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Objective  Systemic sclerosis ( SS c) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous  SS c (lc SS c) and diffuse cutaneous  SS c (dc SS c) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research ( EUSTAR ) database includes data on a prospective cohort of  SS c patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of  EUSTAR  data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained.    Methods  A total of 11,318 patients were registered in the  EUSTAR  database, and 6,927 were included in the study. Twenty‐four clinical and serologic variables were used for clustering.    Results  Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dc SS c or lc SS c prototypes, but others exhibited unique features, such as a majority of lc SS c patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement.    Conclusion  Our findings suggest that restricting subsets of  SS c patients to only those based on 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 a distinct prognosis.

arthritis and rheumatology

Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis