S5026 Sulfasalazine-Induced DRESS and Secondary Hemophagocytic Lymphohistiocytosis (HLH) in Crohn's Disease

Introduction: The association between sulfonamides, including sulfasalazine, and drug reaction with eosinophilia and systemic symptoms (DRESS) is a well described phenomenon with high mortality that requires high clinical suspicion for diagnosis. We report on a patient who developed DRESS and secondary hemophagocytic lymphohistiocytosis after starting sulfasalazine. Case Description/Methods: A 19-year-old woman with juvenile arthritis, psoriasis, and ileocolonic Crohn’s disease treated with risankizumab was started on sulfasalazine for continued GI symptoms with new hand arthralgias. After 2 weeks of sulfasalazine, she developed an otherwise asymptomatic, persistent fever to 40 C for 72 hours. Workup revealed: Hgb 11.2, Platelets 79, AEC 0.17, Eosinophile % 4.2, AST 52, ALT 31, alkaline phosphatase 62, C-reactive protein 121, erythrocyte sedimentation rate 21; and negative COVID 19, Influenza A/B, RSV, and EBV IgG/IgA. Forty-eight hours later, a morbilliform rash appeared on the face and hands with subsequently progressive fever, nausea, and vomiting prompting medical evaluation. Repeat labs showed hemoglobin 10.4, white blood cells 2.11, Eosinophile % 6, AEC 0.13, AST 294, ALT 145, alkaline phosphatase 241, LDH 1215; C-reactive protein 142; and Ferritin 16184. Skin biopsy revealed a superficial and perivascular lymphocytic infiltrate consistent with DRESS while the high LDH and ferritin raised concern for secondary hemophagocytic lymphohistiocytosis. After discussion with internal medicine, GI, rheumatology, and hematology, she was started on systemic and topical steroids and experienced rapid clinical improvement. She was discharged on dexamethasone taper for 41 days and a shortened interval of risankizumab. Discussion: DRESS is a rare condition with an incidence of ∼1 in 100,000 hospitalized patients. However, most cases are due to a subset of high-risk medications that all physicians should be able to recognize. This case highlights the need for vigilance of potential drug reactions and their systemic effects and serves to underscore the crucial role of multidisciplinary care in early detection and appropriate treatment of potentially fatal conditions.