Virological and immunological characteristics of a 19-year-old Japanese female with fatal outcome with Epstein-Barr virus-associated hemophagocytic syndrome.

Hemophagocytic syndrome (HPS) is caused by the hyperactivation of T-cells and macrophages. The clinical characteristics associated with this disease result from overproduction of cytokines including interferon-gamma (INF-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6). HPS presents with fever, liver dysfunction, coagulation abnormalities, pancytopenia, and a benign histiocytic proliferation with prominent hemophagocytosis in bone marrow, lymph node, spleen, and liver. We describe a 19-year-old female with fatal HPS. She had been given corticosteroid every other day for systemic lupus erythematosus (SLE) without flare up. The causative underlying disease was acute primary Epstein-Barr virus (EBV) infection. EBV genomes were detected by the polymerase chain reaction (PCR). To measure the virus load we use a real-time PCR assay to quantify the amount of EBV DNA in peripheral blood lymphocytes, lung, kidney, brain and liver at autopsy. Further in situ hybridisation (ISH) and immunohistochemical studies demonstrated that Epstein-Barr virus encoded small RNA (EBER) was detected in CD8+ T-cells in bone marrow, lung, kidney, brain, liver and spleen. In each organ, mRNA levels of inflammatory cytokines (INF-gamma, TNF-alpha, IL-6) were highly detected compared with beta-Actin mRNA levels. These results suggest that EBV-infected CD8+ T-cells in each organ (peripheral blood lymphocytes, lung, kidney, brain and liver) may have an integral role in the pathophysiology of the HPS.