Undifferentiated Purpuric and Desquamative Drug Eruption After Pembrolizumab and Empagliflozin Exposure: A Clinicopathologic Diagnostic Pitfall
Abstract
Pembrolizumab can be associated with immune-related cutaneous adverse events, including rare purpuric eruptions that may pose a diagnostic challenge when clinicopathologic findings are inconclusive. While pembrolizumab is generally well tolerated, immune-related adverse events (irAEs) can affect multiple organ systems. Vasculitis is a rare irAE, with heterogeneous clinical presentations ranging from cutaneous purpura to life-threatening systemic involvement. We report the case of a 75-year-old male with a history of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) overlap syndrome and stage IIIA lung adenocarcinoma who developed a widespread purpuric eruption with desquamation shortly after the first cycle of pembrolizumab and subsequent exposure to empagliflozin. Infectious workup was negative. Skin biopsy revealed full-thickness epidermal necrosis with re-epithelialization and mild superficial perivascular lymphocytic infiltrate, findings not typical for leukocytoclastic vasculitis (LCV), which usually shows neutrophilic infiltration, leukocytoclasia, and fibrinoid necrosis of vessel walls. The differential diagnosis included immune-mediated small-vessel vasculitis, severe drug eruption, and Stevens-Johnson syndrome/erythema multiforme spectrum, with empagliflozin representing a significant competing potential trigger given the close temporal relationship to rash onset. The atypical histopathology may be attributed to delayed biopsy and prior systemic corticosteroid…
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