A case of T-cell-Epstein–Barr virus-haemophagocytic lymphohistiocytosis and sustained remission following ruxolitinib therapy

Abstract

Objectives: Epstein–Barr virus (EBV) is a common cause of secondary haemophagocytic lymphohistiocytosis (HLH). While B cells are reservoirs for EBV, infection within T cells and NK cells in this disease can be difficult to treat. Methods: A 19-year-old female presented with a 6-week history of coryzal symptoms on a background of Crohn's disease. On examination, she was febrile and tachycardic with mild tonsillar enlargement and splenomegaly. New trilineage cytopenias and elevation in liver enzymes were detected, with acute EBV subsequently confirmed on whole blood PCR. A diagnosis of EBV-associated HLH was supported further with elevated serum ferritin, triglycerides and soluble CD25, low fibrinogen and the presence of haemophagocytosis in the bone marrow. Results: Corticosteroids, IVIG and rituximab were given, and anakinra was subsequently added due to ongoing fevers. EBV infection was then demonstrated within CD8+ T cells on EBER Flow-FISH assay. Ruxolitinib was commenced and her fevers abated on day 5, with improvement in other HLH parameters. She was discharged after a 39-day hospital admission. To date, she has remained in remission of HLH, despite developing COVID-19 infection during the convalescence phase of HLH. Conclusion: EBV viraemia requires adequate treatment to control EBV-associated HLH as rituximab may be insufficient, and corticosteroid resistance can result in continued EBV infection in CD8+ T cells. This entity is known as T-cell-EBV-HLH. Ruxolitinib is a novel treatment strategy in this specific context and has several advantages, including inhibition of corticosteroid resistance to promote apoptosis of EBV-infected T cells.