Dermatology

01 Skin Anatomy & Physiology

The skin is the largest organ in the body, weighing 3.5-10 kg in adults and covering approximately 1.5-2.0 m² of surface area. It functions as a barrier against pathogens, UV radiation, chemical exposure, and mechanical injury; regulates temperature through vasodilation/vasoconstriction and eccrine sweat; synthesizes vitamin D₃ via UV-B conversion of 7-dehydrocholesterol in the epidermis; and provides immune surveillance through resident Langerhans cells, dendritic cells, and dermal macrophages. Understanding its layered architecture is essential for interpreting biopsy reports, selecting surgical depth, and understanding disease pathogenesis.

Epidermis

The epidermis is the outermost layer, avascular, and composed of stratified squamous epithelium. It ranges from 0.05 mm (eyelids) to 1.5 mm (palms and soles). It consists of five layers from deep to superficial:

Dermal-Epidermal Junction (DEJ)

The basement membrane zone (BMZ) anchors the epidermis to the dermis. It consists of (superficial to deep): hemidesmosome attachment plaques in basal keratinocytes, the lamina lucida (containing laminin-332 and BP180/BP230 antigens — targets in bullous pemphigoid), the lamina densa (type IV collagen), and anchoring fibrils (type VII collagen — target in epidermolysis bullosa acquisita). Understanding the BMZ is critical because the level of the split determines the blister type: intraepidermal (pemphigus, flaccid blisters) vs subepidermal (bullous pemphigoid, tense blisters).

Dermis

The dermis lies deep to the epidermis, ranges from 0.3 mm (eyelids) to 3.0 mm (back), and is divided into two zones. The papillary dermis (superficial) consists of thin, loosely arranged type III collagen fibers, capillary loops that nourish the epidermis, and Meissner corpuscles (light touch). The reticular dermis (deep) contains thick, densely packed type I collagen bundles (80% of dermal collagen), elastic fibers (providing skin recoil — loss with aging produces wrinkles), and the cutaneous vascular plexus. The dermis also houses sensory nerve endings (Pacinian corpuscles for pressure/vibration, free nerve endings for pain/temperature), mast cells (central to urticaria and anaphylaxis), fibroblasts (collagen synthesis), and the skin's immune cell population.

Subcutaneous Tissue (Hypodermis)

The subcutis lies below the dermis and consists of lobules of adipocytes separated by fibrous septae containing blood vessels and nerves. It provides insulation, energy storage, mechanical cushioning, and anchors the skin to underlying fascia and muscle. Pathology here includes panniculitis (erythema nodosum involves the septae; erythema induratum involves the lobules), lipomas, and deep infections (necrotizing fasciitis tracks along fascial planes below this layer).

Skin Appendages

Eccrine glands: Distributed across the entire body (highest density on palms, soles, forehead); produce clear, odorless sweat for thermoregulation; innervated by sympathetic cholinergic fibers. Apocrine glands: Located in axillae, groin, areolae, periumbilical; become active at puberty; produce milky secretion that becomes malodorous when metabolized by skin bacteria. Sebaceous glands: Associated with hair follicles (the pilosebaceous unit); produce sebum (lipid mixture) under androgen regulation; hypertrophy leads to sebaceous hyperplasia; blockage leads to comedones and acne. Hair follicles: Cycle through anagen (active growth, 2-6 years on scalp), catagen (regression, 2-3 weeks), and telogen (rest, 2-3 months) phases. Approximately 85-90% of scalp hairs are in anagen at any time. The follicular bulge region contains stem cells critical for wound healing and hair regeneration — destruction of this region in cicatricial alopecia makes hair loss permanent.

02 Dermatologic Terminology — Lesion Morphology

Precise morphologic description is the foundation of dermatologic diagnosis. Every skin finding must be described using standard terminology for primary lesions (the initial morphology), secondary lesions (changes resulting from evolution, trauma, or manipulation), and configuration/distribution patterns. Imprecise descriptions ("rash," "skin lesion") are clinically useless.

Primary Lesions

Secondary Lesions

Configuration & Distribution Terms

03 The Dermatologic Exam

A complete skin exam (CSE) requires examination of the entire skin surface including scalp, ears, interdigital spaces, nails, oral mucosa, and genital skin. Adequate lighting is essential — a handheld magnifying lens or dermatoscope (10x polarized or non-polarized) transforms diagnostic accuracy for pigmented lesions. The exam follows a systematic top-to-bottom, front-to-back approach.

Describing a Lesion — The Standard Framework

Every dermatologic finding is described with a structured vocabulary: number (single vs multiple vs innumerable), color (erythematous, violaceous, hyperpigmented, hypopigmented, flesh-colored, pearly), morphology (using primary lesion terms), size (in mm or cm), shape/configuration (round, oval, annular, linear, irregular), distribution (localized, generalized, symmetric, photodistributed, dermatomal, acral), surface changes (smooth, verrucous, scaly, crusted, ulcerated), and palpation characteristics (firm, soft, fluctuant, tender, blanching vs non-blanching).

Dermoscopy (Dermatoscopy)

Dermoscopy is a non-invasive technique using a handheld device (dermatoscope) with magnification (typically 10x) and a light source (polarized or non-polarized) to examine subsurface skin structures invisible to the naked eye. It dramatically improves sensitivity for melanoma detection (from ~60% with naked eye to >90% with experienced dermoscopy). Key dermoscopic structures include: pigment network (typical = benign melanocytic nevus; atypical = melanoma), globules/dots, streaks/pseudopods (melanoma), blue-white veil (melanoma — dermal melanin + fibrosis), arborizing vessels (BCC), leaf-like structures (BCC), strawberry pattern (actinic keratosis), and comma vessels (dermatofibroma).

Distribution Patterns and Differential Diagnosis

04 Atopic Dermatitis Inflammatory

Atopic dermatitis (AD) is the most common inflammatory skin disease, affecting 15-20% of children and 2-10% of adults worldwide. It is a chronic, relapsing, intensely pruritic eczematous dermatosis driven by a combination of epidermal barrier dysfunction (loss-of-function mutations in the filaggrin gene FLG found in ~30% of patients), Th2-skewed immune dysregulation (IL-4, IL-13, IL-31 overexpression), and environmental triggers. AD is part of the "atopic triad" (AD, allergic rhinitis, asthma) — the "atopic march" describes the typical progression from AD in infancy to rhinitis and asthma in childhood (Weidinger & Novak, Lancet 2016).

Age-Dependent Distribution

Severity Assessment — SCORAD and EASI

The SCORAD (Scoring Atopic Dermatitis) index combines affected BSA (using rule of nines: head 9%, each arm 9%, each leg 18%, anterior trunk 18%, posterior trunk 18%), intensity (erythema, edema/papulation, oozing/crusts, excoriation, lichenification, dryness — each scored 0-3), and subjective symptoms (pruritus and sleep loss, each 0-10 VAS). Total score range: 0-103. Mild < 25; moderate 25-50; severe > 50.

The EASI (Eczema Area and Severity Index) assesses four body regions (head/neck, trunk, upper extremities, lower extremities) for erythema, induration/papulation, excoriation, and lichenification (each 0-3), weighted by BSA involvement. Range: 0-72. Mild 1-7; moderate 7-21; severe 21-50; very severe >50. EASI-75 (75% reduction from baseline) is the primary endpoint in most clinical trials for AD biologics.

Treatment Ladder

05 Contact Dermatitis (Allergic & Irritant) Inflammatory

Contact dermatitis accounts for ~90% of occupational skin diseases. It presents as eczematous dermatitis at sites of exposure and is classified into two mechanistically distinct forms:

Patch Testing

Patch testing is the gold standard for diagnosing ACD. Standardized allergen panels (T.R.U.E. Test has 36 allergens; extended panels from Chemotechnique/SmartPractice have 80+) are applied to the upper back on non-inflamed skin under occlusion. Readings are performed at 48 hours (removal) and 96 hours (delayed reactions). Grading: negative (-), irritant reaction (IR), doubtful/macular erythema (?), weak positive (1+, palpable erythema), strong positive (2+, vesicles), extreme positive (3+, bullous). A positive reaction must be clinically correlated with the patient's exposure history and distribution to confirm relevance.

06 Seborrheic Dermatitis Inflammatory

Seborrheic dermatitis (SD) is a chronic, relapsing inflammatory dermatosis affecting 1-3% of the general population and up to 83% of HIV/AIDS patients. It occurs in areas with high sebaceous gland density: scalp, eyebrows, nasolabial folds, ears, central chest, and intertriginous areas. The pathogenesis involves Malassezia yeast (M. globosa, M. restricta) colonization of sebaceous areas, lipase-mediated hydrolysis of triglycerides in sebum to oleic acid, and an inflammatory response in susceptible individuals. Neurologic associations are strong: SD is markedly more prevalent and severe in Parkinson disease, facial nerve palsy, spinal cord injury, and other conditions that increase sebum production or reduce facial movement.

Presentation: erythematous patches and thin plaques with greasy, yellowish, flaky scale. On the scalp, it ranges from mild dandruff (pityriasis capitis) to thick, adherent plaques. In infants, cradle cap is self-limited seborrheic dermatitis of the scalp. Treatment: topical antifungals (ketoconazole 2% shampoo or cream, ciclopirox 1% shampoo, selenium sulfide 2.5%, zinc pyrithione) are first-line. Low-potency TCS (hydrocortisone 1-2.5%) for acute flares. TCIs (tacrolimus, pimecrolimus) for steroid-sparing maintenance on the face. Refractory cases: oral itraconazole 200 mg/day for 1-2 weeks.

07 Nummular Dermatitis & Stasis Dermatitis Inflammatory

Nummular Dermatitis (Discoid Eczema)

Coin-shaped (nummular), well-demarcated, pruritic, erythematous plaques with fine scale and sometimes exudate/crusting — typically on extensor surfaces of extremities and trunk. More common in men over 50 and in winter (low humidity). Often confused with tinea corporis, but nummular eczema lacks central clearing and KOH is negative. Histology shows spongiotic dermatitis. Treatment: mid-to-high potency TCS (triamcinolone 0.1%, betamethasone valerate 0.1%), emollients, and addressing xerosis triggers. Refractory: phototherapy (NB-UVB).

Stasis Dermatitis

Stasis dermatitis is eczematous inflammation of the lower legs driven by chronic venous insufficiency (CVI). Venous hypertension causes capillary leakage, red blood cell extravasation, and hemosiderin deposition, producing the characteristic brown-red discoloration of the medial lower legs (gaiter area). Progressive changes include scaling, oozing, crusting, lichenification, and ultimately lipodermatosclerosis (fibrotic induration giving the classic "inverted champagne bottle" leg shape). The critical management is addressing the underlying venous disease: compression therapy (30-40 mmHg knee-high stockings — contraindicated if ABI < 0.8), leg elevation, and treatment of superficial venous reflux (endovenous ablation). Topical steroids manage acute flares. Stasis ulcers (venous leg ulcers) are a common complication — characteristically shallow, irregularly bordered, located at the medial malleolus, with a moist granulating base.

08 Psoriasis Papulosquamous

Psoriasis is a chronic, immune-mediated, systemic inflammatory disease affecting 2-3% of the world population. It is driven by the IL-23/Th17 axis: dendritic cells produce IL-23, which activates Th17 cells to secrete IL-17A, IL-17F, and IL-22, driving keratinocyte hyperproliferation, neutrophil recruitment, and angiogenesis. Psoriasis is associated with significant comorbidities: psoriatic arthritis (up to 30% of patients), cardiovascular disease (50% increased risk of MI), metabolic syndrome, depression, and inflammatory bowel disease. It is not merely a skin disease — it is a systemic inflammatory condition with cutaneous manifestations (Armstrong & Read, JAMA 2020).

Clinical Types

Psoriasis Area and Severity Index (PASI)

PASI is the standard clinical trial outcome measure. It evaluates four body regions (head 10%, upper extremities 20%, trunk 30%, lower extremities 40%) for erythema, induration, and desquamation (each scored 0-4) multiplied by area of involvement (0-6 scale). Total range: 0-72. Mild: PASI < 7 or BSA < 3%; moderate: PASI 7-12 or BSA 3-10%; severe: PASI > 12 or BSA > 10%. PASI 75 (75% improvement from baseline) is the standard efficacy benchmark for biologics; many modern agents achieve PASI 90 or PASI 100.

Treatment by Severity

Systemic & Biologic Therapies for Psoriasis

09 Pityriasis Rosea Papulosquamous

Pityriasis rosea (PR) is an acute, self-limited papulosquamous eruption most common in adolescents and young adults (10-35 years). It is likely triggered by reactivation of HHV-6 and/or HHV-7. The classic presentation begins with a herald patch (2-10 cm oval, salmon-colored plaque with a collarette of scale) on the trunk, followed 1-2 weeks later by a secondary eruption of smaller, oval, scaly patches oriented along skin tension lines (Langer lines), producing a characteristic "Christmas tree" distribution on the back. The eruption is self-limited, typically resolving in 6-8 weeks. Pruritus is variable. Treatment is symptomatic: emollients, low-potency TCS, antihistamines, and NB-UVB for severe pruritus. Oral acyclovir (800 mg 5x/day for 1 week) may shorten disease course if started within the first week.

10 Lichen Planus Papulosquamous

Lichen planus (LP) is a T-cell mediated inflammatory dermatosis characterized by the 5 P's: Pruritic, Purple (violaceous), Polygonal, Planar (flat-topped), Papules. Affects 0.5-1% of the population, peak onset 30-60 years. The pathogenesis involves cytotoxic CD8+ T-cell attack on basal keratinocytes, producing a band-like (lichenoid) lymphocytic infiltrate that obscures the dermal-epidermal junction. Histology shows: hyperkeratosis, irregular (sawtooth) acanthosis, wedge-shaped hypergranulosis, civatte bodies (apoptotic keratinocytes), and band-like lymphocytic infiltrate at the DEJ. Direct immunofluorescence shows fibrinogen deposition at the BMZ in a shaggy pattern.

Classic cutaneous LP: violaceous, flat-topped papules and plaques on the flexor wrists, forearms, ankles, and presacral area. Wickham striae — fine white lacy lines on the surface (corresponding to hypergranulosis) — are pathognomonic and best seen with dermoscopy. Koebner phenomenon is common. Oral LP affects 50-70% of cutaneous LP patients: reticular (white lacy pattern on buccal mucosa — most common, usually asymptomatic), erosive (painful red erosions — increased risk of oral SCC; requires monitoring), and plaque forms. Lichen planopilaris is LP of the scalp producing cicatricial (scarring) alopecia with perifollicular erythema and scale. Drug-induced lichenoid eruptions (beta-blockers, ACE inhibitors, thiazides, antimalarials, gold) can mimic LP — drug history is essential.

Treatment: potent topical corticosteroids (clobetasol 0.05% for cutaneous, triamcinolone acetonide oral paste for mucosal); oral corticosteroids for severe widespread disease; systemic retinoids (acitretin); calcineurin inhibitors for mucosal disease; phototherapy (NB-UVB or PUVA). Cutaneous LP typically self-resolves in 1-2 years; oral LP is chronic.

11 Secondary Syphilis & Other Papulosquamous Mimics Papulosquamous

Secondary syphilis is the "great imitator" and must be considered in the differential diagnosis of virtually any papulosquamous eruption. It occurs 6-8 weeks after the primary chancre (which may have been unnoticed) when Treponema pallidum disseminates hematogenously. Key features: diffuse, symmetric, copper-red to pink, maculopapular or papulosquamous rash that classically involves the palms and soles (a crucial discriminator — few conditions do this), condylomata lata (moist, flat, gray-white papules in intertriginous areas — highly infectious), mucous patches (painless gray-white oral erosions), moth-eaten alopecia (patchy, non-scarring hair loss), generalized lymphadenopathy, and constitutional symptoms (low-grade fever, malaise, weight loss). Diagnosis: RPR or VDRL (screening) + FTA-ABS or TP-PA (confirmatory); darkfield microscopy of condylomata lata. Treatment: benzathine penicillin G 2.4 million units IM x1 (same as primary syphilis). Jarisch-Herxheimer reaction (acute febrile reaction within 24 hours of treatment) is common and should be anticipated.

12 Actinic Keratosis & Field Cancerization Cancer

Actinic keratoses (AKs) are UV-induced dysplastic proliferations of epidermal keratinocytes — they represent squamous cell carcinoma in situ and are the most common pre-malignant skin lesion, affecting >58 million Americans. AKs present as rough, gritty, sandpaper-textured papules and patches on sun-exposed skin (face, scalp, dorsal hands, forearms). They are often easier to feel than see. Clinically, they range from flat, pink, scaly macules to hypertrophic, keratotic papules. A cutaneous horn (conical keratinous projection) should be biopsied — SCC is present at the base in ~20% of cases. The risk of any individual AK progressing to invasive SCC is ~0.025-16% per year (wide range in the literature); however, field cancerization — the concept that the entire sun-damaged area harbors subclinical dysplasia — means that patients with visible AKs have diffuse molecular damage in surrounding "normal" skin (Criscione et al., JAMA Dermatol 2009).

Treatment

13 Basal Cell Carcinoma (BCC) Cancer

BCC is the most common human malignancy — approximately 3.6 million cases diagnosed annually in the US. It arises from basal cells of the epidermis and hair follicles, driven by aberrant activation of the Hedgehog signaling pathway (mutations in PTCH1 tumor suppressor gene in ~90% of sporadic BCCs). BCC is locally destructive but metastasizes in < 0.1% of cases (metastasis, when it occurs, usually involves regional lymph nodes or lungs). Risk factors: cumulative and intermittent UV exposure, fair skin (Fitzpatrick I-II), prior radiation therapy, immunosuppression, and basal cell nevus syndrome (Gorlin syndrome — AD mutation of PTCH1 producing multiple BCCs from a young age, odontogenic keratocysts, palmar pits, calcified falx cerebri, skeletal anomalies).

BCC Subtypes

Management

Standard surgical excision with 4 mm clinical margins achieves >95% cure rate for low-risk nodular BCC. Mohs micrographic surgery is indicated for: high-risk anatomic sites (H-zone of face: central face, eyelids, nose, lips, ears, temple), recurrent BCC, morpheaform/infiltrative or micronodular subtypes, large tumors (> 2 cm), perineural invasion, and immunosuppressed patients. Mohs achieves 99% cure rate with maximal tissue conservation. Electrodesiccation and curettage (ED&C) is appropriate for small, low-risk nodular or superficial BCC on the trunk/extremities (not face) — scrape tumor with curette, electrodesiccate base, repeat 2-3 cycles; ~95% cure rate for appropriately selected lesions. Topical imiquimod 5% (5x/week x 6 weeks) and 5-FU (BID x 6-12 weeks) are options for superficial BCC only. For locally advanced or metastatic BCC: vismodegib (Erivedge) 150 mg PO daily or sonidegib (Odomzo) 200 mg PO daily — both are Hedgehog pathway inhibitors (smoothened inhibitors); common side effects include muscle spasms, dysgeusia, alopecia, weight loss; teratogenic (Category D).

14 Squamous Cell Carcinoma (SCC) Cancer

Cutaneous SCC is the second most common skin cancer (~1.8 million cases/year in the US) and the most common skin cancer to metastasize. It arises from malignant proliferation of epidermal keratinocytes, driven primarily by cumulative UV exposure (UVB induces CC→TT signature mutations in p53 tumor suppressor). SCC occurs on a spectrum from in situ disease (Bowen disease) to invasive SCC with potential for regional and distant metastasis. Immunosuppression (organ transplant recipients have 65-250x increased risk of SCC — it is the #1 malignancy in this population) and chronic inflammation (Marjolin ulcer — SCC arising in chronic wounds, burns, scars) are major risk factors (Que et al., JAAD 2018).

High-Risk Features (NCCN Criteria)

AJCC 8th Edition Staging (Cutaneous SCC of Head & Neck)

Management: standard excision with 4-6 mm margins for low-risk SCC. Mohs surgery for high-risk features (same indications as high-risk BCC, plus immunosuppressed patients). Radiation therapy for non-surgical candidates or as adjuvant for perineural invasion/positive margins. Cemiplimab (Libtayo), an anti-PD-1 checkpoint inhibitor, is FDA-approved for locally advanced or metastatic cutaneous SCC not amenable to surgery or radiation — overall response rate ~47% in clinical trials (Migden et al., NEJM 2018).

15 Melanoma Cancer

Melanoma accounts for only ~5% of skin cancers but ~75% of skin cancer deaths. Incidence: ~100,000 new invasive cases/year in the US. Arises from malignant transformation of melanocytes, with key driver mutations: BRAF V600E (~50% of cutaneous melanomas — target for vemurafenib/dabrafenib), NRAS (~20%), NF1 (~14%), and KIT (acral/mucosal melanoma). Risk factors: UV exposure (intermittent intense exposure/sunburns), fair skin (Fitzpatrick I-II), >50 melanocytic nevi, atypical (dysplastic) nevi, family history (CDKN2A mutations), personal history of melanoma (increased recurrence risk), and giant congenital melanocytic nevus.

ABCDE Criteria for Clinical Suspicion

Melanoma Subtypes

Breslow Depth & Clark Level

Breslow depth — measured in millimeters from the granular layer to the deepest identifiable melanoma cell — is the single most important prognostic factor. Clark level (I-V) describes the anatomic level of invasion but has been largely supplanted by Breslow depth (Clark level is no longer in AJCC 8th edition T-staging). Mitotic rate (mitoses/mm²) was removed from AJCC 8th edition staging criteria but remains prognostically relevant.

AJCC 8th Edition TNM Staging — Melanoma

Surgical Margins & Sentinel Lymph Node Biopsy

Systemic Therapy for Advanced Melanoma

The treatment landscape for advanced (unresectable stage III/IV) melanoma has been revolutionized by immunotherapy and targeted therapy. Checkpoint inhibitors: nivolumab (Opdivo, anti-PD-1) + ipilimumab (Yervoy, anti-CTLA-4) combination produces 5-year OS ~52%; pembrolizumab (Keytruda, anti-PD-1) monotherapy 5-year OS ~43%. BRAF/MEK inhibitor combinations: for BRAF V600-mutant melanoma: dabrafenib (Tafinlar) + trametinib (Mekinist), or encorafenib (Braftovi) + binimetinib (Mektovi); rapid response rates (~70%) but median duration of response ~12 months before resistance develops. Adjuvant therapy: pembrolizumab or nivolumab for resected stage III melanoma reduces recurrence by ~35-40% (Luke et al., NEJM 2022).

16 Merkel Cell Carcinoma Cancer

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma of the skin with approximately 3,000 cases/year in the US. Etiology: ~80% are associated with Merkel cell polyomavirus (MCPyV) integration; the remaining ~20% are UV-driven (higher mutation burden). Risk factors: age >65, immunosuppression (10-30x increased risk), fair skin, chronic UV exposure. Presentation: rapidly growing, painless, dome-shaped, firm, violaceous-to-red nodule — the mnemonic AEIOU (Asymptomatic, Expanding rapidly, Immunosuppression, Older than 50, UV-exposed/fair skin) captures the typical profile. Often misdiagnosed as cyst or BCC. Histology: small round blue cell tumor (DDx: lymphoma, small cell lung cancer, melanoma); immunohistochemistry: CK20 positive (perinuclear dot pattern, highly characteristic), TTF-1 negative (distinguishes from small cell lung cancer), chromogranin/synaptophysin positive (neuroendocrine markers).

Staging: AJCC 8th edition uses separate staging for MCC recognizing its aggressive behavior. 5-year OS: localized ~55%, regional ~36%, distant ~14%. Treatment: wide local excision (1-2 cm margins) + SLNB (high rate of occult nodal metastasis ~30%); adjuvant radiation to primary site and draining nodal basin is commonly performed. For advanced/metastatic MCC: avelumab (Bavencio), anti-PD-L1, was the first FDA-approved therapy for metastatic MCC (ORR ~33%); pembrolizumab also shows activity.

17 Bacterial Skin Infections Infections

Impetigo

Impetigo is the most common bacterial skin infection in children. Non-bullous impetigo (~70%): begins as vesicles/pustules that rupture leaving classic honey-colored crusted erosions, caused by Staphylococcus aureus or Group A Streptococcus (GAS). Bullous impetigo (~30%): flaccid, clear-fluid bullae caused specifically by S. aureus producing exfoliative toxins (same toxins responsible for staphylococcal scalded skin syndrome in neonates). Treatment: localized disease — topical mupirocin 2% (Bactroban) or retapamulin 1% (Altabax) TID x 5 days; widespread or refractory — oral dicloxacillin 250 mg QID or cephalexin 250-500 mg QID x 7 days. If MRSA suspected: TMP-SMX DS or doxycycline.

Cellulitis & Erysipelas

Cellulitis: acute bacterial infection of the deep dermis and subcutaneous tissue — erythema, warmth, swelling, tenderness with poorly defined borders. Most commonly caused by beta-hemolytic streptococci (GAS) and S. aureus. Risk factors: skin barrier disruption (tinea pedis is the most common portal of entry for lower extremity cellulitis — treat the tinea to prevent recurrence), lymphedema, venous insufficiency, obesity. Treatment: mild — oral cephalexin 500 mg QID or dicloxacillin 500 mg QID x 5-10 days; moderate/severe — IV cefazolin 1-2 g q8h or nafcillin 1-2 g q4-6h. Erysipelas: more superficial infection (upper dermis/lymphatics) with sharply demarcated, raised, erythematous plaque and prominent lymphatic involvement — classic "butterfly" distribution on the face or well-demarcated patch on the leg; almost always GAS; treat with penicillin VK or amoxicillin.

MRSA Skin Infections

Community-acquired MRSA (CA-MRSA, most commonly USA300/PVL-positive) presents primarily as skin and soft tissue infections — recurrent abscesses, furuncles, and carbuncles, often mistaken for "spider bites." Treatment of abscesses: incision and drainage (I&D) is the primary treatment — antibiotics alone without I&D are insufficient. For surrounding cellulitis or systemic symptoms, add oral TMP-SMX DS BID, doxycycline 100 mg BID, or clindamycin 300-450 mg QID x 7-10 days. Decolonization protocol for recurrent MRSA: mupirocin 2% ointment to anterior nares BID x 5 days + chlorhexidine body washes x 5 days; treat household contacts simultaneously.

Necrotizing Fasciitis

Necrotizing fasciitis is a rapidly progressive, life-threatening deep soft tissue infection that spreads along fascial planes with necrosis of subcutaneous tissue and fascia. Mortality: 20-40% even with treatment. Type I (polymicrobial): mixed aerobic/anaerobic organisms; typically in diabetics, post-surgical, or perianal (Fournier gangrene). Type II (monomicrobial): usually GAS (Streptococcus pyogenes), can occur in healthy individuals after minor trauma. Clinical clues that distinguish from simple cellulitis: pain out of proportion to exam findings, rapid spread, crepitus (subcutaneous gas), dusky/purple skin discoloration, bullae/hemorrhagic bullae, systemic toxicity (sepsis), and failure to respond to appropriate antibiotics. The LRINEC score (Laboratory Risk Indicator for Necrotizing Fasciitis) uses CRP, WBC, hemoglobin, sodium, creatinine, and glucose — score ≥6 suggests necrotizing fasciitis (but clinical suspicion should not wait for scoring). Treatment: emergent surgical debridement (the definitive treatment — delay increases mortality), broad-spectrum antibiotics (vancomycin + piperacillin-tazobactam + clindamycin — clindamycin inhibits toxin production), ICU-level care, serial debridements as needed.

18 Viral Skin Infections Infections

Herpes Simplex Virus (HSV)

HSV-1 and HSV-2 produce grouped vesicles on an erythematous base that ulcerate and crust. HSV-1 classically causes orolabial herpes (cold sores); HSV-2 classically causes genital herpes (though either type can infect either site). Primary infection is typically more severe and prolonged (7-14 days) than recurrences (5-7 days). Eczema herpeticum — disseminated HSV in patients with atopic dermatitis — is a dermatologic emergency: widespread, monomorphic, punched-out erosions/vesicles; requires IV acyclovir. Herpetic whitlow: HSV of the finger. Tzanck smear shows multinucleated giant cells (also seen in VZV — not specific to HSV); PCR is the gold standard. Treatment: acyclovir 400 mg TID x 7-10 days (primary) or 400 mg TID x 5 days (recurrence); valacyclovir 1 g BID x 7-10 days (primary) or 500 mg BID x 3 days (recurrence). Suppressive therapy: valacyclovir 500 mg-1 g daily for frequent recurrences (≥6/year).

Varicella-Zoster Virus (VZV)

Varicella (chickenpox): primary VZV infection producing generalized, pruritic vesicular rash in crops (lesions in various stages — macules, papules, vesicles, crusts simultaneously — "crops of lesions in different stages" is the classic teaching). Herpes zoster (shingles): reactivation of latent VZV in dorsal root ganglia producing painful, unilateral, dermatomal vesicular eruption (does not cross midline). Thoracic dermatomes are most common. Complications: postherpetic neuralgia (PHN) (persistent pain >90 days after rash — risk increases with age), herpes zoster ophthalmicus (HZO) (V1 dermatome — Hutchinson sign: vesicles on the nose tip suggests nasociliary nerve involvement and high risk of ocular complications — urgent ophthalmology referral), and disseminated zoster (immunosuppressed patients — >20 vesicles outside the primary dermatome). Treatment: valacyclovir 1 g TID x 7 days or acyclovir 800 mg 5x/day x 7 days, ideally started within 72 hours of rash onset. Shingrix (recombinant adjuvanted vaccine) recommended for adults ≥50 — 2-dose series; >90% efficacy in preventing zoster and PHN.

Human Papillomavirus (HPV) — Warts

HPV infects keratinocytes through microabrasions. Common warts (verruca vulgaris, HPV 2/4): dome-shaped papules with verrucous surface and thrombosed capillaries ("black dots"). Plantar warts (verruca plantaris, HPV 1): endophytic on soles, painful with lateral pressure (vs callus: painful with direct pressure), disrupt skin lines. Flat warts (verruca plana, HPV 3/10): small, flat-topped papules on face and extremities; numerous. Condylomata acuminata (genital warts, HPV 6/11): soft, flesh-colored, filiform or cauliflower-like papules; oncogenic strains HPV 16/18 cause cervical, anal, and oropharyngeal carcinoma (not the same strains that cause visible warts). Treatment: destructive (cryotherapy, electrosurgery, laser, salicylic acid 17-40%), immunologic (imiquimod 5%), chemical (cantharidin, podophyllotoxin for genital warts). No single treatment is universally effective; ~65% of warts resolve spontaneously within 2 years.

Molluscum Contagiosum

Caused by a poxvirus (Molluscum contagiosum virus). Presents as discrete, dome-shaped, flesh-colored to pearly papules with characteristic central umbilication (dell). Common in children (spread by skin-to-skin contact and fomites) and sexually active adults (genital distribution). Widespread/large molluscum in adults should prompt HIV testing. Self-limited in immunocompetent hosts (6-12 months), but treatment may be sought for cosmesis or to prevent spread: cantharidin (vesicant applied in office), cryotherapy, curettage.

19 Fungal Skin Infections Infections

Dermatophytosis (Tinea)

Dermatophytes (Trichophyton, Microsporum, Epidermophyton) infect keratinized tissue (stratum corneum, hair, nails). Diagnosis: KOH preparation — scrape scale from active advancing border, add 10-20% KOH, examine under microscopy for branching septate hyphae. Fungal culture (Sabouraud agar or dermatophyte test medium/DTM) confirms species.

Cutaneous Candidiasis

Candida albicans (and increasingly non-albicans species) causes superficial infection in warm, moist, occluded areas. Intertriginous candidiasis: beefy-red, erythematous patches with characteristic satellite papules/pustules at the periphery (key distinguishing feature from tinea, which lacks satellites). Oral candidiasis (thrush): white pseudomembranes on buccal mucosa that can be scraped off (DDx: oral hairy leukoplakia — cannot be scraped off, EBV-associated, seen in HIV). Angular cheilitis: erythema/fissuring at oral commissures — often Candida +/- S. aureus. Treatment: topical nystatin cream or clotrimazole cream BID x 2-4 weeks; oral fluconazole 150 mg x 1 for vulvovaginal candidiasis; oral fluconazole 100-200 mg daily for extensive mucocutaneous disease.

Onychomycosis

Fungal nail infection affects ~10% of the general population. Distal lateral subungual onychomycosis (DLSO) is the most common pattern: distal thickening, subungual debris, yellow-brown discoloration, onycholysis. White superficial onychomycosis: white, crumbly patches on the nail plate surface. Proximal subungual onychomycosis: white discoloration at the proximal nail fold — in an immunocompetent patient, consider HIV testing. Always confirm with KOH, culture, or PAS-stained nail clipping before starting systemic therapy. Treatment: terbinafine 250 mg PO daily x 6 weeks (fingernails) or 12 weeks (toenails) — mycologic cure ~70%, complete cure ~40%; itraconazole 200 mg BID x 1 week/month for 2-3 months (pulse dosing); efinaconazole 10% topical solution (Jublia) or tavaborole 5% solution (Kerydin) daily x 48 weeks for mild-moderate disease or patients who cannot take oral therapy. Monitor LFTs with oral antifungals.

20 Parasitic Infestations Infections

Scabies

Caused by the mite Sarcoptes scabiei var. hominis burrowing into the stratum corneum. Hallmarks: intense, generalized pruritus (worse at night, due to mite activity and delayed-type hypersensitivity), burrows (serpiginous, 2-10 mm tracks, most commonly in interdigital web spaces, wrists, axillae, periumbilical, genitalia, buttocks), papules, vesicles, and excoriations. Spares the head in adults (but includes scalp and face in infants/elderly/immunosuppressed). Norwegian (crusted) scabies: massive mite burden (millions vs 10-15 mites in ordinary scabies) in immunosuppressed or neurologically impaired patients — thick, crusted, hyperkeratotic plaques, often misdiagnosed as psoriasis; highly contagious. Diagnosis: mineral oil prep — scrape burrow, examine under microscopy for mites, eggs, or fecal pellets (scybala). Treatment: permethrin 5% cream applied neck-down, left on 8-14 hours, repeated in 1-2 weeks (kills mites but not all eggs — hence repeat); oral ivermectin 200 mcg/kg x 1 dose, repeated in 2 weeks (first-line for crusted scabies; also preferred in institutional outbreaks); treat ALL close contacts and household members simultaneously; wash bedding/clothing in hot water.

Pediculosis (Lice)

Head lice (Pediculus humanus capitis): scalp pruritus, visible nits (eggs) cemented to hair shafts — nits within 6 mm of scalp are viable. Treatment: permethrin 1% lotion (OTC), malathion 0.5% lotion, spinosad 0.9% suspension (Natroba), ivermectin 0.5% lotion (Sklice — single application, no nit combing needed). Body lice (Pediculus humanus corporis): live in clothing seams (not on body); pruritus with excoriations on trunk; associated with homelessness; vector for epidemic typhus (Rickettsia prowazekii), trench fever (Bartonella quintana), relapsing fever (Borrelia recurrentis). Treatment: improved hygiene + laundering clothing at >130 degrees F. Pubic lice (Pthirus pubis): intensely pruritic; found in pubic hair, axillae, eyebrows, eyelashes; treatment: permethrin 1% or malathion; for eyelash involvement: petroleum jelly BID x 10 days (suffocates lice) or ivermectin PO.

Cutaneous Larva Migrans

Caused by penetration of hookworm larvae (Ancylostoma braziliense, A. caninum) through skin in contact with contaminated sand/soil (beaches, sandboxes). Larvae cannot penetrate the basement membrane in humans (accidental host) and migrate through the epidermis, producing characteristic intensely pruritic, serpiginous, erythematous, raised tracks that advance 1-2 cm/day. Usually on feet, buttocks, or hands. Self-limited but slow to resolve (weeks to months). Treatment: oral ivermectin 200 mcg/kg x 1 dose (most effective) or albendazole 400 mg daily x 3 days; topical thiabendazole is an alternative.

21 Pemphigus Vulgaris Autoimmune

Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease caused by IgG autoantibodies against desmoglein 3 (mucosal predominant) and/or desmoglein 1 (mucocutaneous). These desmosomal cadherins are essential for keratinocyte-to-keratinocyte adhesion; antibody binding causes acantholysis (loss of intercellular adhesion) producing flaccid blisters and erosions. Before the steroid era, mortality exceeded 75%; with current therapy it is ~5-10%. Peak onset: 40-60 years.

Presentation: almost always begins with painful oral mucosal erosions (rarely intact blisters — they rupture immediately due to thin mucosal epithelium) that precede skin involvement by weeks to months. Cutaneous lesions: flaccid blisters that rupture easily leaving painful, non-healing erosions; Nikolsky sign positive (lateral pressure on normal-appearing skin adjacent to a lesion causes shearing/blister formation); Asboe-Hansen sign (direct pressure on a bulla causes lateral extension). Diagnosis: skin biopsy for histology (suprabasal acantholysis with "tombstone" pattern — basal cells still attached to basement membrane with detached suprabasal cells), direct immunofluorescence (DIF) of perilesional skin (intercellular IgG and C3 in a "chicken-wire" or "fishnet" pattern — gold standard), and serum anti-desmoglein 1/3 ELISA (antibody titers correlate with disease activity).

Treatment: systemic corticosteroids (prednisone 1-2 mg/kg/day) for acute control, tapered with steroid-sparing agents. Rituximab (Rituxan) — anti-CD20 B-cell depleting antibody — is now considered first-line steroid-sparing therapy based on the RITUX 3 trial (rituximab + low-dose prednisone superior to prednisone alone for complete remission) (Joly et al., Lancet 2017). Other steroid-sparing agents: mycophenolate mofetil (CellCept) 2-3 g/day, azathioprine 2-3 mg/kg/day (check TPMT activity before starting), IVIG (for refractory disease).

22 Bullous Pemphigoid Autoimmune

Bullous pemphigoid (BP) is the most common autoimmune blistering disease, primarily affecting elderly patients (>70 years). IgG autoantibodies target BP180 (collagen XVII) and BP230 at the dermal-epidermal junction (hemidesmosome components), causing subepidermal blistering. Unlike pemphigus, the split is below the epidermis, producing tense blisters that do not rupture as easily. Nikolsky sign is typically negative.

Presentation: prodromal urticarial or eczematous phase (weeks to months — often misdiagnosed as eczema) followed by tense bullae on erythematous or normal-appearing skin, predominantly on the trunk, proximal extremities, and flexural areas. Oral involvement occurs in ~10-30% (vs nearly 100% in PV). Pruritus is often severe. Diagnosis: biopsy shows subepidermal blister with eosinophil-rich infiltrate; DIF of perilesional skin shows linear IgG and C3 along the BMZ (linear, not intercellular — distinguishes from pemphigus); serum anti-BP180/BP230 ELISA.

Treatment: mild/localized — superpotent topical corticosteroid (clobetasol 0.05% to entire body) is as effective as oral prednisone with fewer side effects (landmark trial by Joly et al., 2002). Moderate/severe — oral prednisone 0.5 mg/kg/day (lower doses than PV). Steroid-sparing: doxycycline 200 mg/day (anti-inflammatory properties), methotrexate, mycophenolate mofetil, azathioprine, dapsone, or rituximab for refractory cases. Drug-induced BP (DPP-4 inhibitors/gliptins — notably vildagliptin, linagliptin — are an increasingly recognized trigger; PD-1/PD-L1 checkpoint inhibitors are another important cause).

23 Dermatitis Herpetiformis Autoimmune

Dermatitis herpetiformis (DH) is the cutaneous manifestation of celiac disease (gluten-sensitive enteropathy). IgA antibodies against epidermal transglutaminase (eTG) deposit in the dermal papillae, causing neutrophilic inflammation. ~90% of DH patients have underlying celiac disease on intestinal biopsy (often subclinical). Presentation: intensely pruritic, grouped (herpetiform) vesicles and papules on extensor surfaces — elbows (most common), knees, buttocks, posterior scalp, upper back. Vesicles are often excoriated (patients scratch them before they can be examined intact). Diagnosis: DIF of perilesional uninvolved skin (not the lesion itself) shows granular IgA deposits at the dermal papillae — pathognomonic. Serum: anti-tissue transglutaminase (tTG) IgA and anti-endomysial antibodies (same as celiac disease workup). Treatment: dapsone (diaminodiphenylsulfone) 25-150 mg/day produces dramatic improvement within 24-48 hours (so fast it is almost diagnostic); check G6PD before starting (risk of hemolytic anemia); monitor CBC every 2 weeks x 3 months then every 3 months. Long-term: strict gluten-free diet controls both the skin and intestinal disease and may allow discontinuation of dapsone after 1-2 years.

24 Dermatomyositis Autoimmune

Dermatomyositis (DM) is an autoimmune inflammatory myopathy with characteristic cutaneous findings. The pathognomonic skin findings are: heliotrope rash (violaceous erythema/edema of the upper eyelids), Gottron papules (violaceous, flat-topped papules over the MCP and IP joints, elbows, and knees — DDx: lupus affects the skin between the joints), Gottron sign (macular violaceous erythema over the same distribution), shawl sign (erythema over the posterior neck and upper back), V-sign (V-shaped erythema on the anterior chest/neck), mechanic's hands (hyperkeratotic, fissured skin on the lateral fingers — associated with anti-synthetase antibodies), and periungual telangiectasias with ragged cuticles (dilated nailfold capillary loops visible on dermoscopy/capillaroscopy).

Muscle involvement: symmetric proximal weakness (difficulty rising from chair, climbing stairs, lifting arms above head); elevated CK, aldolase, LDH; EMG shows myopathic changes; MRI shows muscle edema; muscle biopsy shows perifascicular atrophy (pathognomonic). Amyopathic/clinically amyopathic dermatomyositis (CADM): classic skin findings without clinically significant muscle weakness — carries significant malignancy and ILD risk. Autoantibodies: anti-Mi-2 (classic DM, good prognosis), anti-MDA5 (CADM, rapidly progressive ILD — can be fatal), anti-TIF1-gamma (strongly associated with malignancy), anti-NXP2 (calcinosis, malignancy). Malignancy screening is essential: DM carries a 3-8x increased risk of underlying malignancy (most commonly ovarian, lung, GI, breast, lymphoma); risk is highest in the first 3 years after diagnosis; age-appropriate cancer screening plus CT chest/abdomen/pelvis is standard.

Treatment: systemic corticosteroids (prednisone 1 mg/kg/day) + steroid-sparing immunosuppressant (methotrexate, azathioprine, mycophenolate mofetil); IVIG for refractory disease; rituximab. For skin: photoprotection (photosensitive), hydroxychloroquine, topical steroids/calcineurin inhibitors.

25 Cutaneous Lupus Erythematosus Autoimmune

Cutaneous lupus erythematosus (CLE) encompasses three main forms, which may occur independently or in the context of systemic lupus erythematosus (SLE):

Workup for all CLE: ANA, anti-dsDNA, anti-Ro/La, complement (C3, C4), CBC, urinalysis, renal function. Treatment: strict photoprotection (broad-spectrum SPF 50+, sun avoidance — UV can trigger or worsen CLE), topical corticosteroids, topical calcineurin inhibitors, and hydroxychloroquine (Plaquenil) 200-400 mg/day — first-line systemic therapy (requires baseline and annual ophthalmologic screening after 5 years for retinal toxicity). Refractory: quinacrine 100 mg/day (may be added to HCQ), methotrexate, mycophenolate mofetil, thalidomide/lenalidomide (for severe refractory DLE).

26 Morphea & Systemic Sclerosis Autoimmune

Morphea (Localized Scleroderma)

Morphea is a localized fibrotic condition of the skin characterized by excessive collagen deposition in the dermis and subcutis. It is NOT systemic sclerosis — morphea does not involve internal organs, does not cause Raynaud phenomenon, and does not have sclerodactyly. Types: plaque morphea (most common — well-defined, indurated, ivory-white plaque with lilac/violaceous border indicating active inflammation), linear morphea (band-like — when on the face/scalp, called en coup de sabre; can involve underlying muscle and bone in children), generalized morphea (≥4 plaques involving ≥2 body regions), and deep morphea (involves subcutis and fascia). Treatment: active disease (lilac ring present) — topical tacrolimus, mid-to-high potency TCS, phototherapy (UVA1), or systemic methotrexate + corticosteroids for rapidly progressive or disabling disease. Inactive ("burnt-out") morphea may leave atrophic, hyperpigmented patches that do not require treatment.

Systemic Sclerosis (Scleroderma) — Cutaneous Features

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vascular damage, immune activation, and progressive fibrosis of skin and internal organs. Cutaneous features the dermatologist recognizes: Raynaud phenomenon (often the first symptom — triphasic color changes: white→blue→red), sclerodactyly (skin tightening of the fingers), digital ulcers and pitting scars, calcinosis cutis (subcutaneous calcium deposits), telangiectasias (matted perioral and facial telangiectasias), and nailfold capillary changes (dilated loops, avascular areas — visible on dermoscopy/capillaroscopy; distinguishes SSc-associated Raynaud from primary Raynaud). Limited cutaneous SSc (formerly CREST): skin thickening distal to elbows/knees + face; anti-centromere antibodies; pulmonary arterial hypertension risk. Diffuse cutaneous SSc: widespread skin involvement; anti-Scl-70 (anti-topoisomerase I) antibodies; higher risk of ILD, renal crisis, cardiac involvement.

27 Acne Vulgaris Acne/Rosacea

Acne vulgaris is the most common skin condition in the United States, affecting ~85% of adolescents and persisting into adulthood in ~50% of women and ~25% of men. Pathogenesis involves four key factors: (1) androgen-mediated excess sebum production, (2) follicular hyperkeratinization (keratin plugging of the follicular ostium), (3) Cutibacterium acnes (formerly Propionibacterium acnes) colonization and inflammation, and (4) innate immune activation (TLR-2 mediated). These produce the spectrum from non-inflammatory comedones (open/closed) to inflammatory papules, pustules, nodules, and cysts.

Grading

Treatment by Severity

Isotretinoin — Detailed

Isotretinoin (13-cis-retinoic acid) is the only medication that addresses all four pathogenic factors of acne. Dose: 0.5-1.0 mg/kg/day (may start lower to reduce initial flare), total cumulative dose of 120-150 mg/kg to minimize relapse. Take with fatty food (absorption increased 2x). Monitoring: iPLEDGE program (mandatory FDA REMS) — all patients require monthly visits; females of childbearing potential require 2 forms of contraception, monthly pregnancy tests (urine/serum), 1-month negative pregnancy test before starting, and contraception continued 1 month after stopping. Labs: fasting lipid panel and LFTs at baseline, 1 month, and every 1-2 months. Side effects: mucocutaneous dryness (cheilitis ~100%, xerosis, epistaxis, dry eyes — all dose-dependent), myalgias/arthralgias, elevated triglycerides (rarely pancreatitis if TG >500), hepatotoxicity (rare), night vision changes, mood changes (depression/suicidality — contested but requires monitoring); teratogenic — Category X, absolute contraindication in pregnancy.

28 Rosacea Acne/Rosacea

Rosacea is a chronic inflammatory facial dermatosis affecting ~16 million Americans, predominantly fair-skinned individuals aged 30-60. Pathogenesis involves neurovascular dysregulation, innate immune activation (cathelicidin/LL-37 pathway), Demodex folliculorum mite overcolonization, and vascular hyperreactivity. Triggers: heat, sun, alcohol, spicy food, hot beverages, emotional stress.

Rosacea Subtypes (Phenotype-Based Approach Now Preferred)

29 Hidradenitis Suppurativa Acne/Rosacea

Hidradenitis suppurativa (HS) is a chronic, recurrent, debilitating inflammatory disease of the hair follicle (follicular occlusion disease, not a primary apocrine gland disorder as previously thought). Prevalence: ~1-4%; female predominance 3:1; onset after puberty; strong associations with smoking (75% of patients), obesity, metabolic syndrome, and family history (AD inheritance pattern identified in some families with gamma-secretase mutations). Pathogenesis: follicular hyperkeratinization → occlusion → follicular rupture → intense innate immune response (TNF-alpha, IL-1, IL-17 overexpression) → abscess formation → sinus tract development → fibrosis.

Presentation: painful, deep nodules and abscesses in apocrine gland-bearing skin — axillae, groin, inframammary folds, gluteal cleft, perineum. Recurrent abscesses in the same locations is pathognomonic. Chronic disease produces sinus tracts (interconnecting tunnels), scarring, and contractures. Double comedones (two blackheads connected by a subcutaneous tunnel) are characteristic.

Hurley Staging

30 Alopecia — Non-Cicatricial & Cicatricial Hair/Nails

Non-Cicatricial (Non-Scarring) Alopecia

Cicatricial (Scarring) Alopecia

Cicatricial alopecias destroy the hair follicle stem cells in the bulge region, making hair loss permanent. Characterized by loss of follicular ostia (no visible pores in the bald area — distinguishes from non-scarring alopecia). Classification by predominant inflammatory infiltrate: lymphocytic (lichen planopilaris/LPP, frontal fibrosing alopecia/FFA, discoid lupus/DLE, central centrifugal cicatricial alopecia/CCCA) or neutrophilic (dissecting cellulitis, folliculitis decalvans). Diagnosis requires scalp biopsy (two specimens — one for H&E, one for DIF). Frontal fibrosing alopecia (FFA) — a variant of LPP — presents with progressive frontotemporal hairline recession and eyebrow loss, predominantly in postmenopausal women; increasing in prevalence. Treatment goal is to halt progression (regrowth unlikely): hydroxychloroquine, doxycycline, finasteride/dutasteride, topical/intralesional steroids.

31 Nail Disorders Hair/Nails

Melanonychia

Longitudinal melanonychia — a brown-black longitudinal streak in the nail — requires careful evaluation because it may represent benign nail matrix melanocyte activation (common in dark-skinned individuals, where longitudinal melanonychia is a normal variant), subungual melanocytic nevus, or subungual melanoma. Concerning features: new onset in a light-skinned adult, single digit (especially thumb or great toe), width >3 mm, irregular borders, pigment changes, Hutchinson sign (periungual pigmentation extending onto nail fold — concerning for melanoma), nail dystrophy, and personal history of melanoma. Nail matrix biopsy is required for suspicious lesions — a longitudinal excisional biopsy of the pigmented band from the nail matrix is the standard technique.

32 Vitiligo Pigmentary

Vitiligo is an acquired autoimmune depigmenting disorder caused by CD8+ T-cell-mediated destruction of melanocytes, affecting ~1% of the population worldwide. It presents as well-demarcated, chalky-white macules and patches (total absence of melanin, unlike hypopigmentation where some melanin remains). Onset: typically before age 30; associated with other autoimmune diseases (thyroid — screen with TSH/free T4, type 1 DM, pernicious anemia, Addison disease, alopecia areata). Types: non-segmental (generalized) — most common (~90%), symmetric, progressive, often periorificial (around eyes, mouth, genitals), acral; segmental — unilateral, dermatomal, earlier onset, more stable, less associated with autoimmunity, responds better to surgical therapies.

Diagnosis is clinical — enhanced by Wood lamp examination (365 nm UV light): vitiligo fluoresces bright white/blue-white, making subtle lesions visible, especially in fair-skinned patients. DDx: pityriasis alba (ill-defined, hypopigmented, slightly scaly patches in children — associated with AD), tinea versicolor (fine scale, KOH positive), post-inflammatory hypopigmentation (history of prior inflammation), piebaldism (congenital, stable, white forelock). Treatment: ruxolitinib 1.5% cream (Opzelura) — first FDA-approved topical for vitiligo (2022); JAK1/2 inhibitor that blocks the IFN-gamma/CXCL10 signaling that drives melanocyte destruction. Other topicals: tacrolimus 0.1%, pimecrolimus 1% (preferred for face), high-potency TCS for body. NB-UVB phototherapy (311 nm) 2-3x/week is the most effective non-surgical therapy for widespread disease — produces repigmentation (from perifollicular melanocyte reservoirs) in ~50-70% of patients over 6-12 months. Surgical: autologous melanocyte-keratinocyte transplant or suction blister epidermal grafting for stable segmental or localized vitiligo refractory to medical therapy.

33 Melasma & Post-Inflammatory Hyperpigmentation Pigmentary

Melasma

Melasma is a common acquired disorder of hyperpigmentation characterized by symmetric, brown-to-gray patches on the face — centrofacial (forehead, cheeks, nose, upper lip, chin) is the most common pattern; malar and mandibular patterns also occur. Predominantly affects women (Fitzpatrick III-V), triggered by UV exposure, hormonal influences (pregnancy, oral contraceptives, HRT), and genetic predisposition. Three histologic types: epidermal (brown, well-defined, enhanced by Wood lamp — better treatment response), dermal (blue-gray, ill-defined, not enhanced by Wood lamp — more resistant), and mixed. Treatment: triple combination cream (hydroquinone 4% + tretinoin 0.05% + fluocinolone acetonide 0.01% — Tri-Luma) is the gold standard topical; apply nightly x 8-12 weeks. Strict photoprotection is essential (tinted sunscreen with iron oxide blocks visible light, which triggers melasma in dark skin types). Alternatives: azelaic acid 15-20%, tranexamic acid (oral 250 mg BID or topical — inhibits plasmin-mediated melanogenesis), vitamin C serum, cysteamine 5% cream, chemical peels (glycolic acid). Hydroquinone should be cycled (3-6 months on, 2-3 months off) to prevent ochronosis (paradoxical blue-gray discoloration with prolonged use).

Post-Inflammatory Hyperpigmentation (PIH)

PIH is acquired hyperpigmentation following cutaneous inflammation or injury (acne, eczema, trauma, procedures). More common and more persistent in darker skin types (Fitzpatrick III-VI). Epidermal PIH (brown): melanin increased in epidermis — responds to topical lightening agents. Dermal PIH (blue-gray): melanin dropped into dermis (melanin incontinence/melanophages) — slower to resolve, resistant to treatment. Management: treat the underlying inflammatory condition first (to prevent new PIH), photoprotection, topical retinoids, azelaic acid, vitamin C, hydroquinone 2-4%, chemical peels (caution in dark skin — aggressive peels can worsen PIH). Time is often the most effective treatment — most epidermal PIH resolves in 6-12 months; dermal PIH can take years.

34 Morbilliform Drug Eruptions & Urticaria Emergencies

Morbilliform (Exanthematous) Drug Eruption

The most common cutaneous drug reaction (~95% of drug rashes), occurring 7-14 days after drug initiation (or 1-3 days on re-exposure). Presents as widespread, symmetric, erythematous macules and papules that may coalesce — starts on the trunk and spreads peripherally. Pruritic. Mucous membranes spared. No systemic symptoms (distinguishes from DRESS and SJS/TEN). Most common culprits: antibiotics (amoxicillin, TMP-SMX, penicillins, cephalosporins), anticonvulsants (carbamazepine, phenytoin, lamotrigine), allopurinol, NSAIDs. The classic "ampicillin rash" in EBV mononucleosis is not a true drug allergy — it is an immune-mediated reaction that does not predict future penicillin allergy. Management: discontinue offending drug, supportive care (emollients, antihistamines, mild-to-mid potency TCS); resolves 1-2 weeks after drug withdrawal.

Urticaria (Hives)

Wheals (transient, pruritic, edematous papules and plaques) that individually last <24 hours and resolve without bruising. If an individual wheal lasts >24 hours or leaves bruising, consider urticarial vasculitis (biopsy needed). Acute urticaria (<6 weeks): usually identifiable trigger — drugs, foods, infections. Chronic urticaria (≥6 weeks): ~80% are chronic spontaneous urticaria (CSU) with no identifiable trigger; autoimmune etiology in ~30-50% (IgG anti-FceRI or anti-IgE antibodies). Treatment: second-generation H1 antihistamines (cetirizine, loratadine, fexofenadine) at standard then up to 4x standard dose → add H2 blocker (famotidine) or LTRA (montelukast) → omalizumab (Xolair), anti-IgE monoclonal antibody, 150-300 mg SC q4 weeks (FDA-approved for CSU refractory to antihistamines) → cyclosporine for refractory CSU. Avoid systemic corticosteroids for chronic urticaria — short courses only for severe flares.

35 Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Emergencies

SJS and TEN are life-threatening mucocutaneous reactions characterized by extensive keratinocyte apoptosis mediated by cytotoxic T cells and FasL/granulysin. They exist on a spectrum: SJS = <10% BSA detachment; SJS/TEN overlap = 10-30% BSA; TEN = >30% BSA. Mortality: SJS ~5-10%; TEN ~25-35%. Nearly always drug-induced (onset 1-3 weeks after drug initiation). Highest-risk drugs: allopurinol (screen for HLA-B*5801 in high-risk populations — Southeast Asian, African American), carbamazepine (screen for HLA-B*1502 in Southeast Asian populations), lamotrigine, phenytoin, sulfonamides (TMP-SMX), nevirapine, piroxicam (Mockenhaupt et al., J Invest Dermatol 2008).

Presentation: prodromal fever and malaise → painful skin tenderness → erythematous-to-dusky macules, often with targetoid morphology (atypical targets), coalescing into patches → full-thickness epidermal necrosis with bullae → positive Nikolsky sign (epidermal detachment with lateral pressure). Mucous membrane involvement (≥2 sites: oral, ocular, genital, respiratory, GI) is nearly universal and is a key distinguishing feature from other drug eruptions. Ocular involvement can cause synechiae, corneal scarring, and permanent vision loss — urgent ophthalmology involvement is mandatory.

SCORTEN — Severity-of-Illness Score for TEN

Management: immediate discontinuation of the causative drug (early withdrawal reduces mortality), transfer to burn unit or ICU, aggressive supportive care (wound care, fluid/electrolyte management, pain control, nutritional support, infection surveillance — do NOT give prophylactic antibiotics), ophthalmology and urology consults. Specific therapies: cyclosporine 3-5 mg/kg/day has the strongest emerging evidence for mortality benefit; IVIG is commonly used but evidence is mixed; systemic corticosteroids are controversial (some data suggest harm). Etanercept (anti-TNF) shows promise in recent trials (Wang et al., JAMA Dermatol 2021).

36 DRESS Syndrome, Erythema Multiforme & AGEP Emergencies

DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)

Also known as drug-induced hypersensitivity syndrome (DIHS). Onset: 2-8 weeks after drug initiation (longer latency than morbilliform eruption). Hallmarks: widespread morbilliform or erythrodermic eruption + facial edema (especially periorbital) + fever + lymphadenopathy + hematologic abnormalities (eosinophilia ≥ 1,500/mcL and/or atypical lymphocytosis) + internal organ involvement (liver 60-80% — monitor AST/ALT, kidneys 10-30%, lungs, myocarditis, thyroiditis). Highest-risk drugs: anticonvulsants (carbamazepine, phenytoin, lamotrigine, phenobarbital — cross-reactivity among aromatic anticonvulsants ~40%), allopurinol, dapsone, minocycline, vancomycin, TMP-SMX. Strong association with HHV-6 reactivation. RegiSCAR scoring system validates diagnosis. Mortality: ~5-10%. Treatment: withdraw offending drug immediately; systemic corticosteroids (prednisone 1-1.5 mg/kg/day, taper slowly over 8-12 weeks — rapid taper risks rebound; steroid-associated HHV-6 reactivation must be monitored). Late sequelae: autoimmune thyroiditis (monitor TSH for 1 year) and type 1 DM can develop weeks to months after recovery.

Erythema Multiforme (EM)

EM is an acute, self-limited, immune-mediated reaction most commonly triggered by HSV infection (~90% of cases — not drugs). Classic lesion: target lesion (targetoid) — three concentric zones: dusky/necrotic center, pale edematous ring, erythematous outer ring — predominantly on the extremities (acral, symmetric), palms and soles. EM minor: skin only, limited mucous membrane involvement; EM major: more extensive mucous membrane involvement (oral, genital). EM is NOT on the SJS/TEN spectrum — different etiology (infection-triggered vs drug-induced), different target lesion morphology (true targets vs atypical targets in SJS), and different prognosis (EM recurs but has minimal mortality). Recurrent EM: triggered by recurrent HSV — suppressive valacyclovir 500 mg-1 g daily prevents recurrences.

AGEP (Acute Generalized Exanthematous Pustulosis)

Acute onset (within 48-96 hours of drug exposure, much faster than DRESS) of dozens to hundreds of small, non-follicular, sterile pustules on widespread erythematous skin, often starting in intertriginous areas. High fever, neutrophilia (not eosinophilia — distinguishes from DRESS). Most common triggers: aminopenicillins (ampicillin, amoxicillin), macrolides, quinolones, terbinafine, diltiazem, hydroxychloroquine. Histology: subcorneal/intraepidermal spongiform pustules with neutrophilic infiltrate and papillary dermal edema. Treatment: withdraw the causative drug; typically self-limited with spontaneous resolution in 1-2 weeks (pustules desquamate); supportive care; mortality <5% (usually in elderly with comorbidities).

37 Cutaneous T-Cell Lymphoma (Mycosis Fungoides & Sezary Syndrome) Special

Cutaneous T-cell lymphoma (CTCL) is a group of non-Hodgkin lymphomas that primarily manifest in the skin. Mycosis fungoides (MF) is the most common type (~50% of all primary cutaneous lymphomas). It is a malignancy of skin-homing CD4+ T cells and progresses through characteristic clinical stages:

TNMB Staging (ISCL/EORTC)

MF/Sezary staging uses a modified TNMB system: T (skin involvement — T1 patches/plaques <10% BSA; T2 ≥10% BSA; T3 tumors; T4 erythroderma), N (lymph node involvement), M (visceral involvement), B (blood involvement — B0 <5% Sezary cells; B1 ≥5% but <1,000/mcL; B2 ≥1,000/mcL). Stage IA (T1N0M0B0) has excellent prognosis (median survival similar to age-matched controls); stage IVB (visceral involvement) has median survival ~1-2 years.

Treatment: early-stage (IA-IIA) — skin-directed therapies: topical corticosteroids, topical nitrogen mustard (mechlorethamine 0.02% gel — Valchlor), NB-UVB or PUVA phototherapy, localized radiation. Advanced-stage (IIB-IV) — systemic therapies: bexarotene (Targretin — RXR retinoid agonist), vorinostat (Zolinza — HDAC inhibitor), romidepsin (Istodax — HDAC inhibitor), brentuximab vedotin (Adcetris — anti-CD30), mogamulizumab (Poteligeo — anti-CCR4), extracorporeal photopheresis (ECP — particularly for Sezary syndrome), low-dose methotrexate, interferons (IFN-alpha). Allogeneic stem cell transplant is the only potentially curative therapy for advanced CTCL.

38 Granuloma Annulare & Pyoderma Gangrenosum Special

Granuloma Annulare (GA)

GA is a benign, self-limited granulomatous dermatosis of unclear etiology. Classic presentation: annular or arcuate, flesh-colored to erythematous, non-scaly, smooth plaques and papules on the dorsal hands and feet. The lack of scale distinguishes it from tinea corporis (KOH negative). Histology: palisading granuloma with central mucin deposition (Alcian blue positive). Subtypes: localized (most common, self-limited), generalized (widely distributed, may be associated with diabetes mellitus), subcutaneous (deep nodules, especially in children — DDx: rheumatoid nodule), perforating (papules with central crust from transepidermal elimination of degenerated collagen). Treatment: often unnecessary (localized resolves in 50% within 2 years); high-potency TCS, intralesional triamcinolone, cryotherapy; generalized GA: phototherapy (NB-UVB, PUVA), dapsone, hydroxychloroquine, methotrexate.

Pyoderma Gangrenosum (PG)

PG is a neutrophilic dermatosis presenting as a rapidly progressive, painful ulcer with violaceous, undermined borders and a purulent/necrotic base. Classic form begins as a sterile pustule or papule that rapidly expands into a deep ulcer. The key concept is pathergy — new lesions (or worsening of existing lesions) triggered by trauma, including surgical debridement, which is why debridement is contraindicated (a common pitfall). Diagnosis is clinical and histologic (neutrophilic infiltrate, ruling out infection and malignancy — PG is a diagnosis of exclusion). Associated with systemic diseases in 50-70%: inflammatory bowel disease (UC > Crohn), rheumatoid arthritis, hematologic malignancies (MDS, AML, myeloma), and monoclonal gammopathy (IgA). Treatment: high-dose systemic corticosteroids (prednisone 1 mg/kg/day), cyclosporine 3-5 mg/kg/day, TNF-alpha inhibitors (infliximab), topical tacrolimus for small/stable lesions; wound care with non-adherent dressings; AVOID debridement (pathergy risk).

39 Sweet Syndrome & Dermatologic Signs of Systemic Disease Special

Sweet Syndrome (Acute Febrile Neutrophilic Dermatosis)

Sweet syndrome presents with acute onset of painful, edematous, erythematous-to-violaceous papules, plaques, and nodules — classically on the face, neck, and upper extremities — accompanied by fever, neutrophilia, and elevated ESR/CRP. Histology: dense dermal neutrophilic infiltrate without vasculitis (distinguishes from leukocytoclastic vasculitis). Three categories: classical (triggered by URIs, GI infections, or associated with IBD, pregnancy), malignancy-associated (hematologic malignancies, especially AML and MDS — screen with CBC, peripheral smear, bone marrow biopsy if abnormal), and drug-induced (G-CSF, all-trans retinoic acid, TMP-SMX). Treatment: systemic corticosteroids produce dramatic rapid response (prednisone 0.5-1 mg/kg/day — improvement within 48 hours is almost diagnostic); steroid-sparing options include dapsone, colchicine, and potassium iodide.

Dermatologic Signs of Systemic Disease

40 Skin Biopsy Techniques Procedures

Skin biopsy is the most fundamental diagnostic procedure in dermatology. Biopsy site selection is critical — biopsy the most representative, well-developed lesion (not the oldest or most excoriated). For vesiculobullous diseases, biopsy the edge of a fresh blister (not the blister roof or center); for DIF, biopsy perilesional uninvolved skin.

41 Mohs Micrographic Surgery Procedures

Mohs micrographic surgery (MMS) is the gold standard for skin cancer removal in high-risk settings. The technique, developed by Frederic Mohs, achieves the highest cure rate (99% for primary BCC, 95% for recurrent BCC) with maximal tissue conservation — critical on the face where every millimeter of tissue preservation matters.

Procedure

The visible tumor is debulked. A thin layer of tissue is excised around and beneath the defect. The tissue is mapped, color-coded, frozen sectioned, and examined under microscopy by the Mohs surgeon — 100% of the peripheral and deep margins are examined (vs <1% in standard "bread-loaf" histologic sectioning). If residual tumor is identified in any area, that specific area is re-excised and the process is repeated. The cycle continues until all margins are clear, then the defect is reconstructed (primary closure, flap, graft, or second-intention healing depending on size and location).

Appropriate Use Criteria (AUC) — Indications for Mohs

42 Cryotherapy, ED&C & Phototherapy Procedures

Cryotherapy (Liquid Nitrogen)

Liquid nitrogen (LN₂, -196 degrees C) is the most commonly performed procedure in dermatology. Mechanism: rapid freeze → ice crystal formation in cells → thaw → cell membrane disruption → necrosis. Applied via spray gun (most common), cotton-tipped applicator, or cryoprobe. Freeze time varies by lesion: 5-10 seconds for AK, 10-15 seconds for verruca, 20-30 seconds for BCC (superficial). Double freeze-thaw cycle (freeze → thaw → freeze again) is more effective for malignant/premalignant lesions. Side effects: pain, blister formation (expected), dyspigmentation (hypopigmentation common — caution in dark skin), hair loss in treated area. Contraindications: cryoglobulinemia, cryofibrinogenemia, cold urticaria, Raynaud phenomenon in the area, poor circulation.

Electrodesiccation & Curettage (ED&C)

A destructive technique for low-risk BCC and SCC (see Sections 13-14 for appropriate selection criteria). Procedure: local anesthesia → curette the tumor (scrapes soft tumor tissue preferentially, healthy dermis resists curettage — the "feel" of resistance indicates adequate removal) → electrodesiccate the base → repeat 2-3 total cycles. Heals by secondary intention over 4-8 weeks. Produces a round, atrophic, hypopigmented scar. Not appropriate for high-risk tumors, recurrent tumors, or high-risk anatomic sites (face/H-zone — poor cosmetic outcome and limited margin assessment).

Phototherapy

43 Intralesional Injections & Procedural Therapeutics Procedures

Intralesional Corticosteroid Injections

Triamcinolone acetonide (Kenalog) is the workhorse intralesional corticosteroid. Concentration varies by indication: 2.5-5 mg/mL for alopecia areata (scalp), 5-10 mg/mL for inflammatory acne nodules/cysts and keloids, 10-20 mg/mL for hypertrophic scars, 20-40 mg/mL for thick keloids. Injected directly into the lesion using a 30-gauge needle. Complications: dermal/subcutaneous atrophy (depressed scar — usually reversible over months), hypopigmentation (especially in dark skin), telangiectasia. Maximum dose per session is generally limited to avoid systemic absorption (typically <40-60 mg total). For HS nodules: intralesional triamcinolone 3-5 mg/mL provides rapid relief within 24-48 hours.

5-Fluorouracil (Intralesional)

Intralesional 5-FU (50 mg/mL, often mixed with triamcinolone) is used for hypertrophic scars and keloids — the antimetabolite inhibits fibroblast proliferation while the steroid suppresses inflammation. Inject q2-4 weeks; often combined with cryotherapy (triple therapy: cryo + intralesional steroid + 5-FU has best evidence for keloid reduction).

Bleomycin (Intralesional)

Intralesional bleomycin (1 U/mL) is used for recalcitrant warts. Injected directly into the wart or applied via bifurcated needle prick technique. Causes local necrosis of HPV-infected cells. Contraindicated in pregnancy and immunosuppression. Painful injection. Cure rates: 60-90% for common and plantar warts.

Chemical Peels

Chemical peeling agents by depth: superficial (glycolic acid 30-70%, salicylic acid 20-30%, Jessner solution, TCA 10-25% — epidermis only; good for acne, melasma, PIH), medium (TCA 35-50%, combination Jessner + TCA 35% — through papillary dermis; for actinic damage, moderate wrinkles), deep (phenol/Baker-Gordon formula — through reticular dermis; for severe photodamage, deep wrinkles; risk of cardiac arrhythmia from phenol absorption — requires cardiac monitoring). Post-peel: strict sun avoidance, gentle skin care, expect desquamation proportional to peel depth.

44 Classification Systems (All)

45 Medications Master Table Meds

Topical Corticosteroids by Potency Class (US System)

Topical Calcineurin Inhibitors & Non-Steroidal Anti-Inflammatories

Retinoids

Immunosuppressants & Biologics

Antifungals

Antibiotics (Dermatologic Use)

46 Abbreviations Master List

Anatomy & Histology

Diagnoses

Procedures & Therapeutics

Medications & Labs

Scoring Systems & Scales