2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative

Abstract

ObjectiveTo develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA).MethodsA 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.ResultsExperts 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).ConclusionWe 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.

Macrophage activation syndrome in adult systemic lupus erythematosus: report of seven adult cases from a single Italian rheumatology center

“…Although in our experience, MAS and SLE were diagnosed simultaneously and this was also the most frequent scenario in some other previous series (4,8), recent data indicate that MAS may arise in patients with long disease duration in up to 50% of the cases (7). 3 and/or a platelet count of <110,000/mm 3 ; °the cut-off suggested for the classification of reactive MAS in the original study was 169 (11). Other authors suggested a higher cutoff (190.5), in patients with rheumatic diseases (15).…”

Why a second look might be worth it: immuno-modulatory therapies in the critically ill patient

“…Beside fever and excessive cytokine production, hepatobiliary dysfunction (HBD) and hemorrhagic complications (disseminated intravascular coagulation, DIC) are common clinical signs of MAS. This fulminant inflammatory response primarily occurs as complication in systemic rheumatologic diseases and promotes the development of multi-organ failure, fatal disease progresses and death (53).…”

Weathering a Macrophage Storm

“…Other laboratory abnormalities include elevated liver enzymes, D-dimers, lactate dehydrogenase, and triglycerides (TGC). Soluble interleukin 2 receptor α (sCD25) may be elevated, but testing is often not available at an on-site laboratory and therefore is not routinely done at the time of diagnosis 1,2,3,4 . Histopathology often reveals characteristic increased hemophagocytic activity in the bone marrow (and other tissues), with positive CD163 (histiocyte) staining, although this feature is often not present in initial stages and is neither highly sensitive nor specific for MAS 5,6 .…”

“…There are several diagnostic challenges in the early recognition of MAS, particularly in distinguishing it from a flare of sJIA or AOSD. Moreover, there is no single pathognomonic feature of MAS, and many clinical features and laboratory abnormalities overlap with those of systemic inflammatory disorders, making it difficult to distinguish the underlying disease from the life-threatening comorbidity 1,2,3,4 . Further, until very recently, there were no universal validated criteria to aid in diagnosis.…”

“…Further, until very recently, there were no universal validated criteria to aid in diagnosis. However, patient data-based classification criteria for MAS in patients with sJIA were recently reported 1,9 . The criteria were developed in an iterative process over several years and relied on real patient data and controls (> 1100 subjects from 33 countries).…”