toxic epidermal necrolysis

**Definition/spectrum:** SJS/TEN is a spectrum classified by percent BSA with epidermal detachment: SJS <10%, SJS/TEN overlap 10-30%, TEN >30%.

**Pathophysiology:** Delayed (type IV) hypersensitivity reaction. Drug-specific cytotoxic CD8+ T cells and NK cells release granulysin (the main mediator), perforin/granzyme B, and soluble Fas ligand, causing widespread keratinocyte apoptosis and necrosis. This leads to separation at the dermal-epidermal junction (subepidermal split) with full-thickness epidermal necrosis and minimal dermal inflammation. Genetic associations: HLA-B*1502 with carbamazepine (Han Chinese/Southeast Asian), HLA-B*5801 with allopurinol, HLA-B*5701 is abacavir hypersensitivity (not SJS/TEN).

**Causes:** Drugs in about 80-95% of cases. Typical onset is 4-28 days after starting the drug (1-3 weeks). Common culprits are allopurinol, sulfonamide antibiotics (TMP-SMX), aromatic anticonvulsants (carbamazepine, phenytoin, phenobarbital, lamotrigine), nevirapine, oxicam NSAIDs, and aminopenicillins. Mycoplasma pneumoniae and HSV infection are more associated with SJS, especially in children.

**Clinical features:** - Prodrome: fever, malaise, and flu-like symptoms, often with skin tenderness or burning. - Erythematous or dusky macules/targetoid lesions that coalesce into flaccid bullae. - Positive Nikolsky sign (epidermis sloughs with lateral pressure) and Asboe-Hansen sign (bulla extends with pressure). - Mucosal involvement in >90%: oral, ocular, and genital erosions. - Painful, "scalded" skin appearance.

**Diagnosis:** Clinical, confirmed by skin biopsy (full-thickness epidermal necrosis with a subepidermal split and sparse lymphocytic infiltrate). Frozen section can speed diagnosis. Severity is scored with SCORTEN (age >40, malignancy, HR >120, initial BSA detachment >10%, BUN >28 mg/dL, glucose >252 mg/dL, bicarbonate <20 mEq/L).

**Management:** - Immediately discontinue the culprit drug (earlier withdrawal improves prognosis). - Admit to an ICU or burn unit for supportive care: fluid and electrolyte replacement, wound care, nutritional support, temperature control, and pain control. - Ophthalmology consult for ocular involvement (to prevent symblepharon and corneal scarring). - Adjunctive immunomodulation (evidence is limited and varies): cyclosporine, IVIG, etanercept (TNF-α inhibitor), or short-course systemic steroids. - Avoid prophylactic antibiotics. Treat infection only when it is documented.

**Complications:** Sepsis (the leading cause of death, usually S. aureus or Pseudomonas), hypovolemia and electrolyte disturbance, ARDS, GI and respiratory mucosal involvement, and AKI. Long-term sequelae include ocular scarring and dry eyes (most common), cutaneous dyspigmentation, strictures, and nail dystrophy. Mortality is about 25-35% for TEN and about 5-10% for SJS.

**Boards differentials:** - Staphylococcal scalded skin syndrome (SSSS): toxin-mediated (exfoliative toxin cleaves desmoglein-1), split in the stratum granulosum (superficial), no mucosal involvement, and mostly in infants and young children. - Erythema multiforme: targetoid lesions, acral distribution, usually HSV-related, minimal mucosal involvement, and <10% BSA. - Pemphigus vulgaris: intraepidermal acantholysis (anti-desmoglein 3), with a "tombstone" appearance on histology. - Bullous pemphigoid: subepidermal bullae with anti-hemidesmosome (BP180/BP230) antibodies. - DRESS: eosinophilia, facial edema, and organ involvement, with a latency of 2-8 weeks.

**High-yield pearls:** TEN is a dermatologic emergency. Do not rechallenge with the culprit drug or cross-reacting agents (e.g., the aromatic anticonvulsants). HLA screening before carbamazepine is recommended in at-risk Asian populations.