Department of Hematology and Oncology, Graduate School of MedicineUniversity of Tokyo
Letter to the Editor
Cite this article as:
Kagoya, Y., Hangaishi, A., Takahashi, T. et al. Int J Hematol (2010) 91: 326. doi:10.1007/s12185-009-0485-0
Immune thrombocytopenic purpura (ITP) is a hematologic disorder characterized by autoimmune-mediated platelet destruction. Although prednisone (or prednisolone) is generally used for treatment of ITP, high-dose dexamethasone therapy is also effective and leads to rapid recovery of platelet count . In contrast, optimal management of secondary ITP has not been well established. Here, we present a case of significant thrombocytopenia and neutropenia accompanied with Epstein–Barr virus (EBV)-induced infectious mononucleosis (IM).
A 36-year-old male visited our hospital with 2-week history of sore throat and fever. Physical examination showed cervical lymphadenopathy without hepatosplenomegaly. Peripheral blood findings were as follows: hemoglobin 13.5 g/dL, white blood cell count (WBC) 7.1 × 109/L (22.5% neutrophils, 1.5% monocytes, 6.0% lymphocytes, and 70.0% atypical lymphocytes), platelet count 71 × 109/L, aspartate aminotransferase 177 IU/L, alanine aminotransferase 240 IU/L, and lactate dehydrogenase 564 IU/L. The serological examination for EBV infection revealed the following results: the antibodies for viral capsid antigen (VCA) immunoglobulin (Ig) G was ×40, VCA IgM and anti-EB virus nuclear antigen (EBNA) IgG were negative. Also, serum EBV DNA was increased to 4.0 × 106 copies/L. He was diagnosed as EBV-induced IM. His symptom disappeared in a week. However, platelet count continued to decrease, followed by decreased WBC, as shown in Fig. 1. About 60 days after the first symptom appeared, peripheral blood counts were WBC 1.4 × 109/L with 30% neutrophils and platelet count 12 × 109/L. Reticulated platelets were increased to 12.6%. The patient’s serum was positive for anti-neutrophil antibody and platelet-associated IgG (PAIgG) was increased. Anti-neutrophil antibody was detected by flow cytometry method. Neutrophils from normal donors were incubated with serum from the patient or pooled sera from normal volunteers as a negative control. Then, membrane-bound IgG and IgM antibodies were detected using fluorescein isothiocyanate (FITC)-labeled goat anti-human immunoglobulin. The fluorescence intensity was plotted and judged for positivity. Furthermore, bone marrow was slightly hypercellular, with increased megakaryocytes. Based on these findings, a diagnosis of autoimmune neutropenia and ITP secondary to EBV infection was done. Because thrombocytopenia prolonged and gradually decreased for about 2 months (minimum platelet count of 12 × 109/L), we started treatment with high-dose dexamethasone therapy (40 mg/day for consecutive 4 days orally) and then stopped without tapering. His platelet count increased gradually to 55 × 109/L in 2 weeks after the treatment. Also, neutrophil count improved rapidly and exceeded above 2.0 × 109/L in 3 days. Currently, 4 months after the therapy, he is well with platelet count 100 × 109/L and neutrophil count about 1.0 × 109/L. No adverse effects were noted during and after the therapy.
Our patient developed typical symptoms suggestive of IM. Although negative VCA IgM antibody is inconsistent with the present infection, it is reported that VCA IgM antibody by fluorescent antibody test might be negative in 30% of patients with initial EBV infection . In this case, negative EBNA IgG and positive EBV DNA in peripheral blood strongly suggest primary EBV infection. EBV-induced IM is sometimes accompanied by mild thrombocytopenia or neutropenia. In extremely rare cases, however, severe thrombocytopenia (less than 20 × 109/L) or neutropenia (less than 0.5 × 109/L) develops [3, 4]. Although corticosteroids are effective for thrombocytopenia secondary to IM, they usually take several weeks to improve thrombocytopenia . Intravenous immunoglobulin or methylprednisolone pulse therapy has been used in cases where corticosteroids are refractory or urgent increase in platelet count is needed [5, 6]. On the other hand, neutropenia accompanied by IM usually recovers spontaneously within 3–7 days even in severe neutropenic cases and does not need any treatment . In our case, however, severe neutropenia has prolonged for 3 weeks and autoimmune neutropenia was strongly suspected due to positive anti-neutrophil antibody. Therefore, high-dose dexamethasone therapy is considered to have been effective for both thrombocytopenia and neutropenia.
We experienced a case of post-IM prolonged thrombocytopenia and neutropenia, which rapidly responded to high-dose dexamethasone therapy. It might be considered as an initial therapy for prolonged IM-associated thrombocytopenia or neutropenia when autoimmune etiology is highly suspected by confirmation of anti-platelet antibodies or anti-neutrophil antibodies.