EBV‐associated hemophagocytic syndrome
Authors: Konstantinos Liapis, John Apostolidis, Susan Delimpasis
Journal: American Journal of Hematology (2010)

General aspect of the marrow: macrophages with prominent phagocytosis of red cells, platelets, and erythroblasts. The marrow is overall hypocellular (MGG, original magnification ×400). High-power view of two characteristic hemophagocytic macrophages. (A) A macrophage with ingested red cells, platelets, erythroblasts, neutrophil, and assorted debris. (B) A macrophage which has engulfed a large number of erythroblasts (MGG, original magnification ×1,000). Hemophagocytic syndrome or hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by fever, pancytopenia, organomegaly, multiorgan dysfunction, and hemophagocytosis by a large number of macrophages in bone marrow and other tissues [1]. Central to the pathophysiology is the impaired activity of NK and cytotoxic T lymphocytes resulting in uncontrolled immune activation, hypercytokinemia, and proliferation of macrophages. The diagnosis of HLH relies upon well-established criteria [2]. The syndrome has been described in familial conditions or as a secondary phenomenon to infections, malignancies, and collagen vascular diseases. HLH in the context of infection is best described in association with Epstein-Barr virus (EBV). EBV-associated HLH can occur either in primary infection or as a consequence of viral reactivation. EBV can also be the trigger in both familial and secondary cases. Although uncommon, hemophagocytic syndrome is a serious complication of EBV infection and can be fatal in many cases. Early recognition and prompt initiation of treatment are of great importance to reduce the high morbidity and mortality associated with this condition. The history and representative images from a case of EBV-associated hemophagocytic syndrome are described. The patient's consent has been obtained. A 25-year-old woman was admitted with fever, pancytopenia, and hepatic dysfunction. Five weeks previously, she was diagnosed with infectious mononucleosis on the basis of pharyngitis, fever, and positive EBV antibodies. In the weeks after diagnosis, she continued to complain of intermittent fevers and sweating. Past medical and family history were unremarkable. Physical examination revealed temperature 38°C, icteric sclera, and hepatosplenomegaly. Laboratory values included hemoglobin 8.1 g/dL, leucocytes 2,100 μL−1, neutrophils 720 μL−1, platelets 40,000 μL−1, bilirubin 7.4 mg/dL, ALT 135 U/L, LDH 1,080 U/L, triglycerides 459 mg/dL, and ferritin 6,070 ng/mL. Peripheral blood film morphology was unremarkable. The direct and indirect antiglobulin test and screening for cold autoagglutinins gave negative results. The reticulocyte automated count and absolute value were 1.11% and 31,900 μL−1, respectively, indicating impaired production of red cells. Bone marrow aspiration showed numerous macrophages with striking phagocytosis of blood cells and marrow precursors (Images 1 and 2). EBV serologies indicated primary infection, and the EBV-PCR result was 18,000 copies/mL. Genetic testing for familial HLH was negative. The patient was treated with methylprednisolone and intravenous immunoglobulins and eventually recovered completely.