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Paediatric macrophage activation syndrome: clinical features and outcomes across diverse aetiologies
Şeyma Türkmen1, Hazal Ceren Tuğrul2, Murat Hakkı Yarar3
1Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, Istanbul, Turkey.
Insights
Pediatric macrophage activation syndrome (MAS) is diverse, with inflammation and organ issues causing severe outcomes. Genetic factors are linked to worse or recurring disease, guiding treatment strategies.
Area of Science:
- Pediatric Rheumatology
- Immunology
- Genetics
Background:
- Macrophage activation syndrome (MAS) is a severe, life-threatening hyperinflammation.
- Understanding MAS in children is crucial for improving outcomes.
Purpose of the Study:
- To characterize clinical features and outcomes of pediatric MAS.
- To examine associations between MAS and immune-regulatory genetic variation.
Main Methods:
- Retrospective study of 120 children with MAS.
- Analysis of clinical, laboratory, and outcome data.
- Genetic testing for Hemophagocytic Lymphohistiocytosis (HLH)-related variants in a subgroup.
- Multivariable logistic regression for outcome prediction.
Main Results:
- Common etiologies include MIS-C, sJIA, and infection-triggered MAS.
- High rates of ICU admission (60%) and organ failure (45%) were observed, with 17.5% mortality.
- Non-sJIA cases showed higher ICU admission and mortality, while sJIA cases had higher recurrence.
- Immune-regulatory variants were found in 22.4% and associated with severe/recurrent disease.
- Higher ferritin predicted mortality; sJIA etiology was linked to lower mortality.
Conclusions:
- Pediatric MAS is etiologically diverse, with inflammation and organ dysfunction impacting outcomes.
- Immune-regulatory variants correlate with severe or relapsing disease.
- Phenotype-guided stratification is supported for managing pediatric MAS.
Objectives:
To characterize clinical features and outcomes of paediatric macrophage activation syndrome (MAS) and examine associations with immune-regulatory genetic variation.
Methods:
This retrospective study included 120 children with MAS. Clinical, laboratory and outcome data were analysed. A subgroup underwent genetic testing for Hemophagocytic Lymphohistiocytosis (HLH)-related variants. Multivariable logistic regression identified factors associated with outcomes.
Results:
Aetiologies included multisystem inflammatory syndrome in children (MIS-C) (36.7%), systemic juvenile idiopathic arthritis (sJIA) (26.7%), infection-triggered MAS (23.3%), other rheumatologic diseases (10.8%) and lymphoma (2.5%). Intensive care unit (ICU) admission and acute organ failure occurred in 60% and 45%, and mortality was 17.5%. Compared with sJIA, non-sJIA had higher ICU admission (72.7% vs 25.0%, P = 0.02) and mortality (21.6% vs 6.3%, P = 0.04), whereas recurrence was more common in sJIA (28.1% vs 9.1%, P = 0.04). Stratified analyses (MIS-C, other MAS and sJIA) showed higher ICU admission in MIS-C and other MAS, highest mortality in other MAS and highest recurrence in sJIA, with rates of 77.3%, 68.2% and 25.0% (P < 0.001), 6.8%, 36.4% and 6.3% (P < 0.001), and 2.3%, 15.9% and 28.1% (P = 0.01), respectively. Among tested patients, 22.4% carried HLH-related variants. Variant positivity was independently associated with higher ferritin, younger MAS onset, recurrence, acute organ dysfunction and sJIA aetiology. Higher peak ferritin predicted mortality (OR 2.01) and reduced remission off therapy (OR 0.70), whereas sJIA aetiology was associated with lower mortality (OR 0.21).
Conclusion:
Paediatric MAS is aetiologically heterogeneous, with inflammatory burden and organ dysfunction driving poor outcomes. Immune-regulatory variants are linked to severe or relapsing disease, supporting phenotype-guided stratification.
