Objective: Pulmonary hypertension (PH) is a frequent and life‐limiting complication of systemic sclerosis (SSc). However, data on survival rates and their evolution over time, as well as prognostic factors in SSc complicated by PH, are still conflicting. The aim of this study was to conduct a systematic review and meta‐analysis of cohort studies to assess pooled survival and prognostic factors for survival in patients with SSc–associated PH.Methods: For this systematic review and meta‐analysis, we searched the Medline and EMBase databases (January 1960 to January 2012). All cohort studies in which survival and/or prognostic factors for SSc–associated PH were reported were included in the analysis. We calculated the pooled survival rates and analyzed their evolution over time and identified prognostic factors for survival.Results: Twenty‐two studies were included, representing a total of 2,244 patients with SSc–associated PH. The pooled 1‐, 2‐, and 3‐year survival rates were 81% (95% confidence interval [95% CI] 79–84%), 64% (95% CI 59–69%), and 52% (95% CI 47–58%), respectively. Meta‐regression did not reveal a significant change in survival over time, while baseline hemodynamic measures of PH severity were significantly correlated with survival. In patients with SSc complicated by pulmonary arterial hypertension (PAH), age, male sex, diffusing capacity for carbon monoxide (DLCO), pericardial effusion, and the parameters classically associated with the severity of idiopathic PAH, including the 6‐minute walk distance, mean pulmonary artery pressure, cardiac index, and right atrial pressure, were significant prognostic factors. DLCO and pericardial effusion were the only prognostic factors in patients with interstitial lung disease–related PH.Conclusion: Our meta‐analysis revealed a poor pooled 3‐year survival rate of 52% in patients with SSc–associated PH. Baseline hemodynamic measures of PAH severity, but not the period of time during which patients were included in the studies, correlated significantly with survival in patients with SSc–associated PAH. All of the prognostic factors typically observed in idiopathic PAH, including the 6‐minute walk distance and right atrial pressure, were also prognostic factors in SSc–associated PAH.

Pulmonary hypertension (PH) is a frequent and severe complication of systemic sclerosis (SSc). PH in SSc is highly heterogeneous because of the various clinical phenotypes of SSc itself and because the mechanisms of PH can vary from one patient to another. PH in SSc may be due to vasculopathy of the small pulmonary arteries (group 1; pulmonary arterial hypertension), interstitial lung disease (group 3; PH due to lung disease or chronic hypoxia) or myocardial fibrosis leading to left ventricular systolic or diastolic dysfunction (group 2; PH due to chronic left-heart disease). Pulmonary veno-occlusive disease is not uncommon in SSc and may also cause PH in some patients (group 1′). There is a high prevalence of each of these conditions in SSc and, as such, it may be difficult to determine the dominant cause of PH in a particular patient. However, careful phenotyping of PH in SSc is important as the therapy required for each of these underlying conditions is very different. In this review, we will decipher the different phenotypes of SSc-PH.

Objective: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) 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 SSc 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 dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc 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 SSc 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.

Objective: Studies assessing the prevalence of anti–RNA polymerase III (anti–RNAP III) antibodies in systemic sclerosis (SSc) have yielded a wide range of results. The aim of the present study was to describe a new SSc cohort tested for presence of anti–RNAP III and perform a systematic review and meta‐analysis to assess the prevalence of anti–RNAP III in patients worldwide and the potential factors of variability.Methods: Seropositivity for anti–RNAP III was evaluated in a French cohort of SSc patients. A systematic review of the literature was carried out in PubMed and EMBase. Meta‐analysis was performed using available data on prevalence, clinical characteristics of SSc patients, and the types of assays used for anti–RNAP III testing.Results: One hundred thirty‐three French SSc patients were tested for anti–RNAP III, and a prevalence of 6–9% was found in these patients. Thirty studies representing a total population of 8,437 SSc patients were included in the meta‐analysis. Prevalence of anti–RNAP III in this population was highly variable (range 0–41%). The overall pooled prevalence of anti–RNAP III was 11% (95% confidence interval 8–14), but heterogeneity was high among studies (I² = 93%, P < 0.0001). Geographic factors such as continent or country of study origin partially explained this heterogeneity and correlated with the prevalence. No other baseline SSc characteristics were significantly correlated with the prevalence of anti–RNAP III.Conclusion: Data on our new cohort and our meta‐analysis of the literature confirmed that anti–RNAP III prevalence in SSc varies among centers. Geographic factors were significantly associated with prevalence, which underscores the probable implication that genetic background and environmental factors play a role. Heterogeneity among studies remained largely unexplained.