Double Trouble: A Primary Epstein-Barr Virus Infection Causing Cholestatic Hepatitis and Hemophagocytic Lymphohistiocytosis

Primary infection with Epstein-Barr virus (EBV) is very common, often manifesting as mononucleosis syndrome with fatigue, sore throat, fever, and enlarged lymph nodes. Liver involvement occurs in many cases with mildly elevated liver enzymes. However, it is rare to see EBV infection present as cholestatic hepatitis. Another rare complication of primary EBV infection is hemophagocytic lymphohistiocytosis (HLH). We describe a patient with primary EBV infection who presented with fatigue and jaundice, subsequent rash, and reactive lymphocytosis. The patient was noted to have cholestatic hepatitis and was highly suspected to have HLH based on laboratory values, including elevated ferritin, triglyceride, and interleukin-2 levels. He showed clinical improvement with HLH treatment using dexamethasone, etoposide, and rituximab. We further review the clinical manifestations, pathogenesis, and management of EBV-associated cholestatic hepatitis and EBV-HLH. Early diagnosis of primary EBV infection is emphasized in order to properly recognize and treat potentially life-threatening complications.