title: Digital ulcers predict a worse disease course in patients with systemic sclerosis.
abstract: OBJECTIVE
  Systemic sclerosis (SSc) is a systemic autoimmune disease with high morbidity and significant mortality. There is a great need of predictors that would allow risk stratification of patients with SSc and ultimately initiation of treatment early enough to ensure optimal clinical results. In this study, we evaluated whether a history of digital ulcers (HDU) at presentation may be a predictor of vascular outcomes and of overall clinical worsening and death in patients with SSc.
  
  
  METHODS
  Patients from the EULAR Scleroderma Trials and Research (EUSTAR) database, satisfying at inclusion the 1980 American College of Rheumatology classification criteria for SSc, who had a follow-up of at least 3 years since baseline or who have died, were included in the analysis. HDU at presentation as a predictor of disease worsening or death was evaluated by Cox proportional hazards regression analysis.
  
  
  RESULTS
  3196 patients matched the inclusion criteria (male sex 13.2%, 33.4% diffuse subset). At presentation, 1092/3196 patients had an HDU (34.1%). In multivariable analysis adjusting for age, gender and all parameters considered potentially significant, HDU was predictive for the presence of active digital ulcers (DUs) at prospective visits (HR (95% CI)): 2.41 (1.91 to 3.03), p<0.001, for an elevated systolic pulmonary arterial pressure on heart ultrasound (US-PAPs):1.36 (1.03 to 1.80), p=0.032, for any cardiovascular event (new DUs, elevated US-PAPs or LV failure): 3.56 (2.26 to 5.62), p<0.001, and for death (1.53 (1.16 to 2.02), p=0.003).
  
  
  CONCLUSIONS
  In patients with SSc, HDU at presentation predicts the occurrence of DUs at follow-up and is associated with cardiovascular worsening and decreased survival.
authors: Department of Internal Medicine and Rheumatology, Cantacuzino Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors: Carina
authors: C
authors: Mihai
authors: Amsterdam Rheumatology Center/University of Amsterdam & Atrium Medical Center, Heerlen, The Netherlands.
authors: Robert
authors: R
authors: Landewé
authors: Leiden University Medical Center, Leiden, The Netherlands.
authors: Désirée
authors: http://orcid.org/0000-0002-5781-158X
authors: D
authors: van der Heijde
authors: Basel University Hospital, Basel, Switzerland.
authors: Ulrich A
authors: UA
authors: Walker
authors: Department of Internal Medicine and Rheumatology, Cantacuzino Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors: Paul I
authors: PI
authors: Constantin
authors: Department of Internal Medicine and Rheumatology, Cantacuzino Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors: Ana Maria
authors: AM
authors: Gherghe
authors: Department of Internal Medicine and Rheumatology, Sf. Maria Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors: Ruxandra
authors: R
authors: Ionescu
authors: Rheumatology Clinic, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors: Simona
authors: S
authors: Rednic
authors: Rheumatology A Department, Paris Descartes University, Cochin Hospital, Paris, France.
authors: Yannick
authors: Y
authors: Allanore
authors: Rheumatology A Department, Paris Descartes University, Cochin Hospital, Paris, France.
authors: Jérôme
authors: J
authors: Avouac
authors: Department of Rheumatology and Immunology, University of Pecs, Pecs, Hungary.
authors: László
authors: L
authors: Czirják
authors: Internal Medicine Department, Claude Huriez Hospital, Lille, France.
authors: Eric
authors: E
authors: Hachulla
authors: Department of Rheumatology, Charité University Hospital, Berlin, Germany.
authors: Gabriela
authors: G
authors: Riemekasten
authors: Cattedra di Reumatologia, Dip. Medicina Clinica e Sperimentale, Policlinico, University of Padova, Padova, Italy.
authors: Franco
authors: F
authors: Cozzi
authors: Spedali Civili di Brescia, Rheumatology and Clinical Immunology Service, Brescia, Italy.
authors: Paolo
authors: P
authors: Airò
authors: University of Genova, Research Laboratory and Academic Clinical Unit of Rheumatology, Genova, Italy.
authors: Maurizio
authors: M
authors: Cutolo
authors: Department of Rheumatology and Clinical Immunology, Giessen University, Bad Nauheim, Germany.
authors: Ulf
authors: U
authors: Mueller-Ladner
authors: Division of Rheumatology AOUC & Department of Experimental and Clinical Medicine, Department of Biomedicine, University of Florence, Florence, Italy.
authors: Marco
authors: M
authors: Matucci-Cerinic
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology*; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D005385:Fingers; D006229:Hand Dermatoses / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D007674:Kidney Diseases / Q000209:etiology; D008171:Lung Diseases / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011653:Pulmonary Diffusing Capacity; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000150:complications / Q000401:mortality / Q000503:physiopathology*; D012883:Skin Ulcer / Q000209:etiology / Q000503:physiopathology*; D013318:Stroke Volume; D014797:Vital Capacity
keywords: Cardiovascular Disease; Epidemiology; Systemic Sclerosis