New Criteria Released for Macrophage Activation Syndrome in Juvenile Idiopathic Arthritis

Dr. Schneider

“It began with a Delphi survey of the international pediatric rheumatology community to select the most suitable candidate classification criteria,” says Dr. Schneider. “This was followed by the large-scale collection of data from both patients with MAS and relevant controls with ‘confusable’ diagnoses, active systemic JIA or systemic infections from multiple international centers.”

The panelists reviewed hundreds of brief, real patient clinical and laboratory profiles through web-based communication, and were asked to determine whether each one should be classified as having MAS or not, says Dr. Schneider.

“Potential MAS definition criteria were derived from these data and were then further evaluated at an international consensus meeting” held in Genoa on March 21–22, 2014, he says. “Selected definitions of MAS were ranked by the conference participants, and a final definition was determined based on 80% consensus among the participants.”

The broad, international mix of the panelists, along with that high level of consensus of their evaluations, means that the process adequately addressed any potential geographic or regional disparities in MAS classification, says Dr. Schneider.

Why MAS Criteria Matter

In MAS, a malfunctioning immune system causes both macrophages and T-lymphocyte cells to activate continuously. This triggers an overexpression storm of inflammatory cytokines. Patients may experience an array of clinical symptoms as a result, including high fever, liver and spleen swelling, lymphadenopathy, dysfunction of the central nervous system and hemorrhaging.

Patients with JIA are not the only ones at risk for developing MAS. It’s also found in adult-onset Still’s disease, the adult equivalent of systemic JIA. Reports of MAS in patients with both juvenile and adult systemic lupus erythematosus, Kawasaki disease, and periodic fever syndromes are increasing as well, according to the paper Dr. Schneider co-authored.

Knowledge gaps make these new criteria an important step toward improved care for these at-risk, juvenile patients, says Dr. Schneider.

“It is widely recognized that the guidelines for the diagnosis of primary hemophagocytic lymphohistiocytosis are not sufficiently sensitive for the diagnosis of MAS in the context of systemic JIA, particularly with regard to making an early diagnosis,” he says. “Classification criteria for MAS are essential in facilitating research to further our understanding of the pathogenesis of MAS in systemic JIA, and to identify new biomarkers and effective treatments.”

MAS can cause multiple organ failure if a treating physician doesn’t identify and treat it, and recent studies suggest its mortality rate may be about 8%. However, MAS is not easy to recognize, as it doesn’t have telltale clinical and laboratory signs. In fact, doctors may confuse MAS for other conditions, even for a flare of the patient’s systemic JIA. Patients may present with a wide, disparate array of clinical or laboratory features, making early, life-saving intervention a huge challenge.

Collaborative Effort

Developing new, more accurate classification criteria for MAS in systemic JIA was a multistep process. First, the panelists were asked to classify 428 selected patient profiles as having or not having MAS based on clinical and laboratory features at the onset of disease. Out of these 428 profiles, 161 had MAS associated with systemic JIA, and 267 had conditions that could potentially be mistaken for MAS, such as systemic infection.