The Pathogenesis of Systemic Sclerosis

Stern, Edward P.; Denton, Christopher P.

doi:10.1016/j.rdc.2015.04.002

Cited by 109 publications

(89 citation statements)

References 93 publications

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“…Severe functional and structural fibroproliferative abnormalities in the microvasculature; and 3. Humoral and cellular immunologic abnormalities characterized by innate immunity alterations, involvement of macrophages and T-and B-lymphocytes, and the production of numerous disease-specific autoantibodies [1–5]. However, it has not been established which of these processes is of primary importance or how they are temporally related during the development and progression of SSc.…”

Section: Pathophysiologymentioning

confidence: 99%

“…Systemic sclerosis (SSc) is a systemic idiopathic autoimmune disease characterized by exaggerated extracellular matrix deposition in skin and various internal organs, severe fibro-proliferative vasculopathy and cellular and humoral immune response abnormalities [1–5]. These three pathogenic processes occur with variable severity in each particular SSc patient resulting in a highly heterogeneous clinical presentation that reflects SSc complex pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of rapidly progressive systemic sclerosis: current and futures perspectives

Mendoza

Mansoor

Jimenez

2015

Expert Opinion on Orphan Drugs

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Introduction Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by severe and often progressive cutaneous, pulmonary, cardiac and gastrointestinal tract fibrosis, cellular and humoral immunologic alterations, and pronounced fibroproliferative vasculopathy. There is no effective SSc disease modifying therapy. Patients with rapidly progressive SSc have poor prognosis with frequent disability and very high mortality. Areas Covered This paper reviews currently available therapeutic approaches for rapidly progressive SSc and discuss novel drugs under study for SSc disease modification. Expert Opinion The extent, severity, and rate of progression of SSc skin and internal organ involvement determines the optimal therapeutic interventions for SSc. Cyclophosphamide for progressive SSc-associated interstitial lung disease and mycophenolate for rapidly progressive cutaneous involvement have shown effectiveness. Methotrexate has been used for less severe skin progression and for patients unable to tolerate mycophenolate. Rituximab was shown to induce improvement in SSc-cutaneous and lung involvement. Autologous bone marrow transplantation is reserved for selected cases in whom poor survival risk outweighs the high mortality rate of the procedure. Novel agents capable of modulating fibrotic and inflammatory pathways involved in SSc pathogenesis, including tocilizumab, pirfenidone, tyrosine kinase inhibitors, lipid lysophosphatidic acid 1, and NOX4 inhibitors are currently under development for the treatment of rapidly progressive SSc.

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Section: Pathophysiologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Treatment of rapidly progressive systemic sclerosis: current and futures perspectives

Mendoza

Mansoor

Jimenez

2015

Expert Opinion on Orphan Drugs

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“…Although numerous studies have examined the pathogenesis of SSc the exact mechanisms involved are not well understood and have remained elusive [4–7]. However, it has been recognized that the most serious clinical manifestations of the disease and its high mortality are the result of SSc-associated-interstitial lung disease (ILD) or pulmonary arterial hypertension (PAH).…”

Section: Introductionmentioning

confidence: 99%

Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of Systemic Sclerosis-associated pulmonary fibrosis and pulmonary arterial hypertension. Myth or reality?

Jimenez

Piera-Velázquez

2016

Matrix Biology

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Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and multiple internal organs and severe functional and structural microvascular alterations. SSc is considered to be the prototypic systemic fibrotic disorder. Despite currently available therapeutic approaches SSc has a high mortality rate owing to the development of SSc-associated interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), complications that have emerged as the most frequent causes of disability and mortality in SSc. The pathogenesis of the fibrotic process in SSc is complex and despite extensive investigation the exact mechanisms have remained elusive. Myofibroblasts are the cells ultimately responsible for tissue fibrosis and fibroproliferative vasculopathy in SSc. Tissue myofibroblasts in SSc originate from several sources including expansion of quiescent tissue fibroblasts and tissue accumulation of CD34+ fibrocytes. Besides these sources, myofibroblasts in SSc may result from the phenotypic conversion of endothelial cells into activated myofibroblasts, a process known as endothelial to mesenchymal transition (EndoMT). Recently, it has been postulated that EndoMT may play a role in the development of SSc-associated ILD and PAH. However, although several studies have described the occurrence of EndoMT in experimentally induced cardiac, renal, and pulmonary fibrosis and in several human disorders, the contribution of EndoMT to SSc-associated ILD and PAH has not been generally accepted. Here, the experimental evidence supporting the concept that EndoMT plays a role in the pathogenesis of SSc-associated ILD and PAH will be reviewed.

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“…The etiopathogenesis of the disease is not yet fully understood. However, vinyl chloride, organic solvents, benzene, and silica powders have been shown to be associated with the disease [2]. Silicosis is an incurable disease characterized by an irreversible and progressive fibrotic reaction in the lung tissue due to silica crystals of respirable size.…”

Section: Introductionmentioning

confidence: 99%

A Rare Clinical Condition: Erasmus Syndrome

Ugan¹,

Doğru²,

Şahin³

et al. 2016

Ann Clin Anal Med

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ÖzetSistemik Skleroz (SS), cildin ve iç organların fibrozisi ile giden, sebebi tam olarak aydınlatılamayan sistemik otoimmün bir hastalıktır. Hastalığın çevresel faktörler-le ilişkisi olduğu bilinmektedir. Özellikle silica tozlarıyla maruziyetin bir takım immun reaksiyonların tetiklenmesiyle hastalığın patogenezinde rol aldığı düşünül-mektedir. Silikozis ve SS birlikteliği Erasmus Sendromu (ES) olarak tanımlanmak-tadır. Burada 6 yıldır silikozis nedeniyle takipli, kotlama işçisi olarak çalışan 30 yaşında sistemik sklerozlu bir olgu sunulmaktadır. Anahtar KelimelerSilikozis; Sistemik Skleroz; Erasmus Sendromu Abstract Systemic sclerosis (SS) is a systemic autoimmune disease progressing with fibrosis of the skin and internal organs, the cause of which cannot be precisely explained. The disease is known to be associated with environmental factors. In particular, exposure to silica powders is believed to have a part in the pathogenesis of the disease by the triggering of a number of immune reactions. Silicosis and SS association is defined as Erasmus Syndrome (ES). Here, we report on a 30-year-old patient working in denim sandblasting who developed SS while being followed for 6 years due to silicosis.

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The Pathogenesis of Systemic Sclerosis

Cited by 109 publications

References 93 publications

Treatment of rapidly progressive systemic sclerosis: current and futures perspectives

Treatment of rapidly progressive systemic sclerosis: current and futures perspectives

Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of Systemic Sclerosis-associated pulmonary fibrosis and pulmonary arterial hypertension. Myth or reality?

A Rare Clinical Condition: Erasmus Syndrome

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