Adult-onset Still's disease: evaluation of prognostic tools and validation of the systemic score by analysis of 100 cases from three centers

Abstract

Background: Adult-onset Still's disease (AOSD) is rare inflammatory disease of unknown etiology that usually affects young adults. The more common clinical manifestations are spiking fevers, arthritis, evanescent rash, elevated liver enzymes, lymphadenopathy, hepatosplenomegaly, and serositis. The multi-visceral involvement of the disease and the different complications, such as macrophage activation syndrome, may strongly decrease the life expectancy of AOSD patients.

Methods: This study aimed to identify the positive and negative features correlated with the outcome of patients. A retrospective analysis of AOSD patients prospectively admitted to three rheumatologic centers was performed to identify the clinical features present at the time of diagnosis and to predict the possible outcome. Furthermore, we investigated the as yet to be validated prognostic value of the systemic score previously proposed.

Results: One hundred consecutive AOSD patients were enrolled. The mean systemic score showed that the majority of patients had a multi-organ involvement. Sixteen patients showed different complications, mainly the macrophage activation syndrome. A strong increase of inflammatory markers was observed. All patients received steroids at different dosages, 55 patients in association with immunosuppressive drugs and 32 in association with biologic agents. Sixteen patients died during the follow-up. Regression analysis showed that the higher values of the systemic score and the presence of AOSD-related complications, assessed at the time of diagnosis, were significantly correlated with patient mortality. A prognostic impact of the systemic score of ≥ 7.0 was reported.

Conclusions: Our study showed that a higher systemic score and the presence of AOSD-related complications at the time of diagnosis were significantly associated with mortality. Of note, a cut-off at 7.0 of the systemic score showed a strong prognostic impact in identifying patients at risk of AOSD-related death.

Keywords: Adult-onset Still’s disease; Macrophage activation syndrome; Prognostic factor; Systemic score.

Fig. 1

Clinical and laboratory differences among the groups with different clinical outcomes. a Panel shows the values of the systemic score, at the time of diagnosis, among the different groups according the clinical outcome, the highest values are observed in the AOSD-related death group. b and c Panels show the serum levels of C-reactive protein and ferritin, at the time of diagnosis; these levels are statistically higher in AOSD-related death group when compared with the other groups. Values are expressed as mean ± SD (*P < 0.05; **P < 0.001; ***P < 0.0001).

Fig. 2

Kaplan–Meier estimates of survival according to systemic score. a The panel shows the ROC analysis validation for the systemic score. It was performed with an overall performance of the test in terms of the area under the ROC curve (AUC = 0.80 ± 0.06, 95% CI, 0.68–0.91). The sensitivity and specificity were estimated according the Youden criteria, obtaining a systemic score cut-off of 7.0 (sensitivity: 75.00%; specificity: 67.86%). b The panel shows the prognostic impact of systemic score ≥ 7.0. The Kaplan–Meier analysis showed a significant association between a systemic score ≥ 7.0 and mortality (P = 0.0005)