S5958 A Severe Case of Drug-Induced Hypersensitivity Syndrome (DIHS) Presenting as Acute Liver Failure Requiring Urgent Liver Transplantation

Introduction: Drug-Induced Hypersensitivity Syndrome (DIHS), formerly known as Drug Reaction with Eosinophilia and Systemic Symptoms, is a rare but life-threatening condition characterized by delayed-onset systemic inflammation, eosinophilia, and multiorgan involvement. Fulminant liver failure is the leading cause of mortality. We present a case of DIHS leading to acute liver failure and urgent liver transplantation. Case Description/Methods: A 65-year-old man with no prior liver disease presented with 3 weeks of painless jaundice, fatigue, and arthralgias. He had recently started herbal supplements containing multiple botanicals, including ginseng and ashwagandha. He was recently initiated aripiprazole and oral diclofenac 3 weeks prior. Initial labs showed aspartate aminotransferase 2,687, alanine aminotransferase 1810, total bilirubin 14.8, international normalized ratio 1.5 and renal failure. Computed tomography scan showed a normal-appearing liver and multifocal lymphadenopathy. Infectious and toxicology screens were negative. Autoimmune serologies showed an abnormal ANA, antimitochondrial antibody IgG, and F-actin IgG raising suspicion for AIH or drug-induced liver injury (DILI). Liver biopsy revealed a severe active hepatitis with bridging necrosis and marked plasma cell inflammation. Stains for infectious etiologies were negative. On hospital day 4, the patient developed worsening international normalized ratio, acute encephalopathy, and a diffuse morbilliform rash. Liver transplant evaluation was initiated. On hospital day 5, new-onset eosinophilia and a RegiSCAR score of 6 raised strong suspicion for DIHS. Due to rapid liver failure, he underwent urgent liver transplantation on hospital day 8 and improved postoperatively. The liver explant showed features of extensive necrosis and parenchymal loss, consistent with acute liver failure. Discussion: This case highlights the diagnostic challenge of differentiating DIHS from AIH and DILI, particularly in the absence of early eosinophilia. It underscores the importance of considering not only commonly recognized hepatotoxic medications but also potential triggers of DIHS. DIHS should be considered in patients with progressive liver injury, even without eosinophilia. Diagnosis relies on clinical features and RegiSCAR criteria, which include fever, rash, lymphadenopathy, internal organ involvement, and hematologic abnormalities. While eosinophilia is a hallmark feature, it may be absent initially in up to 31% of cases. This case emphasizes the need for early recognition of DIHS and the potential for severe outcomes requiring liver transplantation.