Pathology week x – Skin ver.2

Cells contributing to protective function - squamous epithelial cells (keratinocytes) – majority of epidermal cells, major mechanical barrier, also source of cytokines that regulate cutaneous environment - melanocytes – produce melanin pigment to screen UV light - langerhans cells – dendritic cells process and present antigen to activate the immune system - neural end organs – detect pain and temperature - sweat glands – cooling - hair follicles – hair shafts, repositories for epithelial stem cells

Macroscopic Terms Macule circumscribed lesion < 5 mm, flat, distinguished from surrounding skin by colour Patch circumscribed lesion > 5 mm, flat, distinguished from surrounding skin by colour Papule elevated dome-shaped or flat-topped lesion < 5 mm Nodule elevated lesion, spherical contour > 5 mm Plaque elevated flat-topped lesion, > 5 mm Vesicle fluid-filled raised lesion < 5 mm Bulla fluid-filled raised lesion > 5 mm Blister vesicle or bulla Pustule discrete, pus-filled, raised lesion Wheal itchy, transient, elevated lesion with erythema formed as result of dermal oedema Scale dry, horny, platelike -usually result of imperfect cornification Lichenification thickened, rough skin, prominent skin markings, usually result of repeated rubbing Excoriation traumatic lesion, breakage of epidermis, causing a raw linear area, often self-induced Onycholysis separation of nail plate from nail bed

Microscopic Terms Hyperkeratosis thickening of stratum corneum, often assoc with abnormality of keratin Parakeratosis modes of keratinization, retention of nuclei in stratum corneum Hypergranulosis hyperplasia of stratum granulosum, often due to intense rubbing Acanthosis diffuse epidermal hyperplasia Papillomatosis surface elevation caused by hyperplasia and enlargement of dermal papillae Dyskeratosis abnormal keratinization occurring prematurely within cells below stratum granulosum Acantholysis loss of intercellular connections resulting in loss of cohesion between keratinocytes Spongiosis intercellular oedema of epidermis Hydropic swelling (ballooning) intracellular oedema of keratinocytes, often seen in viral infections Exocytosis infiltration of epidermis by inflammatory or circulating blood cells Erosion discontinuity of skin with incomplete loss of epidermis Ulceration discontinuity of skin with complete loss of epidermis and often portions of dermis Vacuolization formation of vacuoles within/adjacent to cells Lentiginous linear pattern of melanocyte proliferation within epidermal basal cell layer

Disorders of Pigmentation and Melanocytes Vitiligo - common disorder, partial or complete loss of pigment-producing melanocytes within epidermis - lesions asymptomatic, flat, well-demarcated macules and patches of pigment loss - hands, wrists, axillae, and perioral, periorbital, anogenital skin - koebnerization often occurs, where lesions develop primarily at sites of repeated trauma - pathogenesis theories: autoimmunity; neurohumoral factors toxic to melanocytes and released by nerve endings; self-destruction of melanocytes by toxic intermediates of melanin synthesis - autoimmune likely - circulating Ab against melanocytes (assoc w other autoimmune disorders) - trmt UV light, A wavelength, with photosensitizing drug, psoralen (PUVA)

Freckles (Ephelis) - most common pigmented lesions of childhood - small (1-10 mm), light brown macules, appear in early childhood after sun exposure - fade and intensify in a cyclic fashion with winter and summer

1 o cf lentigo - maintains stable coloration independent of sun exposure - normal melanocyte number but increased melanin within basal keratinocytes

Melasma - mask-like zone of facial hyperpigmentation commonly in association with pregnancy/OCP - poorly defined, blotchy, tan-brown macules and patches involving cheeks, temples, forehead - fades postpartum - caused by enhanced melanin transfer and accumulation from melanocytes to other cell types - histo: increased melanin in basal layers (epidermal type); papillary dermal macrophage phagocytosis of melanin released from epidermis (dermal type)

Lentigo - common benign localized hyperplasia of melanocytes at all ages but often in infancy/childhood - cause and pathogenesis unknown - small, oval, tan-brown patches that do not darken with exposure to sunlight - histo: linear basal hyperpigmentation from melanocytes hyperplasia

Melanocytic Nevus (Pigmented nevus, mole) - congenital or acquired neoplasm of melanocytes - tan to brown, uniformly pigmented, small (<6 mm), solid regions of relatively flat (macules) to elevated skin (papules) with well-defined borders - variants: o congenital nevus – present at birth, large variants ↑ melanoma risk o blue nevus - black-blue nodule, often confused with melanoma o spindle and epithelioid cell nevus (Spitz nevus) - children, red-pink nodule o halo nevus - host immune response to nevus cells and surrounding melanocytes o dysplastic nevus - potential precursor of malignant melanoma - pathogenesis: o melanocytes derive from basal cells transformed into round-oval cells o nevi initially form nests along dermoepidermal junction – junctional nevi o eventually extend into underlying dermis – compound nevis o in mature lesions epidermal component may be lost – dermal nevi o with extension into dermis become nonpigmented, resembling neural tissue
melanomas do not show this maturation

Dysplastic Nevi - manifestation of autosomal dominant predisposition to develop atypical acquired nevi - also can be sporadic lesions - may evolve into malignant melanoma (50% by 50s) - larger than typical nevi (>5mm), may occur as hundreds of irregular macules or plaques - on both sun-exposed and nonexposed skin (cf typical moles) - vulnerable to mutagenic effects of UV light

Malignant Melanoma - relatively common - skin, oral/anogenital mucosa, oesophagus, meninges, nailbed, eye - sunlight plays an important role in development o men - commonly on upper back, women on back and legs - lightly pigmented skin at higher risk - other risk factors: pre-existing nevus (dysplastic nevus), hereditary factors, certain carcinogens - clinical warning signs: (ABCDE) o usually asymptomatic o enlargement of pre-existing mole (usually >10mm) o itching or pain in pre-existing mole o development of new pigmented lesion during adult life o irregularity of borders o variegation of colour (black, brown, red, dark blue, gray) - initially radial growth phase o horizontally in epidermal/superficial dermal layers

2 o specific types of radial growth phase melanoma - lentigo maligna, superficial spreading, acral/mucosal lentiginous o no metastatic potential - then vertical growth phase o metastatic potential, proportional to depth of spread o prediction of outcome also related to number of mitoses and degree of infiltrative lymphocytic response

Benign Epithelial Tumours - common, usually biologically inconsequential (psychologic discomfort) - derived from keratinizing stratified squamous epithelium of epidermis and hair follicles (keratinocytes) and ductular epithelium of cutaneous glands - often confused clinically with malignancy – need biopsy - rarely part of specific syndromes associated with potentially life-threatening visceral malignancies multiple trichilemmomas in Cowden syndrome or multiple, benign or malignant sebaceous neoplasms in Muir-Torre syndrome)

Seborrheic Keratoses - common epidermal tumours, most frequently in middle-aged or older - arise spontaneously, may become numerous on trunk - round, flat, coinlike, waxy plaques that vary from millimeters to several centimeters - uniformly tan to dark brown, velvety to granular surface, "stuck on" - may occur in large numbers, as part of a paraneoplastic syndrome (Leser-Trélat sign) o transforming growth factor-α produced by tumour cells

Acanthosis Nigricans - thickened, hyperpigmented zones of skin often with "velvet-like" texture involving flexural areas (axillae, skin folds of neck, groin, anogenital regions) - cutaneous marker for benign and malignant conditions – accordingly divided into two types o benign type (80%) develop gradually, occur in childhood or during puberty
autosomal dominant trait with variable penetrance
assoc with obesity or endocrine abnormalities (pituitary, pineal tumors, DM)
part of a number of rare congenital syndromes - malignant type, in middle age and older o may result from abnormal production of epidermal growth-promoting factors by tumour o association with GI adenocarcinoma

Fibroepithelial Polyp - aka acrochordon, squamous papilloma, skin tag - one of most common cutaneous lesions - middle-aged and older individuals on neck, trunk, face, intertriginous areas - soft, flesh-coloured, baglike tumour attached to the skin surface by a small stalk - usually biologically inconsequential - have been associated with diabetes and intestinal polyposis

Epithelial Cysts (Wens) - common lesions formed by invagination and cystic expansion of epidermis or epithelium forming the hair follicle - cysts are filled with keratin and variable amounts of lipid-containing debris from sebaceous secretions - dermal or subcutaneous, well-circumscribed, firm, and often moveable nodules

Adnexal (Appendage) Tumours - hundreds of benign neoplasms arising from cutaneous appendages - may be confused with certain types of cutaneous cancers (eg BCC) - some associated with Mendelian patterns of inheritance - multiple disfiguring lesions - some serve as markers for internal malignancy - multiple trichilemmomas in Cowden syndrome - nondescript, flesh-colored solitary or multiple papules and nodules - cylindromas, syringomas, trichoepitheliomas

3 Keratoacanthoma - rapidly developing neoplasm that may mimic well-differentiated SCC - often will heal spontaneously - M>F, lesions most frequently affect sun-exposed skin of whites > 50 years - flesh-colored, dome-shaped nodules with a central, keratin-filled plug - crater-like - from 1 cm to several centimeters, mainly face, ears, hands - may represent a form of SCC that regresses as a consequence of interactions with host tissues - majority have mutations in p53 gene

Premalignant and Malignant Epidermal Tumours

Actinic Keratosis - before development of overt malignancy of epidermis, series of dysplastic changes - usually result of chronic exposure to sunlight, associated with build-up of excess keratin - occur in lightly pigmented individuals - also induced by ionizing radiation, hydrocarbons, and arsenicals - <1 cm, tan-brown, red, or skin-coloured, rough, sandpaper-like consistency - some lesions produce a "cutaneous horn" - frequently on sites exposed to sun (face, arms, dorsum of hands) - similar lesions on lips (actinic cheilitis) - malignant potential – remove by gentle curettage, freezing, topical chemotherapeutic agents

Squamous Cell Carcinoma - second most common tumour on sun-exposed sites in older people (< than BCC), M>F - predisposing factors: sunlight, industrial carcinogens (tars and oils), chronic ulcers and draining osteomyelitis, old burn scars, arsenicals, ionizing radiation, in oral cavity tobacco and betel nut - most common exogenous cause: exposure to UV light with subsequent DNA damage - immunosuppressed or xeroderma pigmentosum - increased risk - sunlight, in addition to effect on DNA, has a direct, transient immunosuppressive effect on skin by affecting normal surveillance function of antigen-presenting Langerhans cells in epidermis - DNA sequences of certain viruses (HPV type 36) - potential precursors of SCC - certain chemical agents have direct mutagenic effects by producing DNA adducts with subsequent oncogene activation - can have SCC in situ until cells break through BM - well-demarcated, red-scaly plaques – nodular, prone to ulceration - mucosal involvement – shows leukoplakia - most tumours localized, <5% metastasis

Basal Cell Carcinoma - common, slow-growing tumours that rarely metastasize - occur at sites of chronic sun exposure in lightly pigmented people - incidence ↑ in immunosuppression and with defects in DNA repair (xeroderma pigmentosum) - pearly papules often containing prominent, dilated subepidermal blood vessels (telangiectasias) - advanced lesions may ulcerate, extensive local invasion of bone or facial sinuses - rodent ulcers - variant: superficial BCC, erythematous, occasionally pigmented plaque, may resemble early malignant melanoma

Merkel Cell Carcinoma - rare neoplasm, derived from Merkel cell of epidermis o neural crest-derived cell for tactile sensation in lower animals - ulcerated nodules, resemble eroded BCC or nonpigmented (amelanotic) forms of melanoma - capable of metastasis, potentially lethal

Molecular Genetics of Skin Cancers

Nevoid Basal Cell Carcinoma Syndrome (NBCCS) and Sporadic Basal Cell Carcinomas - aka basal cell nevus syndrome or Gorlin syndrome - autosomal dominant, multiple BCCs, rare - most tumors develop before age 20, accompanied by other conditions o medulloblastomas, ovarian fibromas, odontogenic keratocysts, pits of palms and soles, 4 o systemic manifestations - intracranial calcification, cleft lip/palate, abnormal vertebra, and ribs - pathogenesis: "two-hit" hypothesis o born with germ-line mutation in one of PTCH alleles o second mutation - inactivation by environmental mutagens or random genetic

Squamous Cell Carcinoma - no inherited single gene defect - mutations in p53 in actinic keratoses is high - sunlight causes alterations at early stages of carcinogenesis

Melanomas - 10-15% familial - some dysplastic nevi develop into melanoma - known as dysplastic nevus syndrome or familial melanoma syndrome (FMS) - no predictable inherited phenotypic abnormalities

Tumors of the Dermis - dermis made of cells incl smooth muscle, pericytes, fibroblasts, neural tissue, endothelium - all components can give rise to neoplasia in skin - many of these tumors also arise in soft tissues and viscera (leiomyosarcoma) or as part of a syndrome primarily affecting another organ (cutaneous neurofibromas in neurofibromatosis)

Benign Fibrous Histiocytoma (Dermatofibroma) - heterogeneous family of benign dermal neoplasms of fibroblasts and histiocytes - usually in adults, often occur of legs of young to middle-aged women - firm, tan to brown papules, asymptomatic or tender, mostly <1 cm in diameter - histogenesis unknown – possible abnormal response to injury and inflammation

Dermatofibrosarcoma Protuberans - well-differentiated, primary fibrosarcoma of skin - slow growing, locally aggressive, rarely metastasize - firm, solid nodules most frequently on trunk, often protuberant with a plaque that may ulcerate

Xanthomas - tumour-like collections of foamy histiocytes within dermis - associated with familial or acquired hyperlipidemia, lymphoproliferative malignant neoplasms, or no underlying disorder - five types: o eruptive xanthomas - sudden showers of yellow papules, wax and wane with plasma triglyceride - on buttocks, posterior thighs, knees, elbows o tuberous and tendinous xanthomas - yellow nodules - TA and extensor tendons fingers o plane xanthomas - associated with primary biliary cirrhosis - linear yellow lesions in skin folds, especially palmar creases o xanthelasma (without lipid abnormality) - soft yellow plaques on eyelids

Dermal Vascular Tumours - benign vascular neoplasms (capillary/cavernous haemangiomas), malformations (nevus flammeus/ port-wine stain), multifocal angioproliferative lesions (Kaposi sarcoma, bacillary angiomatosis), vascularized variants of other tumours (sclerosing haemangioma variant of benign fibrous histiocytoma), and malignant vascular tumors (angiosarcomas) - capillary haemangioma most common form of cutaneous haemangioma o in childhood (strawberry haemangioma) or with advancing age - erythematous papules

Tumours of Cellular Immigrants to the Skin - proliferative disorders of cells that have arisen elsewhere but homed to the skin o eg Langerhans cells, T lymphocytes, mast cells

Langerhans Cell Histiocytosis - multiple forms - solitary or multiple lesions, papules, nodules, scaling erythematous plaques - systemic or cutaneous forms

5 Mycosis Fungoides (Cutaneous T-cell Lymphoma) (CTCL) - spectrum of lymphoproliferative disorders affecting skin - variety of types of malignant T-cell disorders: o mycosis fungoides - chronic T-cell lymphoproliferative process o mycosis fungoides d'emblée - nodular eruptive variant o adult T-cell leukaemia/lymphoma type - rapidly progressive downhill course

- mycosis fungoides arises primarily in skin, may evolve into generalized lymphoma - most commonly > age 40 - scaly, red-brown patches; raised, scaling plaques, like psoriasis; fungating nodules - trmt: topical steroids or UV light early lesions, systemic chemotherapy for advanced

Mastocytosis - rare disorders with increased numbers of mast cells in skin and sometimes other organs - localized cutaneous form – children, called urticaria pigmentosa o lesions multiple, 10% have systemic mastocytosis - mast cell infiltration of organs - clinically variable – multiple, widespread lesions, round to oval, red-brown, nonscaling papules and small plaques - may be pruritic or exhibit blister formation - systemic mastocytosis - mast cell infiltration of bone marrow, liver, spleen, and lymph nodes - signs/symptoms due to effects of histamine, heparin, other substances released in degranulation o dermatographism: dermal oedema when stroked with pointed instrument o systemic disease: pruritus and flushing triggered by certain foods, temperature changes, alcohol, and certain drugs (morphine, codeine, aspirin), rhinorrhoea, rarely GI or nasal bleeding, (anticoagulant effects of heparin), bone pain - osteoblastic and osteoclastic - pathogenesis: clonal proliferation of mast cells with a point mutation of c-KIT proto-oncogene o causes activation of receptor tyrosine kinase expressed by mast cells

Disorders of Epidermal Maturation

Ichthyosis - genetically inherited disorder impairs epidermal maturation - excessive keratin build-up (hyperkeratosis) - fishlike scales - apparent around time of birth - acquired (noninherited) variants exist – in adults, assoc with lymphoid and visceral malignancy - pathogenesis: defective mechanisms of desquamation, leading to retention of abnormal scale

Acute Inflammatory Dermatoses Urticaria (hives) - common disorder of skin - localized mast cell degranulation causing dermal microvascular hyperpermeability, culminating in pruritic oedematous plaques – wheals - lesions develop/fade usually <24 hours, and episodes may last for days or persist for months - lesions vary from small, pruritic papules to large oedematous plaques, lesions may coalesce - include any area exposed to pressure - trunk, extremities, ears - persistent episodes may be due to inability to eliminate causative antigen or due to underlying disease (collagen vascular disorders, Hodgkin disease) - pathogenesis: o antigen-induced release of vasoactive mediators from mast cell granules through sensitization with specific IgE Abs o can follow exposure to antigens (pollens, foods, drugs, insect venom) o also IgE-independent urticaria from substances that in certain individuals directly incite degranulation of mast cells - opiates, antibiotics, curare, contrast media
also aspirin - suppress prostaglandin synthesis from arachidonic acid o hereditary angioneurotic oedema due to inherited deficiency of C1 inhibitor that results in uncontrolled activation of early components of complement system and production of vasoactive mediators (complement-mediated urticaria)

Acute Eczematous Dermatitis - red, papulovesicular, oozing, crusted lesions early that develop into raised, scaling plaques 6 - acute lesions prone to bacterial superinfection - yellow crust (impetiginization) - over time, persistent lesions become less wet, become progressively scaly (hyperkeratotic) as epidermis thickens - pathogenesis: o antigens at epidermal surface taken up by dendritic Langerhans cells o migrate by dermal lymphatics to draining lymph nodes o antigens, now processed by Langerhans cell, presented to naive CD4 T cells o CD4 cells activated and develop into effector and memory cells o on re-exposure memory T cells migrate to affected skin sites, release cytokines and factors that recruit numerous inflammatory cells responsible for clinical lesion of spongiotic dermatitis
also results in endothelial activation - endothelial cells express molecules that promote adhesion of circulating memory T lymphocytes
memory T cells enter site of antigen challenge, elaborate lymphokines that recruits of large numbers of inflammatory cells to site of antigen contact
occurs within 24 hours - erythema and pruritus of delayed hypersensitivity

Erythema Multiforme - uncommon, self-limited disorder - hypersensitivity reaction to certain infections and drugs - prototype of a cytotoxic reaction pattern (one typified by extensive epithelial cell degeneration and death) - affects any age, associated with: o infections: HSV, mycoplasma, histoplasmosis, coccidioidomycosis, typhoid, leprosy o drugs: sulfonamides, penicillin, barbiturates, salicylates, hydantoins, antimalarials o malignant disease: carcinomas and lymphomas o collagen vascular diseases: SLE, dermatomyositis, periarteritis nodosa - array of "multiform" lesions, including macules, papules, vesicles, and bullae as well as characteristic target lesion of a red macule/papule with pale, vesicular, or eroded center - may be widely distributed, symmetric involvement of the extremities - extensive and symptomatic febrile form, often in children: Stevens-Johnson syndrome o erosions and haemorrhagic crusts of lips and oral mucosa o may result in life-threatening sepsis - another variant: toxic epidermal necrolysis o diffuse necrosis, sloughing of cutaneous and mucosal epithelial surfaces, similar to burn - superficial perivascular, lymphocytic infiltrate associated with dermal oedema and accumulation of lymphocytes along dermoepidermal junction - target lesion exhibits central necrosis surrounded by a rim of perivenular inflammation - pathogenesis: similar to GVHD, allograft rejection, fixed drug eruptions o epithelial cells killed by CD8+ cytotoxic T lymphocytes

Chronic Inflammatory Dermatoses - months to years - skin roughened as result of excessive or abnormal scale formation and shedding

Psoriasis - common chronic inflammatory dermatosis affecting 1-2% - sometimes associated with arthritis, myopathy, enteropathy, spondylitic joint disease, or AIDS - most frequently affects elbows, knees, scalp, lumbosacral areas, intergluteal cleft, glans penis - well-demarcated, pink to salmon-colored plaque covered by loosely adherent scales that are characteristically silver-white - can be one cause of total body erythema and scaling known as erythroderma - mail changes in 30% - yellow-brown discoloration with pitting, dimpling, separation of nail plate (onycholysis), thickening, and crumbling - rare variant - pustular psoriasis: multiple small pustules form on erythematous plaques o either benign and localized (hands and feet) or generalized and life-threatening, with fever, leukocytosis, arthralgia, diffuse cutaneous and mucosal pustules, secondary infection, and electrolyte disturbances - pathogenesis: o T cell-mediated disease that involves increased keratinocyte proliferation along with inflammation and angiogenesis

Seborrheic Dermatitis 7 - chronic inflammatory dermatosis, more common than psoriasis - involves regions with high density of sebaceous glands - scalp, forehead, external auditory canal, retroauricular area, nasolabial folds, and presternal area - not a disease of sebaceous glands - macules and papules on an erythematous-yellow, often greasy base, with scaling and crusting - fissures may be present (behind ears), dandruff common - aetiology unknown - ? lipophilic yeast Malassezia furfur, associated with tinea versicolor, may play role

Lichen Planus - "pruritic, purple, polygonal papules" on skin and mucous membranes - self-limiting, resolves spontaneously in 1-2 years - malignant degeneration can occur in chronic mucosal and paramucosal lesions - itchy, violaceous, flat-topped papules that may coalesce focally to form plaques - papules highlighted by white dots or lines - multiple lesions, symmetrical distribution, particularly extremities, wrists, elbows, glans penis - pathogenesis not known - ? cell-mediated immune reactions

Lupus Erythematosus - localized, cutaneous form of lupus, no systemic manifestations = discoid lupus erythematosus - either poorly defined malar erythema or large, demarcated erythematous scaling plaques - these "discoid" plaques occur in pure cutaneous or SLE - skin findings in lupus may worsen with sun - epidermal surface of lesions shiny or scaly, dilated and tortuous blood vessels (telangiectasia) and small zones of hypopigmentation and hyperpigmentation - humoral mechanisms of injury may involve formation and deposition of immune complexes and complement components C5b-C9 (membrane attack complex) at dermoepithelial junction

Blistering (Bullous) Diseases - vesicles and bullae (blisters) can be secondary to other conditions (HSV, burns), or primary

Pemphigus - autoimmune blistering disorder resulting from loss of integrity of normal intercellular attachments within epidermis and mucosal epithelium - rare, but without treatment may be life-threatening - usually 40-60s, M=F - Pemphigus vulgaris (80%) – mucosa, skin, esp scalp, face, axilla, groin, trunk, pressure points o superficial, easily ruptured blisters that leave shallow crusted erosions, fatal untreated - Pemphigus vegetans (rare) - no blisters, large, moist, wartlike, vegetating plaques studded with pustules on groin, axillae, and flexural surfaces - Pemphigus foliaceus – benign, epidemic form in South America, affects scalp, face, chest, back o bullae very superficial - only erythema and crusting, sites of previous blister rupture - Pemphigus erythematosus - localized, less severe form of pemphigus foliaceus, selectively involve malar area of face like SLE - all forms have acantholysis - lysis of intercellular adhesion sites in squamous epithelial surface - pathogenesis: blood contains IgG to intercellular cement substance of skin and mucosa o antibody reacts with desmoglein 3, a component of desmosomes that bind keratinocytes

Bullous Pemphigoid - relatively common autoimmune, vesiculobullous disease - affecting elderly, wide range of clinical presentations: o localized to generalized cutaneous lesions and some involvement of mucosal surfaces - lesions <2cm, up to 8cm, tense bullae filled with clear fluid, on normal or erythematous skin - do not rupture easily, heal without scarring - inner thighs, flexor surfaces of forearms, axillae, groin, lower abdomen, oral - caused by autoantibodies against proteins at dermal-epidermal junction - linear zone deposition of immunoglobulin and complement at this site

Noninflammatory Blistering Diseases: Epidermolysis Bullosa, Porphyria 8 - some primary disorders with vesicles and bullae not mediated by inflammatory mechanisms:

Epidermolysis bullosa - group of disorders with blisters that develop at sites of pressure, rubbing, or trauma, at or soon after birth - simplex type - degeneration of basal cell layer of epidermis results in bullae - junctional type - blisters occur in otherwise histologically normal skin at level of lamina lucida - scarring dystrophic types - blisters develop beneath lamina densa - dystrophic epidermolysis bullosa - inherited disease resulting from mutations in gene encoding type VII collagen

Porphyria - group of uncommon inborn or acquired disturbances of porphyrin metabolism - porphyrins: pigments normally present in haemoglobin, myoglobin, cytochromes - cutaneous manifestations: urticaria and vesicles that heal with scarring, exacerbated by sunlight

Disorders of Epidermal Appendages

Acne Vulgaris - may be induced or exacerbated by drugs (steroids, ACTH, testosterone, gonadotropins, contraceptives, trimethadione, iodides, bromides), occupational contacts (cutting oils, chlorinated hydrocarbons, coal tars), and occlusive condition (heavy clothing, tropical climates) - noninflammatory and inflammatory types - noninflammatory: open and closed comedones o open comedones - small follicular papules containing central black keratin plug
result of oxidation of melanin pigment o closed comedones - follicular papules without a visible central plug o keratin plug trapped beneath epidermal surface so potential source of inflammation - inflammatory: erythematous papules, nodules, and pustules - contributing to development: o changes in keratinization with development of keratin plug blocking outflow of sebum o increase in size of sebaceous glands with puberty/increased activity due to hormones o lipase-synthesizing bacteria (Propionibacterium acnes) hair follicle, convert lipids within sebum to pro- inflammatory fatty acids o induction of inflammation in follicle with release of cytotoxic and chemotactic factors

Panniculitis - panniculitis: o inflammatory reaction in subcutaneous fat that may affect:
connective tissue septa separating lobules of fat
lobules of fat themselves o often involves lower legs o many types have subacute to chronic course - erythema nodosum most common form of panniculitis and usually acute o often associated with infections (beta-haem strep, tb, coccidioidomycosis, histoplasmosis, leprosy), drugs (sulfonamide, OCP), sarcoid, IBD, some malignancies o poorly defined, exquisitely tender, erythematous plaques and nodules o fever and malaise o biopsy required o early lesions - oedema, fibrin exudation, neutrophilic infiltration o later - lymphocytes, histiocytes, multinucleated giant cells, occasional eosinophils, septal fibrosis, no vasculitis

Infection and Infestation

Verrucae (warts) - HPV, mainly types 6 and 11 - direct contact or autoinoculation - verruca vulgaris: most common type of wart, frequently on hands o gray-white to tan, flat to convex, 0.1- to 1-cm papules with rough, pebble-like surface - verruca plana: common on face or dorsal surfaces of hands 9 - verruca plantaris and verruca Palmaris: soles and palms - condyloma acuminatum (venereal wart): penis, female genitalia, urethra, perianal areas, rectum o soft, tan, cauliflower-like masses, occasionally reach many centimeters

Molluscum Contagiosum - common, self-limited viral disease of skin caused by a poxvirus - spread by direct contact, particularly children and young adults - multiple lesions may occur on skin and mucous membranes - mainly trunk and anogenital - lesions firm, pruritic, pink to skin-colored umbilicated papules 0.2 to 0.4 cm - curd-like material can be expressed from central umbilication. Impetigo - common superficial bacterial infection of skin - highly contagious, in otherwise healthy children - two forms - impetigo contagiosa and impetigo bullosa - different size of pustules - Staph aureus common cause - usually involves exposed skin, particularly face and hands - characteristic honey-colored crust - pathogenesis of blister formation - bacterial production of toxin that cleaves desmoglein 1 molecule responsible for cell-to-cell adhesion within uppermost epidermal layers

Superficial Fungal Infections - confined to stratum corneum, caused primarily by dermatophytes Tinea capitis : children - dermatophytosis of scalp: asymptomatic, hairless patch of skin with erythema, crust, scale Tinea corporis : common superficial fungal infection, affects all ages, particularly children - predisposing factors: excessive heat and humidity, exposure to infected animals, chronic dermatophytosis of feet or nails Tinea cruris : inguinal areas of obese men during warm weather - heat, friction, maceration all predispose Tinea pedis (athlete's foot) : diffuse erythema and scaling, often initially localized to web spaces - spread to or primary infection of nails referred to as onychomycosis Tinea versicolor : upper trunk, highly distinctive appearance - caused by Malassezia furfur, a yeast rather than a dermatophyte

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