Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but serious condition characterized by a heterogenous rash, eosinophilia, and end organ involvement. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the rarer medications that may induce this severe adverse hypersensitivity reaction.   

Case Presentation: We present a case of a 50-year-old male with extensive trauma history complicated by chronic pain and an unvaccinated status who presented with acute onset fevers and dynamic morbilliform rash covering greater than 50 percent of his body surface area (BSA). A clinical diagnosis of NSAID-induced DRESS was made based on the temporal relationship with the patient’s ibuprofen use, eosinophilia, and organ involvement. Treatment with systemic corticosteroids (1 mg/kg/day) resulted in significant symptom improvement. The patient was discharged on an oral and topical steroid regimen after nine days of admission, with close outpatient dermatology follow-up. 

Conclusion: This case highlights the importance of keeping rare drug-induced hypersensitivity reactions like NSAID-induced DRESS on the differential, particularly in patients with complex medical histories and during a time when there is a rising concern for measles infection, which may initially present with a very similar clinical syndrome.