Nikolsky sign

The sign distinguishes blistering diseases by the level of cleavage. Positive Nikolsky implies a split within the epidermis, so the roof is fragile: pemphigus vulgaris, where IgG autoantibodies target desmoglein 3 and 1 in desmosomes producing suprabasal acantholysis with a 'row of tombstones' basal layer, painful oral erosions preceding flaccid skin bullae, and a net-like intercellular immunofluorescence pattern; staphylococcal scalded skin syndrome, where exfoliative toxin cleaves desmoglein 1 in the granular layer, sparing mucous membranes and typically affecting young children; and Stevens-Johnson syndrome and toxic epidermal necrolysis, in which full-thickness keratinocyte apoptosis causes dermoepidermal detachment with prominent mucosal involvement, usually drug-induced by sulfonamides, anticonvulsants, allopurinol, or nevirapine. Negative Nikolsky with tense bullae suggests bullous pemphigoid, where IgG targets hemidesmosomal BP180 and BP230, sparing mucosa, with linear immunofluorescence along the basement membrane and eosinophils on histology. Management of TEN is burn-unit level supportive care and immediate withdrawal of the culprit drug.