Characteristics of Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis (HLH) in European Children.

Abstract

Hemophagocytic lymphohistiocytosis (HLH) represents a severe sepsis-like disease with massive hypercytokinemia and with proliferating and organ-infiltrating phagocytes leading to cytopenia of different hematopoietic lineages. Besides primary familial cases of HLH, infections can cause secondary forms of HLH, among which Epstein-Barr virus (EBV) infections are the most frequent trigger. Between 2003 and 2005, 10 cases of EBV-associated HLH were analysed at a local subcenter of the international HLH study group. Serial blood samples from these 4 boys and 6 girls (age range: 2–14 years, median of age: 4 years) were examined for EBV load in peripheral blood mononuclear cells (PBMC) and plasma by real-time PCR analysis. EBV loads in both PBMC and plasma were significantly elevated in all HLH patients as compared with healthy controls and also with immunocompetent patients suffering from primary EBV infections. In one patient with excessively elevated EBV load in peripheral blood, analysis of EBV-DNA in separated T and B cells by real-time PCR showed an EBV infection of both cell types. During the course of disease, EBV load in HLH patients reflected the activity of disease. Regarding the clinical course and biochemical markers of disease such as LDH, ferritin or soluble IL2-receptor levels in plasma, patients with EBV-associated HLH did not differ from other patients with HLH. Conclusion: Measurement of EBV-load by real-time PCR facilitates detection of EBV-associated cases of HLH and monitoring of affected patients during the course of disease. EBV load analysis should become part of the initial routine examinations of newly diagnosed HLH patients in order to identify the frequency of EBV-associated forms of HLH. Without molecular diagnosis by means of EBV load measurement in peripheral blood, EBV-associated cases of HLH may be underdiagnosed in non-Asian populations.