S2495 Drug Induced Liver Injury and Concurrent Hemophagocytic Lymphohistiocytosis After Lamotrigine Exposure

Abstract

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH), a rare condition resulting in dysregulated immune activation, is often difficult to diagnose due to lack of specific criteria. HLH commonly causes hepatitis with variable degrees of liver injury. We present a rare case of drug induced liver injury (DILI) and concurrent HLH mimicking acute liver failure (ALF). CASE DESCRIPTION/METHODS: A 31-year-old man with epilepsy presented with a fever, fatigue, and disseminated morbilliform rash. He was encephalopathic upon admission. Initial labs were notable for INR 2.0, creatinine 2.6, AST >20000, ALT 3127, platelets 65, and total bilirubin 6.4. Initial labs and encephalopathy also raised concern for ALF. No definitive cause of liver disease was identified, although DILI was considered because patient was started on lamotrigine 14 days prior. Subsequent labs revealed ferritin >40000, lactate 3.1, and fibrinogen 82. CT showed enlarged liver and normal spleen. Liver transplant evaluation was started, but the fever, rash, and unexplained lab abnormalities were inconsistent with ALF. Hematology was consulted to evaluate for HLH and a liver biopsy was performed, which revealed zone 3 hepatic necrosis with eosinophils and focal endothelial injury, but no specific findings of HLH. Bone marrow biopsy demonstrated increased monocytes and hemophagocytic histiocytes, consistent with HLH. High soluble CD25, high triglycerides, and low NK activity further supported a diagnosis of HLH. DRESS was ruled out due to lack of peripheral eosinophilia. Liver biopsy revealed multiacinar (zone 3) centered hepatic necrosis with eosinophils and focal endothelial injury, raising the suspicion of hypersensitivity drug reaction. He subsequently recovered with discontinuation of lamotrigine and initiation of both dexamethasone and etoposide. DISCUSSION: Although rare, HLH should be considered in patients with acute liver injury, particularly if other organ systems are involved. While this patient had many features suggestive of ALF, the fever, rash, and markedly elevated ferritin raised the possibility of an alternate diagnosis. Lamotrigine may rarely cause acute liver injury with immuno-allergic features including fever and rash. Additionally, in 2018 the FDA reported 8 cases of HLH due to lamotrigine, all of which occurred within 8-24 days after patients started the medication. HLH often causes hepatitis; however, our case was unique in that the patient seemingly had both HLH as well as concurrent, yet separate DILI.