Tislelizumab-induced bullous epidermal necrolysis: case reports and pathogenetic insights

Tislelizumab, a humanized IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1), has demonstrated efficacy in advanced malignancies such as non-small cell lung cancer, nasopharyngeal carcinoma, classical Hodgkin lymphoma, and esophageal squamous cell carcinoma. Bullous epidermal necrolysis (BEN) associated with single-agent PD-1 inhibitors is rare and remains poorly characterized. We report three cases to describe their clinical presentation, histopathologic findings, management, and possible pathogenesis.

Three men aged 56, 81, and 70 years developed rapidly progressive erythema, flaccid bullae, or sheet-like desquamation involving 25%, 40%, and 30% of the body surface area, respectively, within 2-3 days after tislelizumab infusions for retroperitoneal lymph node adenocarcinoma, stage IV lung cancer, and esophageal squamous cell carcinoma. Skin biopsy in Cases 1 and 2 showed full-thickness epidermal or keratinocyte necrosis with subepidermal clefting; direct immunofluorescence in Case 1 was negative. Tislelizumab was discontinued permanently. All patients received systemic methylprednisolone and intravenous immunoglobulin, together with supportive and topical care as appropriate. Re-epithelialization or marked clinical improvement occurred without rechallenge.

Early recognition, immediate drug discontinuation, and immunosuppressive therapy were associated with favorable outcomes. Vigilant assessment and multidisciplinary collaboration are important during immune checkpoint inhibitor therapy. Further studies are needed to define susceptibility factors and optimal targeted interventions.