Cox multivariable regression analysis of risk factors for the time to incident FVC<80% of predicted, PAPsys>40 mmHg, any cardiac dysfunction, diastolic dysfunction, conduction block, pericardial effusion and renal crisis.

<p>ACA, anti-centromere autoantibodies; Anti-RNAP-III, anti-RNA-polymerase-III autoantibodies; Anti-TOPO, anti-topoisomerase-I autoantibodies; cardiac involvement, defined as either the presence of diastolic dysfunction, conduction blocks, left ventricular ejection fraction (LVEF)<50%, or pericardial effusion; CI, confidence interval; FVC, forced vital capacity; HR, hazard ratio; PAPsys, systolic pulmonary artery pressure as estimated by echocardiography; RP, Raynaud's phenomenon.</p

Flow chart of patients included and excluded in the analysis.

<p>Flow chart of patients included and excluded in the analysis.</p

Kaplan-Meier curves of incident cardiac manifestations after RP onset in SSc in the study population.

<p>RP, Raynaud’s phenomenon; Pts, patients; LVEF, left ventricular ejection fraction; hash marks represent censored observations.</p

Definitions of study outcomes.

<p>Definitions of study outcomes.</p

Kaplan-Meier curves of incident organ involvement in SSc patients of the study population after RP onset.

<p>RP, Raynaud’s phenomenon; Pts, patients; DLCO, single breath diffusing capacity for monoxide; GI symptoms, gastrointestinal symptoms, defined as a history of either dysphagia, reflux, early satiety, vomiting, diarrhoea, bloating or constipation; Skin involvement, defined as a modified Rodnan skin score of ≥2 at any part of the body; Cardiac involvement, defined as either the presence of diastolic dysfunction, conduction blocks, a left ventricular ejection fraction (LVEF) < 50%, or a pericardial effusion; FVC, forced vital capacity; PAPsys, systolic pulmonary artery pressure as estimated by echocardiography.</p

Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis: a 10-year longitudinal study from the EUSTAR database

Objectives: To longitudinally map the onset and identify risk factors for skin sclerosis and digital ulcers (DUs) in patients with systemic sclerosis (SSc) from an early time point after the onset of Raynaud's phenomenon (RP) in the European Scleroderma Trials and Research (EUSTAR) cohort. Methods: 695 patients with SSc with a baseline visit within 1 year after RP onset were followed in the prospective multinational EUSTAR database. During the 10-year observation period, cumulative probabilities of cutaneous lesions were assessed with the Kaplan–Meier method. Cox proportional hazards regression analysis was used to evaluate risk factors. Results: The median modified Rodnan skin score (mRSS) peaked 1 year after RP onset, and was 15 points. The 1-year probability to develop an mRSS ≥2 in at least one area of the arms and legs was 69% and 25%, respectively. Twenty-five per cent of patients developed diffuse cutaneous involvement in the first year after RP onset. This probability increased to 36% during the subsequent 2 years. Only 6% of patients developed diffuse cutaneous SSc thereafter. The probability to develop DUs increased to a maximum of 70% at the end of the 10-year observation. The main factors associated with diffuse cutaneous SSc were the presence of anti-RNA polymerase III autoantibodies, followed by antitopoisomerase autoantibodies and male sex. The main factor associated with incident DUs was the presence of antitopoisomerase autoantibodies. Conclusion: Early after RP onset, cutaneous manifestations exhibit rapid kinetics in SSc. This should be accounted for in clinical trials aiming to prevent skin worsening