Chronic active Epstein-Barr virus infection of T cell type presenting with hemophagocytic lymphohistiocytosis in a Caucasian adult

Abstract

Dear Editor, A 70-year-old Caucasian man with a history of hypertension and diabetes mellitus presented with several days of fever, dry cough, and altered mental status. His family noted that he had worsening confusion over the preceding 2 months. He was a never smoker and rarely drank alcohol. He worked as a bus driver and had a remote history of traveling abroad. On evaluation, he was febrile with an irregular heart rate of 140 and blood pressure of 130/69. He was lethargic and only able to answer yes/no questions. He had left eye conjunctivitis and splenomegaly 5 cm below the costal margin. White blood cell count was 0.5 K/μl, absolute neutrophil count 70/μl, hemoglobin 10.3 g/dL, and platelets of 48 K/μl. Creatinine was 2.1 mg/dLwith hepatic enzymes elevated < 2 × upper limit of normal. Ferritin was 5413 ng/mL. Fibrinogen was 104 mg/dL and triglycerides were 377 mg/dL. A fourthgeneration human immunodeficiency virus test was negative. Peripheral blood smear showed marked neutropenia without myeloblasts or dysplasia, normocytic anemia with scattered burr cells, and thrombocytopenia. Epstein-Barr virus (EBV) viral load was positive at 95,000 copies/μl and EBV serologies demonstrated viral capsid antigen (VCA)-IgG (+), VCA-IgM (−), early antigen (EA) IgG (−), nuclear antigen IgG (+), and heterophile IgM (−). Cerebrospinal fluid was positive for EBV with a viral load of 1,100,000 IU/mL. Bone marrow examination demonstrated a hypercellular marrow with dense CD3 (+), CD8 (+), TIA1 (+), CD56 (−) T cell infiltration and numerous macrophages with phagocytized red blood cells (Fig. 1). Flow cytometry showed a T cell population with mild immunophenotypic abnormalities with absent expression of CD5 and CD7. T cell receptor gamma gene rearrangement studies demonstrated these T cells to be polyclonal. EBV encoded RNA (EBER) in situ hybridization detected EBV in CD8 + TIA1+ T cells. Cytogenetics identified 5 of 20 cells with abnormal loss of the Y chromosome. Next-generation sequencing demonstrated alteration of FLT3 (p. L646M) of uncertain significance. The patient was thus diagnosed with chronic active EBV infection (CAEBV) associated with hemophagocytic lymphohistiocytosis (HLH). Within 2 days of admission, the patient had worsening somnolence and required intubation for airway protection. Shortly thereafter, he developed distributive shock and was started on pressor support. He was initiated on dexamethasone and etoposide according to the HLH-94 protocol. Although there was improvement in inflammatory markers after initiating HLH-directed therapy, the patient died with multiorgan failure. This case features an unusual presentation of CAEBV in a Caucasian adult. CAEBV is an EBV associated T or natural killer (NK) cell lymphoproliferative disease that is rare, lifethreatening, and typically limited to East Asian and South American populations [1]. Compared to the pediatric population, adult-onset CAEBV more commonly manifests with HLH and has a higher mortality rate [2], often due to sepsis and multiorgan failure [3]. Early diagnosis is critical, and patients should be initiated on HLH-directed therapy to mitigate * Debbie Jiang [email protected]