Systemic sclerosis (SSc) is a heterogeneous connective tissue disease. The usual subclassification divides patients into limited (lc) and diffuse cutaneous (dc) subsets relying on the skin extension but may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database is a prospective cohort providing data from 137 European referral centers. We performed a cluster analysis to distinguish and characterize homogeneous phenotypes without any a priori, and examined survival among the obtained clusters.
A total of 11,318 patients were registered in the EUSTAR database of whom 6,927 patients were included in the study. Twenty-four variables including clinical and serological variables were used for clusterisation.
Clustering analyses provided a first delineation of 2 clusters showing a moderate stability. We further characterized 6 homogeneous groups in an exploratory attempt which differed regarding their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but other exhibited unique features like a majority of lcSSc with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival beyond the cutaneous involvement.
Our work suggests that restricting the subsets of SSc patients only to the cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with distinct prognosis. This article is protected by copyright. All rights reserved.