A 52-year-old man on trimethoprim-sulfamethoxazole for a urinary tract infection for 10 days develops fever, widespread morbilliform rash, and mucosal erosions. Over 48 hours he develops confluent epidermal necrosis with detachment of 35% BSA. The primary pathological mechanism of keratinocyte death in this condition is mediated through which pathway?

• A Complement-mediated cytolysis via membrane attack complex
• B Direct cytotoxic T-cell perforin release without apoptosis signaling
• C Fas-Fas ligand (CD95-CD95L) and granulysin mediated apoptosis ✓
• D Antibody-dependent cellular cytotoxicity via desmoglein 3 autoantibodies

Explanation

The patient has TEN (detachment >30% BSA) secondary to TMP-SMX. The key mechanism is keratinocyte apoptosis driven by cytotoxic T cells and NK cells releasing granulysin, perforin, and Fas-FasL interaction. Granulysin is considered the principal cytotoxic molecule. Option D describes pemphigus mechanism. Option C correctly identifies the Fas-FasL and granulysin pathway that drives the full-thickness epidermal necrosis.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.