Viral Infection Induced Acute Megaloblastic Anemia: A Case Series.

We have documented a series of ten patients presenting with symptomatic anemia and a recent history of constitutional symptoms such as fever, myalgias and diarrhea. They were mildly icteric and had severe pallor. Lymphadenopathy and organomegaly were absent. Peripheral blood smears showed reactive lymphocytes, which are typically seen in viral infections and in addition severe megaloblastic changes consisting of hypersegmentation of neutrophils, macro ovalocytes, leukopenia and thrombocytopenia were noted. Indirect bilirubinemia, elevated serum LDH and low haptoglobins were documented. Direct Coombs was negative in all the patients. Bone marrow aspiration revealed megaloblastic changes. Autoimmune hemolytic anemia, Pernicious anemia, Malaria, T.T.P, Aplastic anemia and HIV were excluded in all the patients. They had diagnostically low serum cobalamin and folate levels and the cytopenias normalized with parenteral vitamin supplementation. None of the patients received steroids or antiviral treatment.

Was the viral syndrome causally related to the megaloblastic anemia or was a preexisting megaloblastic anemia being brought to the attention of the clinician by the acute viral syndrome? This puzzling question was solved when a patient who had a normal complete blood count in March 2005 at our institute, developed severe pancytopenia after a febrile illness in October 2005. Another patient in the series had normal hemoglobin and had actually donated a unit of blood one month prior to his admission with diarrhea and severe pancytopenia.

The next question that we faced was regarding the identity of the virus. We initially performed a lymphadenitis panel (Euro Immune) consisting of 16 common viral markers. Epstein Barr virus (EBV) was positive in the initial case. An EBV Immunofluorescence panel (Euro Immune) was done in all the subsequent patients. This test was positive in 6 out of the10 patients, they were positive for EBV Capsid IgG, EBV Capsid IgM, and EBV early antigen Ig G (acute infection markers). EBV nuclear antigen IG G (chronic infection marker) was negative.

It should be noted that none of the patients had neurological deficits despite having diagnostically low cobalamine levels and this we presume is due to the acute onset of illness not allowing enough time for the development of neurological symptoms. There were quite a few patients seen in this period of time with typical EBV infection without any megaloblastic changes and similarly there were patients with overt megaloblastic anemia without any features of EBV infection. Hence there must be a patient specific characteristic that predisposes them to acute megaloblastic anemia on developing the viral infection. Since only two of these ten patients are pure vegans and since none were malnourished we have to look for a non nutritional cause for this predisposition. An acute coombs negative hemolytic anemia due to the viral infection can explain the cytpenias but the low B12 levels and the prompt response to B12 supplementation are unexplained.

We feel that this is a new syndrome of reversible viral induced acute onset megaloblastic anemia. There exists a possibility that this is a new strain of EBV virus, and we have stored the sera of all the patients for future epidemiological purposes. We are recommending that physicians should consider B12/folate supplementation in acute EBV syndromes and obtain follow-up CBC one month after the illness. We believe that further work has to be done before a definite association between EBV and megaloblastic anemia can be established.