Rare Presentation of TEN-Like Subacute Cutaneous Lupus Erythematosus Occurring in the Setting of Donepezil Exposure and COVID-19 Infection: A Diagnostic Challenge.

Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous reaction characterized by rapidly progressive epidermal necrosis within hours to days, extensive skin detachment, and high mortality. Rarely, patients present with TEN-like eruptions that evolve slowly, over days to weeks, and have skin changes mostly confined to photodistributed areas, with possible mucosal involvement. The latter scenario is compatible with TEN-like lupus erythematosus. We report a 65-year-old man without prior lupus history who developed a widespread, photodistributed erythematous patchy eruption within 24 h of initiating donepezil for Parkinsonism-associated aphasia. The erythema rapidly progressed to erosions, bullae, and detachment involving 81% total body surface area (TBSA) and a Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) of 2. Initial differential diagnoses included TEN/Stevens Johnson Syndrome (SJS), bullous pemphigoid, generalized bullous fixed drug eruption, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and reactive infectious mucocutaneous eruption (RIME). Histopathology revealed interface dermatitis with diffuse basilar apoptosis, focal full-thickness epidermal necrosis and robust dermal mucin deposits. Direct immunofluorescence study was negative. Serologies showed strongly positive anti-Ro/SSA and ANA titers. COVID-19 testing was positive. The constellation of clinical, pathologic and laboratory features supported a diagnosis of TEN-like subcutaneous lupus erythematosus (SCLE), likely triggered by donepezil and complicated by a concurrent COVID-19 infection. To our knowledge, this is a novel case of TEN-like SCLE associated with donepezil initiation.