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A 30-year-old man was admitted to the hospital with a 2-week history of rash and fever. Four weeks before presentation, he had taken trimethoprim–sulfamethoxazole for the treatment of folliculitis. His body temperature was 39.1°C. Physical examination revealed a morbilliform rash across the trunk, arms, and legs (Panel A), submandibular lymphadenopathy, and facial erythema with periorbital sparing (Panel B). Four days after admission, facial edema developed (Panel C). Peak laboratory values during the hospital stay included an absolute eosinophil count of 3028 per cubic millimeter (reference range, 40 to 350), an alanine aminotransferase level of 989 U per liter (reference value, <36), and an aspartate aminotransferase level of 162 U per liter (reference value, <34). The serum creatinine level was normal, as were a urinalysis, chest radiograph, antinuclear antibody test, and tests for viral hepatitis and Mycoplasma pneumoniae infection. Skin biopsy revealed interface dermatitis with eosinophilic and lymphocytic infiltration. The European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) score was 7, which indicated a definitive diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) related to treatment with trimethoprim–sulfamethoxazole. (RegiSCAR scores range from −4 to 9, with higher scores indicating a more definite diagnosis; a score of >5 indicates a definitive diagnosis.) Treatment with systemic glucocorticoids and cyclosporine was initiated, and the patient was advised to avoid sulfonamide-containing antimicrobial agents. At 1 month of follow-up, his symptoms had abated.Wei-Kai Hung, M.D., and Wen-Hung Chung, M.D., Ph.D. July 14, 2022 N Engl J Med 2022; 387:167 DOI: 10.1056/NEJMicm2116076