The pathophysiology of Epstein–Barr virus (EBV)-associated haemophagocytosis remains poorly understood.1 In EBV-related haemophagocytic lymphohistiocytosis, EBV-infected CD8 T cells and natural killer cells are thought to trigger haemophagocytosis and the associated ‘cytokine-storm’/systemic inflammatory response syndrome (SIRS) directly.2,–,4

By contrast, in the context of uncontrolled proliferation of EBV-infected B cells, hyperactively responding EBV-specific T cells are assumed to mediate haemophagocytosis/SIRS.5 Both the quantity and quality of such deregulated EBV-specific T-cell reactivity remain undefined. Unique insight into basic aspects of the postulated T-cell requirements necessary to trigger haemophagocytosis was provided by the case of a 37-year-old woman with mixed connective tissue disease (ribonucleoprotein-Ab positive, severe pulmonary arterial hypertension, polyarthritis, pericarditis and oesophageal sclerosis). Immunosuppression with azathioprine and ciclosporin, as well as a 3-month trial of oral cyclophosphamide due to progressing pulmonary arterial hypertension was ineffective, yet worsened pre-existing lymphopenia. Based on the severe and cyclophosphamide-resistant course of the disease the indication for haematopoietic stem cell transplantation (HSCT) was established. …