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Macrophage activation syndrome is a term used to identify hemophagocytic lymphohistiocytosis secondary to rheumatic diseases (rheuHLH). It is a severe, potentially fatal condition that occurs in the context of rheumatic diseases, particularly systemic juvenile idiopathic arthritis. It is part of secondary HLH forms, that are clinically and biochemically similar to primary HLH (pHLH), with generalized hypercytokinemia as a major feature. While the triggering mechanism behind pHLH is the defect in cytotoxicity, caused by mutations in genes encoding proteins required for lymphocyte and natural killer cell activity, the rheuHLH pathogenesis is not clearly understood.

Neutralization of Interferon-gamma is efficacious in a mouse model of HLH secondary to chronic inflammation