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Published on: February 24, 2023
Evidence-based diagnosis and treatment of macrophage activation syndrome in systemic juvenile idiopathic arthritis
V Boom1, J Anton2, P Lahdenne3
1Department of Pediatric Rheumatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands. v_boom@hotmail.com.
Background:
Macrophage 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.
Methods:
A 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.
Results:
27 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.
Conclusion:
MAS 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.
Insights
Macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis (sJIA) lacks standardized diagnostic criteria. The new PRINTO criteria show promise for diagnosis, but treatment remains largely experience-based.
Area of Science:
- Rheumatology
- Pediatric Immunology
- Hematology
Background:
- Macrophage activation syndrome (MAS) is a severe complication linked to systemic juvenile idiopathic arthritis (sJIA).
- Current diagnostic and treatment guidelines for MAS in sJIA are lacking.
- This review evaluates literature on MAS diagnosis, biomarkers, and treatment in sJIA.
Purpose of the Study:
- To systematically review diagnostic criteria for MAS in sJIA.
- To provide an overview of biomarkers for diagnosis, disease activity, and treatment response.
- To summarize recent advances in MAS treatment for sJIA.
Main Methods:
- Systematic literature search in MEDLINE, EMBASE, and Cochrane databases.
- Selection and screening of 495 identified papers by multiple authors.
- Validity and evidence level assessment by independent experts using EULAR guidelines.
Main Results:
- No validated diagnostic criteria for MAS in sJIA currently exist.
- Preliminary Ravelli criteria with ferritin showed good performance; new PRINTO criteria demonstrated superior performance in distinguishing MAS.
- High-dose corticosteroids and cyclosporine A are common first-line treatments; anakinra shows promising responses.
Conclusions:
- The PRINTO criteria are recommended for diagnosing MAS in sJIA, pending prospective validation.
- Novel biomarkers require further validation and are not yet widely available.
- MAS treatment in sJIA is primarily experience-based, necessitating early expert consultation for suspected cases.
