Leflunomide-induced DRESS syndrome complicated by diabetic ketoacidosis and autoimmune diabetes: a case report

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe cutaneous adverse reaction with significant multi-organ involvement and potential for delayed autoimmune sequelae, including type 1 diabetes mellitus (T1DM). The occurrence of diabetic ketoacidosis (DKA) in this context is extremely rare. Leflunomide is an uncommon but recognized cause of DRESS. This case report describes a 59-year-old woman with seropositive rheumatoid arthritis who developed fever, facial oedema, a generalized erythematous rash, and eosinophilia 38 days after initiating leflunomide. 
She was diagnosed with DRESS and started on systemic corticosteroids. During hospitalization, DKA was confirmed with marked hyperglycemia and ketonuria. Corticosteroids were discontinued, and she required insulin therapy and intensive care support. Anti-glutamic acid decarboxylase (GAD) antibodies were markedly elevated, confirming new-onset autoimmune type 1 diabetes mellitus. Cyclosporine was initiated with clinical improvement. This case underscores the importance of early recognition, metabolic monitoring, and tailored immunosuppression in DRESS.