Diagnosis and Management Update of Macrophage Activation Syndrome in Children: A Bangladesh Perspective

Abstract

Macrophage activation syndrome (MAS), a form of secondary hemophagocytic lymphohistiocytosis (HLH), represents a life-threatening hyperinflammatory complication of rheumatic disease, most notably systemic juvenile idiopathic arthritis (sJIA). Persistent dysregulation of cytotoxic lymphocytes and macrophages drives a cytokine storm that can precipitate multiorgan failure. MAS occurs across rheumatic conditions, including sJIA, systemic lupus erythematosus (SLE), and Kawasaki disease, and is characterized by high-grade fever, hepatosplenomegaly, lymphadenopathy, hemorrhagic manifestations, and central nervous system involvement. The 2022 European league against rheumatism (EULAR)/ACR recommendations provide diagnostic and treatment guidance for early-stage MAS/HLH, highlighting heterogeneity in practice and the utility of high-dose glucocorticoids combined with interleukin-1 and interferon-γ (IFN-γ) inhibitors; emapalumab has shown promise in trials, whereas etoposide and hematopoietic stem cell transplantation remain reserved for severe or refractory cases. In Bangladesh, MAS is predominantly encountered in sJIA, with less frequent involvement in other pediatric rheumatic diseases. This review synthesizes current understanding of MAS in children, emphasizing pathogenesis (impaired cytotoxic activity, IFN-γ-driven macrophage activation, and subsequent cytokine amplification), clinical and laboratory features (notably hyperferritinemia and evolving cytopenias), diagnostic criteria (HLH-2004 criteria and Pediatric Rheumatology International Trials Organization/EULAR/ACR MAS criteria for sJIA; disease-specific guidelines for SLE), and diagnostic workflows. The review underscores the diagnostic challenges due to overlapping features with primary HLH and disease flares and highlights the ongoing need for standardized guidelines, especially in resource-limited settings, to optimize outcomes for children with MAS.