Hemophagocytic syndrome

Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS), is a severe, life-threatening condition characterized by uncontrolled activation of the immune system. In this disorder, certain immune cells — particularly macrophages, natural killer (NK) cells, and cytotoxic T lymphocytes — become pathologically overactivated, leading to excessive inflammation and tissue damage throughout the body. The hallmark finding is hemophagocytosis, where activated macrophages engulf red blood cells, white blood cells, and platelets in the bone marrow, spleen, liver, and lymph nodes. The condition affects multiple organ systems. Key clinical features include prolonged high fever, enlarged liver and spleen (hepatosplenomegaly), cytopenias (low blood cell counts affecting red cells, white cells, and platelets), hypertriglyceridemia, hypofibrinogenemia, elevated ferritin levels, and elevated soluble IL-2 receptor (sCD25). Liver dysfunction, coagulopathy, and neurological symptoms including seizures and altered consciousness may also occur. Without treatment, the disease can rapidly progress to multi-organ failure and death. Hemophagocytic syndrome can be classified as primary (familial/genetic) or secondary (acquired). Primary forms, known as familial hemophagocytic lymphohistiocytosis (FHL), are caused by mutations in genes such as PRF1, UNC13D, STX11, STXBP2, and others involved in cytotoxic granule-mediated cell killing. Secondary HLH can be triggered by infections (particularly Epstein-Barr virus), malignancies, autoimmune diseases, or immunosuppressive therapies. Treatment typically involves immunosuppressive and cytotoxic therapy based on the HLH-94 or HLH-2004 protocols, which include dexamethasone, etoposide, and cyclosporine A. For familial forms, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option. Emapalumab, an anti-interferon-gamma antibody, has been approved for refractory primary HLH.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Hemophagocytic syndrome