Abstract
BackgroundMacrophage activation syndrome (MAS) is a severe and potentially lethal complication of several inflammatory diseases but seems particularly linked to systemic juvenile idiopathic arthritis (sJIA). Standardized diagnostic and treatment guidelines for MAS in sJIA are currently lacking. The aim of this systematic literature review was to evaluate currently available literature on diagnostic criteria for MAS in sJIA and provide an overview of possible biomarkers for diagnosis, disease activity and treatment response and recent advances in treatment.MethodsA systematic literature search was performed in MEDLINE, EMBASE and Cochrane. 495 papers were identified. Potentially relevant papers were selected by 3 authors after which full text screening was performed. All selected papers were evaluated by at least two independent experts for validity and level of evidence according to EULAR guidelines.Results27 papers were included: 7 on diagnosis, 9 on biomarkers and 11 on treatment. Systematic review of the literature confirmed that there are no validated diagnostic criteria for MAS in sJIA. The preliminary Ravelli criteria, with the addition of ferritin, performed well in a large retrospective case-control study. Recently, an international consortium lead by PRINTO proposed a new set of diagnostic criteria able to distinguish MAS from active sJIA and/or infection with superior performance.Other promising diagnostic biomarkers potentially distinguish MAS complicating sJIA from primary and virus-associated hemophagocytic lymphohistiocytosis.The highest level of evidence for treatment comes from case-series. High dose corticosteroids with or without cyclosporine A were frequently reported as first-line therapy. From the newer treatment modalities, promising responses have been reported with anakinra.ConclusionMAS in sJIA seems to be diagnosed best by the recently proposed PRINTO criteria, although prospective validation is needed. Novel promising biomarkers for sJIA related MAS are in need of prospective validation as well, and are not widely available yet. Currently, treatment of MAS in sJIA relies more on experience than evidence based medicine. Taking into account the severity of MAS and the scarcity of evidence, early expert consultation is recommended as soon as MAS is suspected.
Highlights
Macrophage activation syndrome (MAS) is a severe and potentially lethal complication of several inflammatory diseases but seems linked to systemic juvenile idiopathic arthritis
MAS has been reported to occur in the context of infectious, malignant, metabolic- and autoimmune diseases [4] but seems linked to systemic Juvenile Idiopathic Arthritis, occurring in at least 7–13 % of systemic juvenile idiopathic arthritis (sJIA) patients [1, 5, 6]
SJIA is a subtype of Juvenile Idiopathic Arthritis (JIA) and is characterised by arthritis of unknown origin and extra-articular symptoms like spiking fever, often accompanied with a macular rash, serositis, hepatosplenomegaly and generalised lymphadenopathy due to reticuloendothelial involvement
Summary
Macrophage activation syndrome (MAS) is a severe and potentially lethal complication of several inflammatory diseases but seems linked to systemic juvenile idiopathic arthritis (sJIA). MAS has been reported to occur in the context of infectious-, malignant-, metabolic- and autoimmune diseases [4] but seems linked to systemic Juvenile Idiopathic Arthritis (sJIA), occurring in at least 7–13 % of sJIA patients [1, 5, 6]. SJIA is a subtype of Juvenile Idiopathic Arthritis (JIA) and is characterised by arthritis of unknown origin and extra-articular symptoms like spiking fever, often accompanied with a macular rash, serositis, hepatosplenomegaly and generalised lymphadenopathy due to reticuloendothelial involvement. SJIA is considered an (acquired) auto-inflammatory disease rather than an autoimmune disease because of clear clinical and pathophysiological differences when compared to the other subtypes of JIA. Its disease course can be unpredictable, varying from a monophasic course of relatively mild disease to chronic relapsing periods of severe poly-arthritis accompanied by critical extra-articular symptoms and complications causing significant morbidity and mortality
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