Hemophagocytic Lymphohistiocytosis Masquerading as Alcoholic Hepatitis

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive immune activation. Timely diagnosis can be challenging and prompt treatment is the only hope for survival. A 35 year old male with history of alcohol dependence was sent to the gastroenterology clinic for evaluation of fatigue, bilateral lower extremity edema, and orange colored urine. Lab work showed abnormal liver function tests (AST 295, alkaline phosphatase (ALP) 505, ALT 230, bilirubin 3.4). Exam was significant for lower extremity edema and hepatosplenomegaly. Further testing revealed elevated ferritin (12799 ng/ml) and iron saturation (68%). Repeat LFTs one week later showed AST 356, ALP 569, ALT 155, bilirubin 9.5. The patient was admitted to the hospital for further evaluation. CT scan a month prior incidentally showed hepatosplenomegaly and diffuse lymphadenopathy. PET scan revealed hypermetabolic splenomegaly, mediastinal and retroperitoneal lymphadenopathy, and numerous bone marrow abnormalities. Bone marrow biopsy and endoscopic ultrasound (EUS) were then performed. EUS revealed many abnormal enlarged lymph nodes extending from the supraclavicular region to the liver. Biopsies taken were normal and bone marrow biopsy showed no cytogenetic evidence of an abnormal clone. The patient was started empirically on ganciclovir for possible CMV infection and dexamethasone for suspected HLH while cultures and biopsy results were pending. Viral cultures were positive for CMV IgG and IgM, and EBV IgG and nuclear antibody. A clinical diagnosis of HLH was made and he was started on etoposide, in addition to dexamethasone, but his clinical status deteriorated rapidly and he died of multiorgan failure seven days later. HLH is a rare aggressive disease that is more frequently observed in infants. Immune homeostasis disruption can be triggered by infection, the most common being Epstein-Barr virus. It presents as a febrile illness that mimics infections, fever of unknown origin, hepatitis, and encephalitis, making timely diagnosis especially difficult. Patients typically present with hepatomegaly, lymphadenopathy, cytopenias, and high ferritin levels. High ferritin in the absence of iron overload carries high sensitivity and specificity for this disease. It is important that gastroenterologists keep a high index of suspicion when a patient presents with liver failure, high ferritin, and cytopenia, as they can be the first to evaluate these patients when they present.2259 Figure 1. From: Hemophagocytic LymphohistiocytosisAn Update on Diagnosis and Pathogenesis Am J Clin Pathol. 2013;139(6):713-727. doi:10.1309/AJCP4ZDKJ4ICOUAT Am J Clin Pathol | © American Society for Clinical Pathology