10.3 From notes - Skin Structure and Function

Skin Structure and Function

• The skin is the body's largest organ, accounting for about 20% of body weight.
• It forms the integumentary system along with hair, nails, and glands.
• The skin consists of three major layers: epidermis, dermis, and subcutaneous layer (hypodermis).
• Nails, hair, sebaceous glands, and sweat glands are dermal appendages.

The Epidermis

• It is the outer layer providing a defensive barrier, renewing itself by shedding the stratum corneum.
• Primarily composed of keratinocytes in a lipid matrix, producing keratin for protection.
• Its thickness varies across the body.
• Includes layers: stratum corneum, stratum lucidum (in palmoplantar skin only), stratum granulosum, stratum spinosum, and stratum basale (germinativum).
• The stratum basale and stratum spinosum form the germinative layer, ensuring skin renewal.
• Melanocytes produce melanin for UV protection and skin color; located in the stratum basale.
• Langerhans cells are dendritic cells for immune response, migrating from bone marrow.
• Merkel cells are mechanoreceptors for touch, associated with touch receptors.
• Rete pegs extend into the dermis' papillary layer.

The Dermis

• It is a deeper layer, 1 to 4 mm thick, made of collagen, elastin, reticulin, and a gel-like ground substance.
• The haphazard connective tissue arrangement allows for mobility and stretch.
• Contains hair follicles, sebaceous glands, sweat glands, blood vessels, lymphatic vessels, and nerves.
• The papillary dermis has conelike projections (dermal papillae) that interface with the epidermis, forming rete pegs and providing skin texture.
• Cells include fibroblasts (secrete connective tissue matrix and collagen, important for wound healing), mast cells (release histamine, involved in hypersensitivity), and macrophages (phagocytic, immune response, wound healing).
• Histiocytes are wandering macrophages that collect pigments and inflammatory debris.

Subcutaneous Layer (Hypodermis)

• The lowest layer consists of adipose tissue separated by fibrous septa of collagen and large blood vessels.
• Connects the dermis to underlying muscle.
• Contains macrophages, fibroblasts, fat cells, nerves, blood vessels, lymphatics, and hair follicle roots.
• Dermal collagen is continuous with subcutaneous collagen.

Dermal Appendages

• Nails are protective keratinized plates with six structural units, with continuous growth.
• Hair follicles and sebaceous glands are integrated units arising from the dermis that vary with age, gender, and race.
• Hair growth is cyclic, and color is determined by follicular melanocytes.
• Arrector pili muscles are attached to hair follicles.
• Sebaceous glands secrete sebum (primarily lipids) to oil skin and hair, preventing drying. Growth is stimulated by androgens.
• Sweat glands (eccrine and apocrine) are also dermal appendages.

Skin Blood Supply, Lymphatics, and Nerves

• The skin's blood supply primarily comes from papillary capillaries arising from subpapillary plexuses, which are supplied by deeper arterial plexuses.
• Blood flow is regulated by the sympathetic nervous system.
• Arteriovenous anastomoses in the dermis help regulate body temperature through blood flow and sweat evaporation.
• Lymphatic vessels originate in the papillary dermis and drain into subcutaneous trunks, removing cells, proteins, and immune mediators.
• The skin contains various sensory receptors and free nerve endings, with numbers decreasing with age.

Aging and Skin Integrity

• Aging causes generalized changes in the skin: decreased subcutaneous fat, dermal thickness, and collagen synthesis, leading to thinner, wrinkled skin.
• Elastic fibers degenerate, and cross-linking of collagen occurs.
• There is a reduction in elastin, and the skin's ability to repair itself is diminished.
• Vascularity decreases, leading to paler and cooler skin.
• Melanocyte numbers decrease, potentially leading to uneven pigmentation.
• Clearance of toxic oxidative substances from the dermis is reduced.
• The number of pressure and touch receptors and free nerve endings decreases, reducing sensory perception.

Tests of Skin Function

• Initial evaluation involves historical information, physical examination, and observation of lesions.
• Dermoscopy: Is magnified illumination of skin lesions.
• Reflectance confocal microscopy: Provides high-resolution assessment of cellular details for skin cancer evaluation.
• Skin biopsy: Histologic examination for diagnosis of various skin conditions.
• Microscopic immunofluorescence: Identifies antibodies for diseases like pemphigus and lupus.
• Gram stain: Differentiates bacteria.
• Culture: Identifies bacterial and fungal infections.
• Wood lamp examination: Identifies fluorescing fungi.
• Patch and scratch tests: Evaluate immune responses to allergens.
• Skin scrapings with KOH: Identifies dermatophytes and Candida.
• Side lighting: Evaluates patterns of depression and elevation.
• Diascopy: Differentiates erythema from blood extravasation.
• Tzanck smear: Includes Microscopic examination for vesicular diseases like herpes.

Clinical Manifestations of Skin Dysfunction: Primary Lesions

• Lesions are readily observable and assessed for distribution and structure.
• Identification of primary and secondary lesions is critical.
• Primary Lesions: Develop on previously unaltered skin.
• Macule: Flat, circumscribed color change, <1 cm (e.g., vitiligo).
• Papule: Elevated, firm, circumscribed, <1 cm (e.g., psoriasis).
• Wheal: Elevated, irregular, cutaneous edema, solid, transient (e.g., insect bites).
• Nodule: Elevated, firm, circumscribed, deeper than papule, 1-2 cm (e.g., erythema nodosum).
• Tumor: Elevated, solid, deeper in dermis, >2 cm (e.g., neoplasm).
• Vesicle: Elevated, circumscribed, superficial, serous fluid-filled, <1 cm (e.g., blister).
• Pustule: Elevated, superficial, purulent fluid-filled (e.g., impetigo).
• Cyst: Elevated, circumscribed, encapsulated, liquid or semisolid-filled, in dermis or subcutaneous.
• Telangiectasiae: Fine, irregular red lines from capillary dilation (e.g., rosacea).

Clinical Manifestations of Skin Dysfunction: Secondary and Special Lesions

• Secondary Lesions: Result from changes in primary lesions.
• Scale: Heaped-up keratinized cells, flaky (e.g., seborrheic dermatitis).
• Scar: Fibrous tissue replacing dermis after injury (e.g., healed wound).
• Lichenification: Rough, thickened epidermis from rubbing (e.g., chronic dermatitis).
• Excoriation: Loss of epidermis, linear, hollowed-out, crusted (e.g., scratch).
• Fissure: Linear crack from epidermis to dermis (e.g., athlete's foot).
• Keloid: Irregular, elevated, enlarging scar beyond wound boundaries (excess collagen).
• Erosion: Loss of part of epidermis, depressed, moist (e.g., chemical injury).
• Ulcer: Loss of epidermis and dermis, concave (e.g., pressure injury).
• Atrophy: Thinning of skin surface, loss of markings (e.g., aged skin).
• Special Skin Lesions:
• Comedone: Plugged hair follicle opening (blackhead/whitehead).
• Burrow: Narrow, raised, irregular channel by a parasite.
• Petechiae: Circumscribed blood area <0.5 cm.

Pressure Injury

• Localized skin damage from unrelieved pressure, shearing, friction, and moisture. Interrupts blood flow, leading to anoxic necrosis.
• Develops over bony prominences.
• Individuals with darkly pigmented skin are at higher risk due to difficulty in early detection.
• Risk factors include prolonged pressure/immobilization, shearing forces, thin/fragile skin, impaired perfusion, incontinence, malnutrition, chronic diseases, previous history, critical illness factors (norepinephrine, APACHE II score, anemia, age >40, multiple organ disease, length of stay, ventilator/ECMO use).
• Staging:
  • Stage 1: Nonblanchable erythema of intact skin.
  • Stage 2: Partial-thickness skin loss with exposed dermis.
  • Stage 3: Full-thickness skin loss, subcutaneous tissue damage, may extend to fascia.
  • Stage 4: Full-thickness skin and tissue loss with muscle, bone, or supporting structure exposure.
  • Unstageable: Obscured full-thickness loss by slough or eschar.
  • Deep tissue pressure injury: Persistent nonblanchable deep red, maroon, or purple discoloration.
• Superficial injuries are often due to shearing/friction, deep injuries due to perpendicular pressure.
• Prevention: Education, frequent assessment/repositioning, prophylactic dressings, movement promotion, pressure reduction/removal, moisture elimination, adequate nutrition/oxygenation/fluids.
• Treatment: Pressure relief, debridement, drainage of pockets, tissue repair (flaps), negative-pressure wound healing (for advanced stages), infection treatment (topical/systemic agents), pain control.

Keloids and Hypertrophic Scars

• Keloids: Rounded, firm, elevated scars with irregular margins extending beyond the original injury site. More common in darkly pigmented skin. Excessive deposition of collagen (types I and III) with persistent inflammation and fibrosis. Appear weeks to months after stable scar formation.
• Hypertrophic scars: Elevated erythematous fibrous lesions that do not expand beyond injury borders, primarily type III collagen. Appear within 3-4 months and usually regress within a year.
• Both caused by abnormal wound healing with excessive fibroblast activity and collagen formation, loss of normal tissue repair control. Genetic susceptibility likely.
• Provocative factors: tension, foreign material, infection, trauma (burns). Common sites: shoulders, back, chin, ears, lower legs. Most common in ages 10-30.
• Prevention of keloids is paramount: avoid unnecessary surgery, recognize familial tendency, early detection.
• Management: pressure therapy, topical/intralesional corticosteroids, interferon, bleomycin/5-FU, cryotherapy, radiotherapy, surgical/laser procedures, silicone gel sheeting, onion extract, verapamil (emerging treatment).

Pruritus

• Pruritus (itching) is a common symptom in many skin disorders.
• Mediators include histamine, neuropeptides, serotonin, prostaglandins, bradykinin, substance P, opioids, acetylcholine, interleukins, proteinases, nerve growth factor.
• Small unmyelinated type C nerve fibers transmit itch sensations via specific spinal pathways to the brain. These fibers can interact with dermal eosinophils, lymphocytes, and mast cells.
• Central nervous system mechanisms can modulate itching.
• Chronic itching can lead to scratching and secondary skin lesions, including excoriation, lichenification, and scarring. Both central and peripheral sensitization occur.
• Management depends on the cause, treating the primary condition. Topical and systemic therapies are used.

Disorders of the Skin

• Disruptions in skin integrity can be caused by trauma, abnormal cellular function, infection, inflammation, and systemic diseases. Many are benign and self-limiting, others are severe.

Inflammatory Disorders: Eczema and Dermatitis

• Eczema and Dermatitis: General terms for inflammatory skin response, often used interchangeably.
• Characterized by pruritus, indistinct borders, epidermal changes (erythema, papules, scales), and can be acute, subacute, or chronic.
• Continued irritation leads to edema, serous discharge, and crusting.
• Chronic eczema causes thickened, leathery, hyperpigmented skin (lichenification).
• Location relates to cause.
• Must be differentiated from psoriasis.

Allergic Contact Dermatitis

• T-cell-mediated (type IV) hypersensitivity.
• Allergen binds to carrier protein forming a hapten-specific antigen.
• Langerhans cells process and present to T cells in lymph nodes, causing sensitization and cytokine release, leading to inflammation.
• Latex allergy can be type IV (chemicals) or type I (IgE to latex protein).
• Delayed hypersensitivity shows response hours after exposure.
• Manifestations: erythema, swelling, pruritic vesicular lesions at contact site.
• Chronic AD leads to lichenification, fissuring, thickening, scaling.
• Patch tests aid diagnosis.
• Treatment: allergen removal, topical/systemic steroids.

Irritant Contact Dermatitis

• Nonspecific inflammation from innate immune activation by chemical properties.
• Intensity related to irritant concentration, exposure time, barrier disruption, age.
• Can be caused by many substances, especially with compromised barrier (e.g., soaps, detergents, acids, alkalis, paraffins, preservatives).
• Lesions similar to allergic contact dermatitis.
• Treatment: remove irritant, topical corticosteroids, petroleum-based emollients, nonirritating soaps.

Other Types of Dermatitis

• Atopic Dermatitis (Atopic Eczema): More common in infancy/childhood, can persist throughout life.
• Stasis Dermatitis: Occurs on legs due to venous stasis and edema associated with varicosities, phlebitis, vascular trauma. Pooled blood traps leukocytes releasing proteolytic enzymes. Increased venous pressure causes deposition of RBCs, fibrin, etc. Can progress to stasis ulcers (often painful, with irregular borders and shallow depth). Treatment: improve venous circulation (elevation, support stockings), topical agents (corticosteroids, emollients), wound care for ulcers (moist dressings, compression, vein ablation surgery).
• Seborrheic Dermatitis: Common chronic inflammation of scalp, eyebrows, eyelids, ear canals, nasolabial folds, axillae, chest, back (cradle cap in infants). Theories: genetic predisposition, Malassezia yeasts, immunosuppression, epidermal hyperproliferation. Malassezia causes inflammation with stratum corneum hyperproliferation and incomplete corneocyte differentiation, altering barrier function. Lesions: greasy, scaly, white or yellowish papules, plaques with mild pruritus. Treatment: topical antifungals (ketoconazole shampoo), mild topical corticosteroids, keratolytics (selenium sulfide shampoo).

Psoriasis

• Chronic autoimmune T-cell-mediated inflammatory skin disease with thickened epidermis and dermis, characterized by scaly, erythematous, pruritic plaques.
• Immune system (T cells, dendritic cells, macrophages) and cytokines (TNF-α, IFN-γ, interleukins) are involved.
• Both dermis and epidermis are thickened due to keratinocyte hyperproliferation, altered differentiation, and expanded dermal vasculature. Epidermal shedding time decreases significantly.
• Loose keratin causes silvery, scaly appearance.
• Capillary dilation from angiogenic factors (VEGF) causes erythema.
• Can be mild, moderate, or severe with remissions and exacerbations.
• Types: plaque (most common), inverse, guttate, pustular, erythrodermic.
  • Plaque psoriasis: well-demarcated, thick, silvery, scaly, erythematous plaques on face, scalp, trunk, elbows, knees, trauma sites (Koebner phenomenon).
  • Inverse psoriasis: rare, in skinfolds, smooth, dry, deep red, often misdiagnosed as fungal.
  • Guttate psoriasis: sudden small papules after streptococcal infection.
• Associated with arthritis, nail disease, cardiovascular disease (independent of traditional risk factors).
• Treatment: individualized, maintain moisture (emollients), reduce cell turnover, control pruritus, immunomodulation.
  • Mild lesions: emollients, topical corticosteroids, vitamin D analogs, tar preparations.
  • Moderate to severe: phototherapy, systemic therapies (methotrexate, cyclosporine, retinoids), biologic agents targeting cytokines.

Pityriasis Rosea

• Self-limiting disease, possibly herpes-like virus (HHV-6, HHV-7).
• Starts as a single herald patch: circular, demarcated, salmon-pink, 3-10 cm, usually on trunk.
• Followed by bilateral, symmetrical oval lesions along skin lines resembling a drooping pine tree within 14-21 days, extending to trunk and upper extremities.
• Scales slough from margin forming a collarette pattern.
• Itching is common.
• May have preceding headache, fatigue, sore throat.
• Diagnosis based on clinical appearance.
• Differential diagnoses: secondary syphilis, psoriasis, drug eruption, nummular eczema, seborrheic dermatitis.
• Resolves in a few months with symptomatic treatment for pruritus (UV light, antihistamines, topical corticosteroids). Erythromycin and acyclovir may be used.
• Increased risk of miscarriage/premature delivery if diagnosed during pregnancy, consider antiviral therapy.

Lichen Planus (LP)

• Benign, autoimmune inflammatory disorder of skin and mucous membranes with multiple variations.
• Onset usually 30-70 years.
• Stimulating antigen unknown, involves T cells, adhesion molecules, inflammatory cytokines, perforin, antigen-presenting cells.
• T-cell infiltrate mediates immunoreactivity against basal keratinocytes with altered surface antigens. Linked to hepatitis C virus.
• Begins with nonscaling, purple, flat-topped, polygonal pruritic papules (2-4 mm) on wrists, ankles, lower legs, genitalia.
• New lesions pale pink to dark violet. Persistent lesions can be thickened and red (hypertrophic LP).
• Oral lesions (oral lichen planus) appear as lacy white rings (Wickham striae on magnification), must be differentiated from leukoplakia/oral candidiasis, about 1% precancerous.
• Can also occur on penis and vulvovaginal area.
• Oral lesions usually don't ulcerate but if so are painful and require treatment, 1% become malignant.
• Nail thinning/splitting common, may shed.
• Pruritus is distressing.
• Self-limiting, may last months to years (average 6-18 months).
• Postinflammatory hyperpigmentation common. Recurrence in about 20%.
• Diagnosis: clinical appearance and histopathology.
• Treatment: individualized, topical/intralesional/systemic corticosteroids, systemic acitretin, narrow-band UV light therapy. Antihistamines for itching, short-term glucocorticoids for inflammation. Mucous membrane lesions: potent topical steroids, topical retinoids/immunomodulators, systemic glucocorticoids.

Acne Vulgaris

• Inflammatory disorder of pilosebaceous follicle, common in adolescence.

Hidradenitis Suppurativa (Inverse Acne)

• Chronic, inflammatory, recurring scarring disease of pilosebaceous follicular ducts in skin folds with hair follicles and apocrine glands (axillary, inguinal, inframammary, genital, buttocks, perineal).
• Estimated 1-4% prevalence, more common in females.
• Complex pathogenesis: genetic, hormonal, immune, environmental factors.
• Aggravating factors: smoking (significant, nicotine activates keratinocytes, fibroblasts, immunocytes), tight clothing, heat/perspiration, obesity, stress.
• Aberrant response to follicular bacteria leads to cytokine production, follicular hyperkeratosis, pilosebaceous unit occlusion, perifolliculitis, abscesses, sinus tracts, scarring.
• Sweat glands not primarily involved.
• Lesions: deep, firm, painful subcutaneous nodules that track and rupture horizontally.
• Differentiated from boils (carbuncles) which extend vertically and discharge onto skin.
• Diagnosis can be difficult.
• Treatment: systemic medications, incision/drainage of nodules, culture of exudate, antibiotics (clindamycin/rifampicin), concern for MRSA, intralesional corticosteroids, retinoids, surgery, biologic agents (TNF-α inhibitors). Significantly impacts quality of life. Clinical trials needed for best treatment options.

Acne Rosacea

• Chronic inflammatory skin disease with varied presentations in middle-age adults.
• Four subtypes: erythematotelangiectatic, papulopustular, phymatous, ocular, occurring singly or in combination.
• Cause unknown, familial tendency, several genes identified.
• Involves neurovascular dysregulation, infection, altered innate/adaptive immune response (sun, heat, alcohol, hot drinks, hormones, Demodex mites, stress).
• Common lesions: erythema, edema, papules, pustules, telangiectasia on forehead, nose, cheeks, chin.
• Neurovascular dysregulation: flushing, burning, vasodilation.
• Altered epidermal barrier, T/B cell activation promote inflammation and angiogenic/fibrogenic cytokine production (TGF-β1), leading to telangiectasias, fibrosis, cutaneous thickening.
• Sebaceous hypertrophy, fibrosis, telangiectasia can cause irreversible bulbous nose (rhinophyma).
• Fluorinated topical steroids can worsen telangiectasias.
• Treatment: topical agents (metronidazole, azelaic acid, ivermectin), oral antibiotics (tetracycline, doxycycline), laser/light therapies for erythema/telangiectasia, isotretinoin for severe inflammatory forms, surgical tissue removal for rhinophyma.

Lupus Erythematosus

• Systemic inflammatory autoimmune disease with cutaneous manifestations.
• Cutaneous (or discoid) lupus erythematosus (CLE) limited to skin, often progresses to SLE (70-80%).
• Usually in genetically susceptible adults, particularly women in late 30s/early 40s.
• Cause unknown, thought to be genetic/environmental, altered immune response to unknown antigen or UVB, leading to self-reactive T/B cells, decreased regulatory T cells, increased pro-inflammatory cytokines. Autoantibodies and immune complexes cause tissue damage.
• Diagnosis: symptoms, skin biopsy with direct immunofluorescence (lumpy deposits of IgM, IgG, C3), histologic results. Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) assesses severity. Patients must use sunscreen.
• Treatment: topical steroids, calcineurin inhibitors, antimalarial drugs (hydroxychloroquine sulfate) with caution for side effects. Immunotherapy being evaluated.
• Categories of CLE:
  • Acute CLE: Malar rash (butterfly rash), other erythematous papules/plaques, photosensitivity, can be drug-induced, may have mild systemic disease.
  • Subacute CLE: Photosensitive, nonscarring papules/plaques, can be annular or papulosquamous, associated with certain HLA types and autoantibodies to Ro/SSA.
  • Chronic (Discoid) CLE: Most common form, red to purple macules/papules with brownish scale, scale can penetrate hair follicle ("carpet-tack" appearance), may have residual scarring, dermal atrophy, hypopigmentation, alopecia, telangiectasia, Raynaud phenomenon in some.

Papulosquamous Disorders

• Characterized by papules, scales, plaques, and erythema.
• Examples: psoriasis, pityriasis rosea, lichen planus.

Vesiculobullous Disorders

• Share the characteristic of vesicle or blister formation.
• Examples: pemphigus, bullous pemphigoid, erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis.

Pemphigus

• Group of rare autoimmune blistering diseases of skin and oral mucous membranes.
• Caused by circulating autoantibodies (IgG) directed against desmosomal proteins (desmogleins 1 and 3) causing acantholysis (loss of cell-to-cell adhesion in epidermis).
• Triggers can be genetic predisposition, drugs, UV radiation, surgery, emotional/hormonal stress.
• Presents with painful, superficial erosions prone to infection.
  • Pemphigus vulgaris: Most common, oral lesions precede skin blisters on face, scalp, axilla. Blisters rupture easily due to thin epidermis, causing painful erosions.
  • Pemphigus vegetans: Rare variant, large blisters progress to hypertrophic granulomas with tissue erosion and pustules, usually in tissue folds.
  • Pemphigus foliaceus: Milder, acantholysis at subcorneal level with blistering, erosions, scaling, crusting, erythema of face/chest. Oral mucosa rarely involved.
  • Pemphigus erythematosus: Subset of foliaceus, often with SLE, positive antinuclear antibodies, lesions less widespread.
  • Paraneoplastic pemphigus: Most severe, associated with lymphoproliferative neoplasms. Internal organs also involved (lungs, thyroid, kidney, smooth muscle, GI), termed paraneoplastic autoimmune multiorgan syndrome. Lesions develop from inflammatory papules/macules, not normal skin.
  • IgA pemphigus: Most benign, tissue-bound/circulating IgA antibodies targeting desmosomal/nondesmosomal components in basement membrane. Acantholysis less severe, but still blister formation.
  • Pemphigus herpetiformis: Very rare, resembles dermatitis herpetiformis but with pemphigus immunologic/histologic findings.
• Diagnosis: clinical manifestations, histologic findings of autoantibodies in epidermis/mucosal epithelium. Immunofluorescence shows antibodies at blister formation site.
• Course can be rapidly fatal to benign.
• Treatment: systemic corticosteroids with adjuvant immunosuppressants, in difficult cases: protein A immunoadsorption, IVIG, plasmapheresis, anti-CD20 monoclonal antibody therapy. Newer treatments improved prognosis/decreased mortality.

Bullous Pemphigoid (BP)

• More benign autoimmune blistering disease, blistering at basement membrane of skin, not cell junctions.
• Autoantibodies (IgG/IgE) to transmembrane collagen protein (collagen XVII/BP 180) found. Triggers: drugs, skin trauma.
• Autoantibodies activate complement with inflammatory infiltration of neutrophils, eosinophils, lymphocytes. Inflammatory cytokines cause loss of dermal-epidermal adhesion.
• Lesions begin with localized erythema or pruritic plaques that extend and become edematous, turning reddish-purple in 2-3 weeks with vesicles/bullae on surface.
• Oral lesions can occur. Bullae don't extend with pressure, rupture within 1 week and heal rapidly.
• More common after age 60.
• Diagnostic criteria: age >70, no atrophic scars, mucosal involvement, bullous lesions of head/neck, skin biopsy/immunofluorescence results (subepidermal blistering, eosinophils differentiate from pemphigus).
• Treatment: antihistamines for itching, topical (clobetasol propionate) or systemic corticosteroids. Adjuvant immunosuppressants may be prescribed. Relapse possible with treatment discontinuation.

Erythema Multiforme (EM)

• Inflammation of skin with minimal/no mucous membrane involvement and no systemic symptoms (EM minor) or moderate to severe mucosal involvement and some systemic symptoms (fever, weakness, arthralgia) (EM major).
• Often associated with T-cell-mediated (type IV) hypersensitivity to microorganism, particularly viral (HSV, EBV) or rarely histoplasmosis, Mycoplasma pneumoniae, rarely drug reactions.
• Incidence not well-defined, any age, more common in children/young adults.
• Immune complex formation, complement (C3), IgM, fibrinogen deposition around superficial dermal blood vessels, basement membrane, keratinocytes common histology findings. Edema in superficial dermis leads to vesicle/bulla formation.
• Both minor/major have characteristic "bull's-eye" or "target" lesions on skin surface with central dusky region surrounded by concentric rings or alternating edema/inflammation, commonly on extensor limb surfaces.