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Risk factors for macrophage activation syndrome in systemic juvenile idiopathic arthritis: a systematic review and

Shihao Li1,2,3, Xin Wu1,2,3, Shuolan Jing1,2,3

  • 1Division of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University, Chengdu, China.

Frontiers in Pediatrics
|December 22, 2025
PubMed
Abstract

Insights

Identifying risk factors for macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis (sJIA) is crucial. Central nervous system involvement, low fibrinogen, high ferritin, and leukopenia are key indicators for MAS in sJIA patients.

Area of Science:

  • Rheumatology
  • Pediatrics
  • Critical Care Medicine

Background:

  • Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (sJIA).
  • Early identification of MAS risk factors is critical for reducing mortality in sJIA patients.
  • Existing evidence on MAS risk factors is heterogeneous and lacks clinically translatable conclusions.

Purpose of the Study:

  • To systematically identify and quantify risk factors for MAS in sJIA.
  • To provide clinically relevant insights for early MAS detection and management.

Main Methods:

  • Systematic literature search of multiple databases (PubMed, Web of Science, EMBASE, CNKI, Wanfang, VIP, CBM) up to July 1, 2025.
  • Inclusion of case-control studies investigating MAS risk factors in sJIA.
  • Meta-analysis using RevMan 5.3 and Stata 16.0.

Main Results:

  • Ten studies involving 1,936 patients (643 cases, 1,293 controls) were included.
  • Significant associations found for central nervous system (CNS) involvement (OR 4.30), hypofibrinogenemia (OR 4.03), hyperferritinemia (OR 8.28), and leukopenia (OR 5.98).
  • These factors demonstrated substantial odds ratios, indicating strong associations with MAS in sJIA.

Conclusions:

  • Central nervous system involvement, hypofibrinogenemia, hyperferritinemia, and leukopenia are core risk factors for MAS in sJIA.
  • These identified factors are crucial for early risk assessment and timely intervention in sJIA patients.
  • The findings offer quantified and comparable conclusions to guide clinical practice.
Keywords:
case–control studymacrophage activation syndromemeta-analysisrisk factorssystemic juvenile idiopathic arthritis

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