Abstract

Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of systemic juvenile idiopathic arthritis (sJIA) with features of hemophagocytosis, leading to coagulopathy, pancytopenia, and liver and central nervous system dysfunction. MAS is overt in about 10% of children with sJIA but may occur subclinically in another 30-40% of patients. The diagnosis of MAS in sJIA can be challenging because it may mimic a flare of the underlying disease or be confounded with an infectious complication or a medication side effect. So far, universally agreed upon diagnostic criteria for MAS are not available. A multinational collaborative effort is under way that is aimed to generate new criteria for diagnosing MAS as a complication of sJIA. The first step of the project has led to the identification of, by means of a Delphi survey, the clinical, laboratory and histopathologic features of MAS that were felt to be most important by a large sample of international pediatric rheumatologists with experience with MAS in children with sJIA. The following 9 features were selected by more than 50% of the respondents and were given most frequently the highest ranks: falling platelet count, hyperferritinemia, evidence of macrophage hemophagocytosis in the bone marrow, increased serum liver enzymes, falling leukocyte count, persistent continuous fever ≥38°C, falling ESR, hypofibrinogenemia, and hypertriglyceridemia. In the second phase of the project, which is ongoing, investigators were asked to record data related to the clinical, laboratory and histopathologic features of their own patients with sJIA-associated MAS and of patients with 2 “confusable” conditions (that is, conditions that may mimic MAS clinically), represented by instances of active sJIA without evidence of MAS or non-sJIA patients with febrile systemic infections requiring hospitalization. By the middle of January 2011, data describing a total of 272 patients with MAS, 378 patients with active sJIA without MAS, and 322 non-sJIA patients with acute febrile infections had been entered in the study website (powered by the Pediatric Rheumatology International Trials Organization, PRINTO) by 76 investigators from 27 countries. The final set of criteria is meant to be established in a consensus conference of experts using a combination of statistical and consensus formation techniques. The ultimate goal of the project is to develop a core set of criteria that is both highly sensitive and specific. These criteria will assist physicians in MAS diagnosis in children with sJIA and enable quick institution of appropriate therapy.