The Immunomodulatory Influence of Cytomegalovirus Infection on Pediatric Patients with Chronic Immune Thrombocytopenic Purpura

Abstract

Immune thrombocytopenia (ITP) in children is usually a short self-limiting disease with favorable prognosis characterized by increased platelet destruction and decreased platelet number. However, the condition can become chronic in 5% to 30% of affected children. It may be triggered by viral infection as many reports documenting the relationship of viral infections with ITP. HCMV infection may result in severe, refractory ITP. Treatment with steroids was shown to worsen the course of HCMV-associated ITP. A cross-sectional prospective study was conducted including 37 patients with chronic ITP diagnosed and/or following at Ain-Shams university pediatrics hospital hematology unit in the period between September 2016 and March 2017 with the following aims:  To evaluate frequency of HCMV positivity among pediatric patients with chronic ITP.  To assess the effect of HCMV infection on the course of ITP and to evaluate the effect of HCMV positivity on the INF gamma and its input on bleeding manifestations and outcome in patients with ITP. All patients were subjected to detailed history and physical examination including age, sex, age at diagnosis, clinical presentation suggestive of viral infection e.g. pneumonitis, hepatitis, petechial rashes, mononucleosis-like syndrome, bleeding signs and type of bleeding using ITP BAT score and any organomegaly. Furthermore, Treatment lines and outcome including initial response after 1st line or more than one line when needed and duration of response were included in the study. HCMV serology was done for each chronic ITP patient. HCMV IgG avidity was assessed in HCMV IgM positive cases and IFN gamma was measured by flow cytometry for each chronic ITP patient. Then the differences between positive and negative cases was evaluated according to blood picture, ITP BAT (SMOG score), treatment and response of treatment. Our study results show that HCMV IgM positive was detected in 35.1 % of pediatrics patients with chronic ITP. In addition, all the studied patients with chronic ITP showed HCMV IgG positivity and all HCMV IgM positive patients showed high HCMV IgG avidity. Significant higher IFN gamma levels were observed in patients with chronic ITP (40.76) compared with control group (5.29) (P<0.001). There was negative correlation between INF gamma and HCMV IgG avidity. HCMV IgM positive cases did not differ from HCMV IgM negative cases in terms of age, gender, history of viral illness, clinical presentation, SMOG score, blood picture, platelet count at the time of diagnosis. Response to initial treatment was similar in both HCMV IgM positive patients and CMV IgM negative patients (p=0.466). However, Duration of response to treatment to first line of treatment was higher in patients with HCMV IgM negative than in HCMV IgM positive patients (P=0.043). The differences in response to current treatment were not statistically significant (p=0.399). Keywords: The Immunomodulatory Influence of Cytomegalovirus Infection on Pediatric Patients with Chronic Immune Thrombocytopenic Purpura