Clinical meaning
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent a spectrum of severe, potentially life-threatening mucocutaneous reactions that are most commonly drug-induced. SJS involves less than 10% body surface area (BSA) detachment of the epidermis, SJS-TEN overlap involves 10-30% BSA, and TEN involves greater than 30% BSA detachment. The pathophysiology involves a cytotoxic immune-mediated reaction directed against keratinocytes (the primary cells of the epidermis). Drug-reactive cytotoxic T lymphocytes (CD8+ T cells) and natural killer cells infiltrate the epidermis and release cytotoxic molecules including granulysin, perforin, and granzyme B, which trigger massive keratinocyte apoptosis (programmed cell death). Fas ligand (FasL) and tumor necrosis factor-alpha (TNF-alpha) also contribute to keratinocyte death by activating the caspase cascade. The result is full-thickness epidermal necrosis with separation of the epidermis from the dermis at the dermal-epidermal junction, producing the characteristic findings: widespread erythematous or purpuric macules that rapidly progress to flaccid blisters and sheets of denuded skin. The Nikolsky sign is positive (gentle lateral pressure on uninvolved skin causes the epidermis to separate and slide off), indicating active epidermal detachment. Mucosal involvement occurs in over...