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.

Evaluation of macrophage activation syndrome associated with systemic juvenile idiopathic arthritis: single center experience over a one-year period

“…The significant laboratory findings in MAS include pancytopenia, increased transaminases, hypertriglyceridemia, hyperferritinemia, increased LDH, hypoalbuminemia, increased D-dimer, reduced ESR and reduced sodium level (2). In our study, anemia was found in nine patients (90%), thrombocytopenia was found in six patients (60%) and leukopenia was found in two patients (20%).…”

“…Demonstration of hemophagocytosis which is a characteristic change on bone marrow aspirate helps to make the diagnosis. In addition, hemophagocytic infiltrations may also occur in organs including lymph node, liver and spleen (2).…”

Does Viral Hemorrhagic Fever Represent Reactive Hemophagocytic Syndrome?

“…Like Ebola virus, rHPS has been reported in association with other hemorrhagic fever viruses, such as Crimean-Congo and Dengue, with similar clinical (e.g., MODS including CNS dysfunction and coagulopathy) 5,7,8 and pathologic findings (e.g., hemophagocytosis) 9,10 . As in Ebola virus infection, hyperferritinemia has been observed to be a marker of hemorrhagic manifestation (and adverse outcome) in Dengue as well 11 .…”

“…VHF shares striking similarities with hemophagocytic syndromes (HPS), both familial hemophagocytic lymphohistiocytosis (HLH) and reactive hemophagocytic syndrome (rHPS, also called macrophage activation syndrome, or MAS), which include the following: prolonged fever, coagulopathy, hyperferritinemia, liver enzyme elevations, increased serum interleukin 1 (IL-1) levels, thrombocytopenia, and central nervous system (CNS) dysfunction 4,5 (Table 1) 6 . Moreover, it has recently been elegantly shown in samples from the 2000-2001 Ebola outbreak of Sudan virus-associated VHF that hyperferritinemia, a hallmark of rHPS, was associated with hemorrhage and death 4 .…”

Weathering a Macrophage Storm

“…With a mortality rate of 8% among patients with sJIA, and likely a notably higher one for those with AOSD, it is important for practitioners to recognize MAS early and to treat it aggressively in hopes of improving patient survival 20 . While this current AOSD study has several limitations, including a small patient sample, restriction to hospitalized patients, and lack of treatment outcomes, it serves as an initial study to explore the clinical relevance of the 2016 sJIA MAS Personal non-commercial use only.…”