Pathologic Features of a Fatal Case of Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome

Abstract

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and life-threatening delayed drug hypersensitivity reaction characterized by skin eruption, fever and visceral involvement that typically presents in response to certain medications. Most publications focus on the clinical and dermatologic aspects of this syndrome. However, this report will describe clinicopathologic features of DRESS, focusing on the histologic and immunohistochemical findings in the skin, pericardium and cerebral cortex. This is the case of a 30-year-old African American HIV-positive woman, who was evaluated in the emergency department after experiencing chest pain for 1 week and generalized pruritus for 6 weeks. Highly active antiretroviral therapy (HAART) had been discontinued 1 week before presentation due to suspicion of an allergic reaction. After an extensive workup, her chest pain was diagnosed as pericarditis. Subsequently, she rapidly deteriorated, experiencing seizures and requiring intubation. She developed cerebral edema with transtentorial and uncal herniation on the 14th day of admission. Gross autopsy findings included uncal herniation, fibrinous pericarditis, and a diffuse erythematous rash over the dorsum of the hands and bilateral lower extremities. Microscopic findings included organizing fibrinous pericarditis, diffuse epidermal necrosis and mixed inflammatory infiltrate within vessel walls in the dermis. Sections from the cerebral cortex showed scattered areas with lymphocytic perivascular cuffing and invasion into the vessel walls by CD3-positive T lymphocytes (T cells). These T cells showed staining with TIA-1 and granzyme B, features consistent with a cytotoxic T cell infiltrate. The constellation of findings, including history of HAART, peripheral eosinophilia, pericarditis, and vasculitis in the skin and cerebral cortex, are consistent with DRESS. DRESS is an uncommon disorder; better characterization of the pathologic features will lead to better understanding of its pathogenesis, and potentially more targets for treatment.