Dermatologic Conditions

• Immune-mediated inflammatory disease: psoriasis (Th1/Th17-driven) and atopic dermatitis (Th2-driven, barrier-defective). Chronic, relapsing, non-infectious.
• Keratinocyte and melanocyte neoplasia: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma — all dominated by cumulative or intermittent ultraviolet (UV) damage.
• Severe cutaneous adverse reactions (SCARs): Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug-triggered T-cell-mediated keratinocyte apoptosis; the only true dermatologic emergencies in this group.
• Cutaneous manifestations of connective tissue disease: SLE, dermatomyositis, systemic sclerosis — where the skin is the visible edge of systemic illness.

Why it matters clinically

• Skin cancer is the most common malignancy in the United States, and BCC is the single most common human cancer. Melanoma accounts for a small minority of skin cancers but the large majority of skin-cancer deaths, because it metastasises early via lymphatics once vertical growth begins.
• Psoriasis affects roughly 2–3% of the population with a bimodal onset (late adolescence/young adulthood and again in the fifth to sixth decades) and no sex predilection; the American Academy of Dermatology (AAD) and National Psoriasis Foundation frame it as a systemic inflammatory disease, not a skin-limited one, because of its associations with psoriatic arthritis, metabolic syndrome, and cardiovascular events.
• SJS/TEN is rare — on the order of a few cases per million persons per year — but carries mortality comparable to extensive burns, and risk rises sharply with HIV infection, and with certain HLA alleles.

Immune-mediated/genetic (psoriasis, atopic dermatitis)

• Non-modifiable: *HLA-C\*06:02 (Cw6)* confers susceptibility to early-onset plaque and guttate psoriasis; loss-of-function filaggrin mutations underlie atopic dermatitis and ichthyosis vulgaris. Positive family history in a first-degree relative is the strongest single predictor for both.
• Modifiable/triggers: streptococcal pharyngitis (guttate psoriasis in a child or young adult, 1–3 weeks later), cutaneous trauma (Koebner phenomenon), smoking, obesity, alcohol, and drugs — beta blockers, lithium, antimalarials, NSAIDs, and abrupt systemic corticosteroid withdrawal.

UV-driven carcinogenesis (BCC, SCC, melanoma)

• Non-modifiable: Fitzpatrick skin type I–II (fair skin, red/blond hair, blue eyes, freckling), age, male sex, >50 nevi or dysplastic nevi, family history of melanoma (CDKN2A germline mutation in familial atypical multiple mole–melanoma), xeroderma pigmentosum (nucleotide excision repair defect), and Gorlin (basal cell nevus) syndrome (germline PTCH1 loss).
• Modifiable: cumulative UV exposure and outdoor occupation drive BCC/SCC; intense intermittent exposure and blistering sunburns drive melanoma. Tanning bed use, chronic immunosuppression (solid organ transplant — a large excess of SCC), arsenic, chronic scars/sinus tracts (Marjolin ulcer), and HPV all raise SCC risk.

Drug hypersensitivity (SJS/TEN)

• Non-modifiable: *HLA-B\*15:02* with carbamazepine in patients of Southeast Asian/Han Chinese ancestry — the FDA recommends genotyping before starting carbamazepine in these populations; *HLA-B\*58:01* with allopurinol; slow acetylator status; HIV infection.
• Modifiable: the culprit drug itself. The classic offenders are sulfonamide antibiotics, allopurinol, aromatic anticonvulsants (carbamazepine, phenytoin, lamotrigine — risk increased by rapid titration), nevirapine, and oxicam NSAIDs. Onset is typically within the first 1–8 weeks of a new drug, which is the temporal clue the stem plants.

Psoriasis — the IL-23/Th17 axis

• Plasmacytoid dendritic cells activated by antimicrobial peptide–DNA complexes (LL-37/cathelicidin) release IFN-α; myeloid dendritic cells then secrete IL-23, which sustains Th17 cells producing IL-17A and IL-22, with TNF-α amplifying the loop. This is precisely why anti-TNF, anti-IL-17, and anti-IL-23 biologics work.
• IL-17/IL-22 drive keratinocyte hyperproliferation: epidermal transit time falls from roughly a month to a few days. Keratinocytes reach the surface before terminal differentiation, so nuclei persist in the stratum corneum (parakeratosis) and the granular layer is lost — producing the thick silvery scale.
• The dermal papillae elongate and the overlying suprapapillary plate thins over dilated, tortuous capillaries; scraping the scale shears these vessels, giving the Auspitz sign. Neutrophils tracking into the stratum corneum form Munro microabscesses.

Psoriasis beyond the classic plaque

• Nail disease (up to half of patients): pitting, oil-drop discolouration, onycholysis, subungual hyperkeratosis — nail involvement strongly predicts psoriatic arthritis.
• Guttate: abrupt crop of small "drop-like" scaly papules on the trunk in a child/young adult 1–3 weeks after streptococcal pharyngitis.
• Inverse: shiny, moist, scale-poor plaques in axillae and inframammary/gluteal folds (macerated, so no silvery scale).
• **Pustular (von Zumbusch) and erythrodermic**: fever, sheets of sterile pustules or near-total erythema — systemically ill, often after systemic steroid withdrawal.
• Psoriatic arthritis: dactylitis (sausage digit), enthesitis, DIP involvement, pencil-in-cup deformity, seronegative for RF.

Skin cancers — the stem's demographic

• BCC: elderly, fair-skinned, chronically sun-exposed patient with a pearly, rolled-border papule with arborising telangiectasias on the nose, ear, or medial canthus that bleeds with minor trauma and never heals.
• SCC: hyperkeratotic, indurated, tender nodule or non-healing ulcer on the lip, ear, or dorsal hand; often arises from actinic keratosis; think transplant recipient on chronic immunosuppression.
• Melanoma subtypes: superficial spreading is most common (trunk in men, legs in women); nodular presents late with a rapidly enlarging, symmetric, often amelanotic dome — the ABCDE rule underperforms here; lentigo maligna on the sun-damaged face of an older adult; acral lentiginous on palm, sole, or nail bed and is the subtype disproportionately seen in patients with darker skin — Hutchinson sign (pigment onto the proximal nail fold) is the classic clue.

Psoriasis

• Clinical diagnosis. Punch biopsy only when atypical — shows parakeratosis, loss of the granular layer, acanthosis with regular rete ridge elongation, and Munro microabscesses.
• Quantify with body surface area and the Psoriasis Area and Severity Index (PASI); AAD/NPF define severity partly by BSA and by involvement of special sites (face, genitals, palms/soles, nails). Screen every patient for psoriatic arthritis at each visit (ACR/NPF).

Melanoma

• Initial: full-body skin exam plus dermoscopy; the ugly duckling sign (a nevus unlike the patient's others) outperforms ABCDE for nodular lesions.
• Confirmatory/gold standard: excisional (or complete) biopsy with narrow 1–3 mm margins extending into subcutaneous fat, per NCCN. Superficial shave biopsy risks transecting the base and forfeiting Breslow depth.
• What the pathology report must contain: Breslow thickness in mm, ulceration, and mitotic rate. AJCC staging is built on Breslow depth + ulceration (T), nodal status (N), and metastasis with LDH (M). NCCN supports discussing sentinel lymph node biopsy for lesions ≥0.8 mm thick, or thinner lesions with ulceration. Order BRAF mutation testing in advanced/metastatic disease because it dictates targeted therapy.

SJS/TEN

• Diagnosis is clinical, supported by biopsy showing full-thickness epidermal necrosis with a subepidermal split and sparse lymphocytic infiltrate (frozen section can give an answer within hours and excludes staphylococcal scalded skin syndrome, where the split is intragranular).
• Classify by % BSA of detached/detachable epidermis, counting only detached skin — not erythema alone.
• Prognosticate with SCORTEN, scored in the first 24 hours: age, heart rate, presence of malignancy, BSA detached, and serum urea, glucose, and bicarbonate. Use ALDEN to assign drug causality.

SJS/TEN — immediate, and the emergency of this topic

• Stop the culprit drug immediately — earlier withdrawal correlates with better survival — and never rechallenge.
• Transfer to a burn unit or ICU. Management is supportive and burn-like: fluid and electrolyte resuscitation, warming, nutrition, non-adherent wound dressings with minimal debridement, and analgesia. Obtain urgent ophthalmology consultation to prevent symblepharon and blindness, plus urology/gynaecology for mucosal care.
• Avoid prophylactic systemic antibiotics (select for resistance); treat culture-proven infection. Immunomodulation — systemic corticosteroids, IVIG, cyclosporine, or anti-TNF (etanercept) — remains adjunctive and controversial without a single US guideline endorsement.

Psoriasis (AAD/NPF stepwise)

• Limited disease (first line): topical corticosteroid (e.g., triamcinolone; low-potency on face/folds) plus a vitamin D analogue (calcipotriene); tar, tazarotene, or calcineurin inhibitors for sensitive sites.
• Escalation: narrowband UVB phototherapy, then systemic agents — methotrexate, acitretin, apremilast (PDE4 inhibitor), or cyclosporine for crisis control.
• Biologics for moderate-to-severe or arthritis-associated disease: TNF inhibitors (adalimumab), IL-17 inhibitors (secukinumab), IL-23 inhibitors (guselkumab). Screen for latent TB (IGRA) and hepatitis B before starting.
• Contraindicated: systemic corticosteroids — withdrawal precipitates generalised pustular or erythrodermic flare. Methotrexate is contraindicated in pregnancy; acitretin is teratogenic for years after use.

Disease complications

• Psoriatic arthritis develops in roughly a third of psoriasis patients, usually years after skin disease; erosive and deforming if untreated — dactylitis and DIP involvement are the signals.
• Cardiometabolic disease: chronic systemic IL-17/TNF inflammation accelerates atherosclerosis; psoriasis clusters with metabolic syndrome, NAFLD, and depression. AAD/NPF recommend screening for these comorbidities.
• Erythrodermic and generalised pustular psoriasis — emergencies: loss of the cutaneous barrier over near-total BSA causes high-output heat loss, hypovolaemia, hypoalbuminaemia, and secondary infection. Fever, tachycardia, and hypothermia in a psoriatic patient after steroid withdrawal is the classic setup.
• Melanoma metastasis: lymphatic first, then lung, liver, bone, and brain — melanoma is one of the tumours notorious for haemorrhagic brain metastases; new headache or seizure warrants imaging.
• BCC: rarely metastasises but is locally destructive, invading orbit, nasal cartilage, and bone (rodent ulcer), especially at embryonic fusion planes.
• SJS/TEN acute: sepsis (leading cause of death), hypovolaemic shock, ARDS from tracheobronchial epithelial sloughing, and acute kidney injury — all emergencies. Chronic sequelae: ocular symblepharon, corneal scarring and blindness; oesophageal, urethral, and vaginal strictures; nail loss and dyspigmentation.

Treatment complications

• Methotrexate: hepatic fibrosis, myelosuppression, pneumonitis — monitor CBC and LFTs; supplement folate.
• Cyclosporine: nephrotoxicity and hypertension; limit to short courses.
• TNF inhibitors: reactivation of latent tuberculosis and hepatitis B, demyelination, and worsening of HFrEF.
• IL-17 inhibitors: mucocutaneous candidiasis (IL-17 is required for mucosal antifungal defence) and possible exacerbation of inflammatory bowel disease.
• Immune checkpoint inhibitors: immune-related adverse events — colitis, hepatitis, thyroiditis, hypophysitis, pneumonitis, and myocarditis, which is rare but fulminant and an emergency requiring drug cessation and high-dose corticosteroids.
• Hedgehog inhibitors: muscle spasms, dysgeusia, alopecia; teratogenic — strict contraception required.

• Guttate psoriasis after strep throat: small drop-like papules on the trunk in a teenager 1–3 weeks after pharyngitis. The single most tested trigger; look for antecedent sore throat, not a new drug.
• Never give systemic corticosteroids for plaque psoriasis. The tested consequence of withdrawal is generalised pustular (von Zumbusch) psoriasis or erythroderma. This is the most common management distractor in the vignette.
• Suspicious pigmented lesion → excisional biopsy with narrow margins, full thickness. "Single best next step" questions punish shave biopsy (transects the base, destroys Breslow depth) and punish going straight to wide excision or ordering imaging before tissue diagnosis.
• Breslow depth, not Clark level, drives prognosis and margins; ulceration upstages. Nodular melanoma may be symmetric and amelanotic — a lesion failing ABCDE can still be melanoma if it is growing fast (ugly duckling, EFG: elevated, firm, growing).
• Acral lentiginous melanoma is the subtype over-represented in patients with darker skin; Hutchinson sign (periungual pigment spread) on a longitudinal melanonychia is the buzzword.
• Pearly papule with rolled borders and arborising telangiectasias on the nose = BCC; histology shows peripheral palisading with retraction artefact. Mohs surgery is the answer for high-risk facial sites; BCC essentially never metastasises but is locally destructive.
• New anticonvulsant, sulfonamide, or allopurinol + fever + painful dusky rash + erosions at two or more mucosal sites = SJS/TEN. First step is always stop the drug, then burn-unit transfer and urgent ophthalmology. Positive Nikolsky sign with full-thickness epidermal necrosis distinguishes it from staphylococcal scalded skin syndrome, which spares mucosa and splits within the granular layer.
• The one association examiners love: *HLA-B\*15:02* and carbamazepine-induced SJS/TEN in patients of Southeast Asian ancestry — genotype before prescribing. Its counterpart is *HLA-B\*58:01* with allopurinol.

• Psoriasis affects 2-3% of population; NOT contagious despite appearance
• Melanoma has worst prognosis among skin cancers; ABCDE rule guides clinical recognition
• Atopic dermatitis involves Th2-mediated inflammation and defective skin barrier (filaggrin mutations)
• SLE presents with malar rash, photosensitivity, and positive ANA; major systemic manifestation is lupus nephritis
• Urticaria lasting >6 weeks = chronic; often idiopathic (>80% of cases)

1. 1.Psoriasis Triggers: STRESS = Streptococcal infection, Trauma, Stress, Smoking, NSAIDs, Systemic steroids (withdrawal)

1. 1.Melanoma Risk: Dysplastic nevi, >50 moles, Fitzpatrick skin type I-II, prior sunburns, family history (FAMM syndrome)

1. 1.SLE Manifestations: RASH PAIN CN: Rash, Arthritis, Serositis, Hematologic, Photosensitivity, Antinuclear antibody, Immune complex, Neurologic, Complement↓, Nephritis

1. 1.Atopic Dermatitis Complications: INFECTION: Impaired skin barrier → staph/strep superinfection; herpes simplex → eczema herpeticum (severe disseminated infection)

1. 1.Urticaria Triggers: Medications (ACE-I, NSAIDs, antihistamines withdrawal), foods (shellfish, peanuts), infections, physical stimuli (cold, pressure)

1. 1.Erythema Multiforme vs. SJS/TEN: EM = <10% BSA, no mucosa/systemic; SJS = 10-30%, mucosa involved; TEN = >30%, epidermal necrosis (often drug-induced)

1. 1.Confusing Psoriasis with Eczema: Psoriasis = sharply demarcated, silvery scale, extensor surfaces; Eczema = ill-defined, lichenified, flexural. Patch test negative in psoriasis.

1. 1.Missing SLE Diagnosis: ANA negative in ~5% of SLE; repeat testing or check anti-Ro/anti-La (ANA-negative SLE). Malar rash does NOT equal SLE diagnosis alone—need ≥