What have multicentre registries across the world taught us about the disease features of systemic sclerosis?

2017 ◽  
Vol 2 (3) ◽  
pp. 169-182 ◽  
Author(s):  
Susanna M. Proudman ◽  
Molla Huq ◽  
Wendy Stevens ◽  
Michelle E. Wilson ◽  
Joanne Sahhar ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Manifestations ◽  
Female Gender ◽  
Early Disease ◽  
European League Against Rheumatism ◽  
Prevalent Disease ◽  
Pulmonary Arterial ◽  
Disease Subtypes ◽  
The Impact ◽  
Tendon Friction Rubs

Introduction The aim of this study is to compare the clinical features, mortality and causes of death of systemic sclerosis (SSc) patients in four large multicentre registries. Methods Patients seen at least once in the Australian Scleroderma Cohort Study (ASCS) (n = 1714), the Canadian Scleroderma Research Group (CSRG) (n = 1628), the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) Network (n = 13,996) and the Systemic Sclerosis Cohort in Singapore (SCORE) (n = 500) before August 2016 were included. Clinical manifestations and survival in cohorts and disease subtypes were compared. Results Among 17,838 SSc patients, most were female (86.1%), Caucasian (84.6%) and had the limited cutaneous subtype (lcSSc) (65.0%). The anti-centromere autoantibody was the most prevalent (37.6%). More patients in SCORE had the diffuse subtype (dcSSc) (49.3%) and Scl-70 autoantibody (38.8%) (p<0.001). Patients with dcSSc were more likely to be younger and male (p<0.001) and have shorter disease duration, more calcinosis, tendon friction rubs and synovitis (all p<0.001). Interstitial lung disease (ILD) occurred more frequently in dcSSc but prevalence of pulmonary arterial hypertension (PAH) was similar in both subtypes. More deaths occurred among SCORE patients who had the shortest median survival (p<0.001). The survival of patients with early disease, males and those with dcSSc was shorter than that of patients with prevalent disease, female gender and lcSSc, respectively. SSc-related complications accounted for more than 50% of deaths, with PAH and ILD being the most common. Conclusions This meta-cohort of SSc patients, the largest reported to date, provides insights into the impact of race and sex on disease manifestations and survival and confirms the early mortality in this disease.

scholarly journals Pulmonary hypertension phenotypes in patients with systemic sclerosis

2021 ◽  
Vol 30 (161) ◽  
pp. 210053
Author(s):  
Ashraful Haque ◽  
David G. Kiely ◽  
Gabor Kovacs ◽  
A.A. Roger Thompson ◽  
Robin Condliffe
Keyword(s):  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Left Heart ◽  
Significant Morbidity ◽  
Early Disease ◽  
Pulmonary Haemodynamics ◽  
Pulmonary Arterial

Pulmonary hypertension (PH) commonly affects patients with systemic sclerosis (SSc) and is associated with significant morbidity and increased mortality. PH is a heterogenous condition and several different forms can be associated with SSc, including pulmonary arterial hypertension (PAH) resulting from a pulmonary arterial vasculopathy, PH due to left heart disease and PH due to interstitial lung disease. The incidence of pulmonary veno-occlusive disease is also increased. Accurate and early diagnosis to allow optimal treatment is, therefore, essential. Recent changes to diagnostic haemodynamic criteria at the 6th World Symposium on Pulmonary Hypertension have resulted in therapeutic uncertainty regarding patients with borderline pulmonary haemodynamics. Furthermore, the optimal pulmonary vascular resistance threshold for diagnosing PAH and the role of exercise in identifying early disease require further elucidation. In this article we review the epidemiology, diagnosis, outcomes and treatment of the spectrum of pulmonary vascular phenotypes associated with SSc.

scholarly journals Identifying early pulmonary arterial hypertension biomarkers in systemic sclerosis: Machine learning on proteomics from the DETECT cohort

2020 ◽  
pp. 2002591
Author(s):  
Yasmina Bauer ◽  
Simon de Bernard ◽  
Peter Hickey ◽  
Karri Ballard ◽  
Jeremy Cruz ◽  
...  
Keyword(s):  
Machine Learning ◽  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Early Disease ◽  
Serum Samples ◽  
Neuropilin 1 ◽  
Patients At Risk ◽  
Pulmonary Arterial ◽  
Biomarker Signature

Pulmonary arterial hypertension (PAH) is a devastating complication of Systemic Sclerosis (SSc). Screening for PAH in SSc has increased detection, allowed early treatment for PAH, and improved patient outcomes. Blood-based biomarkers that reliably identify SSc patients at risk of PAH, or with early disease, would significantly improve screening, potentially leading to improved survival, and provide novel mechanistic insights into early disease. The main objective of this study was to identify a proteomic biomarker signature that could discriminate SSc patients with, and without PAH using a Machine Learning approach, and to validate the findings in an external cohort.Serum samples from patients with SSc and PAH (n=77) and SSc without PH (non-PH, n=80) were randomly selected from the clinical DETECT study and underwent proteomic screening using the MYRIAD RBM discovery platform consisting of 313 proteins. Samples from an independent validation cohort (SSc-PAH, n=22 and non-PH, n=22) were obtained from University of Sheffield, UK. Random Forest (RF) analysis identified a novel panel of eight proteins, comprising Collagen IV, Endostatin, IGFBP-2, IGFBP-7, MMP-2, Neuropilin-1, NT-proBNP and RAGE, that discriminated PAH from non-PH in SSc patients in the DETECT discovery cohort (average area under the ROC values (ROC-AUC) of 0.741, 65.1% sensitivity / 69.0% specificity) was reproduced in the Sheffield cohort (81.1% accuracy, 77.3% sensitivity / 86.5% specificity). This novel 8-protein biomarker panel has the potential to improve early detection of PAH in SSc patients and may provide novel insights into the pathogenesis of PAH in the context of SSc.

Haemodynamic phenotypes and survival in patients with systemic sclerosis: the impact of the new definition of pulmonary arterial hypertension

2019 ◽  
Vol 79 (3) ◽  
pp. 370-378 ◽  
Author(s):  
Panagiota Xanthouli ◽  
Suzana Jordan ◽  
Nicklas Milde ◽  
Alberto Marra ◽  
Norbert Blank ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Vascular Disease ◽  
Walking Distance ◽  
Pulmonary Vascular Disease ◽  
Term Survival ◽  
Pulmonary Arterial ◽  
Definition Of ◽  
The Impact

BackgroundIn this study, we investigated the impact of the new haemodynamic definition of pulmonary arterial hypertension (PAH) as proposed by the 6th PH World Symposium on phenotypes and survival in patients with systemic sclerosis (SSc).MethodsIn SSc patients who were prospectively and consecutively screened for PAH including right heart catheterisation in Heidelberg or Zurich, haemodynamic and clinical variables have been reassessed according to the new PAH definition. Patients have been followed for 3.7±3.7 (median 3.4) years; Kaplan-Meier survival analysis was performed. Patients with significant lung or left heart disease were excluded from comparative analyses.ResultsThe final dataset included 284 SSc patients, 146 patients (49.2%) had mean pulmonary arterial pressure (mPAP) ≤20 mm Hg, 19.3% had mPAP 21–24 mm Hg and 29.4% had mPAP ≥25 mm Hg. In the group of mildly elevated mPAP, only four patients (1.4% of the whole SSc cohort) had pulmonary vascular resistance (PVR) values ≥3 Wood Units (WU) and could be reclassified as manifest SSc-APAH. Twenty-eight (9.8%) patients with mPAP of 21–24 mm Hg and PVR ≥2 WU already presented with early pulmonary vascular disease with decreased 6 min walking distance (6MWD) (p<0.001), TAPSE (p=0.004) and pulmonary arterial compliance (p<0.001). A PVR ≥2 WU was associated with reduced long-term survival (p=0.002). PVR and 6MWD were independent prognostic predictors in multivariate analysis.ConclusionThe data of this study show that a PVR threshold ≥3 WU is too high to enable an early diagnosis of PAH. A PVR threshold ≥2 WU was already associated with pulmonary vascular disease, significantly reduced survival and would be more appropriate in SSc patients with mild PAH.

Expert Agreement on EULAR/EUSTAR Recommendations for the Management of Systemic Sclerosis: Table 1.

2011 ◽  
Vol 38 (7) ◽  
pp. 1326-1328 ◽  
Author(s):  
KYLE M. WALKER ◽  
JANET POPE
Keyword(s):  
Systemic Sclerosis ◽  
Research Group ◽  
Response Rate ◽  
Point Scale ◽  
High Agreement ◽  
European League Against Rheumatism ◽  
Pulmonary Arterial ◽  
Esophageal Ulcers ◽  
Level Of Agreement ◽  
European League

Objective.The European League Against Rheumatism/EULAR Scleroderma Trials and Research group (EULAR/EUSTAR) has published recommendations for the management of systemic sclerosis (SSc). Members of the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research Group were surveyed regarding their level of agreement with the recommendations.Methods.A survey containing the 14 EULAR/EUSTAR recommendations asked participants to indicate their level of agreement with each on a 10-point scale, from 0 (not at all) to 9 (completely agree). The survey was sent to 117 people, and 66 replies were received (56% response rate).Results.Exceptions to generally high agreement included the use of iloprost and bosentan for digital vasculopathy, methotrexate for skin involvement, and bosentan and epoprostenol for pulmonary arterial hypertension (PAH; all < 69% agreement, defined as ≥ 7 rating). Vasculopathy and PAH treatment had differences in agreement between North America and Europe (p < 0.006). Respondents who were EULAR/EUSTAR recommendation authors shared a similar level of agreement compared to those who were not, except for the use of proton pump inhibitors for the prevention of SSc-related gastroesophageal reflux disease, esophageal ulcers, and strictures.Conclusion.EULAR/EUSTAR recommendations were relatively well accepted among SSc experts. Overall reduced agreement may be due to the modest efficacy of some agents (such as methotrexate for the skin). Some regional disagreement is likely because of access differences.

scholarly journals HLA Markers for Poor Prognosis in Systemic Sclerosis Brazilian Patients

2013 ◽  
Vol 35 ◽  
pp. 73-78 ◽  
Author(s):  
Ana Paula Toledo Del Rio ◽  
Zoraida Sachetto ◽  
Percival Degrava Sampaio-Barros ◽  
João Francisco Marques-Neto ◽  
Ana Carolina Santos Londe ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Fibrosis ◽  
Arterial Hypertension ◽  
Polymerase Chain Reaction Amplification ◽  
Clinical Manifestations ◽  
Case Series ◽  
Delta Method ◽  
Hla Typing ◽  
Pulmonary Arterial

Objectives. The aim of this study was to evaluate human leukocyte antigen (HLA) involvement in the disease expression and poor prognostic clinical features (pulmonary fibrosis and pulmonary arterial hypertension) in patients diagnosed with systemic sclerosis (SSc) in a multiethnic population.Methods. SSc patients followed up between 2008 and 2011 were included, and clinical data were obtained through records review. Molecular HLA typing was performed (polymerase chain reaction amplification technique using specific primer sequences). The statistical analysis involved Fisher’s exact test and Pearson's corrected chi-square test.P  values≤0.05were considered significant. The delta method was used to estimate the variance of the prevalence ratio (PR).Results. A total of 141 patients (120 women and 21 men) with SSc were studied, including 33.3% with diffuse cutaneous SSc (dcSSc), 62.4% with limited cutaneous SSc (lcSSc), and 4.3% with sine scleroderma. Pulmonary fibrosis was present in 61 patients (43.3%), and the HLA-A*30 and DQB1*04 alleles were related to susceptibility. In contrast, the HLA-DRB1*01 and DQB1*05 alleles were protective. Pulmonary arterial hypertension was diagnosed in 19 patients (13.5%) and was associated with HLA-B*35 and C*04; in contrast, C*03 seemed to be protective.Conclusions. Our current study documents the association of some classes I and II HLA alleles with the most severe clinical manifestations in a multiethnic case series. Our findings differed slightly from the previous data in other populations.

P3676Hemodynamic phenotypes in systemic sclerosis patients screened for pulmonary hypertension (PH): impact of the new definition of PH

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Xanthouli ◽  
N Milde ◽  
A M Marra ◽  
N Benjamin ◽  
C Nagel ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Systemic Sclerosis ◽  
Functional Class ◽  
Walking Distance ◽  
Pulmonary Vascular Disease ◽  
Mean Pulmonary Arterial Pressure ◽  
Right Heart Catheterisation ◽  
Pulmonary Arterial ◽  
Definition Of ◽  
The Impact

Abstract Background Patients with systemic sclerosis (SSc) are at high risk of developing concomitant pulmonary hypertension (PH) which has a crucial impact on the patients' symptoms, quality of life and prognosis. Purpose The aim of this study was to analyse the impact of the new hemodynamic definition of precapillary PH as proposed at the 2018 World Symposium on PH in Nice in patients with SSc. Although recent data suggest that PVR >2 WU could be considered as abnormal in the new definition a conservative cut-off value of PVR ≥3 WU has been used. Methods SSc-patients were screened for PH using clinical assessments as WHO-functional class, 6 minute walking distance and right heart catheterisation. Patients were divided into hemodynamic subgroups according to their mean pulmonary arterial pressure (mPAP) values with mPAP ≤20 mmHg, 21–24 mmHg and ≥25 mmHg. These subgroups were further divided according to their pulmonary vascular resistance (PVR) with PVR <3 WU or ≥3 WU. Results One-hundred-twenty-two patients (79% female, age 57.6±12.7 years, 6MWD 439.5±98.1 meters, 70% diffuse cutaneous SSc, 30% limited cutaneous SSc, 53% WHO-FC II, 25% WHO-FC III) who were prospectively screened for PH were included in the analysis (Figure 1). Among them 26 had a symptomatic manifest PH using the cut-off value of mPAP ≥25 mmHg. Only half of this group presented with PVR ≥3 WU, the others had PVR <3 WU. Eight of these 26 PH-patients presented with PH due to left heart disease. Out of 21 patients with mildly elevated mPAP 21–24 mmHg, two (10%) met the new definition criteria of PH (pulmonary arterial wedge pressure <15 mmHg, mPAP 23 and 24 mmHg, PVR 3.0 and 3.2 WU, CI 2.2 L/min/m2 both, WHO-FC II both, respectively). Out of 75 patients with mPAP <21 mmHg, three presented with PVR ≥3 WU. Overview of systemic sclerosis patients Conclusions The new definition of precapillary pulmonary hypertension may on the one hand allow detecting an additional 10% of PH patients with mild elevated mPAP. On the other hand, eight of 13 patients (62%), who met the former definition of pulmonary arterial hypertension, would be classified as “normal” due to a lack of increase in PVR according to the new definition. The data of this study suggest that for SSc-patients the cut-off value of mPAP >20 mmHg is useful, but the criteria of PVR ≥3 WU may be too strict. Further studies with larger sample sizes will be needed to better characterise these hemodynamic subgroups and to define the extent of pulmonary vascular disease and treatability.

scholarly journals Systemic Sclerosis Patients With Negative Antinuclear Antibodies Have Distinctive Clinical Manifestations: a Multicenter CRDC Cohort in China

2021 ◽  
Author(s):  
Min Hui ◽  
Jiaxin Zhou ◽  
Liyun Zhang ◽  
Xinwang Duan ◽  
Mengtao Li ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Data Center ◽  
Antinuclear Antibodies ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Organ Involvement ◽  
Multicenter Cohort ◽  
Significant Difference ◽  
Critical Organ ◽  
Pulmonary Arterial

Abstract Objective: The presence of circulating antinuclear antibodies (ANAs) is a hallmark of immune dysregulation in patients with systemic sclerosis (SSc). A variety of ANAs are associated with unique sets of disease manifestations and are widely used in clinical practice for diagnosis, clinical subgrouping, and prediction of future organ involvement and prognosis in SSc. This study aimed to investigate the clinical features of SSc patients negative for ANAs in a Chinese Rheumatism Data Center (CRDC) multicenter cohort in China.Methods: Based on the CRDC database, patients were prospectively recruited between April 2008 and June 2019 from 154 clinical centers nationwide, and all cases fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis. Results for antinuclear antibodies were intensively collected. Demographic, clinical, and laboratory data were compared between ANA-positive SSc patients and those negative for ANAs.Results: Antinuclear antibodies were detected in 2129 of 2809 patients enrolled in the study; 4.2% patients were negative. There was a significant difference between patients negative and positive for ANAs based on sex (29/60 vs 294/1746, p＜0.001). The presence of Raynaud’s phenomenon was less common (71.8% vs 91.8%, p＜0.001) in the ANA-negative patients. In addition, the incidence of certain critical organ involvement, including gastroesophageal reflux (5.6% vs 18.5%, p=0.002), interstitial lung disease (65.2% vs 77.9%, p=0.015) and pulmonary arterial hypertension (11.5% vs 29.0%, p=0.006), was significantly lower in ANA-negative patients than in ANA-positive patients. The proportion of abnormal ESR (32.4% vs 47.6%, p=0.013) and IgG elevation (14.3% vs 37.0%, p=0.003), an indicator of disease activity, was significantly lower in ANA-negative patients than in ANA-positive patients.Conclusion: Antinuclear antibodies are strongly associated with the clinical manifestations of systemic sclerosis, with ANA-negative SSc patients tending to exhibit relatively milder disease.

scholarly journals A Unique Presentation of Anti-RNA Polymerase III Positive Systemic Sclerosis Sine Scleroderma

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Cody M. Lee ◽  
Diana Girnita ◽  
Arundhati Sharma ◽  
Surabhi Khanna ◽  
Jean M. Elwing
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Wide Spectrum ◽  
Rna Polymerase Iii ◽  
Clinical Manifestations ◽  
Autoimmune Disorder ◽  
Scleroderma Renal Crisis ◽  
Polymerase Iii ◽  
Digital Ischemia ◽  
Pulmonary Arterial

Systemic sclerosis is a rare autoimmune disorder with a wide spectrum of clinical manifestations and a multitude of autoantibodies that are associated with it. In the past several years, advances in serologic testing have led to research indicating important prognostic and phenotypic associations with certain subsets of autoantibodies. In particular, anti-RNA polymerase III (anti-RNAP III) has been associated with diffuse cutaneous disease, scleroderma renal crisis, a temporal relationship with malignancy, myositis, synovitis, joint contractures, and gastric antral vascular ectasia. However, anti-RNAP III has not been associated with systemic sclerosis sine scleroderma. We describe a patient with an atypical presentation of anti-RNAP III positive systemic sclerosis sine scleroderma who presented without the typical features of anti-RNAP III disease. Instead, she presented with critical digital ischemia, pulmonary arterial hypertension, gastroesophageal reflux disease, interstitial lung disease, and no clinically detectable sclerodactyly.

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