Purpose of the review: One of the most perplexing features of systemic-onset juvenile rheumatoid arthritis is the association with macrophage activation syndrome, a life-threatening complication caused by excessive activation and proliferation of T cells and macrophages. The main purpose of the review is to summarize current understanding of the relation between macrophage activation syndrome and other clinically similar hemophagocytic disorders.
Recent findings: Clinically, macrophage activation syndrome has strong similarities with familial and virus-associated reactive hemophagocytic lymphohistiocytosis. The better understood familial hemophagocytic lymphohistiocytosis is a constellation of rare, autosomal recessive immune disorders. The most consistent immunologic abnormalities in patients with familial hemophagocytic lymphohistiocytosis are decreased natural killer and cytotoxic cell functions. In approximately one third of familial hemophagocytic lymphohistiocytosis patients, these immunologic abnormalities are secondary to mutations in the gene encoding perforin, a protein that mediates cytotoxic activity of natural killer and cytotoxic CD8+ T cells. Several recent studies have suggested that profoundly depressed natural killer cell activity and abnormal levels of perforin expression may be a feature of macrophage activation syndrome in systemic-onset juvenile rheumatoid arthritis as well. Although it has been proposed that in both hemophagocytic lymphohistiocytosis and macrophage activation syndrome, natural killer and cytotoxic cell dysfunction may lead to inadequate control of cellular immune responses, the exact nature of such dysregulation and the relation between macrophage activation syndrome and hemophagocytic lymphohistiocytosis still remain to be determined.