2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis

Abstract

To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ=0.76). We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies.

Juvenile Idiopathic Arthritis: Diagnosis and Treatment

“…In 2005, preliminary diagnostic guidelines for MAS in patients with systemic JIA were published [22, 23]. A multinational collaborative effort aimed at developing new classification criteria for the syndrome has been recently accomplished [24–27] (Table 2).

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Macrophage Activation Syndrome Associated with Adult-Onset Still’s Disease Successfully Treated with Anakinra

“…The leukocytosis likely reflected a concurrent flare of Still's disease and rendered SLE less likely despite the serological findings as discussed below. Our patient did not have hepatomegaly or lymphadenopathy, which are relatively common, but not necessarily present in MAS [8, 9], and the HLH-2004 criteria do not rely on these features [6]. Likewise, hemophagocytosis was not observed in the bone marrow; however, it is important to keep in mind that hemophagocytic picture was noted only in 70% of patients in a recent retrospective case series [10].…”

“…In this regard, whether the HLH-2004 criteria can be extrapolated to MAS remains to be investigated. Our case fulfilled the latest classification criteria for MAS proposed by Ravelli et al and Kostik et al [8, 9]; however, it is important to keep in mind that these criteria were developed for pediatric population, that is, sJIA, but not for Adult-Onset Still's disease [8]. …”

Adult Onset Still’s Disease Associated withMycoplasma pneumoniaeInfection and Hemophagocytic Lymphohistiocytosis

“…Thus, the detection of macrophage hemophagocytosis on bone marrow biopsy specimens is not required for the diagnosis of MAS [15]. Also, in order not to delay the diagnosis, the new classification criteria include only laboratory (high ferritin, triglycerides and aspartate transaminase, and low platelet count and fibrinogen level) and no clinical variables, with the exception of fever [16]. Although designed for use in clinical research, criteria can be applied in individual patients.…”