Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort

Ann Rheum Dis. 2019 May;78(5):648-656. doi: 10.1136/annrheumdis-2018-213455. Epub 2019 Mar 9.


Objectives: To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc).

Methods: We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression.

Results: Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09).

Conclusions: Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice.

Keywords: all-cause death; diffuse cutaneous systemic sclerosis; lung function decline; progressive skin fibrosis; visceral organ progression.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Databases, Factual
  • Disease Progression
  • Europe
  • Female
  • Fibrosis
  • Humans
  • Kaplan-Meier Estimate
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Scleroderma, Diffuse / complications
  • Scleroderma, Diffuse / mortality*
  • Scleroderma, Diffuse / pathology*
  • Severity of Illness Index
  • Skin / pathology*
  • Skin Diseases / etiology
  • Skin Diseases / mortality*
  • Skin Diseases / physiopathology*
  • Survival Analysis
  • Time Factors