Classification of Macrophage Activation Syndrome in JIA

A new set of classification criteria for macrophage activation syndrome (MAS)-complicating systemic juvenile idiopathic arthritis (JIA) can be used to improve clinical study enrollment, according to researchers.

MAS, the potentially life-threatening complication of systemic inflammatory disorders, occurs most commonly in JIA. Prevalence of this overwhelming inflammatory response in JIA has been estimated at approximately 10 percent, but recent reports suggest subclinical MAS might occur in as many as 30 percent-to-40 percent of JIA patients, making timely diagnosis and prompt treatment imperative.

But, identifying MAS early is challenging due to a lack of a single pathognomonic clinical or laboratory feature. Add in the recent treatment advances and understanding of the pathophysiology and underlying genetic defects and there’s a need for accurate criteria physicians can use to correctly classify patients with MAS.

The goal, according to a group of international research collaborators, is to augment the understanding of MAS in systemic JIA, enhancing effective therapies. Investigators from the European League Against Rheumatism, the American College of Rheumatology, and the Pediatric Rheumatology International Trials Organization participated in this initiative.  [[{"type":"media","view_mode":"media_crop","fid":"48008","attributes":{"alt":"©PuwadolJaturawutthichai/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_6610389929687","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5708","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©PuwadolJaturawutthichai/Shutterstock.com","typeof":"foaf:Image"}}]]

The criteria were developed by a 28-expert panel at the International Consensus Conference on MAS Classification Criteria, held in Genoa, Italy in May 2014. They participated in a 6-step, web-based process and classified 428 international patient profiles as being MSA-positive or not based on clinical and laboratory features recorded at disease onset. Their consensus was categorized as the gold standard for disease classification.

Alongside developing the classification criteria, the initiative also ventured to analyze the role changes in laboratory findings over time MAS detection. It’s important to note, researchers added, that the criteria are mostly intended for investigatory use.

“Although possibly useful for diagnostic purposes, the classification criteria are primarily intended for use in clinical trials and research studies,” investigators wrote. “The criteria exhibited high accuracy and face/content validity in consensus and statistical evaluations, but it should be taken into account that they were developed using expert consensus as the gold standard.”

Experts reached consensus on 391 patients – 91.4 percent – 95 of which were classified as having MAS.  They found 10 variables had the greatest ability to identify MAS patients: ferritin level, platelet count, levels of aspartate transaminase, lactate dehydrogenase, triglycerides, alanine transaminase, fibrinogen, central nervous system involvements, hepatomegaly, and hemorrhagic manifestations.

These criteria include mainly laboratory variables because the criteria focus on early-stage diagnosis. The only clinical variable include was fever. The study focused more on laboratory features because previous research indicated clinical features appear later, delaying diagnosis. Consequently, it’s important to note that the classification might not capture all MAS cases encountered in a routine clinical setting.

Ultimately, investigators wrote, the criteria could help standardize the design and implementation of future clinical trials and research studies, as well as contribute to broader MAS understanding and awareness.

References:

Angelo Ravelli, Francesca Minoia, et al. "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," Arthritis and Rheumatology. Article first published online: 9 FEB 2016  DOI: 10.1002/art.39332