P3118 - Watch Out for Off-Label Weight Loss Medication Use: Zonisamide-Induced Drug Reaction with Eosinophilia and Systemic Symptoms and Severe Drug Induced Liver Injury

Raha Sadjadi, MD¹, Elizabeth Cogdell, DO¹, Mohamed Mostafa, MD¹, Florencia Anatelli, MD², Lindsay Ackerman, MD³, Ma Ai Thanda Han, MD^4
1Banner University Medical Center, Phoenix, AZ; ²US Derm Partners, Phoenix, AZ; ³Medical Dermatology Specialists, Phoenix, AZ; ⁴University of Arizona College of Medicine, Phoenix, AZ

Introduction: Drug related eosinophilia with systemic symptoms (DRESS) is a drug induced hypersensitivity reaction causing rash and systemic symptoms. Associated liver injury can range from abnormal labs to liver failure. We report the first case of DRESS with severe liver injury in an adult taking the antiepileptic zonisamide off-label for weight loss.

Case Description/Methods: A 55-year-old female with hypertension was prescribed zonisamide for weight loss. She later developed flu symptoms, jaundice, and a wide spread, coalescing, pruritic, violaceous blanchable rash with mucosal involvement (Fig 1A). Labs showed aspartate amino transferase (AST) 277 units per liter (U/L), alanine amino transferase (ALT) 517 U/L, alkaline phosphatase (Alk Phos) 514 U/L, total bilirubin (TBili) 13.6 milligram/deciliter (mg/dL), and international normalized ratio (INR) 1. No hepatobiliary abnormality was seen on imaging. Liver biopsy showed ductopenia and lobular cholestasis suggestive of vanishing bile duct syndrome and drug induced liver injury (DILI), respectively (Fig 1D - E). She was discharged after improvement in her labs with advice to avoid zonisamide.

A skin punch biopsy showed interface and vascular changes compatible with DRESS (Fig 1B-C). Due to worsened outpatient labs, she was referred to the hospital for impending liver failure. Her admission labs were AST 182, ALT 204, Alk Phos 944, TBili 46.4, and INR 3.3. She received intravenous (IV) n-acetylcysteine, oral ursodiol, and daily IV methylprednisolone. Once her labs improved, she was discharged on prednisone and ursodiol. Incidentally, she was found to have a mediastinal mass that showed inflammation on biopsy.

As an outpatient, she was started on cyclosporine. Attempts to wean her immunosuppression yielded worsened labs and rash. Dupilumab was initiated to help wean prednisone and cyclosporine. Seven months into her course she was readmitted to the hospital and passed away from pneumonia with septic shock. Autopsy showed DRESS syndrome, DILI, necrotizing pneumonia, and a mediastinal mass with Hodgkin lymphoma.

Discussion: Our patient developed DRESS and severe liver injury after using zonisamide. Despite stopping zonisamide, her labs never normalized, reflecting the sometimes prolonged and nonlinear recovery from DRESS. Immunosuppression is key in DRESS treatment, but it has risks. This case reminds us to vigilantly surveil patients on immunosuppression for infections and malignancy. Finally, adequate biopsy specimens are imperative for diagnosing malignancy.



Disclosures:


Raha Sadjadi, MD¹, Elizabeth Cogdell, DO¹, Mohamed Mostafa, MD¹, Florencia Anatelli, MD², Lindsay Ackerman, MD³, Ma Ai Thanda Han, MD⁴. P3118 - Watch Out for Off-Label Weight Loss Medication Use: Zonisamide-Induced Drug Reaction with Eosinophilia and Systemic Symptoms and Severe Drug Induced Liver Injury, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.