Hydroxychloroquine and Leflunomide Induced Dress Syndrome: A Case Report

Background: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a rare but potentially life-threatening hypersensitivity reaction characterized by fever, rash, eosinophilia, and internal organ involvement, typically emerging several weeks after exposure to certain medications. Its diagnosis and management pose significant clinical challenges, especially when compounded by overlapping autoimmune and infectious complications. Case Presentation: This case report describes a 37-year-old female with rheumatoid arthritis who developed DRESS syndrome after initiating hydroxychloroquine and leflunomide therapy. Skin biopsy showed perivascular lymphocytic infiltrates with pigment incontinence, confirming drug-induced hypersensitivity. Laboratory tests revealed eosinophilia, elevated transaminases, and positive Leptospira IgM. The condition was complicated by autoimmune hepatitis (positive anti-smooth muscle antibody), recurrent DRESS episode, gastrointestinal and urinary tract infections (sepsis). Initial treatment with corticosteroids, cyclosporine and prompt withdrawal of the offending drugs led to temporary improvement, but rapid steroid tapering and HCQ re-challenge precipitated relapse. The patient required a multidisciplinary approach including immunosuppressants, IV immunoglobulin, hepatoprotective agents, antibiotics, electrolyte correction, and total parenteral nutrition. Gradual improvement was achieved with close monitoring and slow steroid tapering alongside multidisciplinary supportive measures resulted in clinical stabilization and discharge. Conclusion: This case highlights the complexities of managing DRESS syndrome, particularly in patients with autoimmune comorbidities, and the potential for DRESS recurrence with autoimmune overlap. It underscores the essential role of clinical pharmacists in early recognition, allergy documentation, therapeutic optimization, monitoring for hepatic safety, long-term management to prevent recurrence and patient education, thereby enhancing safety and better therapeutic outcomes. They also had a role in adverse drug reaction detection, reporting and antimicrobial stewardship. Rapid steroid withdrawal and drug rechallenge precipitated relapse, emphasizes the necessity of slow tapering and avoidance of re-exposure. Further research is required to better understand the underlying mechanisms, long-term outcomes, and optimal therapeutic strategies for managing such complex and rare cases.