Clinical Features, Treatment, and Outcome of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A Multinational, Multicenter Study of 362 Patients

Abstract

Objective: To describe the clinical, laboratory, and histopathologic features, current treatment, and outcome of patients with macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA). Methods: In this multinational, multicenter study, pediatric rheumatologists and hemato‐oncologists entered patient data collected retrospectively into a web‐based database. Results: A total of 362 patients, 22% of whom had MAS at the onset of systemic JIA, were included in the study by 95 investigators from 33 countries. The most frequent clinical manifestations were fever (96%), hepatomegaly (70%), and splenomegaly (58%). Central nervous system dysfunction and hemorrhages were recorded in 35% and 20% of the patients, respectively. Platelet count and liver transaminase, ferritin, lactate dehydrogenase, triglyceride, and d‐dimer levels were the sole laboratory biomarkers showing a percentage change of >50% between the pre‐MAS visit and MAS onset. Evidence of macrophage hemophagocytosis was found in 60% of the patients who underwent bone marrow aspiration. MAS occurred most frequently in the setting of active underlying disease, in the absence of a specific trigger. Nearly all patients were given corticosteroids, and 61% received cyclosporine. Biologic medications and etoposide were given to 15% and 12% of the patients, respectively. Approximately one‐third of the patients required admission to the intensive care unit (ICU), and the mortality rate was 8%. Conclusion: This study provides information on the clinical spectrum and current management of systemic JIA–associated MAS through the analysis of a very large patient sample. MAS remains a serious condition, as a sizeable proportion of patients required admission to the ICU or died.