM minor - little or no mucosal and systemic
involvement. EM major - more severe course with positive Nikolsky sign in erythematous
lesions.
May be pruritic or painful (mouth lesions). Systemic symptoms in severe forms (fever,
weakness, malaise, prostration).
Benign course with frequent recurrences. Typically self-limited within 2 weeks.
Treatment
Symptomatic. Anti-inflammatory treatment.
Prophylactic antiviral therapy if HSV-related
Glucocorticoids. In severely ill patients, systemic glucocorticoids are usually given and
quickly tapered.
PAPULOSQUAMOUS, LICHENOID AND ECZEMATOUS DERMATOSES

(Psoriasis; Lichen Planus; Pityriasis Rosea)
PAPULOSQUAMOUS DERMATOSIS
Psoriasis
Chronic-relapsing, polygenic inflammatory disease due to hyperproliferation of
keratinocytes and inflammatory cell infiltration.
Bimodal onset with third or sixth decade; earlier onset, associated with more severe and
long-lasting disease.
M = F; Equator ↓; Poles ↑.
Pathogenetic Factors
Abnormal T cell activation - T cell-mediated autoimmunity toward poorly defined antigens.
Abnormal keratinocytes - ↑ Mitotic activity and leukocyte recruitment; keratinocytes move
to upper layer in 3–5 days (vs. normal 28 days).
Genetics (polygenic and multifactorial) - HLA associations: B27 associated with psoriatic
arthritis.
Triggering Factors:
Physical trauma (Koebner phenomenon); infection (especially streptococcal); drugs (lithium,
β–blocker, antimalarial, ACEI, NSAID, systemic corticosteroid, G-CSF, interferon); stress;
alcohol ingestion.
52
Two major types:
1. Eruptive, inflammatory type.
Acute-onset rain drop-like scaly papules on the trunk and extremities often in young
patients; common triggers include Streptococcal infections, viral infections, stress, and
trauma.
2. Chronic stable (plaque) psoriasis.
Erythematous, scaly sharply demarcated papules and plaques, covered with silver-white
scale over extensor surfaces (knees, elbows), scalp, gluteal cleft, ± genitalia, ± intertriginous
areas; chronic course with flares.
Signs: “wax candle” sign (scales easily removed by scratching); pinpoint bleeding sign
(Auspitz), (scratch and gentle removal of scales cause capillary bleeding); Voronov sign
(hypopigmented ring around the plaques); sign of Popov (lack of eponychium).
Other skin changes: isomorphic phenomenon of Koebner; leuco/melanoderma
psoriaticum.
Stages: advancing (progressing); stable (no dynamic changes); involutive (regressing).
Special locations:
Palms and soles (palmoplantar psoriasis), massive hyperkeratosis, ± cracking, painful
fissures and bleeding.
Intertriginous/flexural areas (inverse psoriasis ), plaques usually not scaly but macerated,
often bright red and fissured.
Seborrhoeic (naso-labial and retro-auricular).
Psoriasis capillitii (corona psoriatica), plaques, sharply marginated, with thick adherent
scales, often very pruritic.
Psoriasis inveterata (prolonged course, resistant to treatment).
Nail psoriasis - nail changes such as pitting, leukonychia, onychodystrophy, oil spots,
onycholysis (nail bed - separation of plate from bed), splinter hemorrhages (↑ capillary
fragility in nail bed).
Severe forms:
Erythroderma - generalized erythema and scaling (>90% skin surface affected), ±
leukocytosis, ↑ ESR, lymphadenopathy, develops suddenly from guttate or stable psoriasis,
usually induced by inappropriate treatment).
Pustular psoriasis. Two types - generalized and localized (palmoplantar pustulosis,
acrodermatitis continua suppurativa). Generalized (von Zumbusch) - presents initially with
malaise and fever, subsequent onset of erythematous macules studded with sterile pustules,
initially in intertriginous areas but quickly spreads to trunk, extremities and nails (skin feels
painful), ↑ risk for infection. Palmoplantar pustulosis - tense, sterile pustules over
palmoplantar surface. Acrodermatitis continua of Hallopeau - variant of pustular psoriasis,
limited to finger tip or digit.
Psoriatic arthritis. Rheumatoid factor negative (seronegative) arthritis, HLA-B27
association. Pain at tendon insertion sites, digital involvement and sacroiliac disease,
asymmetric joint involvement, morning stiffness.
Histology.
Parakeratosis, hyperkeratosis, collection of neutrophils in stratum corneum (Munro
microabscesses) and spinous layer (spongioform pustules of Kogoj), hypogranulosis,
acanthosis with clubbed rete ridges, suprapapillary thinning, dilated blood vessels in
papillary dermis, perivascular lymphocytes.
Sometimes acute guttate psoriasis disappears spontaneously, more often evolves into chronic
plaque psoriasis, which is stable and may undergo remission after months or years, may
reoccur or may be life-persistent.
Treatment
53
Topical treatment (for localized and mild psoriasis): according to the clinical picture -
lubricants/emollients; keratolytics - ac. salicylicum (5–10%), urea (>8%); reductive - tars
(pix lithantracis 5%), dithranol (0,1-5%); topical corticosteroids – for a short time! (face,
folds); topical retinoids; vitamin D3 analogues (i.e. calcipotriol, calcipotriene); calcineurin
inhibitors (pimecrolimus/tacrolimus); fixed combination betamethasone
diproprionate/calcipotriol; topical PUVA.
Systemic treatment (on > 30 % BSA and recalcitrant cases): cytostatics - methotrexate,
hydroxyurea, cyclosporin A, mycophenolate mofetil; aromatic retinoids (tigason,
neotigason); NSAID; antibiotics (tubocin 3 months in eruptive cases); salazopyrin;
sulfasalazine; biologicals (infliximab, etanercept, efalizumab, adalimumab); phototherapy,
UVB and photochemotherapy (psoralen + UVA); retinoids and photochemotherapy
(re-PUVA).
Other: 308 nm-excimer laser; thalassotherapy; balneotherapy (SH-rich water).
Parapsoriasis en Plaques (PP)
Two types: small-plaque (SPP) and large-plaque PP (LPP)
In SPP, lesions are small (<5 cm), round to oval, mostly on the trunk: “digitate dermatosis”,
slightly infiltrated, yellowish, or fawn-colored patches. Minimal scaling, asymptomatic, with
mild itch.
In LPP, lesions are oval or irregularly-shaped patches and > 5 cm. Minimal scaling ±
atrophy, sometimes - poikilodermic.
LPP can progress to MF (mycosis fungoides).
Treatment.
Topical glucocorticoids, phototherapy, narrowband UVB phototherapy, or PUVA.
LICHENOID DERMATOSIS
Lichen Planus (LP)
LP is an acute or chronic pruritic papular disease of skin and mucous membranes.
Age of Onset.
30-60 years. F > M.
Etiology.
Idiopathic in most cases but cell-mediated immunity plays a major role. Drugs, metals (gold,
mercury), infection (hepatit C virus) or stress might play a role.
Onset. Acute (days) or insidious (over weeks).
Sites of predilection. Flexural parts of wrists, anterior aspects of shins, lumbo-sacral zone,
oral and genital mucosa.
Characterized by pink to violaceous, shiny, polygonal or oval papules with flat, glossy
surface, covered with white lines (Wickham striae). Lesions have been characterized by the
4 P′s – papule, purple, polygonal, pruritic
Linear arrangement of papule after trauma/excoriations represents the isomorphic (Koebner)
phenomenon.
Mucosal LP - up to 50% patients with skin disease have oropharyngeal involvement. White
dots or reticular enanthema (often grouped in plaques), typically asymptomatic unless
erosive → pain. Erosive lichen → facultative precancerosis (squamous cell carcinoma).
Scalp – cicatricial alopecia.
Nails – lateral nail thinning, longitudinal ridging, dorsal pterygium, splitting, ± 20 nail
dystrophy.
Main subjective symptom: itch; mouth lesions could be painful.
Histology.
Irregular hypergranulosis, band-like lymphocytic infiltrate at dermoepidermal junction.
Course
54
Usually chronic-relapsing. Lesions last months to years and in few cases may resolve
spontaneously in 5-10 years.
Treatment
Systemic – neuroleptics, tranquilants, antihistamines, cyclosporine, glucocorticoids,
systemic retinoids (acitretin), sulfons, cytostatics (CyA, azathioprine, methotrexate).
Topical - glucocorticoids with occlusion or intralesional, immunomodulators (pimecrolimus,
tacrolimus), cytostatics(CyA).
Oral lesions – glucocorticoids, vit A oleosum, vit A acid (retin A lotion), cyclosporine and
tacrolimus solutions.
Physical therapy - photochemotherapy (PUVA), paravertebral UV radiation, changeable
magnetic field.
Alternative medicine (acupuncture).
High-mountain climatotherapy.
ECZEMATOUS DERMATOSIS
Pityriasis Rosea (PR)
Self-limited, acute erythematous and tiny desquamated exanthematous eruption.
Etiology.
Viral pathogen (human herpesvirus-7, less HHV-6).
Age of onset. 15-40 years.
Season. Spring and fall.
PR is not contagious. Recurrences – rare.
Abrupt onset.
Good general condition.
Missing subjective symptoms.
Skin lesions. Initial herald (medallion, or primary) patch. Few days after oval, slighty raised
salmon-red plaque or patch 2-5 cm with fine scale at periphery (collarette) appear on the
trunk. Characteristic distribution following the lines of cleavage in a “Christmas tree”
pattern on posterior trunk. Localization – trunk and proximal aspects of the arms and legs →
“T-shirt“.
Atypical Pityriasis Rosea.
Lesions only on the face and neck. The primary plaque may be either solitary or multiple, or
in some cases – absent. Pityriasis rosea irritata (urticarial, papular, haemorrhagic,
vesicular, EEM-like, generalized) with itch → results from irritation and sweating, often as a
consequence of inadequate treatment.
DD.
Secondary syphilis (serology), tinea corporis, guttate psoriasis, drug eruptions, etc.
Course.
Spontaneous involution – 4 – 6 weeks.
Prevention of irritation – avoidance of soap washing, hot tubes, wool linen.
Treatment
Systemic – acyclovir.
Symptomatic. If itchy – oral antihistamines and/or topical emollients. UVB phototherapy or
natural sunlight exposure in the first week of eruption. Short course of low doses systemic
glucocorticoids for irritated or protracted cases.
IMMUNOBULLOUS DISEASES (Pemphigus; Pemphigoid; Dermatitis

Herpetiformis)
Intraepidermal
Pemphigus
55
Sub-epidermal
Pemphigoid
Dermatitis herpetiformis
Immunofluorescence (IF) Techniques
Direct IF (DIF) → detects in vivo antibodies bound to tissue antigens in perilesional skin.
Indirect IF (IIF) → detects circulating serum antibodies.
Pemphigus
A serious and often fatal, acute or chronic, bullous autoimmune disease of skin and mucous
membranes, presented by keratinocytic acantholysis.
Classification of Pemphigus
Pemphigus vulgaris
Pemphigus vulgaris: localized and generalized
Pemphigus vegetans: localized
Drug induced
Pemphigus foliaceus
Pemphigus foliaceus: generalized
Pemphigus erythematosus: localized
Fogo selvagem: endemic in rural areas in Brazil
Drug induced
Paraneoplastic pemphigus: associated with malignancy
IgA pemphigus: subcorneal pustular dermatosis and intraepidermal neutrophilic IgA
dermatitis
Age of onset. 40-60 years. M = F.
Two major types: pemphigus vulgaris (PV) and pemphigus foliaceus (PF).
PV: Rare, more common in Jews and people from Mediterranean region.
Fogo selvagem: in children and young adults.
Etiology and Pathogenesis
An autoimmune disorder. Loss of cell-to-cell adhesion in epidermis (acantholysis). Occurs
as a result of circulating antibodies of the IgG class, which bind to desmogleins,
transmembrane glycoproteins in the desmosomes. In PV - desmoglein 3. In PF - desmoglein
1. Autoantibodies interfere with calcium-sensitive adhesion function and thus induce
acantholysis.
Pemphigus vulgaris usually starts in the oral mucosa, and months may elapse before skin
lesions occur.
Skin lesions. Vesicles and bullae with serous content, flaccid (flabby), easily ruptured, and
weeping, arising on normal skin, randomly scattered, discrete. Localized (e.g., to mouth or
circumscribed skin area), or generalized with a random pattern. Positive Nikolsky sign
(dislodging of normal-appearing epidermis by lateral finger pressure in the vicinity of
lesions, which leads to an erosion). Positive Asboe-Hansen sign (pressure to surface of
blister causes lateral spread).
Sites of predilection. Scalp, face, chest, axillae, groin, umbilicus. In bed-ridden patients,
there is extensive involvement of back.
Mucous membranes. Bullae rarely seen, erosions of mouth and nose, pharynx and larynx,
vagina.
No pruritus but burning and pain. Painful and tender mouth lesions may prevent adequate
food intake. Weakness, malaise, weight loss.
PV Variants
Pemphigus vegetans (PVeg). Usually confined to intertriginous regions, perioral area, neck,
and scalp. Granulomatous vegetating purulent plaques that extend centrifugally.
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Drug-induced PV. Clinically identical to sporadic PV. Drugs: captopril, D-penicillamine,
etc.
Pemphigus foliaceus (PF) has no mucosal lesions. Less severe and more superficial than PV.
Skin lesions initially in seborrheic areas, most commonly on face, scalp, upper chest, and
abdomen. Initial lesions are flaccid bullae which rupture easily; often only erythematous
patches, scaly, crusted erosions remain. May stay localized or progress to generalized
disease and exfoliative erythroderma.
PF Variants
Brazilian pemphigus (Fogo selvagem, endemic form of PF): seen in rural Brazil and
clinically identical to PF, related to the black fly ( Simulium spp.).
Pemphigus erythematosus (Senear-Usher syndrome). Localized PF variant with lupus
erythematosus overlap; involves seborrheic areas with erythema, erosions and crusting;
ANA positive in 30%.
Drug-induced PF. As in PV, associated with D-penicillamine and less frequently - captopril.
Paraneoplasic Pemphigus (PNP).
Associated with underlying benign or malignant neoplasm. Mucous membranes primarily
and most severely involved. Lesions combine features of pemphigus vulgaris and erythema
multiforme, clinically (lichenoid papules, flaccid or tense bullae, erythematous macules to
erythema multiforme-like lesions). Autoantigen: various desmosomal proteins including
desmoglein 3, periplakin, envoplakin, desmoplakin 1/2, BPAG1, plectin, 170 kDa Ag, rarely
desmoglein 1.
IgA Pemphigus.
Clinical two types: subcorneal pustular dermatosis (SPD) - serpiginous vesicles or pustules
and intraepidermal neutrophilic type (IEN) → flaccid pustules and bullae involving
intertriginous locations which enlarge forming annular or polycyclic (sunflower-like)
arrangement. Intraepidermal IgA deposits. Autoantigen: desmocollin 1 (SPD), ± desmoglein
1/3 (IEN).
Histology:
PV → suprabasal cleavage with acantholytic keratinocytes, “tombstone row” of basal cells
attached to basement membrane; PF → subcorneal acantholysis with acantholytic cells seen
on blister roof (“cling ons”); PNP → suprabasilar acantholysis, ± necrotic keratinocytes and
vacuolar degeneration of the basal layer, associated with lichenoid dermal lymphocytic
infiltrate; IgA pemphigus → intraepidermal pustule or vesicles with neutrophils, no
acantholysis.
DIF: PV → intercellular IgG≥C3 deposits in lesional and perilesional skin in the
intercellular substance of the epidermis; PF → same as PV (more pronounced in upper
layers); PE (Senear-Usher syndrome) → intercellular and linear IgG at BMZ; PNP →
intercellular + linear IgG/C3 along BMZ; IgA pemphigus → intercellular IgA deposition.
IIF: In PV and PE most sensitive substrate is monkey esophagus , positive in 80–90% cases,
autoantibodies (IgG), titer correlates with disease activity. In PV, autoantibodies against a
130-kDa glycoprotein, desmoglein 3, located in desmosomes of keratinocytes. In PF,
autoantibodies to a 160-kDa intercellular (cell surface) antigen, desmoglein 1, in
desmosomes of keratinocytes; PNP → IgG, most sensitive substrate is rat-bladder
epithelium;
IgA pemphigus → + in 50%, intercellular IgA.
Treatment
Glucocorticoids and concomitant immunosuppressive agents (azathioprine, methotrexate,
cyclophosphamide, mycophenolate mofetil).
Other treatment: plasmapheresis, IVIG, rituximab (monoclonal antibody to CD 20).
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Other measures. cleansing baths, wet dressings, topical and intralesional glucocorticoids,
antimicrobial therapy in bacterial infections. Correction of fluid and electrolyte imbalance.
Drug-induced pemphigus: in most cases the eruption resolves after termination of therapy
with the offending drug.
Pemphigus erythematosus: sun protection, oral/topical corticosteroids.
PNP treatment: directed toward elimination or suppression of malignancy but also require
immunosuppressive agents. Prognosis, associated with underlying neoplasm.
IgA pemphigus: dapsone, oral corticosteroids.
Monitoring.
Clinical, for improvement of skin lesions and drug-related side effects. Laboratory, detection
of antibody titers for disease activity and of hematologic and metabolic parameters as
indicators of drug-induced adverse events.
Pemphigoid
Bullous Pemphigoid
A bullous autoimmune disease with chronic nature, usually in elderly patients (over 60).
Cause.
Autoantibodies against antigens between the epidermis and dermis causing a sub-epidermal
split in the skin
Autoantigen: BPAG2 (collagen XVII) → 180 kDa, transmembrane hemidesmosomal
protein; BPAG1 → 230 kDa, cytoplasmic plaque protein.
Drug-induced: furosemide, NSAIDs, phenactin, PCN-derivates, gold, potassium iodide,
captopril, enalapril, D-penicillamine, sulfasalazine.
Sites of predilection. axillae; medial aspects of thighs, groins, abdomen; forearms; lower
legs (often first manifestation); generalized.
Skin lesions. erythematous, papular, or urticarial-type lesions may precede bullae formation
by months. Bullae: small or large tense, firm-topped, oval or round; arise in normal,
erythematous, or urticarial skin; contain serous or hemorrhagic fluid; rupture less easily than
in pemphigus.
Mucous membranes. 10–35% with oral involvement. Less severe and painful than
pemphigus.
Moderate or severe pruritus.
No constitutional symptoms unless extensive disease.
Hematology ± eosinophilia.
Histology: subepidermal bullous formation with ↑↑ eosinophils and lymphocytes in
papillary dermis, ± neutrophils.
DIF. Linear C3 and IgG at epidermal basement membrane.
IIF: + in 60–80%; IIF on salt-split skin shows binding to epidermal side of split (roof of
blister).
Treatment
Topical therapies for localized disease - topical steroids or topical tacrolimus therapy
Oral therapies for widespread disease – oral steroids, either alone or combined with
azathioprine; tetracycline ± nicotinamide; sulfones (dapsone); other immunosuppressives
(e.g. mycophenolate mofetil, methotrexate, etc.); in refractory cases, IVIG; plasmapheresis.
Good prognosis. Some patients go into spontaneous remission without therapy, others go
into a permanent remission after therapy and do not require further therapy.
Cicatricial Pemphigoid
Synonym: Mucous membrane pemphigoid
58
Rare autoimmune blistering disease, involving the mucous membrane with subsequent
scarring, usually in elderly patients.
Targeted antigens may include BPAG1, BPAG2, integrin subunits β4 and α6, type VII
collagen, and laminin 332.
Drug-induced (similar to BP): thiol-containing (captopril, gold thiosulfate, D-penicillamine),
NSAIDs (indomethacin), topical glaucoma solutions, β-blockers (practolol), clonidine,
sulfadoxine.
Blisters rupture easily → erosions, ocular symptoms - conjunctivitis, burning, dryness or
foreign body sensation, entropion, trichiasis with subsequent corneal irritation, corneal
neovascularization, scarring, fusion of palpebral and bulbar conjunctivae, symblepharon,
and blindness; ± involve other mucous membrane with scarring and stricture formation:
mouth, oropharynx, nasopharyngeal, larynx, esophageal, rectal and genital mucosa; blisters
on skin in roughly 30% of patients.
Histology/DIF: similar to BP
IIF: + in 20% cases; binding to epidermal side of split (roof), however, anti-laminin 5 CP
binds to dermal side.
Treatment
Mild involvement → topical/intralesional corticosteroids, calcineurin inhibitors (tacrolimus,
pimecrolimus).
Moderate and severe involvement → dapsone in combination with prednisone. Some
patients require more aggressive immunosuppressive treatment with cyclophosphamide or
azathioprine, in combination with glucocorticoids, also high-dose IVIGs, rituximab.
Surgical intervention for scarring and supportive measures.
Pemphigoid Gestationis (PG)
A rare pruritic and polymorphic inflammatory bullous dermatosis of pregnancy and the
postpartum period.
Mainly on the abdomen but also on other areas, with sparing of the mucous membranes.
Lesions vary from erythematous, edematous papules and urticarial plaques to vesicles and
tense bullae. Extremely pruritic.
May recur in subsequent pregnancies, at which usually begins earlier.
Histology.
Subepidermal blisters.
DIF. Linear deposition of C3 along the basement membrane zone with concomitant IgG
deposition in roughly 30% of patients.
IIF. Serum contains IgG anti-basal membrane-antibodies in only 20% of patients.
Some 5% of babies born to mothers with PG have urticarial, vesicular, or bullous lesions,
which resolve spontaneously during the first weeks.
Treatment.
Prednisone, 20-40 mg/d; tapered gradually during the postpartum period.
Dermatitis Herpetiformis
Chronic pruritic disease, associated with gluten-sensitive enteropathy (GSE).
Age of onset. Most common at 30-40 years; ± children.
M : F 2 : 1.
Patients have antibodies to transglutaminases (Tgs) that may be the major autoantigens.
Epidermal Tg autoantibody probably binds to Tg in the gut and circulates, either alone or as
immune complexes, to deposit in the skin. IgA activates complement via the alternative
pathway, with subsequent chemotaxis of neutrophils, releasing their enzymes and producing
tissue injury.
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Symmetrical distribution: extensor areas - elbow, knees, buttocks, scapular, and sacral areas.
Often in a “butterfly” fashion. Scalp, face, and hairline are also involved.
Skin lesions. Erythematous papules or wheal-like plaques; tiny firm-topped vesicles,
sometimes hemorrhagic; occasionally bullae. Lesions are arranged in groups (hence, the
name herpetiformis). Scratching results in excoriations, crusts. Postinflammatory hyper- and
hypopigmentation at sites of healed lesions.
Pruritus is intense; episodic burning or stinging of the skin.
Ingestion of iodides and overload of gluten are exacerbating factors.
GSE occurs in nearly all patients.
Usually no systemic symptoms.
Histology:
neutrophilic microabscesses at the tips of the dermal papule, ± subepidermal vesicles.
DIF: granular IgA > C3 deposition on the tips of dermal papillae.
IIF: negative.
Autoantigen → epidermal transglutaminase (TG-3), tissue transglutaminase (endomysial)
→ anti-gliadin/anti-endomysial antibodies in DH/celiac disease.
Immunogenetics. Association with HLA-B8, HLA-DR, and HLA-DQ.
Other studies. Steatorrhea and abnormal D-xylose absorption. Anemia secondary to iron or
folate deficiency. Small bowel biopsy → focal blunting and flattening of the villi in the
small bowel as in celiac disease.
Course
Prolonged, for many years, one third of the patients have spontaneous remission.
Treatment
Systemic therapy. Sulfa drugs: dapsone (obtain a glucose-6-phosphate dehydrogenase level
and monitor the methhemoglobin level); sulfapyridine, if dapsone is contraindicated or not
tolerated (monitor for casts in urine and kidney function).
Diet.
A gluten-free diet, but response is very slow. Gluten proteins found in wheat, rye, and
barley, not found in rice, oats or corn.
CONNECTIVE TISSUE DISEASES (Lupus Erythematosus; Dermatomyositis;

Scleroderma)
Lupus Erythematosus (LE)
LE is autoimmune disease.
Young and middle age. F > M.
LE ranges from life-threatening manifestations of acute systemic LE (SLE) to the limited
and exclusive skin involvement in chronic cutaneous LE (CCLE).
Spectrum with three major forms: systemic LE (SLE), subacute LE (SCLE) and
chronic cutaneous LE (CCLE).
Highly photosensitive.
Chronic Cutaneous Lupus Erythematosus (CCLE)
Without systemic involvement.
Can be precipitated by sunlight.
CCLE may manifest as classic discoid LE (CDLE) (localized or generalized) or variants:
hypertrophic/verrucous DLE; lupus profundus; lupus tumidus (urticarial plaque of LE) ;
chilblains LE; lichenoid DLE (LE/lichen planus overlap); mucosal DLE (oral or
conjuctival).
Chronic Cutaneous LE (CCLE, discoid LE) → Classic Discoid LE (DLE)
Chronic cutaneous form with involvement typically of face/scalp in young women.
Presents
60
with indurated erythematous thin papules with adherent scale and follicular plugging.
Plaques are round or oval, annular or polycyclic, with irregular borders, expand in the
periphery and regress in the center to form atrophy. Positivie “carpet tack” sign → scales of
follicular hyperkeratosis are difficult to be removed and show spines on the undersurface
resembling carpet tacks. Subsequent atrophy, telangiectasias, dyschromia, scarring (SCC
may develop in scars).
Distribution: on face, scalp and/or ears (concha bowl); dorsa of forearms, hands, fingers; less
frequently, the trunk; localized DLE or generalized DLE; ¼ with oral involvement.
Usually no symptoms, rarely ± slightly pruritic or smarting. No general symptoms.
Up to 4% may be disseminated with widespread discoid involvement (↑ serologic
abnormalities have ↑ likelihood to develop SLE).
Variants:
Hypertrophic/verrucous LE - hyperkeratotic or verrucous papules/plaques, similar to warts
over extensor arms ± face/trunk.
Lupus panniculitis/profundus - tender subcutaneous nodules with typical DLE surface
changes involving buttocks, chest, shoulder, face; heals with deep atrophy; 10–15% meet
SLE criteria.
Tumid lupus - deeper, more nodular lesions with erythema and induration mainly involving
face and trunk, no scaling or follicular plugging; dermis with mucin and intense
inflammatory infiltrate.
Chillblain LE - acral dusky purple papules and plaques associated with acrocyanosis,
minimal atrophy/scarring.
¼ with + ANA (low titer).
Histology:
atrophic epidermis with plugged follicles, vacuolar degeneration of basal layer, thickened
basement membrane, melanin incontinence, perivascular/periadnexal lymphocytic
infiltrate, ↑ mucin between collagen bundles.
DIF: 90% of lesional biopsies show diffuse irregular fibrillary band of IgM at BMZ (lupus
band test).
Treatment
Systemic - oral antimalarials (monitor for ocular side effects), thalidomide (teratogenic
effect), systemic corticosteroids.
Topical - sun avoidance, topical/i.l. corticosteroids, topical calcineurin inhibitors, retinoids
(for hyperkeratotic CDLE).
Subacute Cutaneous LE (SCLE)
Overlap between DLE and SLE with photosensitivity.
Drug-induced SCLE: hydrochlorothiazide, terbinafine, diltiazem, ACEI, NSAIDs,
griseofulvin, antihistamines, IFN, PUVA, TNF-α.
Two Types of Skin Lesions:
1. Psoriasiform, papulo-squamous, sharply defined, with slight delicate scaling.
2. Annular, bright red annular lesions with central regression and little scaling.
In both, there may be telangiectasia, but no follicular plugging and induration as in CCLE.
Lesions resolve with slight atrophy (no scarring) and hypopigmentation. Periungual
telangiectasias, diffuse nonscarring alopecia.
Distribution:
scattered, disseminated in photo-exposed areas – shoulders, extensor surface of the arms,
dorsal surface of the hands, upper back, V-neck area of the upper chest.
Limited organ involvement ± fatigue, malaise, fever and arthralgias.
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Patients may have some criteria of SLE, including photosensitivity, arthralgias, serositis,
renal disease; positive non-photo-exposed, non-lesional LBT. 60–80% with positive ANA
titer, all have anti-Ro (SS-A) and most have anti-La (SS-B) autoantibodies.
Phototest:
positive.
Histology:
atrophic epidermis, some vacuolar change of BMZ, sparse inflammatory infiltrate.
Course:
persistent with intermittent flares, up to 50% will eventually meet SLE criteria (but milder
disease). Better prognosis than for SLE.
Treatment
Systemic - antimalarials, oral corticosteroids, thalidomide, dapsone or other
immunosuppressive agents.
Topical – sun protection, topical corticosteroids, pimecrolimus, and tacrolimus.
Systemic LE (SLE)
Multisystem autoimmune disease which involves connective tissue and blood vessels.
Precipitating Factors.
Family history (<5%); sunlight (UVR) is the most effective precipitating factor.
Drug-induced SLE: hydralazine, procainamide, chlorpromazine, INH, quinidine, practolol,
D-penicillamine, PUVA, minocycline.
Skin Lesions:
Butterfly rash (bilateral, confluent, macular butterfly eruption on the face, sharply defined
with fine scaling); erosions and crusts; photosensitivity; diffuse alopecia or discoid lesions,
associated with patchy alopecia; oral ulcerations.
Generalized (papular or urticarial lesions on the face, on the dorsa of hands, arms, and V of
the neck); others (bullae, papules, scaly plaques, discoid plaques, palmar erythema, nailfold
telangiectasias, “palpabre” purpura (vasculitis), urticarial lesions with purpura (urticarial
vasculitis), Raynaud’s phenomenon, livedo reticularis, acrocyanosis, cutaneous signs of
antiphospholipid syndrome.
Sites of predilection. Localized or generalized, preferentially in light-exposed sites. Face;
scalp; presternal, shoulders; dorsa of the forearms, hands, fingers, fingertips.
Extracutaneous Multisystem Involvement.
Arthralgia or arthritis, renal disease, pericarditis, pneumonitis, gastrointestinal (due to
arteritis and sterile peritonitis), hepatomegaly, myopathy, splenomegaly, lymphadenopathy,
peripheral neuropathy, CNS disease, seinzures or organic brain disease. Fatigue, fever,
weight loss, and malaise.
Hematology.
Anemia, leukopenia (>4000/µL), lymphopenia, thrombocytopenia, elevated ESR.
Serology.
ANA positive; peripheral pattern of nuclear fluorescence. Anti-double-strand DNA
antibodies, anti-Sm antibodies, and anti-RNP antibodies specific for SLE; low levels of
complement. Anticardiolipin autoantibodies (lupus anticoagulant) in a specific subset
(anticardiolipin syndrome).
Urinalysis.
Persistent proteinuria, casts.
Histology.
Modest vacuolar changes, perivascular and periadnexal lymphocytic infiltrates, ↑ dermal
mucin.
DIF (LBT). Granular or globular deposits of IgG, IgM, C3 in a band-like pattern along the
dermal-epidermal junction. Positive in lesional skin and in clinically normal skin.
62
Diagnosis.
Need 4 out of 11 criteria of the revised American Rheumatism Association (ARA)
criteria for diagnosis SLE:
1. Malar rash.
2. Discoid rash.
3. Photosensitivity.
4. Oral ulcers.
5. Arthritis – nonerosive.
6. Serositis – a. pleuritis, b. pericarditis.
7. Renal disorder – a. persistent proteinuria(0.5g/d), b. cellular casts.
8. Neurologic disorder – a. seizures, b. psychosis.
9. Hematologic disorder – a. hemolytic anemia, b. leukopenia, c. lymphopenia, d.
thrombocytopenia.
10. Immunologic disorder – a. anti-DNA-antibody to native DNA, b. anti-Sm-presence of
antibody to Sm nuclear antigen, c. positive finding of antiphospholipid antibodies, based on
(1) an abnormal serum level of IgG or IgM anticardiolipin antibodies, (2) a positive test
result for lupus anticoagulant, or (3) a false-positive serologic test for syphilis.
11. Antinuclear antibody.
Treatment
Systemic: Oral corticosteroids, steroid-sparing immunosuppressive agents (azathioprine,
mycophenolate mofetil, methotrexate, cyclophosphamide), antimalarials
(hydroxychloroquine, chloroquine, guinacrine), plasmapheresis, biologicals (anti-TNF-α
agents, anti-interferon-α agents).
Topical: Sun protection, topical corticosteroids.
General Measures:
rest, avoidance of sun exposure.
Dermatomyositis
Heterogeneous group of genetically determined autoimmune diseases, targeting the skin
and/or skeletal muscles.
Juvenile and adult (>40 years) onset.
Etiology.
Unknown. In persons >55 years of age, may be associated with malignancy.
Clinical Spectrum.
Ranges from DM with only cutaneous inflammation (amyopathic DM) to polymyositis with
only muscle inflammation.
Symptoms. Photosensitivity. Muscle weakness, difficulty in rising from supine position,
climbing stairs, raising arms over head, turning in bed. Dysphagia.
Skin lesions. Presents with facial erythema, violaceous poikiloderma of eyelids with edema
(heliotrope sign), violaceous papules over interphalangeal joints (Gottron’s papules), reddish
scaling over knuckles, knees and elbows (Gottron’s sign), ragged cuticles (Samitz sign),
nailfold telangiectasias, photodistributed poikiloderma (mottled discoloration with red,
white, and brown color), ± hyperkeratosis and fissuring of hands (mechanic’s hands), ±
calcinosis, ± nonscarring alopecia. Burning and pruritus of the scalp.
Muscle. Proximal symmetric muscle weakness (inability to comb hair, inability to rise from
seated position or climb stairs).
Occasional involvement of facial/bulbar, pharyngeal, and esophageal muscles.
Other organs. Interstitial pneumonitis, cardiomyopathy, arthritis.
Impaired general condition, ± fever, malaise.
Disease Association.
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Patients >50 years of age with DM have a higher risk for malignancy.
EMG – myogenic impairment.
↑ ESR; muscle enzymes - ↑ creatine kinase (CK, 90%) and aldolase; ↑ transaminases, ↑
LDH; myositis-specific AB (antisynthetizing, anti-Mi2 or anti-SRP); ANA (60%).
Urine. Elevated 24-h creatine excretion (>200mg/24h).
Skin hisrology → not diagnostic.
Muscle histology → segmental necrosis within muscle fibers with loss of cross striations;
myositis. Vasculitis in juvenile DM.
Prognosis is guarded. Successful treatment of an associated neoplasm is often followed by
improvement/resolution of DM.
Treatment
Systemic: corticosteroids, cytostatics, synthetic antimalarials, IVIG, NSAID, TNF-α agents.
Topical: skin protection, corticosteroids.
Symptomatic treatment of complications.
Scleroderma
Group of autoimmune disorders with initial inflammation and subsequent sclerosis; affects
either the skin or the skin and other organs.
Etiology:
unknown; genetic background.
Triggering Factors:
physical and chemical impacts, drugs, infections, endocrine dysorders, stress.
Pathogenesis:
cytotoxic agents which destruct the basal membrane → plugging → enhanced
collagenosynthesis.
Clinical variants:
Morphea (localized scleroderma, circumscribed scleroderma);
Systemic sclerosis (SSc) (progressive systemic sclerosis, systemic scleroderma).
Morphea (Localized Scleroderma, Circumscribed Scleroderma)
Localized form of scleroderma with unknown etiology, possibly due to trauma or infection
(i.e. Borrelia burgdorferi).
Morphea is not related to systemic scleroderma.
Benign course or slowly progressive.
All ages, incl. children. F > M.
Types of Morphea:
Circumscribed: plaques or bands; trunk, limbs, face, genitalia.
Macular: small, confluent patches; shoulders.
Linear scleroderma: upper or lower extremity.
Frontoparietal (en coup de saber): scalp and face.
Generalized/disseminated morphea: initially on trunk, thighs.
Pansclerotic: involvement of dermis, fat, fascia, muscle, bone; on trunk or extremities.
Atrophic: without induration.
Morphea profunda: with deep induration.
Skin Findings.
Plaques – circumscribed, indurated, hard, but poorly defined areas of skin; 2-15 cm in
diameter, round or oval, often better felt than seen. Initially, purplish or mauve. After months
to years, surface becomes smooth and shiny, ivory with lilac-colored edge (“lilac ring”).
Mouth. Linear morphea of head ± hemiatrophy of tongue.
Hair and nails. Linear morphea of the head → scarring alopecia. Linear lesions of
extremities or in pansclerotic morphea → nail dystrophy.
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General Examination
Morphea around joints and linear morphea → flexion contractures. Pansclerotic morphea +
atrophy and fibrosis of muscle; extensive involvement of trunk → restricted respiration.
Linear morphea of the head → atrophy of ocular structures and atrophy of bone.
Symptoms.
Usually none. Linear and pansclerotic morphea → facial or limb asymmetry, flexion
contractures, and disability → severe disfigurement.
Serology.
Serologic testing to rule out B. burgdorferi infection. ± ANA in generalized/disseminated or
linear morphea.
Histology.
Dermis - edematous with homogeneous and eosinophilic collagen. Later, dermis thickened
with few fibroblasts and dense collagen; inflammatory infiltrate at dermal-subcutis junction;
dermal appendages disappear progressively.
Treatment
If + B. burgdorferi → treatment for Lyme disease.
Systemic: Penicillin G; synthetic antimalarials, tetracyclines; in linear scleroderma -
corticosteroids alone or in combination with immunosupressors.
Topical: Topical mild to high potency corticosteroids, topical vitamin D analogue, PUVA or
UVA1.
Systemic Sclerosis (SSc) (Progressive Systemic Sclerosis, Systemic
Scleroderma)
Multisystem disorder characterized by inflammatory, vascular, and sclerotic changes of the
skin, blood vessels and various internal organs, especially the lungs, heart, and GI tract.
Unknown. Primary event might be endothelial cell injury in blood vessels.
Pathogenesis. Vascular dysfunction and endothelial injury. Fibrosis related to TGF-ß,
endothelin-1, PDGF, and connective tissue growth factor (CTGF).
Young and middle age. F > M.
Raynaud phenomenon and skin sclerosis always present.
Cutaneous Manifestations:
Hands/Feet. Early: Raynaud phenomenon (vasospasm of digital arteries secondary to cold
stimulus with classic color change: white → blue → red). Nonpitting edema of hands/feet.
Painful ulcerations at fingertips (“rat bite necrosis”) and knuckles; heal with pitted scars.
Late: sclerodactyly with tapering of fingers (Madonna fingers) with waxy, shiny, hardened
skin, which is tightly bound down and does not permit folding or wrinkling; leathery
crepitation over joints, flexion contractures; periungual telangiectasias, nails grow claw-like
over shortened distal phalanges. Bone resorption and ulceration results in loss of distal
phalanges. Loss of sweat glands with anhidrosis; thinning and complete loss of hair on distal
extremities.
Face. Early → periorbital edema. Late → edema and fibrosis result in loss of normal facial
lines, mask-like appearance (patients look younger than they are), thinning of lips,
microstomia, radial perioral furrowing, beak-like sharp nose. Telangiectasias and diffuse
hyperpigmentation.
Trunk. Tense, stiff, and waxy appearing skin that cannot be folded. Impairment of
respiratory movement of chest wall and of joint mobility.
Other changes. Cutaneous calcification. Occurs on fingertips or over bony prominences or
any sclerodermatous site; may ulcerate and exude white paste.
Color changes. Hyperpigmentation ± perifollicular hypopigmentation (“salt/pepper” sign).
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Mucous membranes. Sclerosis of sublingual ligament; uncommonly, painful induration of
gums, tongue.
Clinical Variant.
CREST syndrome (limited SSc), i.e., calcinosis cutis + Raynaud phenomenon + esophageal
dysfunction + sclerodactyly + telangiectasia. Associated with anti-centromere antibodies,
rarely progresses to SSc, better prognosis than SSc.
General Examination
Gastrointestinal system. Dysphagia, especially with solid foods, diminished peristalsis,
reflux esophagitis. Constipation, diarrhea, bloating, malabsorption, weight loss.
Lung. Exertional dyspnea, dry cough. Pulmonary fibrosis and alveolitis. Reduction in
pulmonary function.
Heart. Cardiac conduction defects, heart failure, pericarditis.
Kidney. Nephrosclerosis, slowly progressive uremia, malignant hypertension.
Liver – biliary cirrhosis.
Joints – contracture; bones – osteoporosis.
Musculoskeletal system. Symmetric synovitis. Migratory polyarthritis. Carpal tunnel
syndrome. Muscle weakness.
Autoantibodies:
ANA (nucleolar/centromeric), anti-Scl-70, anti-fibrillarin, anti-centromere, anti-RNA
polymerase.
Histology:
hyalinized dermis with ↑ collagen deposition, ↓ adnexal structures, loss of subcutaneous fat.
Course - slow (> 10 years) or fast progression (2 - 5 years).
Renal disease is the leading cause of death, followed by cardiac and pulmonary
involvement.
Treatment
Raynaud’s: cold temperature avoidance, calcium channel blockers (nifedipine), low dose
aspirin, prostaglandin E1
Systemic: collagen synthetize blockers – D-penicillamine, colchicin, madecassol; ACEI;
penicillin G; immunosuppressants and glucocorticoids for limited periods early in the
disease; photopheresis.
Cutaneous ulcers: oral endothelin receptor antagonist (i.e. bosentan) → prevent new ulcers.
Physiotherapy. Balneotherapy. Mud therapy.
Immunoablation/stem cell transplantation and oral tolerization to type I collagen: ongoing
studies.
VASCULITIDES AND VASO-OCCLUSIVE DISEASES (Vasculitis; Henoch-Schönlein

Purpura; Polyarteritis Nodosa; Urticarial Vasculitis; Chronic Venous Insufficiency)
Vasculitis
The vasculitides can best be classified according to the size of vessels involved.
Hypersensitivity Vasculitis
Synonyms: Allergic cutaneous vasculitis, necrotizing vasculitis.
Hypersensitivity vasculitis (HV) encompasses a heterogeneous group of vasculitides,
involving only small cutaneous blood vessels, associated with hypersensitivity to antigens
from infectious agents, drugs, or other exogenous or endogenous sources.
Etiology:
infection (bacterial, viral); inflammatory disorder (autoimmune connective tissue disease,
inflammatory bowel disease, seronegative spondyloarthropathy); drugs (NSAIDs, COX-2
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inhibitors, leukotriene inhibitors, penicillins, quinolones, anti-TNF agents, G-CSF,
hydralazine, anti-thyroid agents, etc.); neoplasms; idiopathic – 50%.
Pathogenesis:
deposition in postcapillary venules of circulating immune complexes.
Age of onset. All ages. F = M.
Skin lesions. Occur 7–10 days after exposure to inciting agent. Primarily localized to the
lower legs and the ankles but may spread to the buttocks and arms. The hallmark is
palpablre purpura - palpable petechiae present as bright red → purple/black in the center,
well-demarcated macules and papules with central, dot-like hemorrhages. Lesions are
scattered, discrete or confluent. In the case of massive inflammation, purpuric papules
convert to hemorrhagic blisters, become necrotic, and ever ulcerate.
Symptoms: Pruritus, burning pain.
Systemic vascular involvement: Kidney (microhematuria), muscles (myalgia), joints
(arthralgia), GI tract (abdominal pain), and peripheral nerves (neuritis). ± fever, malaise.
Onset and Course:
acute (days, as in drug induced or idiopathic), subacute (weeks, especially urticarial types),
chronic (recurrent over years).
Hematology. Rule out thrombocytopenic purpura. ↑ ESR.
Serology. Serum complement is reduced or normal, depending on associated disorders.
Urinalysis. RBC casts, albuminuria.
Others. Depending on underlying disease.
Histology.
Leukocytoclastic vasculitis (perivascular neutrophilic infiltration and fibrinoid necrosis of
vascular walls, involving only small cutaneous blood vessels in the upper dermis).
DIF: IgA vasculitis.
Prognosis depends on underlying disease and severity of systemic involvement.
In the idiopathic variant, multiple episodes can occur over the course of years. Usually
self-limited, but irreversible damage to kidneys can occur. Spontaneous resolution - 90%.
Treatment:
rule out systemic vasculitis; treat the underlying cause; remove any trigger; supportive
therapy.
Antibiotics in vasculitis follow bacterial infection. Steroids and immune-suppressors, IVIG
in vasculitis with systemic involvement.
Henoch-Schönlein Purpura (HSP)

Specific subtype of hypersensitivity vasculitis (cutaneous small vessel vasculitis) that occurs
mainly in children but also affects adults associated with IgA deposits in the skin.
There is a history of upper respiratory tract infection (75%), by a group A streptococci.
Presents with palpable purpura (in childhood purpuric macules and papules) with
predilection for lower extremities and buttocks.
Accompanied by arthralgias/arthritis, nephritis with hematuria, acute abdominal pain, ± GI
bleeding and vomiting
Histology.
Leukocytoclastic necrotizing vasculitis.
DIF: IgA immunoreactants, deposited in skin.
Long-term morbidity results from progressive renal disease.
Treatment:
mainly supportive as typically self-limited.
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Polyarteritis Nodosa (PAN)
Multisystem, segmental necrotizing vasculitis of small- and medium-sized muscular arteries
with involvement of the renal and visceral arteries.
Cutaneous PAN is a rare variant with symptomatic vasculitis, limited to skin and at times
peripheral nerves.
Association:
inflammatory disease (IBD, SLE) or infection (HBV, strep), i.e. immune complex
formation.
Skin Lesions.
In 15% of cases. Bilaterally on lower legs and thighs, sometimes - arms, trunk, head, neck,
buttocks. Subcutaneous inflammatory, bright red to bluish subcutaneous nodules (0.5-2 cm),
confluent to form painful subcutaneous plaques, and accompanied by livedo reticularis.
Pathognomonic „starburst” livedo - marks a cluster of nodular lesions. „Punched out”
ulcers follow ischemia of nodules. Duration – days to months. Resolves with residual
violaceous or postinflammatory hyperpigmentation. Identical skin lesions in systemic and
cutaneous PAN.
Skin symptoms: pain, paresthesia.
Systems Review.
Cardiovascular - hypertension, congestive heart failure, pericarditis, conduction system
defects, myocardial infarction. Neurologic - cerebrovascular accident, peripheral nerves -
mixed motor/sensory involvement with mononeuritis multiplex pattern. Muscle - diffuse
myalgias (excluding shoulder and hip girdle), lower extremities. GI system - nausea,
vomiting, abdominal pain, hemorrhage, infarction. Eyes - hypertensive changes, ocular
vasculitis, retinal artery aneurysm, optic disc edema/atrophy. Kidney - renal failure, edema.
Testes - pain and tenderness.
Constitutional Symptoms:
fever, asthma, myalgia.
CBC: neutrophilic leukocytosis; rarely, eosinophilia; anemia of chronic disease. ± ↑ ESR, ↑
serum creatinine, ↑ BUN.
Serology:
± antineutrophilic cytoplasmic autoantibodies (p-ANCA).
Histology:
polymorphonuclear infiltrate in all layers of vessel wall and perivascular areas; fibrinoid
necrosis of vessel wall with compromise of lumen; thrombosis and infarction of tissues,
supplied by involved vessels, with or without hemorrhages.
Course.
Cutaneous PAN - chronic relapsing benign course. Systemic untreated PAN - very high
morbidity and mortality rates. Death from renal failure, bowel infarction and perforation,
cardiovascular complications, intractable hypertension.
Treatment.
Prednisone + cyclophosphamide.
Urticarial Vasculitis
Urticarial vasculitis is a multisystem disease, characterized by cutaneous lesions resembling
urticaria, except that wheals persist for > 24 h and up to 3-4 days.
: immune complex disease, similar to hypersensitivity vasculitis; may be a symptom of SLE;
serum sickness; hepatitis B; or idiopathic.
Skin Lesions
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. Urticaria-like lesions (i.e., edematous plaques and wheals), indurated, erythematous,
circumscribed, occurs in transient crops, occasionally with angioedema. They change shape
slowly, often reveal purpura on blanching and resolve with a yellowish-green color and
hyperpigmentation ± itching, burning, stinging sensation, pain, tenderness.
Extracutaneous Involvement:
joints, GI tract, CNS (pseudotumor cerebri), ocular system, kidneys (diffuse
glomerulonephritis), lymphadenopathy + fever, arthralgia, nausea, abdominal pain, cough,
dyspnea, chest pain, hemoptysis, cold sensitivity.
Laboratory:
↑ ESR, ↓ C, microhematuria, proteinuria.
Histology:
leukocytoclastic vasculitis.
Course.
Depending on underlying disease.
Treatment.
H1 and H2 blockers + cimetidine/ranitidine. Colchicine or dapsone. Steroids +
immunosuppressants. Plasmapheresis. TNF-α blockers.
Chronic Venous Insufficiency (CVI)

Chronic venous insufficiency results from failure of centripetal return of venous blood and
increased capillary pressure; changes include edema, stasis dermatitis, hyperpigmentation,
fibrosis of the skin and subcutaneous tissue (lipodermatosclerosis) of the leg, and ulceration.
Epidemiology
Varicose veins: peak incidence of onset 30-40 years. F > M.
Etiology.
CVI is most commonly associated with varicose veins and the postphlebitic syndrome.
Aggravating Factors.
Pregnancy, increased blood volume, increased cardiac output, increased venocaval pressure,
progesterone.
Pathogenesis.
The damaged valves of the deep calf veins are incompetent to restrict blood backflow.
Damaged communicating veins cause slower blood flows from deep veins to superficial
venous plexus. Fibrin is deposited in the extravascular space and undergoes organization,
resulting in sclerosis and obliteration of lymphatics and microvasculature. Perpetuating
vicious cycle forms: initial event → aggravation of venous stasis and varicose vein dilatation
→ thrombosis → lipodermatosclerosis → stasis dermatitis → ulceration.
Prior episode(s) of superficial phlebitis and DVT.
CVI is commonly associated with heaviness or aching of leg, which is aggravated by
standing and relieved by walking. Lipodermatosclerosis limits ankle motility and causes
pain and further movement limitation, which in turn increases stasis. Leg edema aggravates
by dependency (end of the day, standing), and in the summer season. Night cramps often
exist.
Skin Lesions
Varicose veins. Enlarged superficial leg veins, tortuous, with incompetent valves.
“Blow-out” at sites of incompetent communicating veins. Positive tourniquet test - a
tourniquet is applied to the leg that has been elevated to empty the veins; when the patient
stands up and the tourniquet is released, there is instant filling of a varicose vein due to
absent or ill-functioning valves. Varicose veins are usually associated with starburst
phlebectasia at the area of an incompetent communicating veins. Superficial venulectasias
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(spider phlebectasia) without a starburst pattern can also be seen on thighs and lateral lower
legs in CVI.
Edema on dorsal feet, ankles, lower legs, which is dependent, and improves in the morning
after a night in the horizontal position.
Eczematous (stasis) dermatitis. Occurs the lower legs and ankles. Presented with
inflammatory papules, scaly and crusted erosions; mottled pigmentation, stippled with recent
and old hemorrhages; dermal sclerosis; and excoriations due to scratching. When extensive,
it may become generalized due to autosensitization.
Atrophie blanche. Small ivory-white depressed patches on the ankle and/or foot; stellate and
irregular, coalescing; stippled pigmentation; hemosiderin-pigmented border, usually within
stasis dermatitis.
Lipodermatosclerosis. Inflammation, induration, pigmentation of lower third of leg, creating
“champagne bottle” or “piano leg” appearance with edema above and below the sclerotic
region. “Groove sign” created by varicose veins meandering through sclerotic tissue.
Ulceration. Occur in 30% of cases; common sites - medial malleolar region. Associated with
at least one or all of the symptoms of CVI, very painful; single or multiple; larger superficial
or deep ulcers, sharply defined with deep, irregularly shaped margin and necrotic center,
covered with fibrotic debris. Secondary bacterial colonization may evolve. Rarely, squamous
cell carcinoma forms on long-standing recalcitrant venous ulcers.
Doppler, color-coded duplex sonography and phlebography detects incompetent veins
and venous occlusion.
Imaging. X-ray show subcutaneous calcification.
Treatment
General management. Treatment of underlying disease to prevent recurrences.
Leg elevation and compression stockings/bandaging.
Atrophie blanche. Avoid trauma. Intralesional triamcinolone into painful lesions.
Compression.
Stasis dermatitis. Wet dressings and short term topical glucocorticoids. Topical antibiotic
treatments when secondarily infected.
Varicose veins. Sclerotherapy or surgery. Endovascular techniques. Endoscopic subfascial
dissection of perforating veins and endoscopic endovenous diode laser or radio frequency
thermal heating → occlusion of varicose vein.
Ulcers. Debridement of necrotic material mechanically (surgically) or by enzymatic
debriding agents; antiseptics and antibiotics to counteract infection. Hydrocolloid dressings.
Surgical procedures either by pinch grafts, split-thickness skin grafts, epidermal grafts,
cultured keratinocyte allografts, or composite grafts.
SKIN APPENDICES DISEASES

Disorders of Hair
Non-scarring Alopecias (Alopecia Areata; Androgenetic Alopecia)
Alopecia Areata (AA)
A localized loss of hair in round or oval areas with no apparent inflammation of the skin.
Non-scarring, reversible; hair follicle intact.
Etiology.
Unknown.
Pathogenesis.
Suggests T cell-mediated autoimmune process in patients with genetic predisposition.
Can occur at any age, children more frequently.
Clinical Manifestations
70
Duration of hair loss. Gradual over weeks to months. Patches of AA can be stable and often
show spontaneous regrowth over a period of several months; new patches may appear while
others resolve.
Hair. Single or multiple, round to oval non-scarring patches of terminal hair loss. May
coalesce. Alopecia often sharply defined of normal-appearing skin with accentuated
follicular openings. “Exclamation mark” hairs. Diagnostic broken-off stubby hairs (distal
ends are broader than proximal ends) at the margins of hair loss areas. With regrowth, the
new hairs are fine, often white or gray.
Sites of predilection. Scalp most commonly. Any hair-bearing area. Beard, eyebrows,
eyelashes, pubic hair.
Alopecia areata (AA): Solitary or multiple areas of hair loss.
AAtotalis (AAT): Total loss of terminal scalp hair.
AA universalis (AAU): Total loss of all terminal body and scalp hair.
Ophiasis: Band-like hair loss at periphery of temporal/occipital scalp.
Nails. Most common - fine pitting (“hammered brass”) of dorsal nail plate. Also: mottled
lunula, trachyonychia (rough nails), onychomadesis (separation of nail from matrix).
Associations:
thyroid disease, vitiligo, atopy, polyendocrinopathy, etc.
Histology:
lymphocytes, surrounding lower portion of hair follicle resembling “swarm of bees”, ↑
miniature telogen and catagen follicles.
Course.
Spontaneous remission is common in patchy AA, less in AAT or AAU.
Poor prognosis associated with onset in childhood, extensive hair loss and loss of body hair,
nail involvement, atopy, family history of AA.
Treatment
In many cases, the most important factor is psychological support from the dermatologist,
family and support groups.
Persons with extensive scalp involvement → wear a wig or hairpiece.
Make up eyebrows, tattooed eyebrows.
Glucocorticoids: Topical superpotent corticoids - not usually effective; intralesional
triamcinolone acetonide for few and small lesions of AA; systemic glucocorticoids induce
regrowth, but AA recurs on discontinuation.
Systemic cyclosporine induces regrowth, but AA recurs when drug is discontinued.
Androgenetic Alopecia
In males, pattern extent of hair loss varies from bitemporal recession, to frontal and/or vertex
thinning, progressive loss of all hair except along the occipital and temporal margins
(“Hippocratic wreath”).
Etiology.
Combined effects of androgen on genetically predisposed hair follicles. Genetics: 1)
autosomal dominant and/or polygenic; 2) inherited from either or both parents.
Men - any time after puberty onset. Women – later, in the sixth decade. M >> F.
Classification
Hamilton classified male-pattern hair loss into V stages:
Type I: Loss of hair along frontal margin.
Type II: Increasing frontal hair loss as well as onset of loss of occipital (vertex or crown).
Types III, IV, and V: Increasing hair loss in both regions with eventual confluent and
complete balding on top of scalp with sparing of sides.
Ludwig classified hair loss in women into types I to III.
71
Skin symptoms. Most patients present with complaints of gradually thinning hair or
baldness.
Skin findings. Scalp skin is normal. In young women - signs of virilisation (clitoral
hypertrophy, acne, facial hirsutism).
Males with decreased hair density over bitemporal and vertex of scalp; females with mid
frontoparietal scalp involvement (widened hair part, “Christmas tree” pattern) but
preservation of anterior hair line.
Hair. Hair in areas of pattern hair loss becomes finer in texture (shorter in length, reduced
diameter). In time, hair becomes vellus and eventually atrophies completely.
Trichogram.
The earliest changes are an increase in the percentage of telogen hairs.
Histology.
Abundance of telogen-stage follicles, associated with hair follicles of decreasing size.
Hormone Studies.
In men - ↑ activity of dihydrotestosterone (DHT) and 5 α–reductase (testosterone converted
to DHT). In women - ↑ testosterone (total and free), dehydroepiandrosterone sulfate
(DHEAS) and prolactin.
Treatment
Oral finasteride. If the drug is stopped the hair that had grown will be lost. Side effects -
reversible decrease in libido and erectile function.
Antiandrogens. In women with elevated adrenal androgens – spironolactone, cyproterone
acetate, flutamide, and cimetidine.
Oral PUVA (Photochemotherapy) - variably effective.
Topical 2% and 5% minoxidil solution.
Surgical treatment: Hair transplantation - grafts from androgen-insensitive hair sites
(peripheral occipital and parietal hairy areas); Scalp reduction/rotation flaps.
Induction of allergic contact dermatitis with dinitrochlorbenzene, squaric acid dibutylester,
or diphencyprone. Local discomfort due to allergic contact dermatitis and swelling of
regional lymph nodes.
Hairpiece. Wigs, toupees, prosthetics; hair weaves.
Diseases of Pilosebaceous Unit (Acne Vulgaris; Rosacea; Perioral Dermatitis)

Acne Vulgaris
Inflammation of the pilosebaceous unit (PSU) causing comedones, papulopustules, nodules,
and cysts.
Four key pathogenic factors: abnormal follicular keratinization; bacterial colonization
(Propionibacterium acnes) in sebum; ↑ inflammation; ↑ sebum production due to
androgen-stimulated sebaceous glands.
Occurrence. Over 80% of teenagers aged 13-18 years.
Season. Often worse in fall and winter.
Commonly affects the face, chest and upper back.
Skin lesions. Comedones – open (blackheads) or closed (whiteheads) – comedonal acne.
Papules and papulopustules – papulopustular acne. Nodules or cysts – nodulocystic acne.
Sinuses: draining epithelial-lined tracts, usually with nodular acne. Scars: atrophic or
hypertrophic. Seborrhea of the face and scalp.
Symptoms. Pain (especially nodulo-cystic type).
Special Forms:
Neonatal Acne.
72
Presents with erythematous small papules on nose and cheeks in newborns or infants,
transient, self-healing.
Acne Excoriée.
Mainly seen in young women with emotional or psychological disorders who repeatedly
pick at lesions. Presents as mild acne with several excoriations, crusted erosions and
sometimes ulcerations with subsequent scarring.
Acne with Underlying Endocrinologic Abnormality (Ovarian, Adrenal) –
acne with accompanying hirsutism ± irregular menses, hormonal abnormality (testosterone,
DHEA-S, 17-hydroxyprogesterone).
Acne Mechanica.
Due to repeated obstruction of the pilosebaceous unit through friction/pressure.
Acne Conglobata.
Severe nodulocystic acne with more involvement of the trunk than the face without
systemic manifestations. Part of the follicular occlusion triad (dissecting cellulitis of scalp,
pilonidal cyst and hidradenitis suppurativa).
Acne Fulminans.
Teenage boys. Sudden-onset, severe nodulocystic acne with suppuration and ulceration;
systemic symptoms (malaise, fatigue, fever, myalgias, arthralgias, ↑ WBCs, ↑ ESR, sterile
osteolytic bone lesions typically over clavicle or sternum)
Occupational Acne.
Due to exposure to tar derivatives, cutting oils, chlorinated hydrocarbons.
Chloracne.
Due to exposure to chlorinated aromatic hydrocarbons.
Acne Cosmetica.
Due to comedogenic cosmetics.
Drug-Induced Acne.
Due to corticosteroids, phenytoin, lithium, isoniazid, iodides, epidermal growth factor
receptor inhibitors (EGFRI: cetuximab, erlotinib, gefitinib), anabolic steroids. Presents with
abrupt-onset monomorphic-appearing papules and pustules; typically comedones are not
seen.
Treatment
General measures – no specific food has been identified to cause acne, treatment needs to be
continued for at least 6 weeks to produce effect.
Mild acne. Topical antibiotics (clindamycin and erythromycin), benzoyl peroxide and topical
retinoids (retinoic acid, adapalene, tazarotene), azelaic acid, sodium sulfacetamide/sulfur
and salicyclic acid.
Moderate acne. Oral antibiotics (minocycline or doxycycline) to the above regimen. Oral
isotretinoin to prevent scarring, anti-androgens and oral contraceptive pills (in females).
Severe acne. In addition to topical treatment, systemic treatment with isotretinoin is
indicated for cystic or conglobate acne or for any other acne, refractory to treatment.
Isotretinoin is teratogenic and effective contraception is imperative.
Adjunctive systemic glucocorticoids may be required in severe acne conglobata and acne
fulminans.
Other treatments for acne. For inflammatory cysts and nodules - intralesional triamcinolone.
Performing comedones extraction by micro-surgery.
Rosacea
Chronic inflammatory acneiform condition of facial pilosebaceous units with increased
vascular hyperreactivity. Presents with easy flushing and gradual reddening of complexion;
exacerbating factors may include particular foods (especially spicy), alcohol, exposure to
sun and heat, hot liquids, ± Demodex folliculorum mites within infundibula.
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Age of onset. 30-50 years. F > M, but rhinophyma occurs mostly in males.
Distribution. Symmetric localization on the face. Rarely, neck, chest (V-shaped area), back,
and scalp.
Types:
Type 1 – Erythematotelangiectatic.
Prolonged flushing (>10 min), persistent central facial erythema, ± telangiectasias, ±
burning/stinging sensation, easy irritation.
Type 2 – Papulopustular.
Persistent central facial erythema with telangiectasias, acneiform papules and pustules (no
comedones).
Type 3 – Phymatous.
Indurated erythematous to yellow-brown papules/nodules, pustules with persistent edema;
dense telangiectasias; exclusively in men - rhinophyma (subtype) over distal half of nose.
Type 4 – Ocular.
“Red” eyes as a result of chronic blepharitis, conjunctivitis, and scleritis. Rosacea keratitis -
corneal ulcers → blurry vision.
Skin symptoms. Concern about cosmetic facial appearance.
Eyes symptoms. Xerophthalmia, tearing, pain.
Course.
Prolonged. Recurrences are common. Usually – life-long; in some cases - may disappear
spontaneously.
Treatment
Topical therapy: metronidazole, azelaic acid, antibiotics, benzoil peroxide, sodium
sulfacetamide/sulfur, ivermectin.
Oral therapy: antibiotics (tetracyclines, macrolides), isotretinoin. Ivermectin in case of
massive Demodex infestation.
Surgery or laser surgery for rhinophyma and telangiectasias.
Treatment of choice for ocular rosacea: oral antibiotic.
Sun protection and trigger avoidance.
Perioral Dermatitis
Distinctive dermatitis with discrete papules and pustules with erythematous (sometimes
scaly) base.
Occurs mainly in young women.
Etiology.
Unknown but previous use of fluorinated topical steroids may cause or exacerbate
condition.
Around the mouth, nose, and possibly periorbital area.
Skin lesions. Irregularly grouped, symmetric papulo-pustules on an erythematous
background. Confluent plaques may appear eczematous with tiny scales. No comedones.
Duration of lesions - weeks to months.
Occasional itching or burning, feeling of tightness.
Treatment.
Systemic. Minocycline, doxycycline, tetracycline.
Topical. Metronidazole gel or erythromycin gel. Avoid topical glucocorticoids!
DISEASES OF THE MOUTH

Diseases of the Lips
Angular Cheilitis (Perlèche)
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Predisposing factors: Thumb sucking in children; sagging face and loss of teeth in older
persons; candidal and bacterial infections; vitamin deficiency; irritant dermatitis; isotretinoin
treatment.
Erythema, maceration and fissuring at the lipcommissures. Associated with increased
moisture at commissures, salivation (at sleep).
Treatment:
Identify and treat causes.
Actinic Cheilitis
Actinic/solar keratoses, usually of the lower lip.
Blurring of vermilion border, change intexture/color of lip, ± scale, ulceration.
Precancerous: typically diffuse.
Cheilitis Glandularis
Pinpint red macules on lower lip mucosa, ± enlargement of lower lip.
Dilated/inflamed minor salivary glands; treat w/vermilionectomy.
Orofacial Granulomatosis (Cheilitis Granulomatosa)
Persistent, non-tender enlargement of lips and/or face.
Associated with Melkersson-Rosenthal syndrome (facial nerve palsy, fissured tongue,
granulomatous cheilitis).
Heck’s Disease (Focal Epithelial Hyperplasia)
Pink to white soft papules/plaques with cobblestone appearance over lips, buccal mucosa
and/or lateral sides of tongue.
Infection of mucosa by HPV types 13 and 32.
Conditions of the Tongue, Palate and Mandible

Fissured Tongue (Lingua Fissurata, Lingua Plicata, Scrotal Tongue, Grooved
Tongue, Furrowed Tongue)
Normal variant in up to 11% of population. Asymptomatic.
Nonpainful furrows on dorsum of tongue with “corrugated” appearance.
Associated disorders: Psoriasis, acromegaly, Down syndrome, Sjögren syndrome,
Melkersson-Rosenthal syndrome.
Black or White Hairy Tongue [Lingua Villosa (Nigra)]
Pathogenesis:
Due to keratin accumulation → defective desquamation of filiform papillae resulting in
hair-like projections on the dorsum of the tongue.
Associations: Heavy tobacco use, mouth breathing, systemic antibiotic therapy, poor oral
hygiene, general debilitation, radiation therapy, chronic use of bismuth-containing antacids,
lack of dietary roughage.
Furry plaques on dorsal tongue - elongated and hypertrophic papillae with hair-like
projections on dorsum of tongue.
Chromogenic bacteria or exogenous pigment stain tongue: white, yellow, green, brown,
black.
Gagging sensation, altered taste, halitosis, cosmetic disfigurement.
Management:
eliminate predisposing factors; good oral hygiene.
Oral Hairy Leukoplakia
Pathogenesis:
Epstein-Bar virus infection; low CD4 cell counts.
White corrugated plaques on lateral aspects of tongue.
Leukoplakia
Chronic white plaque/lesion on floor of the mouth, lip, tongue, and soft palate that cannot be
wiped off. Most common premalignant oral lesion → has histologic atypia. Severity linked
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to duration and quantity on tobacco and alcohol use. Leukoplakia is descriptive clinical term
regarding morphology. When diagnosis is definitive histologically, “leukoplakia” is no
longer appropriate. Erythroleukoplakia (speckled leukoplakia) has the highest rate of
malignant transformation.
Erythroplakia
Flat or slightly erythematous sharply marginated patch or plaque.
90% carcinoma in situ or invasive at time of biopsy.
Glossitis
Atrophic, smooth red glistening tongue.
Candidiasis or vitamin deficiency.
Migratory Glossitis (Geographic Tongue)
Etiology:
unknown; possible link with psoriasis and atopic dermatitis.
Incidence:
common; usually asymptomatic.
Irregular areas of dekeratinized and desquamated red filiform papillae surrounded by
elevated whitish or yellow margins.
Median Rhomboid Glossitis
Diamond or oval-shaped erythematous smooth plaque on posterior dorsal tongue.
Asymptomatic, may resolve onown; likely due to C. albicans.
Palate and Mandibular Torus
Pathogenesis:
genetic predisposition, ? autosomal dominant in some series, more common in females,
Native Americans, Eskimos (torus palatine); local stressors (mandibular and palatal tori),
bony protrusions.
Palatal tori are usually in midline of palate and less than 2 cm, but can vary in size through
life; mandibular tori found usually near premolars; rarely bilateral. They are smooth, nodular
protrusions. May be complicated by ulceration; usually asymptomatic.
Management:
not needed; if create ulcerations or complicate dental prosthesios, surgery can be done.
Have been used as autogenous bone grafts.
Frictional Keratosis/Lichen Simplex Chronicus
Keratosis secondary to friction (e.g., sharp tooth, rough or over extended denture border).
Chronic Chewing: Lip, Tongue, Cheek
Form of frictional keratosis. Surface white, rough. On buccal mucosa, wedge-shaped.
Diseases of the Gingiva, Periodontium, and Mucosa

Thrush
Loosely adherent white patches or plaques on mucosal surfaces
Due to candidal infection.
Aphthous Stomatitis
Round to oval painful shallow ulcers with creamy-white base and red halo.
Three forms: minor, major and herpetiform.
Leukoedema
Diffuse grey-white surface along buccal mucosa.
Benign, disappears with stretching of affected area.
Morsicatio Buccarum
Shaggy white plaque on buccal mucosa.
Chronic irritation from biting.
Irritant Contact Stomatitis (Aspirin/Chemical Burn)
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White/painful wrinkled necrotic plaque at site of contact, loosely adherent, easily sloughs off
with subsequent desquamation.
Self-limited; often due to aspirin.
Allergic Contact Stomatitis
Shaggy white hyperkeratotic areas on buccal mucosa resembling oral LP.
Dental amalgam and cinnamon may cause lichenoid changes.
Amalgam Tattoo
Black or bluish-black pigmented macule typically over buccal vestibule.
After tooth extraction, amalgam may incorporate in wound.
Nicotine Stomatitis
Umbilicated papules with central red depression over hard or soft palate.
Inflamed palatal mucous salivary glands due to nicotine.
White appearance resolves with cessation of smoking. Not considered premalignant.
Tobacco Chewer΄s White Lesion
Develops where chewing tobacco is held. Mucosa granular or wrinkled. Location:
mucobuccal fold. Lesion is premalignant. Usually resolves with discontinuation of tobacco.
Lichenoid Mucositis
Etiology:
Lichen planus, drugs (NSAIDs, antihypertensive agents), allergic contact dermatitis,
graft-versus-host disease.
Reticulated white plaques and painful erosions on mucosal surfaces.
Primary Herpetic Gingivostomatitis
Painful vesicles and ulcers; typically with diffuse gingival involvement.
Primary HSV infection.
Erosive Gingivostomatitis
Reaction pattern associated with viral infection, autoimmunity, lichen planus, erythema
multiforme, pemphigus, cicatricial pemphigoid.
Erythema, desquamation, and edema of gingivae. Other mucocutaneous sites may be
affected.
Aphthous Ulceration (see ”Aphthous ulceration“,”Behçet’s disease“)
Gingivitis
Erythema, edema, blunting of interdental papillae without bone loss.
Predisposing factors: poor oral hygiene, tobacco use, diabetes.
Desquamative Gingivitis
Diffuse gingival erythema with erosions, ± mucosal sloughing.
General term for findings in many vesiculo-erosive diseases.
Acute Necrotizing Ulcerative Gingivitis (Trench Mouth, Vincent Disease)
Etiologic Agents.
Many oral bacterial pathogens (Bacteroides fusiformis, Prevotella intermedia, Borrelia
vincentii, Treponema).
Precipitating Factors
. Poor oral hygiene, HIV/AIDS, immunosuppression, alcohol and tobacco use, nutritional
deficiency.
Punched-out ulcers of the interdental papillae. Gingival hemorrhage, severe pain, foul
odor/halitosis, fever, lymphadenopathy; alveolar bone destruction.
Management.
Systemic antibiotics such as clindamycin, metronidazole, amoxicillin. Dental hygiene.
Gingival Hyperplasia
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Hypertrophy of both free and attached gingivae, particularly the interdental papillae being
affected first.
Inflammatory enlargement. Most common cause of gingival enlargement. Caused by edema
and infective cellular infiltration caused by prolonged exposure to bacterial plaque; fibrosis
occurs if untreated.
Drug-induced fibrous hyperplasia of gingivae. May cover the teeth and is associated with:
anticonvulsants – phenytoin, succinimides, valproic acid; calcium channel blockers –
nifedipine, verapamil; cyclosporine.
Systemic conditions/disorders. Pregnancy, puberty, vitamin C deficiency, glycogen storage
disease; chronic myelomonocytic leukemia.
Periodontitis
Chronic infection of connective tissue, periodontal ligament, and alveolar bone; most
common cause of tooth loss in adults.
Course.
Accumulation of subgingival calculus (calcified plaque) and Actinobacillus
actinomycetemcomitans infection results in painless soft tissue edema, insidious alveolar
bone resorption, deepening periodontal pockets, and tooth loss.
Submucosal Nodules
Mucocele (Ranula)
Arise following rupture of minor salivary gland.
Nodule with mucus-filled cavity, with a thick roof. Chronic lesions are firm, inflamed,
poorly circumscribed nodules; bluish, translucent; fluctuant. Develops at sites where minor
salivary glands are easily traumatized: mucous membranes of the lip and floor of the mouth.
Irritation Fibroma
A submucosal nodular scar, occurring at a site of recurrent trauma. Sessile or pedunculated,
well-demarcated nodule, usually 2 cm in diameter (large if neglected). Normal color of the
mucous membrane to pink-red; firm to hard.
Cutaneous Odontogenic (Dental) Abscess
A periapical dental abscess can extend into the overlying soft tissues, tracking and draining
on the face.
Cutaneous Diseases Involving the Mouth

Cutaneous diseases may present in oral mucosa; may be confined to this site for months
before cutaneous involvement occurs.
Biopsy all mucosal lesions that persist for > 3 weeks without definitive diagnosis!
Lichen Planus
Incidence: 40-60% of individuals with LP have oropharyngeal involvement.
Findings: Milky-white papules; Wickham striae - reticulate (netlike) patterns of lacy-white
hyperkeratosis (buccal mucosa, lips, tongue, and gingivae); Hypertrophic LP – leukoplakia
with Wickham striae usually on the buccal mucosa; Atrophic LP – shiny plaque often with
Wickham striae in surrounding mucosa; Erosive/ulcerative LP – superficial erosions with
overlying fibrin clots that are seen on the tongue and buccal mucosa; can be painful; Bullous
LP - intact blisters (rupture and result in erosive LP); Desquamative gingivitis – bright red
gingiva.
Squamous Cell Carcinoma
Indurated plaque, nodule, exophytic mass, ulceror extensive hyperkeratotic white
leukoplakia typically over lips, lateral/ventral tongue and floor of mouth.
Strongly associated with tobacco, alcohol, HPV infection, oral lichen planus and chewing
betel nut.
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Oropharyngeal Melanoma
For the most part, lesions are asymptomatic; often advanced when first detected.
Presents as pigmented lesion with variegation of color and irregular borders; rarely
variegation of color and irregular borders; rarely amelanotic. In situ lesions are macular;
sites of invasion are usually raised within the in situ lesion.
80% arise on pigmented mucosa of the palate and gingival.
Pemphigus Vulgaris (PV)
Blisters are very fragile, rupture easily, rarely seen → sharply marginated extremely painful
erosions of the mouth (buccal mucosa, hard and soft palate, and gingival), interfering with
nutrition. Gingivitis can be a presenting sign.
Paraneoplastic Pemphigus
Painful mucosal erosions. Cutaneous blisters, lichenoid papules and erosions; conjunctival
erythema. Confirmed or occult malignancy.
Bullous Pemphigoid
Uncommonly affects the oropharynx. Initially tense blisters → erosions, practically
indistinguishable from those of PV or cicatricial pemphigoid.
Cicatricial Pemphigoid
Clinical manifestations dependent on sites involved. Persistent painful erosions on mucous
membranes. Desquamative gingivitis with painful erosions on tongue, buccal, and palatal
mucosa. Ocular symblepharon and corneal scarring are feared complications. May be
associated with malignancy.
Lupus Erythematosus
Painless erythematous patches to chronic plaques, sharply marginated, irregularly scalloped
white borders, radiating white striae, and telangiectasia. In older lesions: central depression,
painful ulceration.
Distribution: buccal mucosa; palate, alveolar process, tongue, lips.
In acute systemic lupus erythematosus, ulcers arise in purpuric necrotic lesions of the palate,
buccal mucosa, or gums.
Behçet Disease (see ”Behçet disease“)
Adverse Drug Reaction (see “Adverse drug reaction”)
Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis
The oropharynx is most common affected. Mucosal lesions can precede cutaneous
involvement by 1-3 days. In the mouth, presenting symptoms are burning sensation of the
mouth and decreased oral intake. Erosions are seen in up to 90% of cases. Desquamation can
follow soon thereafter.
HPV: Condyloma Acuminata, Verruca Vulgaris, Squamous Papilloma
Findings: white papules, plaques; small, sessile, papillated, exophytic. Solitary, multiple,
mosaic.
MUCOSAL DISEASES (Chronic Benign Aphthosis. Behçet’s Disease)

Chronic Benign Aphthosis
Recurrent painful mucosal ulcerations.
Etiology.
Idiopathic. Genetic predisposition.
Triggering Factors:
physical trauma; infections (bacterial, viral); drugs; stress, etc. → vascular injured.
Any age onset.
Classification
Simple: 1-3 oral ulcers that recur 1-3 times per year.
Complex: Continuous ulcers and associated with systemic disease or genital ulcers.
Major aphthous ulcers (AU) may persist for ≥ 6 weeks, healing with scarring.
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Behçet disease - persistent oropharyngeal AU, with or without anogenital AU, associated
with systemic findings (eye, nervous system, etc.).
Symptoms. AU can be quite painful, which may impair nutrition → weight loss. At times,
small, painful red macule or papule preceed ulceration.
Small ulcer(s) <1 cm, covered with white-gray fibrin, with sharp, discrete, and at times
erythemo-edematous borders. Most commonly single; at times, multiple or numerous,
shallow, grouped – i.e., herpetiform AU (HAU).
Major AU (> 1cm) may heal with white, depressed scars.
Number of ulcers: Major AU (MaAU), 1-5; MiAU, 1-10; HAU, < 100.
Distribution. Oropharyngeal, anogenital, any site in the GI tract.
General findings. MaAU occasionally with tender regional lymphadenopathy.
Associated disorders.
Behçet disease, acute HIV, AIDS, reactive arthritis, aphthous stomatitis, Crohn disease,
pharyngitic, etc.
Treatment
Topical: intralesional triamcinolone, topical amlexanox 5%, viscous lidocaine 2% only for
control of pain.
Systemic: prednisone, tetracycline or minocycline, thalidomide, TNF-α inhibitors
(adalimumab and infliximab).
Behçet Disease
Etiology
. Idiopathic. Possible T-cell-mediated process in patient with genetic predisposition.
Sometimes HLA-B5 and HLA-B51 association.
Triggering factors: trauma; infections (bacterial, viral); drugs; stress; etc. → systemic
vasculitis.
Third and fourth decades onset. M > F.
Ethnic prevalence - highest in Turkey, Japan, Korea, Southeast Asia, the Middle East,
southern Europe.
Skin and mucous membranes. Recurrent, painful, oral (100%) and genital punched-out
aphthous ulcers. Painful erythema nodosum-like lesions on the arms and legs.
Papulopustular, pustular, acneiform, pseudofolliculitis-type, palpabre purpuric,
inflammatory plaques lesions.
Systemic findings: eyes - anterior and posterior uveitis, iridocyclitis, retinal vasculitis,
vitreitis, hypopyon, secondary cataracts, glaucoma, neovascularization; musculoskeletal -
non-erosive, asymmetric oligoarthritis; neurologic - meningoencephalitis, benign
intracranial hypertension, cranial nerve palsies, brainstem lesions, pyramidal/extrapyramidal
lesions, psychosis; vascular - aneurysm, arterial occlusions, superficial thrombophlebitis,
venous thrombosis, varices, hemoptysis, coronary vasculitis (myocarditis, coronary arteritis,
endocarditis, valvar disease); GI tract - aphthous ulcers throughout.
Pathergy Test.
Upon skin puncture with sterile needle → pustule formation at 24 or 48 h.
Histology.
Ulcerated epidermis or superficial pustule, diffuse neutrophilic infiltrate in dermis ±
vasculitis.
Diagnostic Criteria:
oral ulcers + at least two of the following: recurrent genital ulcers; positive pathergy test;
ocular; vascular; skin lesions.
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Chronic relapsing progressive course with potentially poor prognosis.
Treatment
Aphthous ulcers. Potent topical glucocorticoids, intralesional triamcinolone. Thalidomide,
colchicine or dapsone p.o.
Systemic involvement. Prednisone with or without azathioprine, azathioprine alone,
colchicine, dapsone, cyclophosphamide, chlorambucil, cyclosporine, thalidomide, TNF-α
inhibitors.
BENIGN NEOPLASMS AND HYPERPLASIAS (Nevi; Vascular Tumors;

Miscellaneous Cysts and Pseudocysts; Miscellaneous Benign Neoplasms and
Hyperplasias; Benign Dermal and Subcutaneous Neoplasms and Hyperplasias)
Disorders of Melanocytes
Acquired Nevomelanocytic Nevi (NMN)
Benign, acquired tumors arising as nevus cell clusters at the dermal-epidermal junction
(junctional NMN), invading the papillary dermis (compound NMN), and ending their life
cycle as dermal NMN with nevus cells located exclusively in the dermis where, with
progressive age, there will be fibrosis.
Occur in family clusters. Sun exposure → factor in the induction of nevi. Risk of
melanoma is related to the numbers of NMN and to dysplastic melanocytic nevi (DN)
→ putative precursor of malignant melanoma.
NMN (moles) appear in early childhood and reach a maximum in young adulthood, even
though some NMN may arise in adulthood. Later on there is a gradual involution and
fibrosis of lesions, and most disappear after the age of 60.
NMN are small (<1 cm), acquired, circumscribed pigmented macules, papules, or nodules
with regular,well defined borders.
Distribution: Face, trunk, extremities, scalp.
NMN are asymptomatic. If a lesion persistently itches or is tender - indication of malignant
change → followed carefully or excised.
Treatment.
Indication for removal of acquired melanocytic NMN: lesions on the scalp, mucous
membranes, anogenital area; rapid change in size; color becomes variegated; irregular
borders are present or develop; becomes eroded; begins to persistently itch, hurt, or bleed;
dermoscopy if criteria for melanoma or a dysplastic nevus are present or appear de novo.
If there is an indication for the removal of an NMN → excised for histologic diagnosis and
definitive treatment.
Melanocytic NMN never become malignant because of manipulation or trauma.
Precursors of Cutaneous Melanoma
Precursors of melanoma are benign per se but have the potential of turning to malignant
melanoma: dysplastic melanocytic nevi (NMN) and congenital NMN.
Dysplastic Melanocytic Nevus
Synonym: atypical melanocytic nevus.
DN show some of the features of common NMN and some of SSM, so that they occupy an
intermediary position between these two morphologies.
DN are clinically distinctive from common acquired nevi: usually maculopapular; larger and
more variegated in color, asymmetric in outline, with irregular borders; they also have
characteristic histologic features (atypical melanocytes). There are “fried-egg” and
“targeted” types. DN appear “out of step”, e.g., a mix of large and small, flat and raised, tan
and very dark lesions, whereas common NMN are usually in a roughly comparable stage of
development in a given body region.
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DN arise later in childhood than common acquired NMN (in early childhood). DN continue
to appear throughout life and are believed not to involute; in contrast, common acquired
NMN do not appear after middle age and disappear entirely in older persons. DN are thought
not to undergo spontaneous regression at all or at least much less than common acquired
NMN. Asymptomatic.
Digital dermoscopy permits computerized follow-up of lesions and immediate detection of
any change over time, indicating developing malignancy.
Treatment.
Surgical excision with narrow margins → histopathologic verification.
Patients with DN in the familial melanoma setting need to be followed carefully.
Patients with DN (familial and non-familial) should not sunbathe, use tanning parlours and
always apply sunscreens when outdoors.
Congenital Nevomelanocytic Nevus (CNMN)
CNMN are benign nevomelanocytic neoplasms. All CNMN, regardless of size, may be
precursors of malignant melanoma.
Present at birth (congenital). Some CNMN become visible only after birth (tardive), “fading
in” as a relatively large lesion over a period of weeks.
CNMN may be any size - from very small to large (>20 cm) or very large, light or dark
brown, black, oval or round. Usually distort the skin surface to some degree and are
therefore a plaque with or without coarse terminal dark brown or black hairs (hair growth
has a delayed onset). Sharply demarcated or merging imperceptibly with surrounding skin;
regular or irregular contours. Large lesions may be “wormy” or soft, rarely firm
(desmoplastic type). Skin surface may be smooth or “pebbly”, mamillated, rugose,
cerebriform, bullous, tuberous, or lobular.
Isolated, discrete lesion in any site.
Very large (“giant”) CNMN. Giant CNMN of the head and neck ± involvement of the
leptomeninges - asymptomatic or manifested by seizures, focal neurologic defects, or
obstructive hydrocephalus. Usually a plaque with surface distortion, covering entire
segments of the trunk, extremities, head, or neck.
A papule or nodule arises within CNMN → melanoma.
Treatment.
Surgical excision. Tissue culture and tissue expanders in giant CNMN.
Vascular Tumors (e.g. Hemangiomas, Hemangioma of Infancy (HI) (Formerly

Strawberry, Cherry, Capillary Hemangioma)
Show endothelial hyperplasia.
Hemangioma of infancy are not present at birth but appear postnatally; grow rapidly during
the first year (proliferating phase), undergo slow spontaneous regression during childhood
(involution phase), and remain stable thereafter.
Soft, bright red to deep purple, compressible. On diascopy, does not blanch completely.
Nodule or plaque ± ulceration. Usually solitary and localized or extended over an entire
region. Spontaneous regression with: no residual skin change or atrophy, depigmentation,
telangiectasia, and scarring. Considerable problem during the growth phase is interferance
with vital functions, such as obstruction of vision or of larynx, nose, or mouth.
Treatment.
Each lesion must be judged individually. Pulsed dye laser, cryosurgery, intralesional and
systemic high-dose glucocorticoids, IFN-α, and propranolol.
Pyogenic Granuloma
Pyogenic granuloma is a rapidly developing vascular lesion usually following minor trauma.
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Solitary eroded vascular nodule, which bleeds spontaneously or after minor trauma, smooth
surface, with or without crusts and/or erosion, bright red, dusky red, violaceous, or
brown-black. Occur on the fingers, lips, mouth, trunk, and toes.
Histology.
Lobular aggregates of proliferating capillaries.
DD → MM
Treatment
. Surgical excision or curettage with electrodesiccation at the base.
Miscellaneous Cysts and Pseudocysts

Epidermoid Cyst
Synonyms: Wen, sebaceous cyst, infundibular cyst, epidermal cyst.
Derived from epidermis or the epithelium of the hair follicle. Formed by cystic enclosure of
epithelium within the dermis that becomes filled with keratin and lipid-rich debris.
Dermal-to-subcutaneous nodule, connect with the surface by keratin-filled pores, the content
is keratinaceous material – cream-colored with a pasty consistency and the odor of rancid
cheese. Scrotal lesions may calcify. Usually solitary but may be multiple.
Occurs in young to middle-aged adults on the face, neck, upper trunk, and scrotum.
Trichilemnal Cyst
Synonyms: Pilar cyst, isthmus catagen cyst.
Smooth, firm, dome-shaped, nodules or tumors; lack the central punctum seen in epidermoid
cysts; not connected to the epidermis. The cyst contains keratin - very dense, homogeneous;
often calcified, with cholesterol clefts. Occur on the scalp, and the overlying scalp hair is
usually normal but may be thinned if the cyst is large.
In middle age, more frequently in females. It is often familial and occurs frequently as
multiple lesions.
The cyst wall is usually thick, which allows radical surgical excision.
Milium
1 – to 2-mm, superficial, white to yellow, keratin-containing epidermal cyst, occurring
multiply, located on the eyelids, cheeks, and forehead in pilosebaceous follicles.
Occur at any age, even in infants.
Milia arise either de novo or in association with various dermatoses with subepidermal
bullae or vesicles (pemphigoid, bullous lichen planus, etc.) and skin trauma (dermabrasion,
burns, radiation therapy).
Treatment.
Incision and expression of content.
Miscellaneous Benign Neoplasms and Hyperplasias

Seborrheic Keratosis
Synonym: Verruca seborrhoica.
Benign epithelial tumors, arise in the middle-aged or elderly, varying in extent from a few
scattered lesions to literally hundreds in some elderly patients.
Lesions range from small, barely elevated papules to plaques with a waxy or verrucous
“greasy” surface and a “stuck on” appearance, with or without pigment, round or oval, with
well-defined edges. Isolated or generalized, often multiple. Asymptomatic, rarely pruritic.
Occur on face and trunk. In females - in submammary intertriginous skin.
Dermoscopy:
diagnostic horn cysts.
Histology:
hyperkeratosis, acanthosis of epidermis, papillomatosis, horn pseudocysts, ± increased
melanin in basal layer or throughout entire epidermis.
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Treatment.
Reassurance, cryotherapy, curettage, shave removal, laser treatment. Best - curettage after
slight freezing with cryospray → histopathologic examination.
Benign Dermal and Subcutaneous Neoplasms and Hyperplasias

Lipoma
Benign subcutaneous tumors, single or multiple, soft, rounded, or lobulated and movable
against the overlying skin.
Many lipomas are small but may also enlarge to >6 cm.
Occurs mostly on the neck, trunk, and on the extremities, or anywhere on the body.
Lipomas are composed of fat cells within a connective tissue framework. Angiolipomas
have a vascular component → tender in cold ambient temperature and with compression.
Angiolipomas require excision; other lipomas should be excised only when considered
disfiguring.
Dermatofibroma
Synonyms: Solitary histiocytoma, sclerosing hemangioma, benign fibrous histiocytoma.
Asymptomatic dermal nodule, domed but also sometimes depressed below surrounding skin
(button-like). Surface dull, shiny or scaly. Firm, color variable – skin-colored, pink, brown
or dark chocolate brown; borders ill defined. Dimple sign: lateral compression produces a
“dimple” sign. Rarely tender.
Occurs on the extremities.
Appears gradually over several months, persist without further increase in size for years,
may regress spontaneously.
Treatment not necessary. Excision produces scar, cryosurgery produces a cosmetically more
acceptable scar.
Important only because of its cosmetic appearance or being mistaken for malignant
melanoma when pigmented.
Hypertrophic Scars and Keloids
Hypertrophic scars and keloids are exuberant fibrous repair tissues after a cutaneous injury.
A hypertrophic scar remains confined to the site of original injury.
A keloid extends beyond this site, often with claw-like extensions.
Papules or nodules or large tuberous lesions; color of the normal skin-bright red or bluish;
linear after traumatic or surgical injury, oval or round; firm to hard; smooth surface.
Hypertrophic scars tend to regress, keloids may continue to expand in size.
Distribution. Earlobes, shoulders, upper back, chest.
Usually asymptomatic ± pruritus or pain if touched.
Histology.
Hypertrophic scar → whorls of young fibrous tissue and fibroblasts in haphazard
arrangement. Keloid → features of hypertrophic scar with added feature of thick,
eosinophilic, acellular bands of collagen.
Treatment.
Intralesional glucocorticoids (triamcinolone); silicone cream and silicone gel sheet; surgical
excision with immediate postsurgical radiotherapy.
Skin Tag
Synonyms: Acrochordon, cutaneous papilloma, soft fibroma.
Soft, skin-colored or tan-to-brown, round or oval, pedunculated papilloma vary in size from
>1mm to as large as 10 mm.
More common in females and in obese patients and most often noted in intertriginous areas
(axillae, inframammary, groin) and on the neck and eyelids.
Usually asymptomatic.
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Histology.
Thinned epidermis and a loose fibrous tissue stroma.
Treatment.
Simple snipping with scissors, electrodesiccation, or cryosurgery.
PRECANCEROUS DERMATOSES (Actinic Keratosis; Cutaneous Horn; Squamous

Cell Carcinoma In Situ; Dysplasia and Squamous Cell Carcinoma In Situ;
Keratoacanthoma; Leukoplakia; Erythroleukoplakia)
The most common etiology of NMSC in fair-skinned individuals is sunlight, ultraviolet
radiation (UVR), and human papillomavirus (HPV).
Epithelial precancerous lesions and SCCIS can be classified into: 1. UV-induced: solar
(actinic) keratoses, lichenoid actinic keratoses, Bowenoid actinic keratoses, and Bowen
disease (SCCIS); 2. HPV-induced: low-grade squamous intraepithelial lesions (HSIL) and
Bowenoid papulosis (SCCIS); 3. arsenical-induced: palmoplantar keratoses, Bowenoid
arsenical keratosis; 3. hydrocarbon (tar) keratosis; and 4. thermal keratoses.
Actinic Keratosis
Synonym: Solar keratosis
Etiopathogenesis.
Prolonged and repeated solar exposure in susceptible persons leads to cumulative
keratinocytic damage; most aggressive UVB (290-320 nm) radiation.
Middle age onset. More common in males. Outdoor workers (especially farmers, ranchers,
sailors) and outdoor sportsmen (tennis, golf, mountain climbing, deep-sea fishing).
Sun-exposed areas: face, ears, neck, forearms, and hands (dorsa), shins, and the scalp in bald
males.
Single or multiple, discrete, dry, rough, macules or thin papules with adherent hyperkeratotic
scale, removed with difficulty and pain. Skin-colored, yellow-brown, or brown-“dirty”; like
coarse sandpaper, “better felt than seen” on palpation. Most commonly <1 cm, oval or
round.
Histology:
focal parakeratosis, atypical keratinocytes with nuclear pleomorphism and crowding
(partial-thickness dysplasia), disordered maturation, prominent solar elastosis in the dermis.
Topical Treatment
: cryo- and laser surgery, 5-fluorouracil (5-FU), retinoids, chemical peels (5-10%
trichloroacetic acid), photodynamic therapy (PDT), imiquimod.
Prevention by use of UVB/UVA sunscreens.
Cutaneous Horn (CH)
Appearance of horn with a papular or nodular base. CHs vary in size from a few millimeters
to several centimeters; white, black, or yellowish in color and straight, curved, or spiral in
shape. Arise within areas of dermatoheliosis on the face, ear, dorsum of hands, or forearms,
and shins, also occur upon seborrheic keratoses and warts.
Histology:
hypertrophic actinic keratosis, SCCIS, or invasive SCC at the base.
Treatment:
excised.
Squamous Cell Carcinoma In Situ (SCCIS)
Etiology.
UVR, HPV infection, arsenic, tar, chronic heat exposure, and chronic radiation dermatitis.
Arises in epithelial dysplastic lesions such as solar keratoses or HPV-induced squamous
epithelial lesions. Untreated SSCIS progress to invasive SCC. Nodule formation or onset of
pain or tenderness within SCCIS suggests progression to invasive SCC.
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Clinical Manifestations:
Bowen disease - sharply demarcated, scaling, or hyperkeratotic macule, papule, or
plaque, pink or red, slightly scaling surface or erosions. Solitary or multiple. Often in
sun-exposed sites or mucous membrane; on sun-protected sites presenting as a pigmented
plaque; predilection for lower limbs in women and ear/scalp in men.
Erythroplasia of Queyrat - red, sharply demarcated, non-scaly, glistening macular
or plaque-like SCCIS on the glans penis or labia minora.
Bowenoid papulosis - anogenital HPV-induced SCCIS, red, tan, brown, or black,
eroded lesions ± areas of crusting.
Bowen carcinoma - SCCIS large lesions with annular or polycyclic borders, nodular
lesions appear within the plaque.
Histology.
Carcinoma in situ with loss of epidermal architecture and regular differentiation;
keratinocyte polymorphism, single cell dyskeratosis, increased mitotic rate, and multinuclear
cells.
Treatment. Topical chemotherapy with 5-FU and with imiquimod; cryo- and lasersurgery;
PDT; surgical excision, including Mohs micrographic surgery.
Dysplasia and Squamous Cell Carcinoma In Situ (SCCIS)
Etiology.
Tobacco-related habits [smoking moist snuff, pan (betel nut)]; HPV.
Risk Factors.
Tobacco use, alcohol use, oral lichen planus.
Chronic, ± solitary patch/plaque on oropharyngeal mucosa. ± reddish velvety appearance
with either stippled or patchy regions of leukoplakia; ± smooth patch with minimal or no
leukoplakia; usually <2 cm.
Location. Floor of mouth (men), tongue and buccal surface (women).
Course. Most dysplasias do not progress to invasive SCC.
Biopsy all lesions without definitive diagnosis that persist for >3 weeks!
Keratoacanthoma
Keratoacanthoma (KA) is considered as a pseudocancer, but regarded by most as a variant of
SCC.
Etiology.
HPV, UVR and chemical carcinogens (pitch, tar).
Over 40 years onset. M : F 2:1.
Rapidly growing epithelial tumor with potential for tissue destruction and (rare) metastasis;
in most cases spontaneous regression. A dome-shaped nodule with central keratotic plug.
Firm but not hard. Skin-colored, slightly red, brown. Removal of keratotic plaque results in
a crater. Usually isolated but may be multiple. Predilection for sun-exposed sites.
Histology.
Not always possible to rule out highly differentiated SCC.
Treatment.
Excision.
Leukoplakia
Chronic white plaque/lesion in the oropharynx that cannot be wiped off and cannot be
diagnosed as any other distinct lesion. May be premalignant or malignant.
Histology.
Premalignant leukoplakia → atypic cells. Severity linked to duration and quantity of
tobacco and alcohol use.
Location.
Lip, tongue, floor of mouth.
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Erythroleukoplakia (Speckled Leukoplakia)
has the highest rate of malignant transformation.
Persistent fixed erythematous plaque in the mouth.
Histology.
Dysplasia, carcinoma in situ or invasive carcinoma.
MALIGNANT SKIN TUMORS

Basal Cell Carcinoma (BCC)
Most common cancer of the epidermal keratinocytes.
Older than 40 years onset. M > F.
Etiology.
UVR, PTCH gene mutation in many cases.
Predisposing Factors.
Skin phototypes I/II and albinos with prolonged sun exposure, history of frequent or severe
sunburn in childhood, previous therapy with X-rays.
Distribution. >90% occur in the face.
Locally invasive, aggressive, and destructive but slowly-growing, usually asymptomatic,
erosion or bleeding with minimal trauma may be first symptom, anecdotally metastasizes.
Five clinical types BCC: nodular (most common), ulcerating, pigmented, sclerosing
(cicatricial, morphoeic), and superficial (plaque-like).
Nodular BCC: most common; translucent or “pearly” papule or nodule;
skin-colored or reddish, well-defined, firm, smooth surface with telangiectasias, ±
ulceration, ± pigment. Over time borders often become rolled and pearly with central
ulceration (“rodent ulcer”).
Ulcerating BCC: ulcer (often covered with a crust) with a rolled border (rodent
ulcer), which again is translucent, pearly, smooth with telangiectasia, and firm.
Sclerosing (cicatricial, morphoeic) BCC: indurated firm plaque with ill-defined
borders resembling morphea or a superficial scar, skin-colored, whitish but also with
peppery pigmentation, aggressive growth pattern.
Superficial (plaque-like) multicentric BCCs: pink or red thin plaques with pearly
border and telangiectasias, ± scale, ± pigment, commonly seen on trunk or limb. This is the
only form of BCC that can exhibit a considerable amount of scaling.
Pigmented BCC: may be brown to blue or black, smooth, hard, glistening surface,
sometimes cystic with depressed center (“umbilicated”).
Histology.
Proliferating atypical basal cells with little anaplasia and infrequent mitoses, palisading
arrangement at periphery, variable amounts of mucous stroma.
Treatment
Surgical excision with primary closure, skin flaps, or grafts. Mohs surgery (microscopically
controlled surgery).
Topical treatments. Radiotherapy (40Gy) when surgery is not appropriate or in very old age.
For small and low-risk lesions - cryosurgery; electrocautery with curettage; PDT; topical
destruction with 5-FU, Imiquimod, TCA or Solcoderm. For multiple Ca – aromatic retinoids
(etretinate, isotretinoin). For advanced Ca - intralesional α-interferon (roferon-A, intron-A),
targeted therapy with Hedgehog pathway inhibitors such as Vismodegib.
Prevention.
Photoprotection. Avoidance of artificial UV exposure → tanning devices.
Squamous Cell Carcinoma (SCC)
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Second most common type of epithelial skin tumors. Often presents as erythematous
keratotic papule, plaque or nodule, typically in sun-exposed areas. Risk for metastasis.
Causes.
Risk factors include excessive and chronic UV exposure or ionization, pre-malignant skin
conditions (e.g. actinic keratoses), chronic dermatoses (tuberculosis, syphilis, lepra, lupus
erythematosus chronicus discoides, chronic radiation dermatitis, and lichen planus of oral
mucosa), genodermatoses (albinism, etc.), chronic inflammation (e.g. leg ulcers, wound
scars), HPV infections, immunosuppression and genetic predisposition.
Age of onset. Older than 55 years of age, in areas that have many days of sunshine annually
(Australia, New Zealand and southwestern United States) - in their twenties and thirties. M
> F.
Persons working outdoors - farmers, sailors, lifeguards, etc.
Two types SCCs:
Differentiated SCCs, which always show signs of keratinization either within or on
the surface (hyperkeratosis) of the tumor. These are firm and hard upon palpation. Present as
indurated papule, plaque, or nodule; adherent thick keratotic scale or hyperkeratosis; when
eroded or ulcerated may have a crust in the center and a firm, hyperkeratotic, elevated
margin. Horny material may be expressed from the margin or the center of the lesion.
Erythematous, yellowish, skin color; polygonal, oval, round, or umbilicated and ulcerated.
Usually isolated but may be multiple. Usually exposed areas. Sun-induced keratotic and/or
ulcerated lesions especially on the bald scalp, cheeks, nose, lower lips, ears, preauricular
area, dorsa of the hands, forearms, trunk, and shins (females). The majority of UVR-induced
lesions are differentiated and have a low rate of metastasis;
Undifferentiated SCCs, which do not show signs of keratinization and clinically
appear fleshy, granulomatous, and soft on palpation. Fleshy, granulating, easily vulnerable,
erosive papules and nodules, and papillomatous vegetations. Bleeds easily, often forms a
hemorrhagic crust. Solitary or multiple, particularly on the genitalia, trunk, lower
extremities, or face. Undifferentiated SCC and SCC in immunosuppressed individuals are
more aggressive with a greater incidence of metastasis.
Histology
. Atypical keratinocytes invasion into the epidermis and dermis. Keratin/corneal pearls
(concentric layers of keratinocytes, keratinizing towards the center).
More rapid growth than BCC. Local tissue destruction. Potential for metastases to regional
lymph nodes.
Treatment.
Surgical excision with primary closure, skin flaps, or grafting. Mohs micrographic surgery
for ill-defined, large, recurrent tumours. Radiotherapy for large, non-resectable tumours.
Cutaneous Melanoma. Lentigo Maligna

Cutaneous Melanoma
Aggressive tumor resulting from melanocytes and affecting younger population (peak age
20–45 y).
Etiology and Pathogenesis -
unknown.
Risk Factors:
genetic markers (CDKN2a, BRAF, MC1R); skin phototypes I/II; family history of
dysplastic nevi or melanoma; personal history of melanoma; ultraviolet irradiation,
particularly sunburns during childhood and intermittent burning exposures; number (>50)
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and size (>5mm) of melanocytic nevi; congenital nevi; number of dysplastic melanocytic
nevi (>5); dysplastic melanocytic nevus syndrome.
Six signs of malignant melanoma (The “ABCDESymptoms′ Rule”- major suspicious
features):
Asymmetrical shape*
Border irregularity
Colour irregularity
Diameter >6mm
Evolution of lesion (e.g. change in size and/or shape)*
Symptoms (e.g. bleeding, itching)
Common sites - legs in women and trunk in men.
Clinical Presentations of Melanoma
Four major types of melanoma:
Superficial spreading melanoma: most common (70% in white population);
presents as darkly pigmented macule or thin plaque, ± notched border, varying shades of
brown, possible areas of regression; most common site is back (men) and lower legs
(women), grows - months to years.
Nodular melanoma: second most common type in light-skinned patients, darkly
blue or blue-black pigmented papule or nodule with rapid progression - weeks to a few
months; any site - trunk, head, neck.
Lentigo maligna melanoma: least common; evolves from lentigo maligna, often in
sun-exposed areas (head, neck, forearms) in older age group; presents as hyperpigmented
patch with varying shades of brown, irregular border; slow growth – years.
Acral lentiginous melanoma: most common type seen in darker-skinned older
males (≥60 years); presents as hyperpigmented patch with varying shades of brown or black
and irregular borders; site – palms, soles, subungual; grows slowly over months to years.
Amelanotic melanoma. All types of melanoma can be amelanotic → diagnostic challenge. In
most cases, only biopsy will reveal the correct diagnosis.
Staging of Melanoma
. Staging of melanoma depends on its TNM classification (primary Tumor, regional Nodes,
Metastases) and is strongly correlated with survival.
Dermoscopy increases diagnostic accuracy by more 50%.
Histology.
Atypical malignant melanocytes occur singly and in nests into epidermis, dermis and
beyond (expand into the deeper tissues).
Treatment
Basically early surgical treatment. Wide excision with split skin grafting ± sentinel lymph
node biopsy (sentinel lymph node - the first node draining a lymphatic basin predicts the
presence of clinically non-detectable metastatic melanoma within regional lymph nodes).
Adjuvant therapy: interferon-α-2b, interleukin-2.
Management of distant metastases: chemotherapy (dacarbazine/temozolomide, cisplatin,
vinblastine, etc.); chemoimmunotherapy; melanoma vaccination, radiotherapy, targeted
therapy.
Prevention:
regular follow-up; early detection and surgical excision of the suspicious pigmented lesions;
avoidance of sun exposure and burning.
Lentigo Maligna
Uniformly flat macule, 0.5 cm or larger, up to 20 cm. Usually well-defined, in some areas
with blurred or highly irregular borders. Early lesions tan, advanced lesions: striking
variations in hues of brown and black (speckled), appears like a “stain”; haphazard network
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of black on a background of brown. No hues of red and blue. Single isolated lesion on the
sun exposed areas.
Histology.
Increased numbers of atypical melanocytes distributed in a single layer along the basal layer
and above the basement membrane of an epidermis that shows elongation of rete ridges.
Atypical melanocytes are usually singly dispersed but may also aggregate to small nests and
extend into the hair follicles, reaching the middermis, even in the preinvasive stage of LM.
In LMM, they invade the dermis (vertical growth phase) and expand into the deeper tissues.
Treatment.
Very early LM lesions – imiquimod. Excise with 1 cm beyond the clinically
visible lesion. Sentinel node to be done in lesions >1.0 mm in terms of thickness.
INFECTIOUS DISEASES
Viral Infections (Human Herpesviruses Diseases; Human Papillomavirus Infections;
Poxvirus Diseases)
Human Herpesviruses (HHV) Diseases
Herpes Simplex Virus Disease
Etiology.
Herpes simplex virus 1 and 2 (HHV1, HHV2).
Neurotropic virus which hides in the dorsal root ganglion until reactivation.
HSV-1 associated with orolabial herpes, HSV-2 with genital herpes.
Pathogenesis.
Primary HSV infection occurs through close contact with person shedding virus at a
peripheral site, mucosal surface, or secretion.
Transmission occurs via inoculation onto susceptible mucosal surface or non-intact skin.
Primary Infections:
Primary herpetic gingivostomatitis: typically in children; presents with abrupt
onset of striking gingivitis (erythematous, friable gingiva); painful vesicles, clustered on oral
mucosa, tongue, lips, and/or perioral skin → vesicles rupture, leaving small ulcers with
characteristic gray base; ± pharyngitis, tonsillitis, difficult to eat and swallow, ± regional
lymphadenopathy, ± systemic symptoms (fever, headache, malaise, anorexia, myalgia).
Primary genital infection: more severe and prolonged than recurrent infection,
presents with constitutional symptoms and painful grouped vesicles in genitalia → progress
to pustules, crusting and exquisitely tender ulcers, ± painful lymphadenopathy, cervicitis,
urethritis, proctitis.
Recurrent Infections
Factors for Recurrence:
skin/mucosal irritation - ultraviolet (UV) radiation, menstruation, fever, common cold,
altered immune states; site of infection (genital herpes recurs more frequently than labial);
host defense defections - HIV disease, malignancy (leukemia/lymphoma), transplantation
(bone marrow, solid organ), chemotherapy, systemic glucocorticoids, other
immunosuppressive drugs, and radiotherapy.
Pathogenesis.
After primary infection at inoculation site, HSV ascends peripheral sensory nerves and
enters sensory or autonomic nerve root (vagal) ganglia, where latency is established.
Periodically, HSV may reactivate from its latent state → virus particles travel along sensory
neurons to skin and mucosal sites to cause recurrent disease episodes.
Herpes labialis: most common HSV-1 manifestation triggered by pyrexia, stress,
sunburn, and/or trauma; prodrome (pain, burning, itching, tingling) precede the eruption at
24 hours; grouped vesicles on erythematous base which typically evolve into pustules like
lesions and then erosions and crusts, often involving vermilion border.
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Genital herpes: ± prodrome followed by grouped vesicles → pustules like lesions
→ erosions.
Systemic symptoms usually absent.
Other Types of Infections:
Eczema herpeticum (Kaposi varicelliform eruption): HSV-1>HSV-2; rare
disseminated form of HSV, mainly seen with atopic dermatitis; common sites - face, neck,
and trunk; more common in children. Presents as monomorphic umbilicated
vesiculo-pustules or punched out ulcerations with hemorrhagic crust; lesions are not grouped
but disseminated within the dermatosis → later spread to normal-appearing skin. ± fever,
malaise, irritability, regional lymphadenopathy. May progress to life-threatening infection.
Recurrent episodes tend to be milder ant not associated with systemic symptoms. Common
secondary infection with S. aureus.
Herpes-associated erythema multiforme (HAEM): self-limited eruption,
associated with HSV infection; presents with typical concentric target plaques; begins on
extremities and spreads centripetally, ± mucosal involvement, ± regional lymphadenopathy.
Disseminated herpes simplex infection: prematurely born, kids (6 month up to 3
years), adults with host defence defects (immunosuppression, HIV, leukemia/lymphoma,
autoimmune diseases, bone marrow transplantation, malnutrition). Disseminated infection ±
vesicles, erosions, ulcers. Life-threatening complications – pneumonitis, encephalitis,
destruction of the adrenal glands, hepatitis, urinary retention, disseminated intravascular
coagulation, etc.
Complications in pregnant women with herpes simplex: abortion, preliminary delivery,
intrauterine or neonatal herpes fetal anomalies (microcephaly, microphthalmus, encephalitis,
meningitis → mental retardation, paralysis, intracerebral calcifications, chorioretinitis,
hepatitis, pneumonia, skin, mouth, and eye lesions, multiorgan failure → death. Sectio
Caesarea necessary!
Neonatal herpes simplex. Risk factors for neonatal HSV infection: primary genital herpes in
mother at time of delivery, absent maternal anti-HSV antibody, procedures on fetus, father
with HSV infection. HSV-2 > HSV-1, HSV-1 more virulent in the newborn and associated
with higher morbidity and mortality.
Transmission - in utero, intrapartum, postnatal acquisition.
- vesicles and erosions on skin, eyes, mouth.
Tzanck smear shows acantholytic keratinocytes or multinucleated giant acantholytic
keratinocytes, does not differentiate between HSV and VZV.
Viral culture or direct fluorescent antibody (DFA) → detect and differentiate HSV antigens
on smear from lesion.
Histology
shows keratinocyte edema causing ballooning degeneration and acantholysis, intranuclear
inclusion bodies, and dense inflammatory infiltrate ± epidermal/adnexal necrosis.
Treatment
Spontaneous resorption.
Topical antiviral therapy. Acyclovir, Penciclovir.
Oral antiviral therapy. Acyclovir, valacyclovir, and famciclovir → in severe and in recurrent
cases.
Recurrences → continuous oral maintenance therapy.
Prevention.
Avoid skin-to-skin contact during outbreaks. Avoid contact with patients, who have atopic
eczema and with immunosupressed.
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Varicella Zoster Virus Disease (HHV3, VZV, Herpes Zoster, Shingles)
Etiology
. VZV, a herpesvirus type 3.
Primary VZV infection → varicella or chicken pox characterized by disseminated pruritic
polymorphic lesions. During primary infection, VZV establishes lifelong infection in
sensory ganglia. When immunity to VZV declines, VZV reactivates within the nerve cell,
traveling down the neuron to the skin, where it erupts in a dermatomal pattern, i.e., HZ or
shingles.
With host defence defects, primary and reactivated VZV infections is often more severe,
associated with higher morbidity rates and some mortality.
VZV vaccine has reduced the incidence of varicella and HZ.
Transmission.
Airborne droplets and direct contact. Patients are contagious several days before varicella
exanthema appears and until last crop of vesicles. Crusts are not infectious. VZV can be
aerosolized from skin of persons with HZ, causing varicella in susceptible contacts.
Herpes zoster manifests in three distinct clinical stages: (1) prodrome, (2) active infection,
and (3) post-herpetic neuralgia.
Prodrome. Pain, tenderness, paresthesia in the involved dermatome. Pain can mimic angina,
migraine, cardiac or pleural disease, or acute abdomen, or vertebral disease. Allodynia:
heightened sensitivity to mild stimuli. Zoster sine herpete - nerve involvement without
cutaneous zoster. ± Flu-like constutional symptoms during prodrome and active infection.
Dermatomal lesions. Grouped, painful erythematous macules/papules on erythematous,
edematous base (24 hours) → vesicles/bullae (48 hours) → pustules like lesions (96 hours)
→ crusts (7-10 days). New lesions continue to appear for up to 1 week. Lesions are
infectious until dry. Crusting usually resolves in 2-4 weeks.
Distribution.
Unilateral, along single sensory dermatome (don’t cross midline).
Site of predilection. Thoracic (>50%), trigeminal, lumbosacral, and cervical.
Mucous membranes. Vesicles and erosions occur in mouth, vagina, and bladder, depending
on dermatome involved.
± Regional lymphadenopathy.
Sensory or motor nerve changes. Detectable by neurologic examination. Sensory defects
(temperature, pain, touch) and (mild) motor paralysis, e.g., facial palsy.
Ophthalmic Zoster.
Nasociliary involvement of V-1 (ophthalmic) branch of the trigeminal nerve,
heralded by vesicles on the side and tip of the nose. Complications include uveitis, keratitis,
conjunctivitis, retinitis, optic neuritis, glaucoma, proptosis, cicatricial lid retraction, and
extraocular muscle palsies. Delayed contralateral hemiparesis → headache and hemiplegia
in a patient with recent history of HZ ophthalmicus.
Ramsay–Hunt Syndrome.
Infection of geniculate ganglion (VIIIth – n. oticus) - ear canal/auricle/tympanic
membrane involvement with painful vesicles, facial paralysis/paresis, ipsilateral hearing
loss. Pain, tinnitus, headache, vertigo, vomitus, deafness.
Oral Herpes Zoster.
Unilateral grouped vesicles in the mucous membranes and on the skin in trigeminal
nerve involvement.
Disseminated zoster in AIDS and in immunocompromised patients: ≥20 lesions
outside the affected or adjacent dermatomes, may cross midline, may present with verrucous
or crusted lesions.
Complications:
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postherpetic neuralgia (PHN) – constant, severe, stabbing or burning, dysesthetic pain,
persist for months or years, especially in elderly; scarring; secondary bacterial infection.
Other neurological complications: meningoencephalitis, cerebral vascular syndromes,
cranial nerve syndromes [trigeminal (ophthalmic) branch (HZ ophthalmicus → ocular
blindness), facial and auditory nerves (Ramsay Hunt syndrome → deafness)], peripheral
motor weakness, motor paralysis and transverse myelitis.
Visceral complications: pneumonitis, hepatitis, pericarditis/myocarditis, pancreatitis,
esophagitis, enterocolitis, cystitis, synovitis, encephalitis.
Histopathology:
balloon degeneration.
Treatment
Antiviral best 48–72 h within appearance of rash (can ↓ PHN risk). Oral famciclovir,
valaciclovir or acyclovir for 7 days. Mildly immunocompromised patients → for up to 10
days. Severely immunocompromised patients → acyclovir i.v. for 7-10 days.
Supportive therapy. Bed rest, sedation, pain management with narcotic analgesics; moist
dressings.
Postherpetic neuralgia. Gabapentin, pregabalin, tricyclic antidepressants, i.e., doxepin,
capcaicin cream topically. Nerve block.
Prevention.
Vaccination against VZV with a live attenuated vaccine reduces the burden of illness and
incidence of zoster.
Human Papillomavirus Infections

Etiology.
Papillomaviruses - viruses of Papovavirus class, non-enveloped double-stranded DNA
viruses; more than 100 different HPV types; infects squamous epithelia of skin and mucous
membranes.
Transmission mainly via direct skin contact, less likely via fomites; basal keratinocytes are
target of HPV (long-term reservoir of viral DNA).
May cause non-genital or genital infections; divided into low risk (HPV 6/11) and high risk
(HPV 16/18) types.
Clinical Manifestations of HPV Infection:
Common, Plantar, and Flat Warts (Verruca Vulgaris, Plantaris, and Plana)
Condyloma Acuminata
Common Wart (Verruca Vulgaris)
Incubation period – from 4 weeks to months. Common in children. Firm papules, 1-10 mm
or larger, hyperkeratotic, clefted surface, with vegetations. Isolated lesion, scattered discrete
lesions. Occur at sites of trauma (Koebner phenomenon): hands, fingers, and knees. The
periungual warts are painful. Palmar lesions disrupt the normal line of fingerprints.
Characteristic “red or brown dots” are pathognomonomic, representing thrombosed dermal
papilla capillary loops.
Plantar Warts (Verruca Plantaris)
Risk groups – children, athletes, sportsmen. In the beginning: small, shiny,
sharply-demarkated papule. Later: plaque with rough hyperkeratotic surface, studded with
brown-black dots (thrombosed capillaries). As with palmar warts, normal dermatoglyphics
are disrupted. Warts heal without scarring. Endophytic growth due to constant pressure and
friction on the soles → enormous pain.
Flat Warts (Verruca Plana)
Often – children and adolescent. Sharply defined, flat papules (1-5 mm); “flat” surface; the
thickness of the lesion is 1-2 mm. Skin-colored or light brown. Round, oval, polygonal,
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linear lesions (inoculation of virus by scratching). Occur on face, beard area, dorsa of hands,
and shins.
Histology.
Papillomatosis, massive orthokeratosis, columns of parakeratosis, coarse keratohyalin
granules of variable size, vacuolated cells (koilocytes), dilated and thrombosed capillaries.
Treatment
Topical: 10-20% salicylic acid and lactic acid in collodion, imiquimod cream, podophyllin
25-50%, formalin 3-6%, azelaic acid, vitamin A acid, hyperthermia, cryosurgery,
electrosurgery, CO2 laser surgery, surgical excision.
Systemic: immunomodulators.
Spontaneous resolution in months or a few years.
Condyloma Acuminata - Genital Warts → Sexually Transmitted Disease
Mucosal human papilloma virus (HPV) infections are the most common sexually
transmitted infection (STIs).
Etiology.
More than 20 serotypes; most common HPV 6, HPV 11.
Transmission. Sexually transmitted, young men and women. Children – intrauterine, during
delivery or after sex abuse.
Localization – anogenital and rectal in MSM, oral mucosa, external genitalia, perineum,
cervix, oropharynx.
Usually asymptomatic.
Four clinical types: small papular; condyloma acuminatum - cauliflower-floret (acuminate or
pointed) lesions; keratotic warts; flat-topped papules/plaques (most common on cervix).
Skin-colored, pink, red, tan or brown. Solitary, scattered, or forming voluminous confluent
masses with deep crypts. In immunocompromised individuals, lesions may be huge.
Pap smear. Detection of HPV DNA.
Serological screening for other venereal diseases (syphilis, HIV/AIDS, etc.) is necessary.
Treatment
Topical: imiquimod 5% cream, podophyllin 10-25%, trichloroacetic acid 80-90%,
intralesional bleomycin, cryosurgery, electrodesiccation, CO2 laser, surgical excision.
Systemic: immunomodulators.
Prevention.
Use of condoms reduces transmission. HPV vaccine protects against four strains of HPV (6,
11, 16, 18).
Poxvirus Diseases
Molluscum Contagiosum
Etiology.
Molluscum contagiosum virus → Poxvirus family. Transmitted by skin-to-skin contact.
More common in children and sexually active adults. M > F.
Papules, nodules, tumors with central umbilication or depression (helpful diagnostic sign).
Skin-colored or pink/reddish. Round, oval, hemispherical. Isolated single lesion; multiple,
scattered discrete lesions; or confluent mosaic plaques. Larger mollusca may have a central
keratotic plug, which gives the lesion a central dimple or umbilication.
Distribution. Any site of skin and mucosal membranes may be infected. Autoinoculation
spreads lesions. Mollusca may be widespread in areas of atopic dermatitis.
Histology.
Molluscum bodies (intracytoplasmic inclusion bodies → histological hallmark).
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Treatment
Curettage → iodine tincture, catharidin, imiquimod 5% cream, trichloroacetic acid,
cryosurgery, electrodessication.
Orf (Contagious Pustular Dermatosis, Ecthyma Contagiosum)

Etiology.
Parapox → Orf virus
One to few papules at contact site with infected goat/sheep, ± fever, lymphadenitis.
Clinical types: maculopapular, targetoid, papillomatous.
Mainly in shepherds, veterinarians, goat herders, and butchers.
Treatment.
Supportive treatment.
Self-limited disease.
Bacterial Infections (Pyococcal Infections; Mycobacterial Infections; Spirochetal

Infection)
Pyococcal Infections
Gram-Positive Infections (Staphylococcal Infections; Streptococcal Infections)
Staphylococcal Infections
Skin and soft-tissue infections, commonly caused by Staphylococcus aureus and group A
Streptococcus (GAS) → referred to a “pyoderma”.
S. aureus colonizes the nares and intertriginous skin intermittently, can penetrate the stratum
corneum, and cause skin infections, e.g., impetigo, folliculitis. Deeper infection results in
soft-tissue infections. Methicillin-resistant S. aureus (MRSA) is an important pathogen for
community-acquired (CA-MRSA) and health-care-acquired (HA-MRSA) infections.
S. aureus: aerobic, gram-positive catalase-positive bacteria, arranged in clusters.
Best defense: intact skin.
S. aureus toxins: Toxic shock syndrome toxin-1 (TSST-1) - superantigen, involved in toxic
shock syndrome (TSS); Exfoliative toxin (ET-A, ET-B) - protease activity, splits epidermal
desmoglein 1, involved in staphylococcal scalded skin syndrome (SSSS) and bullous
impetigo; Panton–Valentine leukocidin (PVL) - in many community-acquired MRSA
strains, associated with ↑ virulence.
Impetigo
Highly contagious infection, primarily in children.
Facial lesions associated with S. aureus colonization of nares.
Two types: nonbullous and bullous.
Nonbullous: S. aureus most common cause, less common Gr. A strep (GAS).
Erythematous macule → pustule/vesicle → erosion with golden-yellow crust (+ culture from
exudate under crust).
Bullous: only S. aureus.
Flaccid, transparent bullae → rupture leaving shiny, dry erosion with no surrounding
erythema, ± fever, diarrhea, weakness.
Often asymptomatic ± itch → satellite lesions by autoinoculation.
Cleavage at granular layer due to ET (A/B) binding to desmoglein 1. S. aureus at site of
lesion.
Treatment
with topical mupirocin, if extensive → oral antibiotic (i.e., cephalexin, dicloxacillin, etc.).
Prevention.
Benzoyl peroxide wash. Check family members for signs of impetigo, eliminate S. aureus
from the nares (Mupirocin). Ethanol or isopropyl gel for hands and/or involved sites.
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Staphylococcal Scalded Skin Syndrome (SSSS)
Exfoliative disease mainly in neonates and young children; can occur in adults with renal
insufficiency or if immunocompromised (mortality > 50%).
Presents with fever, conjunctivitis, initial tenderness of skin and erythema over body folds
→ a scald-like skin appearance is followed by large flaccid bulla → generalized wrinkled
appearance with subsequent exfoliation (“sad man” facies), perioral crusting/fissuring,
positive Nikolsky sign. Severe pain.
S. aureus phage II present at a distant site (extralesional): ET (A/B) - binds desmoglein 1 in
granular layer causing superficial bulla.
Culture of bullae - negative (infection at remote site).
Treatment.
Penicillinase-resistant penicillins, fusidic acid, or cephalosporins, i.v. fluid support and
analgesia.
Bacterial Folliculitis
Superficial infection of hair follicle, due to S. aureus.
Predisposing Factors
: shaving hairy regions such as the beard area, axillae, or legs facilitates follicular infection;
extraction of hair such as plucking or waxing; topical glucocorticoid preparations; diabetes
mellitus; immunosuppression.
Presents with pustules in follicular distribution, associated with hairs.
Can be either superficial folliculitis (infundibular) or deep (sycosis) (extension beneath
infundibulum) with abscess or furuncle formation. Superficial infection heals without
scarring.
Distribution:
face, beard (sycosis barbae), scalp, neck, legs, trunk, buttocks.
Non-tender or slightly tender ± pruritus.
In cases of chronic relapsing folliculitis → culture nares and perianal region for S. aureus
carriage.
Treatment.
Antibacterial wash (chlorhexidine or triclosan), antibacterial ointments (mupirocin, if
widespread + oral antibiotic.
Prophylaxis
. Correct underlying predisposing condition. Washing with antibacterial soap or benzoyl
peroxide preparation or isopropyl/ethanol gel.
Furuncle, Carbuncle, Abscess
Typically due to S . aureus (MSSA, MRSA).
Depth of infection determines presentation.
Furuncle: deep-seated red, hot, tender nodule of hair follicle → fluctuant, with
abscess formation ± central pustule → scar; distribution - any hair-bearing region; solitary or
multiple lesions. Recurrent furunculosis in diabetics and immunocompromised.
Carbuncle: coalescing of adjacent furuncles with multiple draining sinuses
(typically involves nape of neck or back of thighs).
Abscess: inflamed walled-off collection of pus; a tender red nodule → pus collects
within a central space → fluctuance of the central portion of the lesion.
Symptoms.
Folliculitis ± slightly tender. Deep infection + pain and tenderness. Carbuncles ± low-grade
fever and malaise.
Treatment
Simple furuncle (no fluctuance): warm compresses.
Fluctuant furuncle or abscess: incision and drainage.
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Oral antibiotics if: located near midface (due to concern for cavernous sinus thrombosis) or
external auditory canal; recurrent or recalcitrant; very large or with surrounding cellulitis.
Carbuncle: incision and drainage plus systemic antimicrobial therapy.
Streptococcal Infections
GAS usually colonizes the skin first and then the nasopharynx. Group B streptococcus
(GBS; Streptococcus agalactiae) and group G β-hemolytic streptococci (GGS) colonize the
perineum of some individuals → cause superficial and invasive infections.
Gram-positive bacteria arranged in chains or pairs.
Most pathogenic → group A β-hemolytic streptococci (S. pyogenes, GAS ).
Positive antibodies after infection with GAS: antistreptolysin O (ASO), antihyaluronidase,
and anti-DNase-B.
Certain strains with erythrogenic toxins: S. pyogenes exotoxins (SPE-A, SPE-B, SPE-C).
Infectious intertrigo
β-hemolytic streptococci group A, B or G.
Inflammation of opposed skin (inflamammary regions, axillae, groins, gluteal folds,
redundant skin folds of obese persons).
Usually asymptomatic. Discomfort indicates infection rather than colonization.
Treatment.
Antibacterial wash (chlorhexidine or triclosan), antibacterial creams/ointments, if
widespread + oral antibiotic.
Prophylaxis.
Correct underlying predisposing condition, washing with antibacterial soap or benzoyl
peroxide preparation or isopropyl/ethanol gel.
Erysipelas and Cellulitis
Pathogens gain entry via any break in the skin or mucosa. Tinea pedis and leg and foot
ulcers are common portals.
Distribution.
Lower leg most common site in adults. Arm: in young male, consider i.v. drug use; in
female, postmastectomy. Trunk: operative wound site. Face: following rhinitis,
conjunctivitis, pharyngitis; associated with colonization of nares by S. aureus and of pharynx
by GAS.
Risk Factors.
Host defense defects, diabetes mellitus, drug and alcohol abuse, cancer and cancer
chemotherapy, immunosuppression, chronic lymphedema (postmastectomy, previous
episode of erysipelas/cellulitis), wounds, leg ulcers, toeweb intertrigo, and minor skin injury.
Local signs of inflammation – swelling (tumor), erythema (rubor), warmth (calor), pain
(dolor), functio laesa.
Erysipelas (St. Anthony’s Fire)
Superficial type of cellulitis involves the dermis and upper subcutaneous tissue with
significant dermal lymphatic involvement due to GAS.
Presents as a well-defined, bright red indurated plaque with sharp, raised borders commonly
on the face or legs, ± constitutional symptoms.
Lymphadenitis ± lymphangitis.
Complications.
Local necrosis, abscess and septicaemia.
Treatment of Choice.
PCN (if PCN-allergic can use macrolide).
Supportive care including rest, leg elevation, sterile dressings and analgesia.
Prophylaxis:
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depot-penicillin.
Cellulitis
Infection of the dermis and deep subcutaneous tissue, mostly due to GAS (S. aureus less
common).
Presents as an ill-defined area with erythema, swelling, and tenderness, ± fever, chills.
Lymphadenitis ± lymphangitis.
Complications
as in erysipelas.
Treatment.
Antibiotics with good Gram-positive coverage.
Supportive care as in erysipelas.
Necrotizing Fasciitis
Rapidly progressive necrosis of subcutaneous tissue and fascia due to GAS, but typically
mixed infection (anaerobic and aerobic bacteria) with mortality up to 75%.
Risk factors include advanced age, diabetes, peripheral vascular disease, and/or history of
alcohol abuse.
When skin necrosis is not obvious, diagnosis must be suspected if there are signs of severe
sepsis and/or some of the following local symptoms/signs: severe spontaneous pain;
indurated edema; bullae; cyanosis; skin pallor; skin hyperesthesia; crepitation; muscle
weakness; foul smelling exudates.
Presents as tender, erythematous tense plaque, recalcitrant to antibiotics, which progresses
at an alarming rate → necrosis of fascia and fat renders watery foul-smelling fluid →
involved soft tissue becomes dusky blue in color + vesicles or bullae.
Severe pain → anesthetic. Prominent fever and other constitutional symptoms. Presence of
crepitus (subcutaneous emphysema). X-ray may show soft tissue gas (absence should not
exclude the diagnosis).
Treatment.
Urgent extensive surgical debridement in combination with high-dose intravenous
antibiotics.
Ecthyma
Deeper form of non-bullous impetigo with ulceration due to GAS but quickly contaminated
by S. aureus.
Presents as “punched out” shallow ulcer with thick, yellow-gray crust, commonly in lower
legs.
If diagnosis uncertain → punch biopsy with deep-tissue Gram stain and culture.
Treatment.
Dicloxacillin or first-generation cephalosporin.
Mycobacterial Infections (Tuberculosis; Leprosy)

Mycobacteria → obligate, acid-fast, aerobic, intracellular, filamentous bacteria with a waxy
coating.
Tuberculosis (TB)
Etiology.
Multiorgan infection due to Mycobacterium tuberculosis. Commonly infects lungs, rarely
skin.
Transmitted via saliva droplets, inhalation, or inoculation.
BCG: vaccination with attenuated M. bovis enhance immunity to tuberculosis; only given to
TB (-) persons; reduces childhood TB up to 75%; can cause complications → tuberculids,
lupus vulgaris, scrofuloderma, regional lymphadenitis.
PPD: positive 2–10 weeks after exposure and remains positive for many years; measure true
induration (not erythema) 48-72 hrs - > 5mm (+).
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Exogenous inoculation to skin. Primary inoculation tuberculosis (PIT), i.e., tuberculous
chancre: occurs at inoculated site in non-immune host. Tuberculosis verrucosa cutis (TVC):
occurs at inoculated site in individual with prior tuberculosis infection. Tuberculosis due to
bacilli Calmette-Guérin (BCG) immunization.
Endogenous spread to skin. Direct extension from deeper tissues, lymphatics,
hematogenous, body fluids (sputum, feces, urine). Lupus vulgaris. Scrofuloderma.
Metastatic tuberculosis abscess. Acute miliary tuberculosis. Orificial tuberculosis.
Pathogenesis
Type of clinical lesion depends on route of cutaneous inoculation and immunologic status of
the host.
Cutaneous inoculation results in a tuberculous chancre in the non-immune host and TVC in
the immune host.
Direct extension from underlying tuberculous infection, i.e., lymphadenitis or tuberculosis of
bones and joints, results in scrofuloderma.
Lymphatic spread to skin results in lupus vulgaris.
Hematogenous dissemination results in acute miliary tuberculosis, lupus vulgaris, or
metastatic tuberculosis abscess.
Autoinoculation from body fluids such as sputum, urine, feces results in orificial
tuberculosis.
Tuberculous Chancre (PIT)
Clinical finding: Painless red-brown papule at inoculation site → nonhealing, nontender
undermined ulcer with painless regional lymphadenopathy (chancriform syndrome).
Immunity: non-sensitized (no prior immunity).
Route: exogenous (direct inoculation); primary infection.
Tuberculosis Verrucosa Cutis (TVC, Warty TB)
Clinical finding: Small indurated hyperkeratotic papule → warty, firm plaque with
serpiginous borders; usually single; over hand, ankle, or buttock; no lymphadenopathy.
Spontaneous resolution with scarring.
Immunity: sensitized host (moderate to high immunity).
Route: exogenous (direct inoculation at site of trauma); reinfection.
Lupus Vulgaris
Clinical finding: Gelatinous soft and friable, reddish-brown nodules/irregular plaque with
brown-yellow color (“apple-jelly”) on diascopy ± ulcer; usually solitary; involving head or
neck. Lesions on ears or nose can result in destruction of underlying cartilage. Prominent
scarring. New brownish infiltrates within atrophic scars.
Complication: squamous cell carcinoma in chronic ulcers.
Immunity: sensitized host (moderate to high immunity).
Route: hematogenous, lymphatic or contiguous.
Scrofuloderma
Clinical finding: Deep subcutaneous nodule, typically bilateral over cervical lymph node →
turns deep-seated node or plaque, fluctuant and suppurative → ulcerates/discharging sinuses
→ prominent scarring.
Immunity: sensitized host (low immunity).
Route: contiguous spread (from affected lymph nodes or tuberculous bones or joints).
Tuberculous Gumma
Clinical finding: Firm, deep subcutaneous nodule over trunk, head, or extremities → turns
soft, non-tender, “cold”, and fluctuant → coalescing with overlying skin → ± fistulas and
ulcers. Single or multiple lesions, often at sites of previous trauma.
Immunity: immunosuppressed host.
Route: hematogenous.
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Miliary Tuberculosis
Clinical finding: Tiny bluish-red papules (teeming with bacilli) ± umbilicated vesicles or a
central necrosis → crust; disseminated on all parts of body, particularly trunk; mainly infants
or immunosuppressed patients.
Immunity: nonsensitized (low immunity).
Route: hematogenous dissemination.
Tuberculosis Cutis Orificialis
Clinical finding: Painful yellow or red papule/nodule → ulcerates with undermined borders;
single or multiple; TB of mucous membranes and skin surrounding orifices (usually by
autoinoculation); in patients with TB of internal organs (GI, lung, genitourinal); mouth most
commonly affected site; prognosis poor (advanced internal disease).
Immunity: sensitized host (impaired cellular immunity).
Route: autoinoculation from underlying visceral infection.
Tuberculids
Cutaneous immunologic reaction to TB elsewhere; stains negative; most likely the result of
hematogenous dissemination in patients with high degree of immunity; rapid response to
antiTB treatment; strongly positive PPD; most exhibit tuberculous features histologically.
Papulonecrotic Tuberculid
Clinical finding: Symmetric, dusky red, symptomless, pea-sized papules in crops over the
extremities → central necrosis and crust formation; children and young adults.
Immunity: sensitized.
Route: hypersensitivity reaction to distant focus of TB.
Lichen Scrofulosorum
Clinical finding: Lichenoid, asymptomatic, yellow to pink, follicular or parafollicular, tiny
papules (tuberculids) ± minute horny spine or fine scales; on trunk of children and
adolescents with TB in lymph nodes/bone.
Immunity: sensitized.
Route: hypersensitivity reaction to distant focus of TB (tuberculid).
Erythema Induratum (Bazin Disease)
Clinical finding: Dusky-red, subcutaneous, 1-2 cm tender nodules ± ulceration on posterior
calves; middle-aged women.
Immunity/Route. Associated with past or active TB.
Isolation of M. tuberculosis on culture or by PCR.
Histology.
Epithelioid granulomas with caseation necrosis.
Treatment.
Prolonged antituberculous treatment (6 - 9 months) with at least two drugs is indicated for
all cases of cutaneous TB except for TVC that can be excised.
Standart antituberculous treatment:
Isoniazid
Rifampin
Supplemented in initial phases with:
Etambutol
Streptomycin
Pyrazinamide
Leprosy (Hansen’s Disease)

Deforming and stigmatizing chronic granulomatous disease caused by M. leprae; affects
primarily skin and peripheral nerves (Schwann cell basal lamina); principally acquired
during childhood/young adulthood.
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Etiology.
Mycobacterium leprae. Obligate intracellular acid-fast bacillus. Humans are main reservoirs
of M. leprae.
Transmission.
Uncertain. Likely spread from person to person in respiratory droplets.
Pathogenesis.
Clinical spectrum of leprosy depends exclusively on variable limitations in host′s capability
to develop effective cell-mediated immunity to M. leprae. Organism is capable of invading
and multiplying in peripheral nerves and infecting and surviving in endothelial and
phagocytic cells in many organs.
Disease of developing world.
Classification of Disease Based on Clinical, Immunologic, and Bacteriologic Findings.
LL (lepromatous leprosy) ↔ BL (borderline lepromatous) ↔ BB (midborderline) ↔ BT
(borderline tuberculoid) ↔ TL (tuberculoid leprosy).
Of note, patients can move through spectrum of disease via upgrading and downgrading
reactions.
Immunologic Responses
. Immune responses to M. leprae can produce several types of reactions, associated with a
sudden change in the clinical status.
Lepra type 1 reactions. Acute or insidious tenderness and pain along affected nerve(s),
associated with loss of function.
Lepra type 2 reactions. Erythema nodosum leprosum (ENL). Seen in half of LL patients,
usually occurring after initiation of antilepromatous therapy, generally within the first 2
years of treatment. Massive inflammation with erythema nodosum-like lesions.
Lucio reaction. Individuals with diffuse LL develop shallow, large polygonal sloughing
ulcerations on the legs. The reaction appears to be either a variant of ENL or secondary to
arteriolar occlusion.
Incubation period is 2-40 years (most commonly 5-7 years). Onset is insidious and painless;
first affects peripheral nervous system with persistent or recurrent painful paresthesias and
numbness without any visible clinical signs ± transient macular skin eruptions; blister, but
lack of awareness of trauma. Neural involvement leads to muscle weakness, muscle atrophy,
severe neuritic pain, and contractures of the hands and feet.
Tuberculoid Leprosy (TL)
Clinical presentation. Localized skin involvement and/or peripheral nerve involvement. One
to few well-demarcated erythematous slow-growing plaques with central clearing; lesions
typically become anesthetic, anhidrotic, and hypopigmented. Tender, thickened nerves
(predilection for superficial nerves with cooler temperature). May present with neural
involvement alone.
↓↓ Viable organisms (paucibacillary). High-resistance tuberculoid response.
Borderline (or “Dimorphic”) Leprosy (BL)
BL, BB, BT. In order of decreasing resistance, the spectrum is TL, BT, BB, BL, LL.
Features of both Tuberculoid leprosy (TL) and Lepromatous leprosy (LL). Usually many
bacilli present, varied skin lesions → macules, plaques. Progresses to TL or regresses to LL.
Lepromatous Leprosy (LL)
Clinical presentation. Generalized involvement including skin, upper respiratory mucous
membrane, reticulo-endothelial system, adrenal glands, testes. Poorly defined symmetric
skin-colored to erythematous macules, papules, nodules, and/or plaques; dermal infiltration
leads to: face → “leonine facies”, eyebrows → lateral alopecia (madarosis). Enlarged
peripheral nerves, “stocking/glove” anesthesia. Testicular infection → sterility.
Lagophthalmos and corneal anesthesia.
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↑↑ Viable organisms (multibacillary). Low- or absent-resistance lepromatous pole.
Complications of Leprosy:
squamous cell carcinoma in chronic neurotrophic ulcers on the lower extremities; secondary
amyloidosis with hepatic and renal abnormalities.
Slit-skin smears. Examined with Ziehl-Neelsen staining. Acid-fast bacilli in tissue sections
or smears are positive with Fite stain.
Culture.
M. leprae grow when inoculated into the mouse foot pad or nine-banded armadillo (has not
been cultured in vitro).
PCR. Detected M. leprae DNA.
Histology
. In LL, macrophages loaded with bacteria and have foamy appearance (lepra cells or
Virchow cell), in TT epithelioid tubercles surrounded by lymphocytes.
Treatment
General principles of treatment:
Tuberculoid: dapsone plus rifampin; 6-month duration.
Lepromatous: dapsone plus clofazimine plus rifampin; 12-month duration.
Prevent and treat reactions (prednisone, thalidomide).
Educate patient to deal with neuropathy and anesthesia.
Treat complications of nerve damage.
Rehabilitate patient into society.
Treatment involves a broad multidisciplinary approach including orthopedic, surgery,
pediatry, ophthalmology, and physical therapy.
Of note, patients are no longer infectious after first or second dose of rifampin!
Spirochetal Infection
Spirochetes → Gram-negative bacteria with spiral-shaped cells, which move via twisting
motion (due to axial filaments in the flagella).
Include Treponema spp., Borrelia spp., and Leptospira spp.
Lyme Disease
Etiologic Agent.
Borrelia burgdorferi (Borrelia spirochetes).
Vector.
Tick (USA: Ixodes dammini; Ixodes pacificus, Europe: Ixodes ricinus feeds on infected
host (white footed mice, white tailed deer) → transmission to humans by the bite, via
infected tick saliva.
Pathogenesis.
After inoculation into the skin, spirochetes replicate and migrate centrifugally, producing
the erythema migrans (EM) lesion, and invade vessels, spreading hematogenously to other
organs. The spirochere has a particular trophism for tissues of the skin, nervous system, and
joints. The organism persists in affected tissues during all stages of the illness.
Incubation period. 3-32 days after tick bite. Ixodes tick bites are asymptomatic.
Stage 1 early localized disease. Flu-like symptoms (fever, chills, myalgia, headache,
weakness, photophobia) + EM: expanding erythematous patch at site of tick bite with central
clearing ± burning, sensation, itching, or pain. Initial erythematous macule or papule,
expanding centrifugally within days to form lesion with a distinct red border at the bite site.
Maximum diameter 15 cm. As EM expands, site may remain uniformly erythematous, or
several rings of varying shades of red with concentric rings (targetoid or bull′s eye lesions)
may form. Center may become indurated, vesicular, ecchymotic, or necrotic. Spontaneous
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resorption within 4 weeks ± postinflammatory hyperpigmentation, transient alopecia, and
desquamation. Common sites: thigh, groin, axilla.
Borrelial lymphocytoma. Usually arises at the site of tick bite. Some patients have a history
of EM; others may show concomitant EM located around or near the lymphocytoma.
Presents as a solitary bluish-red nodule, 3-5 cm in diameter. Common sites: earlobe
(children), nipple/areola (adults), scrotum.
Other cutaneous findings. Malar rash, diffuse urticaria, subcutaneous nodules.
Stage 2 early disseminated disease. Days to weeks post tick bite. Secondary lesions
resemble EM → few or dozens, smaller, migrate less, lack central induration, may be scaly,
can become confluent. Lesions occur at any site except the palms and soles.
Meningitis, cranial neuritis (facial nerve common), radiculoneuritis, peripheral neuritis.
Carditis + AV nodal block. Migratory musculoskeletal pain, migratory joint pain.
With disseminated infection → malaise, fatigue, lethargy, headache, fever, chills, stiff neck,
arthralgia, myalgia, backache, anorexia, sore throat, nausea, dysesthesia, vomiting,
abdominal pain, photophobia.
Stage 3 late disseminated disease. Months or years later. Acrodermatitis chronica
atrophicans: Initially, diffuse or localized violaceous erythema, usually on one extremity,
accompanied by mild to prominent edema, extends centrifugally over several months to
years - loss of subcutaneous fat with thin, atrophic skin. Localized fibromas and plaques as
subcutaneous nodules around the knees and elbows.
Chronic encephalopathy or polyneuropathy and intermittent or persistent arthritis.
PCR, tissue culture, serologic tests. Specific IgM antibodies peak between third and sixth
weeks after disease onset. The specific IgG response develops gradually over months.
Treatment
Oral treatment: Adults, children (>8 years old) - doxycycline; Pregnant women, children (<8
years old) - amoxicillin. Intravenous therapy - ceftriaxone.
Fungal Infections (Tinea Versicolor; Dermatophytosis; Candidiasis)

Classified into: superficial (invade stratum corneum, hair, and nails), subcutaneous (usually
due to implantation) and deep (systemic) infection.
Further subdivided into true and opportunistic pathogens.
Definitions
Yeast: Unicellular fungus, round to ovoid organisms with asexual reproduction (budding or
binary fission), pseudohyphae (long chain of yeast cells with constrictions rather than true
septae), form moist colonies.
Mold: Multicellular filamentous fungus with hyphae (tubular branching cells, regular
septae), reproduction via spore development and dispersal; can be geophilic (growth
primarily in soil), zoophilic (predominantly infects animals), or anthrophilic (infects
humans), cell membrane with unique sterol (ergosterol).
Mycelium: Large intertwined mass of hyphae; different types. Types of Mycelia
Spores: reproducing bodies of fungi; asexual or sexual.
Conidia: Free spores produced directly from hyphae or supporting conidiophores, different
types.
Superficial Mycoses
Includes only fungi, invading keratinized tissues (hair, nails, stratum corneum).
Divided into non-inflammatory (tinea versicolor) and inflammatory (dermatophytosis,
candidiasis).
Pityrosporum Folliculitis (Malassezia Folliculitis)
Rare Malassezia furfur infects hair follicles.
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Presents as monotonous acne-like folliculocentric papules typically over back → evolving
into pustules → heal with brown, easily removed crust.
Treatment.
Topical imidazole, systemic fluconazole or ketoconazole.
Tinea Versicolor (Pityriasis Versicolor)
Etiology.
Malassezia furfur (yeast form: Pityrosporum ovale or P. orbiculare). It is implicated in the
pathogenesis of seborrheic dermatitis.
Yeast part of normal cutaneous flora, but pathogenic when transforms into mycelial form;
requires lipid enrichment when growing.
Pathogenesis.
Malassezia changes from blastospore form to mycelial form under the influence of
predisposing factors.
Predisposing Factors
. Sweating. Warm season or climates. Hyperhidrosis. Oily skin.
M. furfur produces azelaic acid (adicarboxylic acid) → blocks melanin synthesis causing ↓
pigmentation.
Clinical Findings.
Presents as chronic, well-demarcated, round or oval, varying in size, hyper- and
hypopigmented macules with fine scale in lipid-rich areas of skin, most commonly on the
trunk.
Chronic course. Usually asymptomatic. Cosmetic concerns about dyspigmentation.
Dyspigmentation persists for months after infection has been eradicated.
Wood′s lamp. Blue-green fluorescence of scales.
Direct microscopic examination of scales prepared with KOH. “Ziti and meatballs” (short,
thick hyphae with grape-like spores).
Culture requires lipid enrichment (olive oil overlay).
Treatment
Topical agents: ketoconazole shampoo; selenium sulfide lotion or shampoo; terbinafine
solution; azole creams (ketoconazole, econazole, micronazole, clotrimazole).
Systemic treatment: ketoconazole; fluconazole; itraconazole.
Secondary prophylaxis: topical agents weekly or systemic agents monthly. s in late sions.
Dermatophytosis
Dermatophytes are a unique group of fungi, capable of infecting non-viable keratinized
cutaneous structures including stratum corneum, nails, and hair → caused dermatophytosis.
Clinical infection by structure involved. Epidermal dermatophytosis. Dermatophytosis of
hair and hair follicles. Onychomycosis or tinea unguium: dermatophytosis of the nail
apparatus.
Epidemiology and Etiology
Etiology. Three genera of dermatophytes (“skin plants”): Trichophyton, Microsporum,
Epidermophyton.
Trichophyton rubrum - the most common cause of epidermal dermatophytosis and
onychomycosis.
Trichophyton tonsurans, Microsporum audouinii, Trichophyton violaceum - the most
common cause of tinea capitis. Children have scalp infections (Trichophyton,
Microsporum), young and older adults - intertriginous infections.
Transmission.
Dermatophyte infections can be acquired from three sources: most commonly from another
person; from animals such as puppies or kittens; least commonly from soil.
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Classification of Dermatophytes.
Based on their ecology → anthropophilic - person-to-person transmission by fomites and by
direct contact, zoophilic - animal-to-human by direct contact or by fomites, geophilic -
environmental.
Predisposing Factors.
Host factors - atopic diathesis, topical and systemic glucocorticoids, systemic
immunocompromised. Local factors - sweating, occlusion, occupational exposure,
geographic location, high humidity.
Classification
In vivo, dermatophytes grow only on or within keratinized structures and, as such, involve
the following:
Epidermal dermatophytosis. Tinea facialis, tinea corporis, tinea cruris, tinea manus, tinea
pedis.
Dermatophytoses of hair and hair follicle. Dermatophytic folliculitis, Majocchi
granuloma, tinea capitis, tinea barbae.
Dermatophytoses of nail apparatus. Tinea unguium (toenails, fingernails).
Onychomycosis (more inclusive term, including nail infections caused by dermatophytes,
yeast, and molds).
Dermatophytoses of epidermis
Epidermal dermatophytoses are the most common dermatophytic infection.
Synonym: Ringworm.
Tinea Corporis
Dermatophyte infections of the trunk, legs, arms, and/or neck, excluding the feet, hands, and
groin.
Etiology.
T. rubrum most common; may spread from fungal infection of feet (T. rubrum, T.
mentagrophytes), infected animal (M. canis), or soil (M. gypseum).
Presents as erythematous, sharply marginated, scaly plaque with raised, advancing border;
typically with central clearing and annular or arcuate shape.
Clinical Variants:
Tinea imbricata (T. concentricum) - distinct scaly plaques arranged in concentric rings.
Tinea profunda - marked inflammatory response to a dermatophyte (analogous to kerion on
scalp).
Tinea incognito - variably inflamed patches; involved sites often have exaggerated features
of epidermal dermatophytoses, being a deep red or violaceous; scaling often not apparent;
papules or pustule within involved sites (dermatophytic folliculitis); usually due to prior
treatment with topical corticosteroids.
Majocchi’s granuloma - T. rubrum (most common), granulomatous folliculitis due to
dermatophyte entering hair follicles.
Tinea Cruris (Tinea Inguinalis)
Subacute or chronic dermatophytosis of the upper thigh and adjacent inguinal and pubic
regions, ± buttocks, rarely scrotum and penis.
Large, scaling, well-demarcated dull red/tan/brown plaques. Central clearing ± raised,
serpiginous scaly border with papules and pustules.
Tinea Faciei
Dermatophytosis of the glabrous facial skin.
Etiology.
T. rubrum, T. mentagrophytes, or M. canis
Well-circumscribed erythematous macules to plaques of variable size. Minimal scaling.
Annular elevated borders and central regression.
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Tinea Pedis
Synonyms. Athlete′s foot. Jungle rot.
Dermatophytic infection of the feet.
Etiology.
T. rubrum.
Different Types:
Moccasin type - well-demarcated scaling with dull erythema with minute papule on margin,
fine white scaling, and hyperkeratosis involving sole and sides of foot. More common
bilateral.
Inflammatory/bullous type - vesicles or multilocular bullae often located along the instep
(arch) → erosions with ragged ringlike border.
Interdigital type - two patterns: dry scaling; erythema, maceration, scaling, fissuring of toe
webs ± spread to adjacent areas of feet.
Chronic course. Usually asymptomatic ± pruritus. Fissures and erosions → portal of entry
for bacterial infections.
Tinea Manuum
Chronic dermatophytosis of the hand(s).
Often unilateral.
Well-demarcated scaling patches, hyperkeratosis, fissures on palmar hand. Borders - well
demarcated; central clearing. May extend onto dorsum of hand with follicular papules,
nodules, and pustules with dermatophytic folliculitis. Dyshidrotic type: papules, vesicles,
bullae on palms and lateral fingers.
Frequently pruritus.
Chronic course. Fissures and erosions provide portal of entry for bacterial infections.
Dermatophytoses of Hair
Dermatophytes are capable of invading hair follicles and hair shafts, causing:
Tinea capitis
Tinea barbae
Majocchi granuloma
Two types: Ectothrix - mycelia and arthroconidia on the surface of the hair follicle
(extrapilary) (Microsporum spp.); endothrix - hyphae and arthroconidia within the hair shaft
(intrapilary) (Trichophyton spp.).
Tinea Capitis
Dermatophytic trichomycosis of the scalp, predominantly in pre-adolescent children.
Clinical presentations vary widely: Noninflammatory scaling; Scaling and broken-off hairs.
Infections can become epidemic in schools and institutions, especially with overcrowding.
Etiology –
T. tonsurans, T. violaceum. Less commonly, M. canis.
Noninflammatory infection. Caused by T. tonsurans, T. violaceum. Fine scaling with fairly
sharp margin. Hair shaft becomes brittle, breaking off at or slightly above scalp. Broken-off
hairs at surface of scalp give appearance of “dots” (“black dot” tinea capitis). Several or
many small patches coalesce → larger patches. Tends to be diffuse and poorly
circumscribed. Partial alopecia showing numerous coating of arthrospores. Inflammatory
response minimal ± low-grade folliculitis ± occipital or posterior auricular
lymphadenopathy.
Microsporum species show green fluorescence with Wood′s lamp.
Kerion. Caused by zoophilic (T. verrucosum, T. mentagrophytes) or geophilic species.
Inflammatory mass in which remaining hairs are loose. Boggy, purulent, inflamed nodules,
and plaques. Drains pus from multiple openings, like honeycomb. Hairs do not break off but
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fall out and can be pulled without pain. Follicles may discharge pus; sinus formation;
mycetoma-like grains. Thick crusting with matting of adjacent hairs. Usual single plaque,
multiple lesions with involvement of entire scalp ± lymphadenopathy, ± scarring alopecia.
Usually painful.
Favus. With yellow cup-shaped crusting (scutula) on scalp; arthroconidia and airspaces
within hair shaft - T. Schoenleinii, T. violaceum, M. gypseum. Early cases show
perifollicular erythema and matting of hair. Later, thick yelow adherent crusts (scutula)
composed of skin debris and hyphae that are pierced by remaining hair shafts. Fetid odor.
Shows little tendency to clear spontaneously. Often scarring alopecia. ix nf
Tinea Barbae (Tinea Sycosis)
Dermatophytic folliculitis involving the androgen-sensitive beard and moustache areas.
Etiology.
M. canis , T. mentagrophytes, or T. verrucosum
Pustular folliculitis, i.e., hair follicles surrounded by red inflammatory papules, pustules,
nodules, or plaques. Involved hairs are loose and easily removed. Less follicular
involvement → scaling, circular, reddish patches in which hair is broken off at the surface. ±
Regional lymphadenopathy, ± pain.
Majocchi Granuloma
Dermatophytic folliculitis with foreign-body granuloma in response to keratin in dermis and
immune reaction to dermatophyte.
Etiology.
Most commonly T. rubrum, T. tonsurans.
Risk Factors.
Topical glucocorticoids application. Host defense defects.
Follicular type with local immunosuppression (topical glucocorticoid use).
Subcutaneous nodular type with systemic immunocompromised. Solitary or multiple.
Folliculocentric papules and pustules arise within an area of epidermal dermatophytosis such
as tinea incognito.
Distribution: Any hair-bearing area; scalp, face, forearms, dorsum of hands/feet, shaved
legs.
Onychomycosis
Infection of the nail plate, most commonly due to T. rubrum, but also by other
dermatophytes, yeast, and nondermatophytic molds.
Four types:
Distal subungual onychomycosis - involvement of distal nail bed and hyponychium;
typically due to T. rubrum.
White superficial onychomycosis (WSO) - chalky white superficial infection of nail plate;
due to T. mentagrophytes (T. rubrum in HIV patients).
Proximal subungual onychomycosis - least common form, presents with areas of
leukonychia in proximal nail plate near lunula; usually due to T. rubrum; can be a sign of
HIV infection.
Candida onychomycosis - destruction of nail and massive nail bed hyperkeratosis, in
patients with mucocutaneous candidiasis; due to C. albicans.
Wood′s lamp → fluorescence.
Direct microscopy. Potassium hydroxide (KOH) preparation (potassium hydroxide 5-20%
solution) → dissolves keratin but leaves behind the hyphae. Multiple, septated, tube-like
structures (hyphae or mycelia) and spore formation.
Fungal cultures. Culture on Sabouraud′s glucose medium - gold standard.
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Histology.
PAS or methenamine silver stains.
Treatment
Topical agents: keratolytics – benzoic, salicylic, undecylenic acid; antiseptics – jodasept,
vioform, tinctura Castellani, iodochlorhydroxyquinvioform; imidazoles (clotrimazole,
miconazole, ketoconazole, econazole,etc.); allylamines (terbinafine); naphthionates
(tolnaftate); substituted pyridine (ciclopirox olamine).
Systemic antifungal agents: Benzofurans (Griseofulvin); Alillamines (Terbinafine, Lamisil);
Itraconazole (Orungal, Sporanox); Azols (Fluconazole, Ketoconazole, Nizoral, Miconazol,
Fungolon, Diflucan,).
General measures: correct predisposing factors (e.g. moist environment, underlying
immunosuppression).
Avoid the use of topical steroids → lead to tinea incognito.Phergy test. LR-+
Candidiasis
Etiology.
Most commonly caused by the yeast Candida albicans. Less often by other Candida species
(C. tropicalis, C. parapsilosis, C. krusei, C. glabrata, etc.). Require a warm humid
microenvironment.
Candida albicans common inhabitant of skin, GU, and GI tract.
Opportunistic organism, can become pathogen in skin, nails, and mucous membranes.
Clinical Manifestation:
Cutaneous candidiasis. Intertriginous and occluded skin.
Mucosal candidiasis. Otherwise healthy individuals → oropharynx and genitalia.
Host defense defects → in the esophagus and tracheobronchial tree.
Disseminated candidemia. Host defense defects, especially neutropenia. Usually
after invasion of GI tract.
Predisposing Factors:
Antibiotic therapy; glucocorticoid therapy (topical and systemic); pregnancy, oral
contraception, and intrauterine devices; Age (very young, very old); Host defense defects,
diabetes mellitus, obesity; hyperhidrosis, warm climate, maceration; polyendocrinopathies;
glucocorticoids; chronic debilitation.
Cutaneous Candidiasis
Cutaneous candidiasis occurs in moist, occluded sites.
Candidal intertrigo. Initial pustules on erythematous base become eroded and
confluent. Subsequently, fairly sharply demarcated, polycyclic, erythematous, moist, eroded
patches with small pustular lesions at the periphery (satellite pustulosis).
Distribution: Intertriginous areas (inframammary or submammary, axillae, groins, perineal,
and intergluteal cleft).
Pruritus, tenderness, pain.
Interdigital (Erosio interdigitalis blastomycetica). Most common in obese elderly.
Maceration between webspace of fingers/toes. Initial pustule becomes eroded, with
formation of superficial erosion or fissure.
Distribution: webspace usually between third and fourth fingers, similar in toes but usually
fourth webspace affected.
Candidal paronychia. Redness, tenderness, edema of nailfold; associated with
chronic exposure to moisture and irritants.
Diaper dermatitis. Erythematous patches + erosions in groin, ± satellite
papules/pustule, scale at the margins of lesions.
Distribution: genital and perianal skin, inner aspects of thighs and buttocks.
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Irritability, discomfort with urination, defecation, changing diapers.
Perineal candidiasis. Perianal dermatitis with erythema, maceration, burning, and
pruritus (due to mechanical chafing ± incontinence).
Follicular candidiasis. Small, discrete pustules in ostia of hair follicles. Usually in
occluded skin (under occlusive dressing, under cast, on back in hospitalized patient).
Mucosal Candidiasis
Oropharyngeal Candidiasis
Incidence. Often mucosal candidiasis occurs in otherwise healthy individuals. In advanced
HIV disease oropharyngeal candidiasis is common.
Pseudomembranous candidiasis (Thrush, Moniliasis). White cottage cheese-like flecks
(colonies of Candida) on any mucosal surface; vary in size from 1-2 mm to extensive and
widespread. Removal with a dry gauze pad leaves an erythematous mucosal surface.
Distribution: Dorsum of tongue, buccal mucosa, hard/soft palate, pharynx extending down
into esophagus and tracheobronchial tree.
Erythematous or atrophic candidiasis. Dorsum of tongue is smooth, red, atrophic. Areas
of thrush may also be present.
Candidal leukoplakia. White plaques that cannot be wiped off but regress with anticandidal
therapy.
Distribution: buccal mucosa, tongue, hard palate.
Angular cheilitis (Perleche). Transverse fissuring and maceration of oral commissures
± white colonies of Candida.
Often asymptomatic. Burning or pain on eating spices/acidic foods, diminished taste
sensation. Cosmetic concern about white curds on tongue. Odynophagia. In HIV disease,
may be the initial presentation.
Genital Candidiasis
Occurs on the non-keratinized genital mucosa – vulva, vagina; preputial sac of the penis.
Usually represents overgrowth of Candida in mucocutaneous microbiome.
Epidemiology
. More than 20% of women have vaginal colonization by Candida.
Incidence.
Most vaginal candidiasis occurs in healthy population. Often associated with vulvar
candidiasis, i.e., vulvovaginal candidiasis.
Risk Factors.
Diabetes mellitus, HIV disease. Females: often none; pregnancy. Males; uncircumcised.
Vulvitis. Erosions, edema, erythema, swelling, removable curd-like material. Pustule on
lateral vulva and adjacent skin.
Vulvovaginitis. Vaginal erythema and edema; white plaques that can be wiped off vaginal
and/or cervical mucosa. May be associated with candidal intertrigo of inquinal folds and
perineum. Subcorneal pustules at periphery with fringed, irregular margins. In chronic cases,
vaginal mucosa glazed and atrophic.
Onset often abrupt, usually the week before menstruation. Symptoms may recur before each
menstruation. Pruritus, vaginal discharge, vaginal soreness, vulvar burning, dyspareunia, and
external dysuria.
Balanoposthitis, balanitis glans, and preputial sac: papules, pustules, erosions.
Maculopapular lesions with diffuse erythema. Edema, ulcerations, and fissuring of prepuce,
usually in diabetic men; white plaques under foreskin.
Direct microscopy. KOH preparation visualizes pseudohyphae and yeast forms (budding
yeast forms and sausage-like pseudohyphal forms).
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Sabouroud culture.
Immunology method (IIF).
Treatment
Systemic antifungals. Fluconazole, itraconazole, ketoconazole. Nystatin – in GI candidiasis.
Amphotericin B for severe resistant disease.
Topical antifungals. Nystatin, azole, or imidazole cream.
Of note, genital candidiasis → treat sexual partners.
General measures. Correct predisposing factors (e.g. moist environment, underlying
immunosuppression, diabetes, etc.).
Prevention.
Keep intertriginous areas dry, wash with benzoyl peroxide bar and use imidazole powder.
Der
Ectoparasitic Diseases (Scabies; Pediculosis)
Scabies
Etiology agent.
Sarcoptes scabiei var. hominis.
Incubation period 3-4 weeks.
Transmission
. Usually spread by skin-to-skin contact and fomites.
Intense pruritus (worse at night). Intraepidermal burrows located within stratum corneum.
Skin colored ridges with minute vesicle or papule at end of tunnel (female mite with eggs
and feces). Localization – symmetric interdigital webs of hands, wrists, elbows, ankles,
buttocks, axillae, breasts in women, genital area in men. In infants – palms, feet, head and
neck.
Hyperinfestation (crusted or hyperkerarotic or Norwegian scabies). Persons are often
immunocompromised or have neurologic disorders.
Secondary changes: excoriations, prurigo nodules, secondary eczema and bacterial infection.
Diagnosis: mineral oil scraping from burrow and view S. scabiei mites, eggs, and fecal
pellets under microscope.
Treatment
of all contact persons at the same time. Application should be to all skin sites from the neck
down; wash of thoroughly after 8 h.
Topical scabicide: permethrin, lindane, crotamiton, sulfur, benzyl benzoate, ivermectin.
Systemic. Oral ivermectin for heavy infestation or in immunocompromised individuals,
epidemic and endemic scabies. Do not use in infants, young children or pregnant/lactating
women.
Decontamination of environment.
Pediculosis
Pediculosis Capitis (Head Lice)
Etiology.
Pediculus humanus capitis. Feeds on scalp and neck and deposits/cemented its eggs on hair.
Transmission:
head-to-head contact; shared hats, caps, brushes, combs; theater seats; pillows.
Clinical manifestation.
Scalp pruritus with nits behind ears and at nape of neck. Sites of predilection: head lice
nearly to scalp, especially occipital and postauricular regions. Rarely, infest beard, other
hairy sites and the eyelashes (pediculosis palpebrarum). Bite reactions: papular urticaria on
the neck. Secondary lesions: eczema, excoriation, lichen simplex chronicus on occipital
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scalp and neck due to chronic scratching/rubbing. Secondary infection with S. aureus of
eczema or excoriations ± occipital and/or cervical lymphadenopathy.
Treatment.
Topically applied insecticides. Malathion, permethrin, pyrethrin, lindane.
Systemic. Oral ivermectin.
Pediculosis Corporis (Body Lice)
Etiology.
Pediculus humanus corporis.
Epidemiology.
Occur in poor socio-economic conditions. Risk factors: poverty, war, natural disasters,
indigence, homelessness, and refugee-camp populations.
Body lice are vectors of many systemic infections (epidemic typhus, trech fever, relapsing
fever, endocarditis, etc.).
Lice and nits in clothing seams. Lice grab on to body hairs to feed. Bite reactions, such as
papular urticaria, similar to those of head lice. Secondary changes: excoriations, eczema,
lichen simplex, infection with S. aureus, and postinflammatory hyperpigmentation.
Treatment
as pediculosis capitis.
Decontamination of clothing and bedding. Hygiene measures.
Pediculosis Pubis (Pubic Lice)
Etiology.
Phthirus pubis.
Transmission during close physical contact: sharing bed.
Mild-to-moderate pruritus. Most commonly inhabit the pubic area; hairy parts of the chest
and axillae; upper eyelashes; also, perineum, thighs, lower legs, trunk. In children, eyelashes
and eyebrows without pubic involvement. At sites of feeding, around hair follicles,
erythema, papular urticaria (small erythematous papules) ± maculae caeruleae (taches
bleues) → slate-gray or bluish-gray non-blanching macules; excoriations.
Sometimes secondary bacterial infection ± regional lymphadenopathy.
Treatment
as pediculosis capitis.
Treat sex partners.
Decontaminate clothing and bedding.
VENEREOLOGY
SEXUALLY TRANSMITTED INFECTIONS (STIs)
Classification, Epidemiology, Diagnosis, Treatment, Patient Education, Prophylaxis,
Public Health Considerations
STIs are infections transmitted primarily through sexual contact with an infected person.
Classification
Common Sexually Transmitted Infections
Classic venereal diseases Other sexually transmitted infections
Syphilis HIV/AIDS
Gonorrhea Candidal balanitis and vulvovaginitis
Chlamydia infections Condylomata acuminata
Chancroid Herpes genitalis
Lymphogranuloma venereum Cytomegalovirus
Granuloma inguinale Hepatitis B and hepatitis C
Bacterial vaginosis Pediculosis pubis
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Scabies
Epidemiology
The global incidence of STIs is high. In 2012, WHO estimates 357 million new infections of
the four curable. STIs - chlamydia, gonorrhoea, syphilis and trichomoniasis.
Diagnosis of STIs
1. History taking
Some patients may not be comfortable talking about their sexual history, sex partners, or
sexual practices. Putting patients at ease is an important part of the medical approach.
Topics that should be openly discussed:
• Partners
• Sexual practices
• Protection from STIs
• Past history of STIs
• Prevention of pregnancy
Information about patient's risk factors, such as number of current or past sex partners,
condom use or drug use should also be obtained. In certain situations the subjects of
abstinence, monogamy, condom use, the patient’s perception of his own risk and his partner’s
risk, and the issue of testing for STIs need to be explored.
2. Microscopy in diagnosis of gonorrhea
Microscopy is used for detection of Gram-negative intracellular diplococci in stained
preparations. The specimen choice and collection method depends on the age, sex and sexual
behavior of the patient - urine, vaginal, cervical, urethral, anal or oropharyngeal secretions,
specimen form affected conjunctiva. For staining with aniline dyes the preparation is fixed by
passing the slide through a burner. Aqueous methylene blue solution or Loeffler’s methylene
blue staining may be used. A direct smear for Gram staining may be performed as soon as the
swab specimen is collected from the urethra, cervix, vagina or rectum. Under oil immersion
(1000x magnification) specimens contain intracellular Gram-negative diplococci in
polymorphonuclear leukocytes. The presence of extracellular Gram-negative diplococci is an
equivocal finding that must be confirmed by culture or nucleic acid test.
3. Microbiological tests:
3.1 Culture tests
Gonorrhea
The swabs with the tested specimen is inoculated directly onto growth medium or placed in
swab transport medium immediately after sampling. Media that are used are based on
chocolate agar (Thayer-Martin, Martin Lewis, etc.) and contain antimicrobial agents to
inhibit the growth of commensal bacteria and fungi. Several methods are available to confirm
the identification of N. gonorrhoeae, including biochemical testing, serological testing,
colorimetric testing and nucleic acid methods.
3.2 Cell culture
Culture is the only procedure that confirms the presence of viable organisms. Chlamydiae
are labile bacteria, and viability can be maintained by keeping specimens cold and
minimizing the time between specimen collection and processing in the laboratory. For
successful culture of chlamydiae, swabs, scrapings and small tissue samples should be
forwarded to the laboratory in a special chlamydial transport medium.
3.3 Antigen or nucleic acid detection
- Enzyme immune assay (EIAs)
A number of commercial EIAs are available for the detection of chlamydial antigens in
clinical specimens. Most EIAs take several hours to perform. The sensitivity profiles range
from 65% to 75% compared with nucleic acid amplification (NAA) tests. Without
confirmation, the tests have a specificity of 97%. The appropriate application of confirmatory
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tests increases the specificity to approximately 99.5%.
- Direct fluorescent antibody test (DFA)
DFA has approximately 75% to 85% sensitivity and 98% to 99% specificity compared with
culture, and lower sensitivity (approximately 70%) compared with NAA tests. This procedure
offers rapid diagnosis, taking only 30 min to perform.
- Nucleic acid detection with and without amplification
Molecular detection methods allow more rapid and specific diagnosis of fastidious pathogens
that are difficult to be cultured. Nucleic acid methods developed for sexually transmitted
pathogens are rapid, highly sensitive and specific. Nucleic acid methods are suitable for
detecting N. gonorrhoeae in specimens that may not contain viable organisms. When
specimens are collected for DFA, enzyme immunoassay (EIA), nucleic acid hybridization
(NAH) or NAA (nucleic acid amplification) tests, the instructions given in the product's
package should be followed. It should be taken into consideration that antigens, nucleic acids
or antibodies can be present in the absence of viable infectious particles. Single detection
systems or dual detection tests for C. trachomatis and N. gonorrhoeae are now commercially
available.
4. Dark-field microscopy
Dark-field microscopy allows visualization of live treponemes from skin and mucosal
lesions. Serous fluid from hard chancre, mucous patches and condylomata lata in secondary
syphilis are appropriate specimens for this test. Dry skin lesions usually do not contain
sufficient number of organisms for its performance. Dark-field testing is useful also in
diagnosis of early congenital syphilis (snuffles, vesiculobulous skin lesions). The tested
lesion should be cleansed and serous fluid yielded on a slide. The microscopy should be
performed within 20 minutes after specimen collection. Definitive identification of T.
pallidum depends on visualizing of its typical morphology and motility. The sensitivity of
dark-field microscopy in primary syphilis is approximately 80% but it declines over time and
with topical antibiotic applications. Oral specimens are not used for dark-field microscopy
because of the presence of saprophytic treponemes that may be indistinguishable
from T. pallidum.
Treatment
Several factors have an influence on the therapeutic approach in case of STIs: etiological
agent’s susceptibility to the chosen medication, pharmacokinetics, toxicity, side-effects, and
price of the drug; probability for concomitant infection. A single-dose treatment is preferred
only in case of young promiscuous patients, with tendency to lower compliance with the
treatment.
Patients Education
Education of the adolescent population and consultation of sick individuals on preventive
STIs measures include abstinence, monogamous sexual relationships and condom use during
all sexual practices.
Prophylactic measures for prevention of STIs transmission. Evaluation of social and
demographic factors contributing to transmission of STIs, identification of risk groups in the
population; early diagnosis of individuals with STI and identifying their sexual partners;
rapid and effective treatment of infected subjects; variety of screening programs for
vulnerable population groups. In Bulgaria, there is mandatory testing for syphilis and HIV
prior to marriage and for those who start working in healthcare, kindergartens and public
restaurants.
Public health considerations. Every country has public health regulations, indicating which
infectious diseases must be reported, who must report them and how patient confidentiality is
to be preserved. STI, left untreated, increase the risk of HIV transmission and lead to
complications, such as pelvic inflammatory disease, infertility, ectopic pregnancy,
miscarriage, fetal death and congenital infections. Prevention and control of STIs has
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significant public importance. In 2007, WHO published the Global Strategy for Prevention
and Control of STIs. A key element of this strategy is the surveillance providing information
on the global burden of STIs, regional and country levels; identifies vulnerable population
groups; monitors the impact of interventions and provides treatment recommendations. The
majority of countries (108 out of 198) have an STI surveillance system in place. However,
there is still a lack of general standardization among countries.
Syphilis (Lues)
Chronic systemic infection caused by Treponema pallidum, involving multiple organs
including skin, cardiac, neurologic, and skeletal system. Transmission can be sexual (contact
with infectious lesion), transplacental, or from blood products (rare).
Epidemiology
The World Health Organization (WHO) estimates that the annual global incidence of syphilis
is approximately 12.2 million cases. In 2008, approximately 1.4 million pregnant women
globally had active syphilis. WHO's report on global sexually transmitted infection
surveillance 2015 shows that median syphilis rate is 25.1 cases per 100 000 adult population
(range 0.1-1664) among the 55 included countries. Syphilis is an important public health
concern due to the highly destructive nature of disease late stages and HIV co-morbidity.
Etiology.
Treponema pallidum is a spirochete (6 to 15 μm in length and is 0.2 μm in diameter) with
10–20 spirals. The organism is very sensitive and scarcely survives in the environment.
Treponema cells are Gram-negative and do not take up Giemsa stain easily. Silver
impregnation stain and dark-field microscopy is used for its visualization. T. pallidum is
microaerophylic and cannot be cultivated in artificial media without losing its pathogenicity.
To obtain sufficient organisms for experimental manipulation, T. pallidum must be
propagated in rabbits. T. pallidum doubles every 30 to 33 h in vivo.
Clinical Classification
Early syphilis. All disease manifestations and the latent period during the first 2
years after the beggining of the infection. It is presented by: 1. Primary syphilis: 3–8 weeks
after the primary infection, inflammation affects the site of inoculation and the regional
lymph nodes; 2. Secondary syphilis: Around 9 weeks (between 6 and 12weeks) after the
inoculation, bacteremia, generalized exanthem, systemic signs and symptoms, and production
of antibodies. Rarely, this stage may be prolonged by inadequate antiobiotic therapy; 3.
Latent syphilis: Symptom-free period following secondary syphilis.
Late syphilis. Syphilis occurring more than 2 years after primary infection.
Characteristic granulomatous inflammation causes most of the pathological findings. Few
organisms are found in lesions. Marked cellular immune response is present. Most commonly
affects skin, bones, cardiovascular system, and CNS.
Congenital syphilis. Follows transplacental transmission of T. pallidum.
Stage Time after infection (years) Disease

Early syphilis 0–2 Primary syphilis
Secondary syphilis
Latent syphilis
(seropositive)
Late syphilis >2 Tertiary syphilis

Latent syphilis
(seronegative)
Pathogenesis
T. pallidum has a small genome and lacks genes that encode many metabolic functions and
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classical virulence factors. The organism is extremely sensitive to environmental conditions
and has not been continuously cultivated in vitro. Nonetheless, T. pallidum is highly
infectious and survives for decades in the untreated host. Early syphilis lesions result from
the host's immune response to the treponemes. Bacterial clearance and resolution of early
lesions results from a delayed hypersensitivity response. Syphilis is acquired by direct
contact, usually sexual, with active primary or secondary lesions. Infection also occurs when
organisms cross the placenta to infect the fetus in a pregnant woman. T. pallidum
transmission is by close tissue contact with entry through minor points of injury. After
reproducing in tissues spirochetas reach regional lymph nodes and than with the bloodstream
are disseminated all over the body. Blood vessels are specifically affected with formation of
lympho-plasmocytic infiltrate and clinical presentation of vasculitis. Extragenital and indirect
transmission of syphilis is also possible via oral contact, breastfeeding, use of contaminated
utensils, medical devices, etc. Vertical transmission - from sick mother to her child during
pregnancy or delivery, together with blood transfussion or organ transplantation inoculation,
are also possible.
On the place of acquisition of Treponemas natural killer cells, T-lymphocytes and
plasmocites are activated. Antibodies formation starts 3-5 days after inoculation. First appear
antiproteid antibodies, next antipolissacharid antibodies. Specific IgM may be detected 5
days before appearance of syphilitic chancre with IgM-FTA-Abs test. Immobilizing
antibodies are being produced from 5-10 day after inoculation, but their titer reaches
detectable levels 2 months after contraction of the infection. Antilipoid antibodies are not
specific and are formed 16-22 days after the beginning of the infection. The maximal titer of
those antibodies is reached in secondary period of syphilis, while in tertiary infection it
decreases and may even be absent.
Immunity
There is no innate or persistent acquired immunity against syphilis. Passive immunization
through injection of immune sera is also impossible. There is an infectious/chancre immunity
which disappears after treatment. The immunity level increases and reaches its maximum in
secondary syphilis. In late stages of the infection the level of immunity gradually decreases.
Allergy
In the early stages of syphilis (primary and secondary) hypersensitivity is not significant. It is
the highest during tertiary stage of the disease, which manifests with the positive intradermal
tests to luetin.
Superinfection
During incubation period superinfection is possible, with formation of hard chancre. It can
still occur during second incubation period, but with appearance of papular rash. The
presence of secondary luetic rash makes superinfection impossible. In tertiary syphilis,
superinfetion can also occur.
Reinfection
Present treatment strategies give full clearance of T. pallidum and the reinfection is proving
it. Reinfection should be differentiated from the so-called ulcus reducs (reinduracio), which is
a relapse of preexisting primary lesion. Syphilitic reinfection is certain only if the new hard
chancre appears after the expected incubation period and is located at a new site. The
diagnostic approach in this case includes history for recent sexual partner with contagious
syphilitic lesions, dark-field microscopy and serologic tests.
Primary Syphilis
Clinical features: dark red nodule develops about 3 weeks after inoculation; it becomes
eroded and then ulcerated. Chancre (ulcus durum): Firm, approximately 1 cm, circumscribed
ulcer with hard basis on palpation. The size of ulcers varies greatly. Heals spontaneously over
3–8 weeks. Location: Any location is possible. Most commonly genitalia, mouth, fingers.
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Usually chancres are asymptomatic; about 50% are overlooked. Anal lesions and lesions with
mixed infection are more likely to be painful. Regional lymphadenopathy appears 1–2 weeks
after chancre; usually unilateral; 1–2 cm, nontender lymph nodes without inflammation of
overlying skin.
Diagnostic approach: Dark-field examination – T. pallidum shows three characteristic
motions: rotation on the long axis, sharp folds, and minimal motion forward and backwards.
Dark-field shows limited utility for mucosal lesions as there are many normal spirochetes in
the mouth. Secretions can be dried on a slide which is then studied with the fluorescent
treponemal antibody (FTA) technique. Serologic testing: FTA-IgM is positive 2 weeks after
initial infection. If clinical suspicion exists, but the darkfield and serology are negative, the
patient should be re-checked in 1–2 months.
Differential diagnosis: Herpes genitalis, traumatic ulcers, chancroid, lymphogranuloma
venereum, erythroplasia of Queyrat, plasma cell balanitis of Zoon, fixed drug eruption.
Secondary Syphilis
Clinical features: Syphilis was formerly described as the great imitator. Multiple exanthems
and enanthems called syphilids are associated with secondary syphilis. All result from local
inflammation caused by T. pallidum during its bacteremic phase. The rashes of secondary
syphilis are usually asyptomatic. Macular syphilid: Initially pale irregular pink macules
(syphilitic roseola) typically on side of chest, trunk, palms, and soles with typical red-brown
color. Nonpruritic, nonscaling, blanchable with diascopy. Papular syphilid: red-brown
papules appearing in varying numbers. The smallest papules are known as lenticular syphilid.
Annular or circinate syphilid: spread of papules with central clearing and peripheral growth.
Corona venerea: papules along the hair line. Palmoplantar syphilid: papules on palms and
soles with red-brown color and scale (clavi syphilitici). Lichen syphiliticus: tiny follicular
papules, resembling milia; rare and occurs late. In immunosuppressed patients necrotic
papulopustular lesions which ulcerate with dirty crust; fever, chills (malignant syphilid) or
crusted (rupial syphilis). Syphilitic leukoderma: any of the secondary lesions can heal with
postinflammatory hypopigmentation. Condylomata lata: eroded papules in moist, prone to
friction body sites. Syphilitic alopecia: “moth-eaten” hairloss; usually numerous small spots
of incomplete hairloss. Mucosal changes: Mucous plaques - small papules on oral mucosa,
which rapidly become eroded; Opaline plaques - later stage with glossy gray membranous
covering; Plaques fouée - dark red plaques on tongue; Syphilitic angina - involvement of
tonsils with swelling and erythema; usually unilateral.
Systemic changes: Generalized lymphadenopathy - painless firm lymphadenopathy involving
antecubital, axillary, nuchal, preauricular, and other nodes; Liver - acute hepatitis; Kidneys -
acute glomerulonephritis with deposition of immunoglobulins and complement; Spleen -
enlarged in almost 100% of cases; CNS - meningitis or meningoencephalitis, 25% have CSF
abnormalities; Musculoskeletal abnormalities - periostitis → typical sites tibia, sternum, and
medial end of clavicle, pain worse at night, polyarthritis, tenosynovitis.
Diagnostic approach: Serology (100% positive); dark field of eroded lesions.
Prognosis: All lesions resolve and many patients never develop further manifestations.
Latent Syphilis
Definition: The phase following the resolution of secondary syphilic lesions, the patient is
asypmtomatic but has a positive serology.
Diagnostic approach: If the FTA-IgM tests positive in an asymptomatic patient, a complete
examination is needed. Essential examination: 1. CSF examination and neurological
evaluation; 2. Assessment of aorta (ultrasonography or imaging techniques); 3.
Ophthalmologic consultation.
Tertiary Syphilis
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Cutaneous manifestations: Changes are much less serious and much more responsive to
therapy than the other late manifestations. Red-brown papules and nodules (1–2 cm) that
clear centrally and expand peripherally over years. Often annular or curved pattern
(tuberoserpiginous syphilid). More often on upper arms, back, or face. Gumma: firm, 1–3 cm
subcutaneous nodules that are painless and usually solitary, but frequently ulcerate
discharging a gum-like substance. Typical sites are palate, nose, scalp, and face. May also
involve liver, bone, or testes.
Musculoskeletal disease: periosteitis; osteolysis sometimes progressing to sclerosis of the
entire marrow cavity - ivory bones; gummata involving bone; juxtaarticular nodes - gummata
with no tendency to liquefication.
Cardiovascular diseases: about 10% of untreated patients develop cardiovascular syphilis. T.
pallidum involves the vasa vasorum and leads to aortic insufficiency and aneurysm
formation. Eighty per cent of the patients with syphilitic aortic disease die despite the
combined antibiotic therapy and surgery.
CNS diseases: in late syphilis, most neurological symptoms are caused by chronic vessel
inflammation. Asymptomatic neurosyphilis → CNS involvement is only detected by
examination of CSF, no signs or symptoms. Meningovascular neurosyphilis → main finding
in meningeal inflammation, usually with persistent headache. Numerous CNS thromboses
cause a variety of neurological and psychiatric symptoms. Gummata may also caused focal
defects. Diagnosis is based on CSF examination for cells and protein, serology and
neurologic examination
Late parenchymal problems, generally irreversible: 1. General paresis (Paralysis progressiva):
formerly known as general paresis (or paralysis) of the insane. About 2% of untreated
patients advance to this stage; symptoms appear 20–25 years after initial infection. The
anterior gray matter lobes are affected, which causes a wide spectrum of neurological and
psychiatric disease; 2. Tabes dorsalis - as common as general paresis. Changes in the dorsal
roots and posterior columns of spinal cord. Divided into three stages: 1. Anesthetic stage -
hypesthesia especially on the feet leads to neurotropic ulcers (mal perforant); lancinating
abdominal and extremity pain, and paralysis of ocular nerves. Argyll Robertson pupil
describes a pupil that is miotic and responds to accommodation effort but not to light. Pupil
abnormalities must be present for the diagnosis of tabes dorsalis; 2. Ataxic stage -
uncoordinated movements with typical slap walk and positive Romberg sign; 3.
Pseudoparetic stage - patients also develop signs and symptoms of paresis.
Diagnostic approach: CSF examination for cells and protein, serology and neurologic
examination.
Congenital Syphilis
Definition: Syphilis acquired in utero. Two subtypes: 1. Early congenital syphilis - lesions
occur during the first 2 years of life (analogous to primary syphilis, without chancre); 2. Late
congenital syphilis - lesions occur after 2 years of life (analogous to secondary syphilis).
Pathogenesis: The degree of fetal damage depends on the time of onset of mother infection
and appropriate treatment.
Early Congenital Syphilis
The fetus’s immature immune response allows syphilis to run a rapid and damaging course.
Prognosis is especially poor if signs and symptoms are present at birth.
Clinical findings:
– Present at birth - low birth weight, abnormally large placenta, hepatosplenomegaly,
blisters and erosions mainly on palms and soles (pemphigus syphiliticus), osteomyelitis.
Mortality rate 50%.
– Developing in first months in untreated infants - snuffles (chronic runny nose, often
bloody), periorificial rhagades, periosteitis and osteochondritis of long bones so painful that
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infants can not move limbs (Parrot pseudoparalysis), CNS disease (50%), glomerulonephritis
with nephrotic syndrome. Pemphigus syphiliticus may also appear here in delayed pattern.
Late Congenital Syphilis
Resembles late syphilis, but cardiac involvement is uncommon.
Clinical findings:
– Interstitial keratitis - appears at age 10–30 and affects about 10%, usually bilateral;
initially iritis, then corneal neovascularization and clouding. Treatment is topical
corticosteroids; sometimes corneal transplantation needed.
– Salt and pepper retina.
– Sensory deafness - develops at 10–20 years of age in 10–30%, usually bilateral.
– Neurosyphilis - late onset but affects 30–50%.
– Skin manifestations - gummata and nodular lesions.
Stigmata: Clinical lesions that develop secondary to congenital syphilis, even after treatment
- saddle nose, frontal bossing, maxillary hypoplasia, Higouménaki sign (thickening of medial
end of clavicle), saber shins, Clutton joints (effusions into large joints), gothic palate (high
arched palate), Parrot lines (periorificial furrowed scars). Dental changes - Hutchison incisors
(incisors shaped like tip of a screwdriver, often notched), Mulberry molar (first molars with
complex surface). The Hutchinson triad consists of Hutchison incisors, sensory deafness, and
interstitial keratitis.
Serologic Diagnosis of Syphilis

There are a number of serologic tests for syphilis. Two screening tests and two confirmatory
tests suffice for almost all circumstances. There are two basic categories of tests: 1.
Nontreponemal tests → identify antibodies against phospholipids such as lecithin or
cardiolipin. They are cheaper and more sensitive; 2. Treponemal tests → identify antibodies
against T. pallidum, more specific.
Treponema Pallidum Hemagglutination Test (TPHA Test)
Basis: Sheep erythrocytes coated with T. pallidum antigens are incubated with patient serum;
if antibodies are present, the red cells agglutinate.
Indications: Screening.
Evaluation: Highly specific; false positive under 0.1%; becomes positive in third week and
remains positive for life of patient.
Advantages: Easy to perform.
Disadvantages: Standardized reagents not available, expensive.
Venereal Disease Research Laboratory Test (VDRL Test)
Basis: Flocculation test. Nonspecific antibodies that react with both T. pallidum cell wall
phospholipids and cardiolipin are identified. The patient’s serum is mixed in a solution of
cholesterol, lecithin, and cardiolipin. If antibodies are present, a precipitate occurs. The serum
is diluted and the level at which precipitation occurs is verified. After treatment, the titer of
antibodies drops over months.
Indications: Screening and monitoring of therapy.
Evaluation: Highly sensitive non-treponemal test, 100% positive in secondary syphilis.
Advantages: Cheap, reproducible, worldwide usage, ability to titrate makes it quantitative.
Disadvantages: 10–20% false-positive results in diabetes, cirrhosis, autoimmune diseases,
pregnancy, viral diseases, advanced systemic malignancies, multiple blood transfusions,
advanced age, i.v. drug abuse.
Fluorescent Treponema pallidum Antibody Absorption Test (FTA–ABS Test)
Basis: A slide is coated with T. pallidum. Patient’s serum is absorbed with nonpathogenic
treponemes and then applied to slide. Antibodies bound to T. pallidum are identified with
immunofluorescence.
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Indications: Confirmatory.
Evaluation: Becomes positive in fourth week and remains so forever.
Advantages: Very sensitive and specific.
Disadvantages: Standardized reagents not available so reproducibility varies.
IgM–FTA–ABS Test
Basis: Same as FTA–ABS test, but only labeled anti-IgM antibodies are used to determine if
patient has IgM antibodies against T. pallidum.
Indications: Early diagnosis - IgM antibodies are the first to be produced, they can be found
before a chancre appears; Assessing disease activity - IgM production continues as long as
living T. pallidum are present in body, so it can determined weather latent phase is present or
not; Evaluating therapy - the IgM–FTA–ABS test usually turns negative 1 month after
therapy; always within 1 year; Diagnosis of congenital syphilis - IgM cannot cross the
placenta, so if the infant has IgM antibodies, T. pallidum has crossed the placenta;
Recognition of reinfection - increase in IgM antibodies coupled with VDRL titer increase
suggests second infection without clinical signs.
Advantages: Very sensitive and specific.
False-positive reactions: If the patient has a positive rheumatoid factor and treated syphilis,
then persistent IgG antibodies will bind to treponemes on the slide; rheumatoid factor
molecules bind to them and are identified by the labeled anti-IgM.
19S–IgM–FTA–ABS Test
Basis: If a patient has a large amount of IgG antibodies against T. pallidum and only a small
amount of IgM, then the IgG can block the test treponemes on the slide, giving a
false-negative test for IgM. To correct this, the 19 S fraction of serum where IgM is found is
separated out and only this portion used for testing.
Indications: Negative IgM–FTA–ABS test but appropriate history.
Evaluation of Serologic Tests
Confirmation of infection with T. pallidum: two positive tests with Treponema
pallidum-specific tests. Blood should be re-drawn for the confirmatory testing. An endemic
treponematosis must be excluded.
Assessing degree of activity: IgM–FTA–ABS becomes negative when T. pallidum has been
eliminated. VDRL titer 1:64 also suggests active disease.
Second infection: new appearance of IgM antibodies, and rapid increase in VDRL titer by 2
dilutions or more.
CSF Serologic Diagnosis
Absolute indications:
- Confirmed and treated early syphilis with delayed drop in titer (IgM still present 1
year after therapy).
- Confirmed early or late syphilis (treated or not) and development of
neuropsychiatric signs and symptoms.
- Patient with newly discovered positive serology, no previous documentation, and
neuropsychiatric signs and symptoms.
- Follow-up examination after positive CSF examination, 1 year after therapy.
- HIV infection.
Relative indications:
- Any early syphilis except primary syphilis.
- Latent syphilis without suitable history and documentation.
Technique: The CSF tests are analogous to the blood tests. At the same time, the CSF is
analyzed in routine fashion for cells and protein.
Therapy of Syphilis
Overview: Syphilis is a reportable disease in most countries. Therapy should be started after
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the diagnosis is completely confirmed (identification of T. pallidum or confirmatory
serological testing). Examination of sexual partners is recommended. Sexual contacts should
be avoided until treatment is completed.
Penicillin therapy: Penicillin G remains the treatment of choice; still no evidence of resistant
T. pallidum. Therapeutic serum level of 0.03 IU/mL must be maintained for 7 days. Tertiary
syphilis: treatment course 2–3 weeks. Intramuscular injections are preferred to oral therapy,
because of both unreliable patients and unreliable absorption. If PCN allergic: use TCN,
doxycycline, or azithromycin.
Endotoxine Shock (Jarisch-Herxheimer)
Jarisch and Herxheimer observed this reaction in syphilitic patients treated with mercury and
later during antibiotic treatment of the disease. It presents with anxiety, fever, rigor,
hypotension, tachycardia, vasodilation, myalgias and worsening of the skin lesions. Such
reaction is provoked by endotoxins released from bacterial cell membrane destruction after
initiation of antimicrobial treatment. Endotoxine reaction develops within the first few hours
after first dose of the antibiotic application and should be differentiated from
drug-hypersensitivity reaction. It may be observed in 50% of patients with primary and
about 90% of patients with secondary syphilis, but is self-limitining.
GONORRHEA
Common sexually-transmitted infection caused by Neisseria gonorrhoeae, affecting mucosa
and transitional epithelium; typically leading to urethritis in men and to an often
asymptomatic cervicitis in women.
Epidemiology.
WHO estimates 25.5 cases per 100 000 adult males as median rate in adult males. Peak ages:
18–25; more than 50% are under 25 years of age.
Sexually transmitted except for blennorrhea in newborns and some cases of vulvovaginitis in
prepubertal girls. Asymptomatic infection, usually in women is a significant reservoir of
gonorrhoea. Development of resistant N. gonorrhoeae strains is a worldwide problem.
Etiology and Pathogenesis.
N. gonorrhoeae is a Gram-negative coffee-bean shaped diplococcus. Initially mucosal
surfaces are infected: urethra, rectum, endocervix, pharynx, conjunctiva. There may be
regional and systemic complications.
Gonorrhea in Men
After intercourse with an infected women about 35% of men become infected. Incubation
period varies between 2-14 days, but most men develop signs between 3–6 days after
acquisition of the infection.
Clinical Presentation
Urethritis: In 70–85%, dysuria and purulent discharge. Between 15 and 30% of the infected
individuals are asymptomatic. Without treatment spontaneous resolution is expected within
days to weeks.
Regional complications: Acute epididymitis, chronic prostatitis, tysonitis, littreitis,
cowperitis. Systemic spread of the infection - joints, skin.
Differential diagnosis: Nongonococcal urethritis.
Gonorrhea in Women
After intercourse with an infected men 60–90% of women become infected. Incubation
period for urethritis is approximately 5–8 days. Often interpreted as cystitis. Eigthy per cent
of cases are asymptomatic. In case of cervicitis signs may be mild cloudy discharge and
erythematous ostium, but usually it is asymptomatic.
Regional complications:
- Inflammation of fallopian tubes (salpingitis); more common around menses.
- Peritonitis and perihepatitis (Fitz-Hugh–Curtis syndrome). May cause adhesions.
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- Pelvic inflammatory disease: chronic abdominal pain, dyspareunia, infertility, and tubal
pregnancy.
Anorectal gonorrhea: Present in 40–50% of women with cervical or urethral gonorrhea;
higher percentage of male homosexuals. Often overlooked clinically; usually asymptomatic
(85%) or mistaken for normal discharge.
Pharyngeal gonorrhea: Disease of women and male homosexuals; not clinically distinctive.
Asymptomatic in 90% of cases.
Disseminated Gonococcal Infection (Gonococcal Sepsis)
Epidemiology:
Disseminated gonococcal infection occurs in 1–3% of patients with gonorrhea. At greatest
risk are menstruating females who are asymptomatic carriers.
Pathogenesis:
Strains of N. gonorrhoeae that cause this complication are usually exquisitely
penicillin-sensitive.
Clinical Features
Patients usually have systemic signs and symptoms: fever, chills, malaise. Polyarthralgia
without arthritis. Tenosynovitis. Dermatitis → tender grey pustules on erythematous base,
often over joints, histologically characteristics of septic vasculitis.
Gonococcal arthritis → at start, polyarthritis (knee, ankle, hand), later monoarthritis (almost
always knee). Diagnosis is based on isolation of N. gonorrhoeae in joint aspirate.
Other rare systemic complication are endocarditis and meningitis.
Gonorrhoea in Children
– Vulvovaginitis in children: the vagina is more easily infected in prepubertal girls. N.
gonorrhoeae causes a purulent vulvovaginitis. Differential diagnosis includes other bacterial
infections (from perianal region, herpes simplex, foreign bodies, irritating bubble baths).
Microbiology culture test for gonococci should be performed. Sexual abuse should be taken
into consideration in cases of vaginal discharge in a prepubertal girl.
- Gonococcal blennorrhea: infection is inoculated through direct spread of bacteria during
passage through birth canal; less often in adults by direct contact. Erythema and swelling of
the lids, conjunctivitis, and pus-laden discharge. Risk of corneal ulceration. Extremely rarely
because of the obligatory prophylaxis of newborn babies with 1% Silver nitrate (method of
Credé).
Diagnosis
Direct smear. Urethral or cervical smear with Gram or methylene blue stain.
Indirect identification. Dried smear labeled with immunoassay; not suited for pharyngeal or
rectal smears.
Culture. Specimen from culture urethra, cervix, rectum, oropharynx is used. Also first-catch
urine sediment following centrifugation. Selective medium (most commonly Thayer–Martin)
is used and cultivated at 37oC with CO2 enrichment. The colonies appear after 24–36
hours.They stain dark with dimethyl-paraphenylene diamine (oxidation reaction). Positive
microscopy and oxidation reaction together have more than 99% accuracy.
Therapy
As co-infection with chlamydia is frequent (25–50%), many countries recommend adding
anti-chlamydial therapy to any regimen for gonorrhea.
Another important consideration is increased numbers of penicillinase-producing Neisseria
gonorrhoeae (PPNG) strains, as well as multi-resistant strains in different parts of the world.
Uncomplicated urethral gonorrhea:
Intramuscular spectinomycin 2 g or ceftriaxone 250 mg, each as single dose.
Oral cefixime 400 mg, ciprofloxacin 500 mg, ofloxacin 400 mg, azithromycin 1 g, each as
single dose. Azithromycin also covers chlamydial infection.
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For treatment of co-infection with chlamydia: doxycycline 100 mg b.i.d. for 7 days or
azithromycin 1 g in a single dose.
Pharyngeal gonorrhea: Intramuscular ceftriaxone is preferred but oral quinolones are also
used.
Anal gonorrhea: Intramuscular therapy is preferred.
Complicated/disseminated gonorrhea:
Ceftriaxone 1–2 g i.m. or i.v. 1 daily for 7 days (b.i.d. if meningitis or endocarditis).
Cefotaxime 1.2 g i.v. t.i.d. for 7 days.
Alternatives for β-lactams allergy:
Spectinomycin 2 g i.m. b.i.d. for 7 days;
Erythromycin 500 mg i.v. q.i.d. for 7 days.
If epididymitis is present, prednisolone 30 mg daily and NSAIDs are added.
Mixed infections: Because of the high likelihood of coexistent chlamydial or anaerobic
infections, most regimens for pelvic inflammatory disease recommend broader coverage, e.g.
second-generation cephalosporin and metronidazole or doxycycline, clindamycin and
gentamicin.
Pregnancy: Erythromycin 500 mg i.v. q.i.d. for 7 days.
Blennorrhea:
Adults - Ceftriaxone 1 g i.m. (single dose usually suffices).
Infants - Ceftriaxone 25–50 mg/kg i.v. or i.m. (single dose usually suffices). Rinsing eyes
with physiological saline.
Children – Ceftriaxone 25–50 mg/kg i.v. or i.m. 1 x daily for 7 days (10–14 days if signs and
symptoms persist); Cefotaxime 25 mg/kg i.v. or i.m b.i.d. for 7–14 days. If over 50 kg, adult
dose.
Additional measures: Treatment of sexual partners.
Ruling out syphilis or HIV co-infections.
Follow-up: Culture 4–7 days after therapy. Rectal culture on all women with gonorrhea.
Rectal and pharyngeal cultures on all homosexual men with gonorrhea.
Recurrent gonorrhea: Culture and treatment of all sexual partners, rectal and pharyngeal
cultures.
URETHRITIS
Urethritis is a clinical syndrome characterized by urethral inflammation resulting from
infectious and non-infectious etiological agents. It may be asymptomatic in up to half of the
affected individuals.
Classification of Urethritides
Gonococcal - 20% of the cases, caused by N. gonorrheae.
Non-gonococcal:
- Chlamydia trachomatis 15-40%
- Ureaplasma urealyticum 10-40%
- Mycoplasma genitalium 15-25%
- Trichomonas vaginalis 5-15%
- Herpes simplex – unknown frequency
- Candida and other bacteria (Haemophilus spp., enteric, anaerobes, E. coli) <5%
- Noninfectious - autoimmune, chemical, allergic, etc.
Epidemiology.
Significantly under-reported.
Worldwide incidence: 89 million new cases of non-gonococcal urethritis are reported each
year. US 3 million new cases annually.
No racial predilection. Peak age 20-24 years. Both sexes are affected equally. Up to 75% of
female patients can be asymptomatic or may present with symptoms of cystitis, vaginitis, or
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cervicitis.
Clinical presentation.
Dysuria, urethral discharge, pain, itch, systemic symptoms (fever, chills, nausea, eye
symptoms, joint tenderness, rash). Asymptomatic urethritis in 25 % of all cases.
A. Sexually-Transmitted Urethritis
Acute or chronic urethritis, caused by pyogenic aerobic or anaerobic bacteria. Can be

complicated with epididimitis or prostatitis. Diagnosis is made after microbiological
exclusion of gonococcal, chlamydial and mycoplasma infections.
Etiology
Gram(+) cocci - Staphylococcus aureus, St. epidermidis, St. albus, Streptococcus gr. B, gr. D;
Gram (-) cocci - Haemophylus; Other Gram (-) bacteria - Escherichia coli, Shigella spp.,
Proteus spp., Acinetobacter; Anaerobic bacteria - Gram (+) (Peptococcus,
Peptostreptococcus, Clostridium, Bacteroides); Gram (-) (Mobiluncus), etc.
Predisposing factors: Sexual intercourse during menstuation, anal intercourse, immunological
factors (Reiter's syndrome, erythema multiforme).
Epidemiology.
No exact data on prevalence. Males are affected, heterosexual males twice more commonly.
Urethral discomfort, burning sensation during urination, mild itch in distal urethra, erythema
of urethra orifice, scarce mucous or purulent discharge.
Laboratory Tests.
Gram stain of urethral exudate; microbiological culture test, leucocytosis in first-catch urine.
Diferential diagnosis: other bacterial, viral, or mycotic urethritis, not sexually transmitted
urethritis.
Treatment
Doxycycline 2 x 100 mg/daily 7 days; Erythromycine 4 x 500 mg/daily 14 days;
Azythromycine 1 g single dose. Reccurencies are expected in 20 - 40 % in the next 6 weeks.
Patients should avoid sexual contacts during treatment. Sexual partners from previous month
should also be tested. In case of anaerobic infection - Metronidazole 2 x 500 mg/daily for 7
days or 2 g single dose.
B. Not – Sexually Transmitted Urethritis
Etiology
Viral urethritis - herpes simplex; Bacterial urethritis – caused by Staphylococcus aureus,
Streptococcus, Escherichia coli, Proteus mirabilis; Mycotic urethritis – Candida albicans;
Traumatic urethritis - foreign bodies, nephrolytiasis, medical procedures; Urethritis caused by
chemical factors - desinfectants, alcohol, spicies; Allergic urethritis - local anesthetics, drugs
(sulphonamides, antibiotics, spermicides), food, cosmetics; Congestive urethritis - excessive
sexual behaviour, sports - horse riding, biking, motorcycle-riding.
Frequent miction, sensation for incomplete urination, premature ejaculation, involuntary
ejaculation, pain radiating to the perineum, urethral discharge, dysuria, urinary frequency and
urgency, urethral itching or irritation may persist between voids, sexual disturbances.
Examination:
Microscopic evaluation of urethral secretion, Gram stain, microbial culture test.
Treatment
. Infectious urethritis is treated with appropriate antibiotic or antimycotic drug. Allergic
urethritis is treated with antihistamines or steroids. Uroantiseptics
(trimethoprim/sulfamethoxazole; nitrofurantoin) may be prescribed in case of inconclusive
evidence for infectious etiology of the urethritis. Patients should avoid alcohol consumption,
coffeine, carbonated drinks, hot spices, sexual intercourse during treatment. Sufficient fluid
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intake.
HIV INFECTION AND AIDS

Epidemic infection with the human immunodeficiency virus HIV-1 or HIV-2.
AIDS: Acquired immunodeficiency syndrome — advanced stage of HIV infection defined by
the presence of AIDS-defining illnesses and reduction in CD4 cells (CD4 T cells).
Epidemiology.
HIV-1 began to spread in the 1970s. It presumably arose from monkey retroviruses in Africa.
Groups with high seropositivity: Male homosexuals with multiple partners, intravenous drug
abusers, recipients of blood or organs, sexual contacts of HIV individuals, infants born to
HIV positive women. HIV-2 started in West Africa in the 1980s and spread to India in the
1990s; does not play a role in Western Europe or USA.
At the end of 2004, around 40 million people worldwide were infected with HIV, with 5
million new infections yearly. There were 3 million deaths from AIDS in 2004.
Etiology.
HIV-1 and HIV-2 are retroviruses in the lentivirus group. They are single-stranded RNA
viruses employing reverse transcriptase with an affinity for CD4 cells which exert cytopathic
and cytolytic effects. In the course of the infection, new mutations in HIV appear.
Pathogenesis. Methods of Transmission
Sexual intercourse - most common; men more likely to infect women than vice versa;
male homosexuals still a risk group.
Perinatal - during birth or in the perinatal period by nursing.
Blood inoculation - shared needles among drug abusers; improper sterilization of
needles; injuries to health care workers and laboratory personnel.
Transfusions - risk of receiving HIV-infected blood very small when proper screening
procedures used.
Organ transplantation - risk also very small.
Saliva - controversial; risk extremely low, if any.
No transmission by close personal contact or insects.
Clinical Classification (According to Centers for Disease Control Staging)
HIV infection is divided into three clinical categories (A, B, C) and three levels of CD4 cells.
Once the infection has reached a given stage, there is no upgrading, even in the face of
clinical improvement or increasing CD4 counts.
CD4 T-cell Clinical Category A Clinical Category B Clinical Category C

Counts Category (Asymptomatic) (not A or C) (AIDS Indicator
Condition)
≥500/mm³ A1 B1 C1
200-499/mm³ A2 B2 C2
<200/mm³ A3 B3 C3
Category A: Documented HIV infection but none of the conditions listed in B or C:

- Asymptomatic HIV infection. Persistent generalized lymphadenopathy (lasting 3 months
in at least two extrainguinal locations).
- Acute primary HIV infection. Resembles infectious mononucleosis with
lymphadenopathy, fever, malaise, and a rash on the trunk.
Category B: Documented HIV infection, accompanying illnesses which are not
AIDS-defining (category C) but suggest immunodeficiency:
- Bacillary angiomatosis.
- Candidiasis, oropharyngeal (thrush). Candidiasis, vulvovaginal, balano-postitis;
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persistent, frequent or poorly responsive to therapy.
- Cervical dysplasia or carcinoma in situ.
- Constitutional symptoms (fever 38.5oC or diarrhea for one month).
- Zoster involving multiple dermatomes or recurrent.
- Idiopathic thrombocytopenic purpura.
- Listeriosis.
- Pelvic inflammatory disease, especially with complications.
- Oral hairy leukoplakia.
- Peripheral neuropathy.
Category C: Documented HIV infection, AIDS-defining illness.
- Candidiasis of bronchi, trachea, or lungs. Candidiasis, esophageal.
- Cervical carcinoma, invasive.
- Coccidioidomycosis, disseminated or extrapulmonary.
- Cryptococcosis, extrapulmonary.
- Cryptosporidiosis, chronic (1 month).
- Cytomegalovirus (CMV) infection (other than liver, spleen, or lymph nodes). CMV
retinitis (with loss of vision).
- Encephalopathy, HIV-related.
- Herpes simplex virus infection: chronic (1 month) ulcers or herpetic bronchitis,
pneumonia, or esophagitis. Histoplasmosis, chronic (1 month); disseminated or
extrapulmonary.
- Isosporiasis, chronic (1 month).
- Kaposi sarcoma.
- Lymphoma (Burkitt lymphoma, primary effusion lymphoma, or CNS lymphoma, as
well as others).
- Mycobacterium avium-intracellulare or Mycobacterium kansasii infections,
disseminated or extrapulmonary.
- Mycobacterium tuberculosis, any site.
- Mycobacterium, other or unidentified species, disseminated or extrapulmonary.
- Pneumocystis carinii pneumonia (main signs and symptoms → dry cough, dyspnea,
fever).
- Pneumonia, recurrent.
- Progressive multifocal leukoencephalopathy (JC virus).
- Salmonella septicemia, recurrent.
- Toxoplasmosis of brain (main signs and symptoms → focal neurologic findings,
headache, loss of consciousness, seizures, fever).
- Wasting syndrome (HIV cachexia).
Patients in subcategories A3, B3, and C3 meet the immunologic criteria for AIDS, those in
C1, C2, and C3 meet the clinical criteria.
Cutaneous and mucosal manifestations of HIV infection
1.Infections
1.1. Fungal infections
- Candida infections of the oral mucosa; appearance in adult life without explanation
or with ulceration. Heartburn in an HIV-positive patient is candidal esophagitis until proven
otherwise.
- Severe seborrheic dermatitis.
- Onychomycosis, tinea pedis or disseminated tinea corporis.
- Cutaneous cryptococcosis (nodules resembling molluscum contagiosum).
1.2. Bacterial infections:
- Acneiform exanthems triggered by Staphylococcus aureus (superficial folliculitis) or
Malassezia species. Occasional no causative agent is found.
125
- Pyoderma, ecthyma.
- Mycobacterial infections → Mycobacterium avium-intracellulare.
- Bacillary angiomatosis (caused by Bartonella). Differential diagnosis: Kaposi
sarcoma, pyogenic granuloma.
- Exanthems associated with variety of infections. All STIs are more common
(syphilis, chancroid, herpes genitalis).
1.3. Viral infections:
- Ulcerated persistent (usually perianal) herpes simplex.
- Zoster appearing at young age, often recurrent. Condylomata acuminata, recurrent,
therapy-resistant, widespread.
- Common and plane warts, widespread, therapy-resistant.
- Mollusca contagiosa, numerous, occasionally giant.
- Kaposi sarcoma.
- Oral hairy leukoplakia.
Other Skin Diseases Associated with HIV/AIDS
Xerosis, acquired ichthyosis, pruritus
Psoriasis
Reiter syndrome
Pityriasis rubra pilaris
Anal dermatitis
Eosinophilic folliculitis, papular dermatitis of AIDS (perhaps identical)
Increased number of drug reactions
Alopecia
Elongated eye lashes (acquired trichomegaly)
Nail changes include yellow nail syndrome, leukonychia, splitter hemorrhages, linear
hyperpigmentation secondary to antiretroviral therapy
Vasculitis, such as polyarteritis nodosa or leukocytoclastic vasculitis
Telangiectasias, cherry angiomas
Scabies, often crusted scabies
Idiopathic thrombocytopenic purpura
Aphthae
Kaposi Sarcoma
Vascular tumor caused by human herpes virus 8. It classically affects elderly men in Europe,
but affects children in Africa and is seen with both HIV infection and iatrogenic
immunosuppression. The skin is most often involved, but the gastrointestinal tract and other
internal organs may also be affected. Typical lesions are red-brown macules or papules,
usually initially following skin lines. Later nodules and ulcerated plaques. Oral involvement
is particularly common in HIV/AIDS. Probability for HIV/AIDS is higher if Kaposi sarcoma
is identified in a young patient, or occurs on the face or in the mouth.
Oral Hairy Leukoplakia
One of the most sensitive clinical signs for HIV/AIDS, and a poor prognostic sign. Fine
filamentous strands are found on the lateral edges of the tongue. They are asymptomatic but
firmly adherent. The primary cause is Epstein–Barr virus, but the lesions frequently contain
human papillomavirus (thought to be a co-factor) and are colonized by candida albicans.
Usually improves with highly active antiretroviral therapy (HAART). Topical retinoids may
also produce improvement.
Extracutaneous Manifestations of HIV/AIDS
Almost every organ can be involved in HIV/AIDS. Common complications: pulmonary
infections; retinal CMV infection with risk of sudden blindness; neurological and psychiatric
problems; chronic diarrhea; several unusual lymphomas, and a broad spectrum of drug side
effects including life-threatening toxic epidermal necrolysis.
126
Diagnostic Approach
History
- Travel - Southeast Asia, Africa.
- Sexual practices - Homo-, bi-, heterosexual; number of partners; unprotected sexual
intercourse; contact with prostitute, members of risk groups or individuals known to have
HIV/AIDS. Sexually transmitted infections (syphilis, gonorrhea, others).
- Other infectious diseases - hepatitis B, hepatitis C, zoster, candidiasis, tuberculosis,
histoplasmosis, coccidioidomycosis.
- History of intravenous drug use, blood transfusions or other blood product
replacement, organ transplantation, injuries with contact with infectious materials.
- Other diseases with intrinsic or iatrogenic immunosuppression.
Clinical examination:
- Inspection of entire skin surface and accessible mucosa. Close search for skin
infections that are common in HIV/AIDS.
- Evaluation of lymph nodes with documentation.
- Weight.
- Auscultation and percussion of lungs.
- Palpation of abdomen (liver, spleen, other masses).
- Neurological status.
- Retinal examination (CMV retinitis).
Laboratory examination:
- CD4 absolute count and CD4/CD8 ratio.
- Complete blood count (CBC).
- Hepatic and renal function tests.
- Serology - antibodies against hepatitis A, B, and C, syphilis, toxoplasmosis, CMV,
Epstein–Barr virus.
Diagnosis of HIV
Legal aspects. HIV testing can only be done with the written permission of the
patient. The results of the test are absolutely confidential. The confidentiality can legally be
broken to protect others at risk of HIV/AIDS, such as sexual partners or a health care worker
exposed to patient’s blood or serum.
Technical aspects. ELISA test is used for screening, confirmation with Western blot.
Two different blood specimens (not two different tests) must be positive before the patient is
considered HIV-positive.
Meaning of a positive test. HIV infection is present, this does not equate to AIDS. The
prognosis of an HIV infection cannot be stated at the time of first diagnosis, there are too
many variables.
Meaning of a negative test. The possibility of an HIV infection acquired in the past 3–6
months is not excluded.
Further Testing
Viral load. Quantification of HIV load. Several techniques are used: RNA–PCR,
branched DNA signal amplification assay (b-DNA-SA) or nucleic acid sequence based
amplification (NASBA). In order to allow the viral load tests to be compared, results are
expressed in copies/mL.
HIV resistance analysis (genotypic). Should be carried out before switching retroviral
therapy.
Therapeutic Principles
The treatment of HIV infection with retroviral agents is one of the most rapidly changing and
complex areas of medicine. Physicians should be familiar with the most recent national or
international therapeutic guidelines. The success of the various HAART regimens means that
many patients with newly diagnosed HIV infections will not die from their disease. The first
127
regimen prescribed should be highly active and contain multiple agents. The quicker the viral
load is reduced, the longer the treatment is likely to be effective. More than 20 agents are
approved worldwide for antiretroviral therapy. In each case, individual decisions should be
based on methods of administration, side effects and cross-reactions, as well as associated
diseases. Lymphocyte sub-populations and HIV load should be measured every 3 months.
Routine blood work including CBC, liver, and kidney function should be checked every 4–6
weeks initially, and then less often as indicated.
In the case of therapy failure, resistance analysis should be carried out.
Three classes of therapeutic agents are available.
1. Fusion inhibitors block the entry of HIV into cells.
2. Reverse transcriptase inhibitors (RTI) block the translation of viral RNA into DNA.
- nucleoside analogs (NRTI)
- one nucleotide analog (NtRTI)
- non nucleoside inhibitors (NNRTI)
3. Protease inhibitors (PI) block the maturation and discharge of new viral particles.
Indications: The tendency is to treat in as soon as the diagnosis is made, but most recent
guidelines should be followed. Patients with a reduced CD4 cell count or manifestations of
disease are generally treated.
Therapeutic Approach
Treatment is usually started with 2 NRTI combined with a NNRTI or a PI. An effective
response is indicated by a 10–100-fold reduction in the viral load in the first 2–4 weeks. A
less rapid drop suggests suboptimal therapy. After 3 months, the viral load should be below
measurable levels. Opportunistic infections are treated as indicated by infectious disease
guidelines and consultation. The use of HAART has reduced the need for prophylaxis, but
after the occurrence of an infection, prophylactic measures should be reviewed.
Treatment of Kaposi sarcoma. Cosmetically or functionally disturbing stable lesions →
excision, cryotherapy, intralesional injection of vinblastine, ionizing radiation.
Disseminated non-pulmonary disease with CD4 cell count 200 L → HAART plus IFN-α.
Disseminated progressive disease with CD4 cell count 200 L → HAART plus liposomal
doxorubicin.
Prevention of HIV
Education of all at-risk groups, widespread availability of condoms, consideration of needle
exchange programs for drug abusers, and screening of prostitutes.
BALANITIS AND BALANOPOSTHITIS

Balanitis.
Inflamatory process affecting glans penis.
Balanoposthitis.
Inflamatory process affecting glans penis and the internal sheet of prepuce.
Etiology
Trauma; chemical irritants → soaps, detergents, etc.; infectious agents → yeasts (Candida),
dermatophytes, bacteria (Streptococcus spp., Staphylococcus spp., Pseudomonas aeruginosa,
Chlamydia trachomatis, Mycoplasma, Neisseria gonorrhoeae, Treponema pallidum,
Haemophilus ducreyi, Calymmatobacterium granulomatis, Bacteroides spp., Gardnerella
vaginalis, Mycobacterium tuberculosis); parasites (Entamoeba hystolyticum, Trichomonas
vaginalis); viruses (Herpes simplex, Human papilloma virus, etc.);
medications → foscarnet for example causes nectoric and ulcerous lesions on glans penis and
prepuce.
128
Erythema, varying degree of exudation. Yellow-to-black discoloration and desquamation may
also be observed. Balanoposthitis may be associated with lichenification, or HPV lesions.
An association exists between nonspecific balanoposthitis and the uncircumcised penis.
Laboratory Studies
Potassium hydroxide (KOH) slide preparation for candidal hyphae visualization and culture
for Candida species. Microbiology culture test for pathogenic bacteria.
Biopsy is used when premalignant or malignant lesions need to be excluded.
Treatment
Topical antibiotics and antifungals.
Low-potency steroid creams for contact dermatitides.
Proper hygiene with frequent washing and drying of the prepuce is an essential preventive
measure.
Circumcision may be advocated in recurrent and recalcitrant cases.
Other Skin Diseases with Lesions on Glans Penis
Bipolar aphthosis (Behcet's disease).
Circinate balanitis (Reiter's syndrome): Classic triad → arthritis, urethritis, conjunctivitis.
Typical skin manifestations are circinate balanitis, plantar keratoderma, stomatitis.
Tests → HLA-B27 (75% of the patients), enteric pathogens (Salmonella enteriditis, Yersinia
enterocolitica, Shigella, Mycoplasma spp., Campylobacter).
Balanitis plasmocellularis (Zoon). Balanitis resembling erythroplasia with benign evolution,
histopathology shows plasmocytic infiltrate.
Erythroplasia Queyrat. Single or multiple slowly spreading red velvety plaques with
well-demarkated edges. Nodular lesions covered with crusts or easily bleeding may appear.
Itch, pain, bleeding are the commonest complaints. Histopathology → intraepithelial
neoplasia. Metastases in 30% of the patients.
VULVITIS AND VULVOVAGINITIS
Vulvitis.
Inflammation of the vulva including minor and major labia, clitoris and introitus.
Vaginitis.
Inflamation of vaginal mucosa, and usually co-exists with vulvitis.
Classification
Infectious vulvovaginitis: viral (Herpes simplex);
bacterial (Neisseria gonorrhoeae, Staphylococcus aureus, Streptococcus, Escherichia coli,
Chlamydia trachomatis, Mycoplasma hominis, Fusobacterium fusiforme, Leptothrix,
Corynebacterium minutissimus, Proteus mirabilis, etc.); mycotic (Candida albicans).
Parasitical vulvovaginitis: protozoan (Trichomonas vaginalis).
Bacterial vaginosis.
Traumatic vulvovaginitis.
Vulvovaginites caused by chemical substances (antiseptics, irritants).
129
Allergic vulvovaginitis (local contraceptives, drugs, cosmetics, etc.).
Cyclic vulvovaginitis.
Vulvar vestibulitis.
Vaginal discharge, erythema and edema of vaginal and vulvar mucosa. Pain, burning
sensation, itch, discomfort.
Laboratory Studies
Wet-mount test
Gram stain
Vaginal culture test
Viral Vulvovaginitis
Primary herpetic vulvovaginitis – incubation period 3-7 to 20 days, general malaise, fever,
headache. Vesicles on erythematous base, erosions, crusts. Pain, burning sensation and
pruritus are the leading complains. Enlarged lymph nodes, sometimes dysuria and retention
of urine. Evolution 2-6 weeks.
Relapses of Herpetic Vulvovaginitis
Provoking factors: menstrual cycle, other infections, febrile states, UVB exposure, fatigue,
trauma, stress, medical procedures.
Clinical Picture:
crop of vesicles, forming erosions, healing without scars.
Symptoms: paresthesias, itch, burning.
Evolution: 6-7 days.
Active herpetic lesions increase the risk of viral transmission from mother to child during
delivery. Herpes simplex virus may cause life-threatening complications in the newborn.
Chlamydial Vulvovaginitis
Affects 8-10 % of females with chlamydial infection. Presents with vaginal discharge, itch,
burning sensation. Sometimes pain during sexual intercourse is the only symptom.
Gonogoccal Vuvlovaginitis
Little girls are affected. The infection is transmitted during delivery or use of objects,
contaminated with Neisseria from female patients. Clinically presents with erythema and
edema of vulva and vagina, and purulent vaginal discharge.
Non-Specific Bacterial Vulvovaginitis
Caused by saprophytic microorganisms, which become pathogenic due to other bacterial
infections, prolonged antibiotic therapy, hormonal or immunological abnormalities,
contraceptive methods, congenital malformations, medical procedures, etc. Often those
vaginitis is caused by Staphylococcus aureus, Streptococcus spp., Escherichia coli,
Fusobacterium fusiforme, Borrelia vincentii and Leptothrix. Proteus mirabilis, Pseudomonas
aeruginosa and Klebsiela may also cause inflammation of vagina and vulva, but the clinical
presentation is nonspecific.
Treatment
is dependent on etiology.
130
CHLAMYDIAL GENITAL INFECTIONS
Etiology
. Chlamydia trachomatis (serotypes D–K).
Men
Urethritis: Incubation period varies from 1 to 3 weeks. Presents with minimal discharge and
dysuria. In smear, 5 WBC per oil immersion field without gonococci. Spontaneous resolution
is possible, but recurrences are expected. In 25–50% of cases, accompanying gonorrhea.
Epididymitis: usually unilateral swelling and induration of testes. Fever and severe pain.
Usually associated with urethritis.
Reiter syndrome: Urethritis, arthritis, conjunctivitis, psoriasiform skin lesions. Chlamydia are
common triger along with bowel flora.
Proctitis: Usually MSM (man having sex with man) are affected. Presents with rectal pain,
discharge, diarrhea. Microbiology for gonococci is negative, neutrophils in rectal smear may
be found.
Women
Cervicitis: purulent or watery vaginal discharge with cervical erosions.
Salpingitis (pelvic inflammatory disease) → most common cause of acute infection.
Urethritis: painful urination without hematuria or urge, often associated with cervicitis.
Children
Pneumonia → acquired during delivery, often leading to permanent lung damage.
Conjunctivitis → common, but rare long-term complications.
Laboratory Studies
Smear and methylene blue stain; 4 WBC/oil immersion field and no
gonococci; fluorescent-labeled monoclonal antibodies also available.
Method of choice: PCR or ligase chain reaction (LCR) of cervical smear (women) or first
urine (men); almost 100% specificity and over 80% sensitivity.
Cultures and serologic procedures not necessary for routine practice.
Treatment
Doxycycline 100 mg b.i.d. for 7 days or Azithromycin 1 g in single dose.
Alternatives: Tetracycline 500 mg q.i.d. for 7 days, Erythromycin 500 mg b.i.d.for 14 days.
In pregnancy → Erythromycin.
With chronic disease, longer courses (10–14days).
Epididymitis: Hospital treatment, prednisolone 30 mg daily and NSAIDS.
Pelvic inflammatory disease: Hospital treatment with Minocycline and Ciprofloxacin.
Mandatory treatment of sexual partners.
TRICHOMONIASIS
Caused by the protozoan Trichomonas vaginalis. Symptoms vary, most people are
asymptomatic.
Epidemiology
W>M. Incubation period is thought to be between 5 and 28 days.
Older women are more likely to become infected. In women vulva, vagina, cervix and urethra
131
are affected. In men the most common clinical presentation is urethritis. About 70% of
infected individuals are asymptomatic.
Clinical Picture in Men
Symptoms range from mild to severe urethritis, complicated with prostatitis. Discharge
(purulent to mucoid in character), dysuria, and urethral pruritus. Some patients report pain in
the urethra, testicular pain, or lower abdominal pain.
Clinical Picture in Women
Abnormal vaginal discharge (may be purulent, frothy, or bloody). Abnormal vaginal odor
(often described as musty). Vulvovaginal itching, burning, or soreness. Dyspareunia and
dysuria (pain during urination). Patients may also complain of postcoital bleeding and lower
abdominal pain. Cervicitis due to trichomoniasis is characterized by 2 major signs: purulent
discharge in the endocervical canal and easily induced endocervical bleeding. The infection
may persist for months or years without treatment. Trichomoniasis increases the risk of
acquiering other sexually transmitted infections. Pregnant women with trichomoniasis are
more likely to have preterm delivery. Babies born by infected mothers are more likely to have
a low birth weight.
Laboratory Studies
Wet mount microscopy has a low sensitivity (estimated at 50-70%). Culture is the current
standard for diagnosis → more sensitive and specific than microscopy, always useful in
individuals with suspected resistant trichomoniasis. Culture is especially important for
diagnosing trichomoniasis in men, in whom wet mount preparations are particularly
unreliable.
Molecular Techniques for Detecting Antigen, DNA, or RNA.
These tests are highly specific for T. vaginalis with specificity ranging from 92% to 100%.
Nucleic acid amplification tests' sensitivity ranges from 76% to 100% making these tests
suitable for screening of asymptomatic patients.
Treatment
Metronidazole or Tinidazole taken orally. To prevent reinfection: no sexual intercourse for
7-10 days after the treatment.
132
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DERMATOLOGY AND VENEREOLOGY

HANDBOOK FOR MEDICAL, DENTAL AND PHARMACY STUDENTS

Sonya Márina, MD, PhD

Valentina Broshtilova, MD, PhD

Filka Georgieva, MD, PhD

Zhenya Dimitrova, MD, PhD

This handbook is a humble contribution and modest attemp to provide a comprehensive

Ultimately, it may be a useful tool for all Board-preparatory specializing dermatologists.

Temperature Regulation and Secretory Function

Diagnostic Approach to Skin Diseases

Skin Histopathology Changes

Skin Allergic Tests

Wood Lamp Examination

Antiviral drugs,????/ Pregnancy Category Miscellaneous

Vitamins for Systemic Treatment

Photosensitization and Photoprotective Drugs

Vasodilators and Vasotonic Drugs

Topical Preparations According to Mechanism of Action

Ciclopirox olamine 1% is a synthetic broad-spectrum fungistatic agent that inhibits fungal

Lasers (Light Amplification by Stimulated Emission of Radiation)

Cryosurgery. Electrosurgery. Curettage

Climatotherapy. Thalassotherapy. Balneotherapy

Atopic Dermatitis (AD)

ADVERSE CUTANEOUS DRUG REACTIONS (ACDRs)

PIGMENTARY DISORDERS (Vitiligo; Oculocutaneous Albinism; Melasma;

ERYTHEMATOUS DISEASES (Erythema Nodosum; Erythema Multiforme)

Erythema Multiforme (EM)

PAPULOSQUAMOUS, LICHENOID AND ECZEMATOUS DERMATOSES

IMMUNOBULLOUS DISEASES (Pemphigus; Pemphigoid; Dermatitis

CONNECTIVE TISSUE DISEASES (Lupus Erythematosus; Dermatomyositis;

VASCULITIDES AND VASO-OCCLUSIVE DISEASES (Vasculitis; Henoch-Schönlein

Henoch-Schönlein Purpura (HSP)

Chronic Venous Insufficiency (CVI)

SKIN APPENDICES DISEASES

Diseases of Pilosebaceous Unit (Acne Vulgaris; Rosacea; Perioral Dermatitis)

DISEASES OF THE MOUTH

Conditions of the Tongue, Palate and Mandible

Diseases of the Gingiva, Periodontium, and Mucosa

Cutaneous Diseases Involving the Mouth

MUCOSAL DISEASES (Chronic Benign Aphthosis. Behçet’s Disease)

BENIGN NEOPLASMS AND HYPERPLASIAS (Nevi; Vascular Tumors;

Vascular Tumors (e.g. Hemangiomas, Hemangioma of Infancy (HI) (Formerly

Miscellaneous Cysts and Pseudocysts

Miscellaneous Benign Neoplasms and Hyperplasias

Benign Dermal and Subcutaneous Neoplasms and Hyperplasias

PRECANCEROUS DERMATOSES (Actinic Keratosis; Cutaneous Horn; Squamous

MALIGNANT SKIN TUMORS

Squamous Cell Carcinoma (SCC)

Cutaneous Melanoma. Lentigo Maligna

Human Papillomavirus Infections

Orf (Contagious Pustular Dermatosis, Ecthyma Contagiosum)

Bacterial Infections (Pyococcal Infections; Mycobacterial Infections; Spirochetal

Mycobacterial Infections (Tuberculosis; Leprosy)

Leprosy (Hansen’s Disease)

Fungal Infections (Tinea Versicolor; Dermatophytosis; Candidiasis)

Stage Time after infection (years) Disease

Late syphilis >2 Tertiary syphilis

Serologic Diagnosis of Syphilis

Acute or chronic urethritis, caused by pyogenic aerobic or anaerobic bacteria. Can be

HIV INFECTION AND AIDS

CD4 T-cell Clinical Category A Clinical Category B Clinical Category C

Category A: Documented HIV infection but none of the conditions listed in B or C:

BALANITIS AND BALANOPOSTHITIS