Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary manifestations (original) (raw)
Related papers
Systemic Sclerosis-associated Pulmonary Arterial Hypertension
American Journal of Respiratory and Critical Care Medicine, 2010
Pulmonary arterial hypertension (PAH) is a devastating vascular complication of a number of connective tissue diseases, including systemic sclerosis (SSc), where it has a dramatic impact on the clinical course and overall survival and is the single most common cause of death in patients afflicted with this syndrome. Although remarkable advances have been achieved in elucidating the pathogenesis of PAH over the past 2 decades, leading to the development of diseasetargeted therapies for the idiopathic form of this condition (IPAH), the response to therapy is suboptimal in SSc-related PAH (SSc-PAH), and survival remains very poor. Factors accounting for striking clinical and prognostic differences between these two syndromes are unclear but may include a more pronounced autoimmune, cellular, and inflammatory response, and a higher prevalence of comorbidities in SSc-PAH, including cardiac and pulmonary venous and parenchymal involvement. Furthermore, currently available markers of disease severity and clinical tools to assess response to therapy, which may be reliable in IPAH, are either limited or lacking in SSc-PAH. Thus, a more focused approach, including a better understanding of the pathogenesis and genetic factors underlying the development of SSc-PAH, a search for more specific and reliable tools to adequately assess functional impairment and monitor therapy, as well as the design of novel targeted therapies, are all urgently required to alter the dismal course of this syndrome.
Arthritis Care & Research, 2014
Methods. The Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma registry is a prospective registry of SSc patients at high risk for PAH or with definite pulmonary hypertension diagnosed by right-sided heart catheterization within 6 months of enrollment. Only patients with World Health Organization group I PAH (mean pulmonary artery pressure >25 mm Hg and pulmonary capillary wedge pressure <15 mm Hg without significant interstitial lung disease) were included in these analyses. Results. In total, 131 SSc patients with incident PAH were followed for a mean ؎ SD of 2.0 ؎ 1.4 years. The 1-, 2-, and 3-year cumulative survival rates were 93%, 88%, and 75%, respectively. On multivariate analysis, age >60 years (hazard ratio [HR] 3.0, 95% confidence interval [95% CI] 1.1-8.4), male sex (HR 3.9, 95% CI 1.1-13.9), functional class (FC) IV status (HR 6.5, 95% CI 1.8 -22.8), and diffusing capacity for carbon monoxide (DLCO) <39% predicted (HR 4.2, 95% CI 1.3-13.8) were significant predictors of mortality. Conclusion. This is the largest study describing survival in patients with incident SSc-associated PAH followed up at multiple SSc centers in the US who had undergone routine screening for PAH. The survival rates were better than those reported in other recently described SSc-associated PAH cohorts. Severely reduced DLCO and FC IV status at the time of PAH diagnosis portended a poor prognosis in these patients. Dr. Chung has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromGileadandActelionandresearchsupportfromGilead,UnitedTherapeutics,andPfizer.Dr.Bolsterhasservedasanexpertwitnessontherelationshipbetweenpulmonaryarterialhypertensionandunderlyingautoimmunediseases.Dr.Fischerhasreceivedconsultingfees,speakingfees,and/orhonoraria(morethan10,000 each) from Gilead and Actelion and research support from Gilead, United Therapeutics, and Pfizer. Dr. Bolster has served as an expert witness on the relationship between pulmonary arterial hypertension and underlying autoimmune diseases. Dr. Fischer has received consulting fees, speaking fees, and/or honoraria (more than 10,000each)fromGileadandActelionandresearchsupportfromGilead,UnitedTherapeutics,andPfizer.Dr.Bolsterhasservedasanexpertwitnessontherelationshipbetweenpulmonaryarterialhypertensionandunderlyingautoimmunediseases.Dr.Fischerhasreceivedconsultingfees,speakingfees,and/orhonoraria(morethan10,000 each) from Gilead and Actelion. Dr. Furst has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromGileadandActelion.Dr.Gomberg−Maitlandhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000 each) from Gilead and Actelion. Dr. Gomberg-Maitland has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromGileadandActelion.Dr.Gomberg−Maitlandhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000 each) and research grants from Actelion, Gilead, Glaxo-SmithKline, Medtronic, Novartis, and United Therapeutics. Dr. Khanna has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromActelion,Gilead,Genentech,Bristol−MyersSquibb,Bayer,Roche,Digna,andUnitedTherapeuticsandhasreceivedresearchfundingfromActelion,thePulmonaryHypertensionAssociation,theSclerodermaFoundation,andUnitedTherapeutics.Dr.Molitorhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000 each) from Actelion, Gilead, Genentech, Bristol-Myers Squibb, Bayer, Roche, Digna, and United Therapeutics and has received research funding from Actelion, the Pulmonary Hypertension Association, the Scleroderma Foundation, and United Therapeutics. Dr. Molitor has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromActelion,Gilead,Genentech,Bristol−MyersSquibb,Bayer,Roche,Digna,andUnitedTherapeuticsandhasreceivedresearchfundingfromActelion,thePulmonaryHypertensionAssociation,theSclerodermaFoundation,andUnitedTherapeutics.Dr.Molitorhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000) from Actelion. Dr. Preston has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromActelion,Bayer,Gilead,Novartis,andUnitedTherapeuticsandresearchgrantsfromActelion,Aires,Gilead,Novartis,andUnitedTherapeutics.Dr.Schiopuhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000 each) from Actelion, Bayer, Gilead, Novartis, and United Therapeutics and research grants from Actelion, Aires, Gilead, Novartis, and United Therapeutics. Dr. Schiopu has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromActelion,Bayer,Gilead,Novartis,andUnitedTherapeuticsandresearchgrantsfromActelion,Aires,Gilead,Novartis,andUnitedTherapeutics.Dr.Schiopuhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000) from United Therapeutics. Dr. Simms has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromActelionandGileadandhasreceivedresearchsupportfromGilead,Actelion,andUnitedTherapeutics.Dr.Steenhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000 each) from Actelion and Gilead and has received research support from Gilead, Actelion, and United Therapeutics. Dr. Steen has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromActelionandGileadandhasreceivedresearchsupportfromGilead,Actelion,andUnitedTherapeutics.Dr.Steenhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000 each) from Actelion, Gilead, and United Therapeutics and has received research support from Actelion, Gilead, Pfizer, and United Therapeutics.
Rheumatology : Current Research, 2012
Study background: Insufficient or absent angiogenesis are hallmarks of scleroderma (SSc). Microvascular change is an early manifestation of SSc followed by intimal proliferation and fibrosis of arterioles resulting in reduced blood flow and tissue ischemia. This ongoing vasculopathy in the lungs presents clinically as pulmonary hypertension and characteristically precedes lung fibrosis in patients.
Evaluation and management approaches for scleroderma lung disease
Therapeutic Advances in Respiratory Disease, 2017
Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are leading causes of morbidity and mortality in systemic sclerosis (SSc). As symptoms are often under-reported in SSc, early screening of ILD and PAH is of paramount importance, and early treatment may be associated with better clinical outcomes. Serologies are particularly helpful in identifying patients at risk for pulmonary involvement. Pulmonary function testing, high-resolution computed tomography of the chest and echocardiography are important tools in the initial screening of these patients. Extensive research has also led to an improved understanding of the mediators involved in the pathogenesis of ILD and PAH. As a result, there have been significant advances in the development of novel targeted therapeutics and an increase in the number of early-phase clinical trials in SSc.
Lung involvement in systemic sclerosis
La Presse Médicale, 2011
Scl eroderma or systemic sclerosis (SSc) is a heterogeneous disorder characterized by endothelial dysfunction, dysregulation of fibroblasts resulting in excessive production of collagen, and profound abnormalities of the immune system [1]. These changes cause progressive fibrosis of the skin and internal organs, system failure and death. While the etiology of SSc is generally unknown, genetic and environmental factors are thought to contribute to host susceptibility [2]. SSc, whether presenting in the limited or diffuse form, is a systemic disease with the potential for multiple organ system involvement including the gastrointestinal, cardiac, renal, and pulmonary systems [3]. Pulmonary manifestations of SSc include, but are not limited to, pulmonary vascular diseases such as pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease
Diagnosis and management of pulmonary hypertension in systemic sclerosis
Current rheumatology reports, 2010
Patients with systemic sclerosis (SSc) can develop pulmonary hypertension (PH; mean pulmonary artery pressure ≥ 25 mm Hg) caused by pulmonary arterial hypertension (PAH), left ventricular disease, or pulmonary fibrosis. PAH is a pulmonary vascular disease, the diagnosis of which requires pulmonary capillary wedge pressure less than 15 mm Hg, pulmonary vascular resistance greater than 3 Wood Units, and exclusion of thromboembolism and parenchymal lung disease. Molecular mechanisms underlying PAH-SSc include activation of inflammatory and fibrogenic pathways in the vasculature and right ventricle. Circulating autoantibodies trigger endothelial damage and