Bosentan for the treatment of systemic sclerosis-associated pulmonary arterial hypertension, pulmonary fibrosis and digital ulcers

2006 ◽  
Vol 7 (11) ◽  
pp. 1487-1501 ◽  
Author(s):  
Manu Jain ◽  
John Varga
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Fibrosis ◽  
Arterial Hypertension ◽  
Digital Ulcers ◽  
Pulmonary Arterial

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.

Characteristics of patients with systemic sclerosis suffering from a lower limb amputation: Results of a French collaborative study

2020 ◽  
Vol 5 (3) ◽  
pp. 224-230
Author(s):  
Julien Bertolino ◽  
Elisabeth Jouve ◽  
Sophie Skopinski ◽  
Christian Agard ◽  
Aurélie Achille ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Lower Limb ◽  
Lower Limb Amputation ◽  
Limb Amputation ◽  
Digital Ulcers ◽  
Multicentric Study ◽  
Limb Segment ◽  
Pulmonary Arterial

Objective: Systemic sclerosis mainly affects the microvascular network. However, macrovascular manifestations have been reported. We aimed to investigate the characteristics of systemic sclerosis patients with an amputation of a lower limb segment. Methods: We designed a retrospective, case–control, multicentric study on systemic sclerosis patients with amputation of a lower limb segment secondary to critical ischemia via the French Research Group on Systemic Sclerosis. For each case, a control (systemic sclerosis patient without lower limb symptom) was matched with sex, age (±5 years), and cutaneous subset of systemic sclerosis. Results: In total, 26 systemic sclerosis patients (mean age of 67.2 ± 10.9 years, 20 females, 21 limited cutaneous forms) with a lower limb amputation and 26 matched controls (mean age of 67.3 ± 11.2 years, 20 females, 22 limited cutaneous forms) were included. At the time of amputation, the mean disease duration was 12.8 (±8.6) years. In comparison to controls, systemic sclerosis patients with amputation had more digital ulcers (p = 0.048), history of digital ulcers (p = 0.026), and a higher prevalence of pulmonary arterial hypertension (p = 0.024). Systemic sclerosis patients with amputation were more often smokers (p = 0.008) and under corticosteroids (p = 0.015). In the multivariate model, pulmonary arterial hypertension, smoking status, and corticosteroids were independent markers associated with lower limb amputation in systemic sclerosis. In the follow-up, 10 patients (38.5%) had recurrent ischemia requiring a new limb amputation, and five patients (19.2%) had an amputation of the contralateral limb. Conclusion: This study identifies some markers associated with lower limb amputation in systemic sclerosis such as digital ulcers and pulmonary arterial hypertension and points out the high risk associated with tobacco consumption and corticosteroid use.

scholarly journals AB0564 HEART VALVULAR ALTERATIONS IN A MULTICENTRE ITALIAN COHORT OF SSC PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1579.2-1579
Author(s):  
M. Colaci ◽  
C. Schinocca ◽  
Y. Dal Bosco ◽  
M. L. Aprile ◽  
G. Guggino ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Aortic Valve ◽  
Arterial Hypertension ◽  
Disease Duration ◽  
Digital Ulcers ◽  
Flow Profile ◽  
Calcific Aortic Valve Disease ◽  
Valve Insufficiency ◽  
Pulmonary Arterial

Background:systemic sclerosis (SSc) in a chronic autoimmune disease characterized by endothelial dysfunction, diffuse microangiopathy, and fibrosis of skin and visceral organs. Typical cardiac involvement may includes microvascular ischemia, contraction band necrosis, and patchy fibrosis, leading mainly to arrythmias and conduction defects, diastolic dysfunction, or right ventricular failure (secondary to pulmonary arterial hypertension) [1]. Valvular diseases are poorly described and generally not considered a typical sign of SSc [2-4].Objectives:we aimed to describe valvular alterations in a multicentre cohort of SSc patients.Methods:we consecutively recruited 118 SSc patients (M/F: 14/104, mean age 56.7±12.4 years, median disease duration 10 years, limited/diffuse skin subsets: 95/23, anti-centromere/anti-Scl70/others autoantibodies: 35/37/46) in 3 Rheumatology Centres in Sicily, Italy, from January to December 2019.Considering the cardiovascular risk factors, 40 (34%) patients were smokers, 7 (6%) diabetics, 12 (10%) showed hypercholesterolemia, 38 (32%) arterial hypertension, while none was obese. Transthoracic echocardiogram was carried out in all patients during their follow-up.Results:valvular abnormalities were as follow: mitral valve: insufficiency 85 (72%) cases - mild in 77/85, stenosis 2 (2%) - mild in 25/28, sclerosis/tickening 36 (30%), and calcification 9 (8%) patients; aortic valve: insufficiency 28 (24%), stenosis 4 (3%), sclerosis 29 (25%), and calcification 7 (6%) patients; tricuspid valve: insufficiency 91 (77%) cases, no cases of stenosis, sclerosis 5 (4%), and calcification 1 (1%) patients; pulmonary valve: insufficiency in 13 (11%) patients.As expected, tricuspid insufficiency (TI) was associated with pulmonary arterial hypertension (PAH) (moderate TI in 20% of patients with every TI and PAH vs. 4% of patients with TI without PAH, p=0.019).Aortic sclerosis (AS) was associated with the presence of arthritis (AS in 35% of patients with arthritis vs. 16% of patients without, p=0.029).No association was found with age, gender, disease duration, skin subset, autoantibodies, capillaroscopic patterns, presence of digital ulcers, lung, renal, or digestive involvements.Conclusion:in this multicentre SSc cohort study, we found that cardiac valve alterations are very common, even though generally not clinically relevant. The presence of PAH was associated with more severe TI. Finally, AS was associated with arthritis that could be considered sign of chronic inflammatory state, which is often linked with accelerated atherosclerosis and remodeling process of aortic valve [5].References:[1]Lambova S. Cardiac manifestations in systemic sclerosis. World J Cardiol 2014; 6:993-1005.[2]D’Angelo W, Fries JF, Masi AT, Shulman LE. Pathologic observations in systemic sclerosis (scleroderma).A study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med 1969; 46:428-440.[3]Kazzam E, Caidahl K, Hallgren R, et al. Mitral regurgitation and diastolic flow profile in systemic sclerosis. Int J Cardiol 1990; 29:357-363[4]Wranicz J, Zielińska M, Cygankiewicz I, et al. Early cardiovascular involvement in patients with systemic sclerosis (SSc). Med Sci Monit. 2002; 8:CR78-82.[5]Coté N, Mahmut A, Bosse Y, et al. Inflammation is associated with remodeling of calcific aortic valve disease. Inflammation 2013; 36:573-581.Disclosure of Interests:Michele Colaci: None declared, Claudia Schinocca: None declared, Ylenia Dal Bosco: None declared, Maria Letizia Aprile: None declared, Giuliana Guggino Grant/research support from: Pfizer, Celgene, Speakers bureau: Celgene, Sandoz, Pfizer, Ilenia De Andres: None declared, Alessandra Azzurra Russo: None declared, Domenico Sambataro: None declared, Gianluca Sambataro: None declared, Lorenzo Malatino: None declared

scholarly journals A Novel Multi-network Approach Reveals Tissue-specific Cellular Modulators of Fibrosis in Systemic Sclerosis, Pulmonary Fibrosis and Pulmonary Arterial Hypertension

2016 ◽  
Author(s):  
Jaclyn N Taroni ◽  
Casey S Greene ◽  
Viktor Martyanov ◽  
Tammara A Wood ◽  
Romy Christmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Fibrosis ◽  
Arterial Hypertension ◽  
Gene Expression Signature ◽  
Alternative Activation ◽  
Tissue Specific ◽  
Expression Signature ◽  
Pulmonary Arterial

We have used integrative genomics to determine if a common molecular mechanism underlies different clinical manifestations in systemic sclerosis (SSc), and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension (PAH). We identified a common pathogenic gene expression signature - an immune-fibrotic axis-indicative of pro-fibrotic macrophages in multiple affected tissues (skin, lung, esophagus and PBMCs) of SSc, PF, and PAH. We used this disease-associated signature to query tissue-specific functional genomic networks. This allowed us to identify common and tissue-specific pathology of SSc and related conditions. We rigorously contrasted the lung- and skin-specific gene-gene interaction networks to identify a distinct lung resident macrophage signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct macrophages alternative activation transcriptional programs in SSc-PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. Our results suggest that the innate immune system is central to SSc disease processes, but that subtle distinctions exist between tissues. Our approach provides a framework for examining molecular signatures of disease in fibrosis and autoimmune diseases and for leveraging publicly available data to understand common and tissue-specific disease processes in complex human diseases.

Sign in / Sign up

Export Citation Format

Share Document