Joint and Tendon Involvement Predict Severe Disease Progression in Systemic Sclerosis: A Prospective Study

Background/Purpose: Joint involvement is frequent and strongly contributes to impaired quality of life in systemic sclerosis (SSc). In a previous cross-sectional study, synovitis and tendon friction rubs (TFRs) were associated with systemic inflammation and disease activity. Therefore, the aim of the present study was to determine whether joint synovitis and TFRs can predict the progression of SSc over time. Methods: We included patients from the EUSTAR database (MEDS online) with early disease duration (first non Raynaud’s symptom equal or less than 3 years) and with a follow-up of at least two years. We extracted data regarding the presence or not of synovitis and TFRs and data related to disease progression. Skin progression was defined by a 30% worsening of the modified Rodnan skin score (mRSS). Lung progression was defined by the new onset of pulmonary fibrosis on high resolution CT scan, or the deterioration of lung volume (10% of forced vital capacity, FVC). Cardiovascular worsening was defined for skin by new ischemic digital ulcers (DU), for lung by pre-capillary pulmonary arterial hypertension (PAH) on right heart catheterization, and for heart by the reduction of the left ventricular ejection fraction below 50% on echocardiography. Renal progression was defined by the occurrence of scleroderma renal crisis. Overall disease progression was defined according to the occurrence of at least one organ progression. Results: From the 9165 patients included in the database, 1301 patients (1079 females) met our inclusion criteria (mean SD age of 5515 years, mean SD follow-up: 4.52.2 years). During the follow-up period, 579 patients (45%) experienced skin and/or lung and/or cardiovascular progression with a mean time to development of 3.21.9 years. Joint synovitis (Hazard Ratio, HR: 1.26, 95% confidence interval, CI, 1.01–1.59) and TFRs (HR: 1.32, 95%CI 1.03–1.70) were both independently predictive of overall disease progression, as were also the diffuse cutaneous subset (HR: 1.30, 95%CI 1.05–1.61) and positive antitopoisomerase-I antibodies (HR: 1.25, 95%CI 1.02–1.53). The mean change of mRSS over the follow-up period was 9.44.11, and 99/123 patients (80%) had a progression of at least 5 points. Joint synovitis (HR: 1.63, 95%CI 1.05–2.55) and TFRs (HR: 1.67, 95%CI 1.01–2.75) were independently predictive of skin progression. Joint synovitis was predictive of the occurrence of new digital ulcer(s) (HR: 1.45, 95%CI 1.08–1.96) and decreased left ventricular ejection fraction (HR: 2.20, 95%CI 1.06–4.57); TFRs were confirmed to be an independent predictor of scleroderma renal crisis (HR: 2.33, 95% CI 1.03–6.19). Conclusion: This first report of the prospective follow-up of EUSTAR patients identified for the first time the merit of baseline synovitis and extended previous data for tendon friction rubs in early SSc patients. These results obtained through the largest worldwide database support the use of these easily detected clinical findings for the risk stratification of SSc patients. These parameters might be used in the future to select high-risk patients, guide therapies and might be regarded as potential surrogate markers for severity. Disc