Macrophage activation syndrome

Macrophage activation syndrome (MAS) is a severe, potentially life-threatening condition classified as a form of secondary hemophagocytic lymphohistiocytosis (HLH). It occurs most commonly as a complication of systemic autoimmune and autoinflammatory diseases, particularly systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease, though it can also occur in the context of systemic lupus erythematosus and other rheumatic conditions. MAS is characterized by excessive activation and uncontrolled proliferation of T lymphocytes and macrophages, leading to an overwhelming inflammatory response sometimes referred to as a "cytokine storm." The condition affects multiple organ systems simultaneously. Key clinical features include persistent high fever, hepatosplenomegaly (enlargement of the liver and spleen), lymphadenopathy, liver dysfunction, coagulopathy (including disseminated intravascular coagulation), and cytopenias — particularly a paradoxical drop in white blood cell count, platelet count, and erythrocyte sedimentation rate in a patient who was previously showing elevated inflammatory markers. Characteristic laboratory findings include markedly elevated serum ferritin (often dramatically so), elevated triglycerides, elevated liver transaminases, elevated soluble IL-2 receptor (sCD25), and low fibrinogen levels. Hemophagocytosis — the engulfment of blood cells by activated macrophages — may be observed on bone marrow biopsy, though its absence does not exclude the diagnosis. MAS can be triggered by infections (particularly viral infections such as Epstein-Barr virus), medication changes, or disease flares, though in many cases no clear trigger is identified. Without prompt treatment, MAS can rapidly progress to multi-organ failure and death. Treatment typically involves high-dose intravenous corticosteroids (pulse methylprednisolone) as first-line therapy. Cyclosporine A is frequently used as a second-line agent. In refractory cases, biologic therapies such as anakinra (an IL-1 receptor antagonist) and emapalumab (an anti-interferon-gamma monoclonal antibody, approved for primary HLH) have shown efficacy. Etoposide, a chemotherapeutic agent used in primary HLH protocols, may be considered in severe refractory cases. Early recognition and aggressive treatment are critical, as mortality rates remain significant despite advances in therapy.

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

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