Pediatric Macrophage Activation Syndrome: Clinical Features and Prognosis

Abstract

Background: Macrophage activation syndrome (MAS) is a rare but life-threatening pediatric emergency belonging to the spectrum of secondary hemophagocytic lymphohistiocytosis. Diagnosis is challenging because of nonspecific clinical features often mimicking severe sepsis, and mortality remains high, particularly in resource-limited settings. Objectives: To describe the epidemiological, clinical, biological, etiological and therapeutic characteristics of pediatric MAS and to identify factors associated with poor outcomes in a Tunisian tertiary care center. Methods: A retrospective descriptive and analytical study was conducted including 40 children hospitalized for MAS between 2010 and 2025. Diagnosis was mainly based on HLH-2004 criteria. Clinical, laboratory, etiological, therapeutic and outcome data were collected. Univariate analysis was performed to identify prognostic factors. Results: Median age at diagnosis was 28 months, with a predominance of children under four years of age. Infectious causes accounted for 50% of cases, mainly viral infections and visceral leishmaniasis. Overall mortality reached 42.5%. Factors significantly associated with unfavorable outcomes included younger age, prolonged fever, ferritin levels ≥ 500 µg/L, fibrinogen ≤ 1.5 g/L, prothrombin time < 50%, and elevated gamma-glutamyl transferase and alkaline phosphatase levels. Conclusion: Pediatric MAS remains a severe condition with high mortality. Early identification of simple and accessible biological prognostic markers may improve risk stratification and optimize therapeutic management.