Cytomegalovirus Infection Presenting as Severe Sepsis, Hepatitis, and Autoimmune Hemolytic Anemia in an Immunocompetent Child in Pediatric Intensive Care Unit

To the Editors: We report 11-month-male who presented with 3 day history of fever associated with 1 day history of jaundice, abdominal distension and dark colored stools. At presentation, he had compensated shock, tachypnea, severe pallor, icterus, edema, moderate ascites, and hepatomegaly. His initial investigations revealed hemoglobin of 7 g/dL, which rapidly fell to 5 g/dL in 48 hours, total leukocyte count—28,800/mm3, platelet of 90,000/mm3. His liver function test revealed total bilirubin 3.8 mg/dL, conjugated bilirubin of 2.8 gm/dL, aspartate aminotransferase 180U/L, alanine aminotransferase 112U/L, alkaline phosphatase 228 IU/L and albumin 2.2 g/dL. Clotting studies were deranged with INR of 1.9. Malaria, Enteric fever, dengue, scrub typhus HIV and leptospira were ruled out. Blood culture was sterile. There was progressive increase in serum bilirubin from 5.6mg/dL on day 3 to 7.8 mg/dL on day 5 after admission, maximum increase of alanine aminotransferase to 780 U/L, aspartate aminotransferase to 912 U/L. Initially, cross matching was not feasible despite multiple trials. His indirect Coombs test was grade 3 positive with weakly positive direct coombs test. His hemolytic anemia work up revealed C3d and IgG positivity suggesting warm antibody autoimmune hemolytic anemia (AIHA). His work up was negative for Hepatitis A, E, B, C, HIV, EBV and mycoplasma. Considering febrile illness with warm antibody autoimmune hemolytic anemia with progressive hepatitis, cytomegalovirus (CMV) infection was considered on differential and CMV viral load resulted positive with copies of 17,998/mL. He was treated with ganciclovir (6 mg/kg daily for 14 days) and intravenous immunoglobulin (IVIG) (2 gm/kg over 48 hours). He started to improve after 3 days of starting of ganciclovir and IVIG with fever defervescence, without any further hemolysis and improvement in hepatitis. He continues to have normal liver function and growth parameters over last 12 months. Discussion Acquired CMV infection is usually clinically inapparent in immunocompetent child and is rarely associated with complications.1 This case presented with features of severe sepsis, progressive hepatitis with subsequent finding of AIHA posing a diagnostic challenge and CMV was considered as a possibility. There are reports of CMV causing warm AIHA and hepatitis in children.2 There is dearth of literature on different complications of CMV in immunocompetent children. A retrospective cohort study concluded that CMV hepatitis is a self-limited illness and does not need a specific antiviral therapy while another study reported effectiveness of ganciclovir in progressive CMV hepatitis without significant side-effects.3,4 We used ganciclovir in our case because of the progressive severe hepatitis, hemolysis and fulminant course. Usually, intravenous methylprednisolone followed by oral prednisone is preferred for treatment of warm AIHA. IVIG is considered in steroid unresponsive/partial responsive patients, however, because steroid resistance or high-dose dependence may occur especially in children <2 years age, IVIG was given. Steroid maintenance was not needed in this with reversal of hemolysis with a decrease in CMV viremia. In conclusion, CMV infection can present as severe sepsis, hemolytic anemia and fulminant hepatitis in immunocompetent child.