The diagnosis of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is challenging due to its variable clinical presentation and long latency period. We report a case of a woman in her 60s who developed Vancomycin-induced DRESS after treatment for cellulitis and septic arthritis. The patient presented with cutaneous, renal, pulmonary, and gastrointestinal involvement, but notably without hepatic injury. HLA testing confirmed HLA-A*32:01 positivity which suggested Vancomycin-induced DRESS. Withdrawal of Vancomycin and initiation of corticosteroids led to clinical improvement. However, a relapse occurred during the steroid tapering phase. Cyclosporine was commenced as a second line agent, which led to sustained remission. This case highlights the diagnostic and therapeutic challenges of DRESS, the potential for atypical organ involvement, HLA testing in determining pharmacogenetic susceptibility, and the importance of multidisciplinary input to optimize the care of the patient. Clinicians should consider DRESS in patients presenting with cutaneous and systemic symptoms after drug therapy, maintain vigilance for relapses during corticosteroid tapering, and recognize the utility of Cyclosporine in steroid-dependent or refractory cases.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Drug hypersensitivity, Vancomycin, HLA-A*32:01, Pharmacogenetics