Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients

Arthritis Rheumatol. 2014 Nov;66(11):3160-9. doi: 10.1002/art.38802.


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.

Publication types

  • Multicenter Study

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use*
  • Arthritis, Juvenile / complications*
  • Biological Products / therapeutic use*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cyclosporine / therapeutic use*
  • Etoposide / therapeutic use*
  • Female
  • Fever / epidemiology
  • Hepatomegaly / epidemiology
  • Humans
  • Intensive Care Units / statistics & numerical data
  • International Cooperation
  • Macrophage Activation Syndrome / drug therapy*
  • Macrophage Activation Syndrome / etiology*
  • Macrophage Activation Syndrome / mortality
  • Male
  • Prevalence
  • Retrospective Studies
  • Splenomegaly / epidemiology
  • Survival Rate
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Biological Products
  • Etoposide
  • Cyclosporine