Background/Purpose:  Macrophage activation syndrome (MAS) is acute systemic inflammation arising in the context of various autoimmune and autoinflammatory conditions, which is often life-threatening. In 2016, EULAR/ACR/PRINTO Collaborative Initiative group developed new criteria for the classification of MAS in patients with systemic onset juvenile idiopathic arthritis (JIA) (1). Adult onset Still’s disease (AOSD) is considered to be an adult counterpart of systemic onset JIA. Therefore, we evaluated the clinical significance of 2016 EULAR/ACR/PRINTO classification criteria for MAS in patients with AOSD.

Methods:  We retrospectively reviewed the Severance Hospital’s electronic medical records of patients hospitalized with fever and AOSD. From 2005 to 2015, 64 patients were identified. According to the 2016 classification criteria for MAS, patients were defined as having MAS when they had fever, ferritin level of over 684, and fulfilled more than 2 of the following 4 criteria: platelet count ≤181,000, AST > 48 units/L, triglycerides > 156 mg/dL, fibrinogen ≤ 360 mg/dL. Clinical and laboratory data of patients with and without MAS were compared using the two-tailed Student’s t-test or the chi-square test. Delta ferritin level was calculated by dividing the maximum level of ferritin level during the admission by i) the initial ferritin level on the date of MAS diagnosis for patients with MAS or ii) on the date of admission in patients without MAS. Univariate and multivariate analysis were used to evaluate factors associated with in-hospital mortality.

Results:  Among 64 patients with AOSD, 36 patients (56.2%) were classified as MAS. There were 12 deaths (33.3%) in patients with MAS while there was no death (0.0%) in patients without MAS (p<0.001). Comparison of baseline characteristics between patients with and without MAS showed differences in gender, platelet, ESR, AST, ALT, total protein, lactate dehydrogenase (LDH), fibrinogen, triglyceride and ferritin levels (Table 1). In patients with MAS, total protein (p=0.044) and delta ferritin≥50% (p=0.007) was significantly associated with in-hospital mortality. Multivariate analysis with variables with p-values < 0.05 in univariate analysis revealed that delta ferritin≥50% was associated with in-hospital mortality (OR 8.097, 95% confidence interval, 1.422-46.097, p=0.018) (Table 2).

Conclusion: These findings suggest that MAS is a frequent complication in patients with AOSD and is associated with in-hospital mortality. Furthermore, in patients with MAS, delta ferritin levels of over 50% were also associated with in-hospital mortality. Although early recognition is important for the proper management of MAS, there has been no single specific test to detect MAS. We demonstrated that the new 2016 classification criteria, composed of 5 simple laboratory tests, are significantly associated with poor outcome in febrile AOSD. Therefore, patients with AOSD should be monitored carefully for development of MAS based on 2016 EULAR/ACR/PRINTO classification criteria.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/application-of-the-2016-european-leage-against-rheumatism-eular-american-college-of-rheumatology-acrpaediatric-rheumatology-international-trials-organisation-printo-classification-criteria-of/