The Silent Culprit: Drug-Induced Fever Associated With Trimethoprim-Sulfamethoxazole

Drug-induced fever (DIF) is often misdiagnosed, particularly when it occurs alongside an infection. Its hallmark is the resolution of fever upon drug withdrawal and rapid recurrence upon re-exposure. Although five potential mechanisms have been proposed to explain this phenomenon, they remain poorly understood, making DIF a challenging diagnosis. We report a case of trimethoprim-sulfamethoxazole-induced drug fever, demonstrated by reproducible symptom onset following a drug provocation test, with supportive evidence from positive intradermal and lymphocyte transformation tests. The diagnosis of DIF requires a high degree of suspicion and the thorough exclusion of other causes of fever, such as infections or inflammatory conditions. Increased awareness and understanding of DIF are essential to improve diagnostic accuracy and patient outcomes.