Clinical and laboratory features associated with macrophage activation syndrome in Still's disease: data from the international AIDA Network Still's Disease Registry

Abstract

To characterize clinical and laboratory signs of patients with Still's disease experiencing macrophage activation syndrome (MAS) and identify factors associated with MAS development. Patients with Still's disease classified according to internationally accepted criteria were enrolled in the AutoInflammatory Disease Alliance (AIDA) Still's Disease Registry. Clinical and laboratory features observed during the inflammatory attack complicated by MAS were included in univariate and multivariate logistic regression analysis to identify factors associated to MAS development. A total of 414 patients with Still's disease were included; 39 (9.4%) of them developed MAS during clinical history. At univariate analyses, the following variables were significantly associated with MAS: classification of arthritis based on the number of joints involved (p = 0.003), liver involvement (p = 0.04), hepatomegaly (p = 0.02), hepatic failure (p = 0.01), axillary lymphadenopathy (p = 0.04), pneumonia (p = 0.03), acute respiratory distress syndrome (p < 0.001), platelet abnormalities (p < 0.001), high serum ferritin levels (p = 0.009), abnormal liver function tests (p = 0.009), hypoalbuminemia (p = 0.002), increased LDH (p = 0.001), and LDH serum levels (p < 0.001). At multivariate analysis, hepatomegaly (OR 8.7, 95% CI 1.9-52.6, p = 0.007) and monoarthritis (OR 15.8, 95% CI 2.9-97.1, p = 0.001), were directly associated with MAS, while the decade of life at Still's disease onset (OR 0.6, 95% CI 0.4-0.9, p = 0.045), a normal platelet count (OR 0.1, 95% CI 0.01-0.8, p = 0.034) or thrombocytosis (OR 0.01, 95% CI 0.0-0.2, p = 0.008) resulted to be protective. Clinical and laboratory factors associated with MAS development have been identified in a large cohort of patients based on real-life data.

Keywords: Arthritis; Autoinflammatory diseases; Diagnosis; MAS; Prognosis.

Fig. 1

Types of arthritis in Still’s patients according to the number of joints involved. Patients with macrophage activation syndrome (MAS) showed significantly different distributions in the number of joints involved by arthritis, when compared to patients without MAS. p values were obtained with the Chi-squared test or the Fisher’s exact test were according to frequency counts and expected frequencies

Fig. 2

Results of multivariate logistic regression analysis. Odds Ratios and 95% confidence interval of variables significantly associated with MAS development; x-axis was represented with logarithmic scale to facilitate graphical description. As noted, patients with a normal platelet count or even more with thrombocytosis have a lower probability to develop MAS; similarly, this probability decreases along with the increase of the age at the time of disease onset, provided as decades of life at the time of disease onset. On the contrary, patients with monoarthritis and hepatomegaly are more prone to develop MAS. The figure represents the outcome of a stepwise multivariate logistic regression analysis. Forty non-MAS patients characterized by an inadequate retrospective data collection (less than 80% of data required) were not considered for regression analysis

Fig. 3

Systemic scores for Still’s disease severity. Patients with macrophage activation syndrome (MAS) reported significantly higher Pouchot et al. score [29] and Rau et al. score [30], compared to the non-MAS group, as represented in A and B, respectively. p values were obtained using the Mann–Whitney test for non-normally distributed continuous data. The lower whiskers correspond to 1.5 times the first quartile; the upper whiskers correspond to 1.5 times the third quartile