The features and prognosis analysis of central nervous system Epstein-Barr virus infection in children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.

UNLABELLED: The purpose of the study is to analyze the clinical features, treatment, and survival outcomes of Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) with positive cerebrospinal fluid (CSF) EBV-DNA in children. Patients diagnosed with EBV-HLH admitted to our center from January 2019 to August 2024 were enrolled and divided into a CSF-EBV group and a non-CSF-EBV group based on CSF EBV-DNA test results. Neurological manifestations were observed in only 33.3% (13/39) of children with CSF-EBV positivity, while 48.7% (19/39) showed abnormal brain magnetic resonance imaging findings. The CSF-EBV group had a higher blood EBV-DNA load (P = 0.002) and a lower CD4+/CD8+ ratio (P = 0.034) compared with the non-CSF-EBV group. A strong positive correlation was observed between CSF EBV-DNA load and CSF cell count (r = 0.800, P < 0.0001). Overall survival was shorter in the CSF-EBV group (P = 0.017). Multivariate Cox regression identified EBV-associated central nervous system (EBV-CNS) infection as a potential independent risk factor for poor prognosis (HR = 6.077, 95% CI: 1.345-27.435, P = 0.019). Intrathecal methotrexate and dexamethasone effectively reduced CSF viral load (P = 0.003) and cell count (P = 0.042), but did not significantly improve overall survival (P = 0.3).

CONCLUSION

EBV-CNS infection may be an independent risk factor for poor prognosis in pediatric EBV-HLH, underscoring the importance of CSF EBV-DNA testing, particularly in patients with high blood loads. Although intrathecal therapy effectively reduced CNS viral load and inflammation, its survival benefit requires further validation in large-scale prospective studies.

WHAT IS KNOWN: • CNS involvement is a well-established poor prognostic factor in HLH. • EBV-CNS infection is an independent prognostic risk factor in adult EBV-HLH.

WHAT IS NEW: • EBV-CNS infection is an independent prognostic risk factor in pediatric EBV-HLH. •While intrathecal therapy effectively reduces CSF viral load and inflammation, its survival benefit still requires further validation through large-scale prospective studies.