Epstein-Barr virus infection and prognosis in haemophagocytic lymphohistiocytosis patients with underlying rheumatic diseases: a single-centre retrospective study.

Objectives: Haemophagocytic lymphohistiocytosis (HLH) with underlying rheumatic diseases (rHLH) is a lethal disease, in which Epstein-Barr virus (EBV) infection is a causative factor. Whether EBV infection is associated with treatment response and prognosis of patients with rHLH remains unclear. This study explored the clinical features of patients with Epstein-Barr virus-positive rHLH.

Methods: In this retrospective study, we included 137-patients and divided them into EBV-negative (n=116) and EBV-positive (n=21) groups. We compared the clinical characteristics, treatment responses, and prognoses between the two groups. Propensity score matching (PSM) was used to match patients between groups. Kaplan-Meier analysis was used to elucidate the relationship between the EBV-infected cell type and prognosis.

Results: EBV-positive patients were more likely to have relapsed or refractory rHLH. The survival time of the EBV-negative group was significantly longer than that of the EBV-positive group (p=0.012). Further analysis of EBV-infected lymphocyte subsets revealed a significant decrease in survival in the NK and/or T lymphocyte groups compared to the other cell types (p<0.01).

Conclusions: Patients with EBV-positive rHLH are more likely to experience relapse or refractoriness. For patients with rHLH, prompt testing of EBV-infected lymphocyte subsets should be performed upon EBV infection. An etoposide-based regimen is recommended for patients with EBV-positive rHLH, and rituximab may be effective in patients with refractory or relapsed rHLH with EBV-infected B lymphocytes. However, for patients with EBV-infected NK and/or T lymphocytes, treatment should be aligned with that for EBV-HLH.