A systematic review of juvenile dermatomyositis complicated by macrophage activation syndrome.

BACKGROUND: Macrophage activation syndrome (MAS) is a rare but potentially life-threatening complication of juvenile dermatomyositis (JDM). Data on its clinical presentation, diagnosis, treatment, and outcomes remain limited. OBJECTIVE: To systematically review the literature on MAS occurring in patients with JDM. METHODS: A systematic search of PubMed and Embase was performed for studies published between 1997 and 2025 reporting JDM-associated MAS/hemophagocytic lymphohistiocytosis. Three reviewers independently screened studies according to PRISMA guidelines. Due to marked heterogeneity and the predominance of case reports, a qualitative synthesis was conducted. RESULTS: Twenty-eight studies, including 39 patients, were analyzed. MAS occurred within three months of JDM diagnosis in most cases and frequently presented at disease onset. Diagnostic approaches were highly heterogeneous, with reliance mainly on clinical judgment and inconsistent application of HLH-2004 criteria. Anti-MDA5 was the most frequently reported autoantibody, followed by anti-NXP2. Corticosteroids, cyclosporine, and intravenous immunoglobulins were the most commonly used therapies, while biologic and targeted agents were increasingly reported. Mortality remained substantial. CONCLUSIONS: MAS is an underrecognized early complication of JDM associated with significant morbidity and mortality. The absence of disease-specific diagnostic criteria and standardized therapeutic strategies represents a major unmet clinical need. SYSTEMATIC REVIEW REGISTRATION: Not registered.