Toxic Epidermal Necrolysis (Advanced)

Toxic epidermal necrolysis (TEN) is the most severe form of a drug-induced immunological reaction spectrum that includes Stevens-Johnson syndrome (SJS) and SJS-TEN overlap. Classification is based on body surface area (BSA) of epidermal detachment: SJS (<10% BSA), SJS-TEN overlap (10-30%), TEN (>30%). TEN involves a cytotoxic T-cell-mediated immune response against drug antigens presented by keratinocytes. The primary effector mechanism involves granulysin — a cytolytic protein released by CD8+ cytotoxic T cells and NK cells — which is the key mediator of keratinocyte death. Fas-FasL interaction (death receptor pathway) and perforin/granzyme B contribute to the massive keratinocyte apoptosis. The result is full-thickness epidermal necrosis with dermal-epidermal separation at the basement membrane zone. The most common causative medications (onset typically 1-3 weeks after starting the drug): allopurinol (most common overall), sulfonamide antibiotics (TMP-SMX), aromatic anticonvulsants (carbamazepine, phenytoin, lamotrigine, phenobarbital), nevirapine, and NSAIDs (oxicam class). HLA associations increase susceptibility: HLA-B5801 (allopurinol — test before prescribing in Southeast Asian, African American, and Korean populations), HLA-B1502 (carbamazepine — test before prescribing in Asian populations). SCORTEN (SCORe of Toxic Epidermal Necrolysis) predicts mortality: 7 parameters assessed...