Taglietti et al. Journal of Medical Case Reports 2010, 4:334 http://www.jmedicalcasereports.com/content/4/1/334 Mild anemia was present: hemoglobin (Hb), 11.3 g/dL; and increased inflammatory indexes: C-reactive protein, 30.9 mg/L (n.v., < 6), erythrocyte sedimentation rate (ESR), 19 mm/h. No antiviral treatment was started because the patient was immunocompetent. After hospital discharge, the fever persisted, and the patient complained of progressive asthenia. At admission to our hospital, the patient appeared pale and asthenic. Physical examination revealed a body temperature of 38°C, heart rate of 100 beats per minute, and moderate hepatosplenomegaly. The blood examina- tions showed acute hemolytic anemia: red blood cells (RBCs), 2,430,000/mm3; Hb, 7.9 g/dL; reticulocyte count, 16.7%; LDH, 778 mU/mL; total bilirubin, 2.4 mg/ dL; indirect bilirubin, 2 mg/dL; and undetectable serum haptoglobin. Noninfectious causes of hemolytic anemia, including hemoglobinopathies (such as glucose-6-phosphate dehy- drogenase deficiency), drug toxicity, autoimmune dis- eases, and malignancies, were excluded. Of note, direct and indirect Coombs tests were negative, although mildly positive for cold agglutinins and cryoglobulins. A total- body computed tomography scan was negative for solid tumors, revealing only moderate hepatosplenomegaly. Serologic and virologic examinations showed CMV IgM/IgG, positive; CMV antigenemia, negative; CMV viremia, positive (< 400 cp/mL); parvovirus B19 IgM/ IgG, positive, with blood polymerase chain reaction (PCR) negative; and EBV VCA IgM/IgG, positive, with blood PCR negative. Blood cultures, antibodies to HIV, hepatitis B and C virus, human herpesvirus-6, herpes simplex virus 1-2, Toxoplasma, Mycoplasma, Legionella, and hepatitis B surface antigen were negative. The clinical picture was attributed to primary CMV infection. The Hb level was 6.7 g/dL at day four and decreased to 5.4 g/dL at day seven. The patient remained febrile. Considering the rapid decrease of Hb levels, specific antiviral treatment with ganciclovir, 900 mg/day (5 mg/kg/b.i.d., i.v.) was administered to the Page 2 of 3 patient. After hematologic consultation, blood transfu- sions were prescribed. The patient remained febrile, with hemoglobin levels ranging between 5 and 6 g/dL. At day 20, CMV antigenemia, viremia, and blood PCR were negative. Considering the poor clinical response to antiviral treatment, we hypothesized an immunologic pathogenetic mechanism of hemolytic anemia, and ster- oid therapy with methylprednisolone, 1 mg/kg/day i.v. was started. Gancyclovir therapy was continued. The clinical condition of the patient improved. At discharge (day 30), blood examinations showed RBCs, 276,0000/mm3; Hb, 9.7 g/dL; reticulocytes, 5.4%; haptoglobin, 105 mg/dL (n.v., 40 to 130). Treatment with 900 mg/qd oral valganciclovir, and oral prednisone, 1 mg/kg/day, was continued. At day 90, the patient was asymptomatic with an hemoglobin level of 12.2 per deciliter. Valganciclovir and steroids were stopped. Discussion This is an uncommon case of severe hemolytic anemia during primary CMV in an immunocompetent patient. An immunologic mechanism was supported by the clini- cal improvement with steroid therapy, whereas the clini- cal picture remained unvaried during antiviral therapy alone. This hypothesis was indirectly confirmed by the demonstration of the abnormal immunologic activation occurring during CMV infection (that is, the positivity of the serologic tests for parvovirus B19 and EBV, together with the negativity of blood PCR for these two viruses), which was likely interpreted as a cross-reaction. An interesting finding in our case was the negativity of the Coombs test. A positive Coombs test could have helped in identifying an autoimmune mechanism, thus making the patient eligible for early steroid therapy. However, the presence of an underlying autoimmune mechanism could not be ruled out, based only on the negativity of Coombs test. The literature provides Table 1 Hemolytic anemia during acute cytomegalovirus infection in adult immunocompetent patients: data from the literature Number of patients Coombs test Steroids Anti-CMV therapy Outcome Authors/Year Rafailidis M./2008 [7] Veldhuis et al./2004 [5] Salloum et al./1994 [9] Van Spronsen D. et al./1996 [2] Gavazzi G. et al./1999 [1] Horwitz et al./1984 [3] 5* 1 2 1 1 2 BT, blood transfusion; Neg, negative; NS, not specified. *Among 290 apparently immunocompetent patients with severe cytomegalovirus infection who were included in a review. NS Neg Case 1: Pos Case 2: Pos Neg Pos Case 1: Pos Case 2: Neg BT NS No No No No No Yes No NS No Yes No Yes Yes Yes No NS No No Yes Yes No Cured Cured Cured Cured Cured Cured