Journal Article

Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment

Ravelli, A, Behrens, E M, Cron, R Q, Grom, A A

2012

Overview

Macrophage activation syndrome (MAS) is a severe, frequently fatal complication of systemic juvenile idiopathic arthritis (sJIA) with features of hemophagocytosis leading to coagulopathy, pancytopenia, and liver and central nervous system dysfunction. MAS is overt in 10% of children with sJIA but occurs subclinically in another 30–40%. It is difficult to distinguish sJIA disease flare from MAS. Development of criteria for establishing MAS as part of sJIA are under way and will hopefully prove sensitive and specific. Mutations in cytolytic pathway genes are increasingly being recognized in children who develop MAS as part of sJIA. Identification of these mutations may someday assist in MAS diagnosis. Defects in cytolytic genes have provided murine models of MAS to study pathophysiology and treatment. Recently, the first mouse model of MAS not requiring infection but rather dependent on repeated stimulation through Toll-like receptors was reported. This provides a model of MAS that may more accurately reflect MAS pathology in the setting of autoinflammation or autoimmunity. This model confirms the importance of a balance between pro- and anti-inflammatory cytokines. There has been remarkable progress in the use of anti-pro-inflammatory cytokine therapy, particularly against interleukin-1, in the treatment of secondary forms of MAS, such as in sJIA.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/208/2489/144 / 631/80/313/1727 / 692/699/1670/427/1304 / 692/699/249/1623 / Adrenal Cortex Hormones - pharmacology / Animal models / Animals / Antirheumatic Agents - pharmacology / Arthritis / Arthritis, Juvenile - genetics / Arthritis, Juvenile - immunology / Arthritis, Juvenile - physiopathology / Autoimmunity / Biomedical and Life Sciences / Biomedicine / Bone marrow / Cancer Research / Care and treatment / Cell activation / Central nervous system / Child / Children / Complications and side effects / Cyclosporine - pharmacology / Cytokines / Development and progression / Diagnosis / Disease / Disease Models, Animal / Fever / Gene Expression / Genes / Genetic aspects / Health aspects / Human Genetics / Humans / Immunology / Infection / Inflammation / Interleukin 1 / Interleukin 1 Receptor Antagonist Protein - pharmacology / Leukocytes / Liver / Macrophage Activation Syndrome - diagnosis / Macrophage Activation Syndrome - drug therapy / Macrophage Activation Syndrome - genetics / Macrophage Activation Syndrome - immunology / Macrophage Activation Syndrome - physiopathology / Macrophages / Mice / Mutation / Nervous system / Pancytopenia / Pathophysiology / Pediatrics / Receptors, Interleukin-1 - antagonists & inhibitors / Receptors, Interleukin-1 - drug effects / Receptors, Interleukin-1 - immunology / Receptors, Interleukin-10 - antagonists & inhibitors / Receptors, Interleukin-10 - immunology / review / Rheumatoid arthritis in children / Sepsis / Syndromes / Toll-Like Receptor 9 - immunology / Toll-like receptors