The successful treatment of haemophagocytic syndrome in patients with human immunodeficiency virus-associated multi-centric Castleman's disease

Abstract

Both virus-associated haemophagocytic syndrome (HPS) and human immunodeficiency virus-associated multi-centric Castleman's disease (HIV-MCD) induced by human herpesvirus-8 (HHV-8) are extremely rare. We therefore wished to investigate their occurrence together, and establish the degree of cytokine activation present. From a prospective cohort of individuals with HIV-MCD, we investigated the incidence and outcomes of HPS and measured 15 inflammatory cytokines and the plasma HHV-8 viral loads before and during follow-up. Of 44 patients with HIV-MCD with an incidence of 4.3/10,000 patient years, four individuals (9%) were diagnosed with HPS. All are in remission (range 6-28 months) following splenectomy, etoposide and rituximab-based therapy. Plasma HHV-8 levels were raised markedly at presentation (median 3,840,000 copies/ml). Histological samples from spleen, splenic hilar lymph nodes and bone marrow demonstrated increased phagocytosis by histiocytes and presence of HHV-8-infected plasmablasts outside the follicles. Surprisingly, many known inflammatory plasma cytokines were not elevated, although interleukin (IL)-8 and interferon-gamma were increased in all cases and IL-6 levels were raised in three of four patients. HPS in the setting of HIV-MCD is common and treatment can be successful provided the diagnosis is made appropriately. Systemic activation of cytokines was limited, suggesting that immunosuppressive therapy with steroids is not indicated in HHV-8-driven HPS.