(514) Secondary Hemophagocytic Lymphohistiocytosis Triggered by Concurrent EBV and Ehrlichia Infections

Introduction: Hemophagocytic lymphohistiocystosis (HLH) is an insidious, life-threatening disease which is difficult to diagnose and causes immune system overactivation. Here is a case of a previously healthy adult developing HLH due to co-infection of Epstein-Barr Virus (EBV) and Ehrlichia.

Description: A 55-year-old female who presented with persistent fevers for nine days initially attributed to a urinary tract infection. She exhibited high fever, tachycardia, and severe hypotension, prompting admission for impending shock. Shortly after admission to the critical care unit, the patient developed ischemic hepatitis with a ferritin level of 32,099 ng/mL. Routine labs revealed a platelet count of 37 K/uL, normal erythrocyte sedimentation rate, C-Reactive Protein of 22 mg/dL, and negative hepatitis panel and HIV tests. Ultrasound noted splenomegaly, and a disseminated intravascular coagulation panel indicated early-stage disease.
Further investigation resulted in elevated fasting triglycerides of 642 mg/dL, elevated EBV IgM titer of 84 U/mL, and positive Ehrlichia chaffeensis blood polymerase chain reaction. Peripheral flow cytometry revealed absolute neutropenia and an expanded gamma-delta T cell population, suggesting immune system overactivation. HLH was ultimately ruled in after observing elevated levels of soluble interleukin-2 receptor of 3,880 pg/mL. Treatment included an eight-week tapered course of dexamethasone for HLH, as well as valacyclovir for EBV and doxycycline for Ehrlichia.

Discussion: Prompt recognition and treatment are crucial for improving the poor prognosis of HLH; however, delays in diagnosis occur due to nonspecific findings in the early disease course that mimic other more common conditions. The patient reported here met diagnostic criteria for HLH based on the findings of prolonged fever, profound hyperferritinemia, bicytopenia, splenomegaly, fasting hypertriglyceridemia, and elevated soluble IL-2 receptor. While infectious mononucleosis and ehrlichiosis are each documented triggers for secondary HLH, cases of concurrent EBV and Ehrlichia-induced HLH are not readily found in the literature. Although EBV is typically a self-limiting disease not requiring antiviral therapy, EBV-induced HLH represents one of the rare cases necessitating such therapy.