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Aplastic Crisis Secondary to Parvovirus B19 Infection as the First Manifestation of an Undiagnosed Hereditary Spherocytosis: Report of a Pediatric Series of Spanish Patients.

To the Editor: Human Parvovirus-B19 (HPV-B19) infection is a well-known cause of aplastic crisis in patients with chronic hemolytic anemia, such as hereditary spherocytosis (HS).1–5 In the pediatric population HS may have not been diagnosed when HPV-B19 infection occurs; therefore, it might be difficult to suspect hemolysis when the presenting symptom is a severe aregenerative anemia.6 We describe 8 pediatric patients in whom the first manifestation of an undiagnosed HS was an aplastic crisis due to HPV-B19. We performed a retrospective study between January 2008 and June 2015 in a Pediatric University Hospital in Barcelona. Table 1 shows patients characteristics. In brief, there were 5 women. The median age at diagnosis was 9.5 years (range, 4 to 12y). Presenting symptoms in most cases were fever, abdominal pain, and vomiting. Only 1 patient developed an exanthema. All patients presented moderate to severe microcytic/normocytic anemia (median hemoglobin, 58g/L; range, 31 to 86) with low reticulocyte count in 7 of them. One patient had leukopenia. Direct antiglobulin test was negative in all cases. Although corrected reticulocyte count was low, other signs of hemolysis, such as mild unconjugated hyperbilirubinemia, increased lactate dehydrogenase, or decreased haptoglobin were present. Serologic assay (anti-HPV-B19 IgM) was positive in all cases. HPV-B19 is the cause of erythema infectiosum, which is a common and self-limited exanthematous illness of childhood. The prodromal phase consists of fever, headache, and flu-like symptoms. The hallmark is a characteristic rash that appears after this phase. In healthy children, this virus is frequently associated to mild aregenerative anemia and in some cases to leukopenia and/or thrombocytopenia.4 Patients with hematologic diseases may not present the characteristic typical course. As described in pediatric patients with HS7 the characteristic rash was not observed in our series of pediatric patients except for 1 case.8 All patients presented with fever and most of them had abdominal pain and severe aregenerative anemia.1,7 In mild forms of HS, hemolysis is compensated and some children may not be diagnosed until a viral infection may trigger an aplastic crisis and uncover the underlying defect.1 Thus, in a patient presenting with unexplained acute moderate to severe aregenerative anemia, the possibility of an aplastic crisis secondary to HPV-B19 infection in an undiagnosed mild HS has to be considered, even in patients without a known family history. To confirm this diagnosis, other clinical and laboratory signs of hemolysis should be sought and an expert should evaluate a blood smear. As not always a hematopathologist is available, it is important to keep a blood smear for further evaluation, before transfusion. In our series, spherocytes could be observed in all cases. In addition, should these patients require hospital admission, the suspicion of HPV-B19 infection is important, as it will prompt to avoid their admission in a hemato-oncology ward to prevent an infectious outbreak in susceptible patients. Special precaution should be taken to avoid contact of the patient with pregnant women because HPV-B19 can cause severe intrauterine infections. In conclusion, severe aregenerative anemia by HPV-B19 infection may be the presenting symptom of HS in children. Anna Alonso-Saladrigues, MD* Albert Català, MD* Rubén Berrueco, MD, PhD* Mireia Camós, MD, PhDw Montserrat Torrebadell, MDw Susana Rives, MD, PhD* *Department of Pediatric Hematology and Oncology wLaboratory Department, Molecular Genetics, Hospital Sant Joan de Déu de Barcelona, University of Barcelona Barcelona, Spain