Current management of the gastrointestinal complications of systemic sclerosis

Emmanuel, Anton

doi:10.1038/nrgastro.2016.99

Cited by 67 publications

(86 citation statements)

References 134 publications

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“…There are four layers that form this barrier: mucosa, submucosa, muscularis externa, and serosa (or adventitia) [23,48]. Each one of them has different characteristics and cellular composition depending on their corresponding roles [64,65], as described next.

Mucosa: This is the surface layer of the GI tract and also responsible for mucus secretion.

…”

Section: The Oral Route: Physiology and Immunologymentioning

confidence: 99%

Current state and challenges in developing oral vaccines

Ramirez

Sharpe

Peppas

2017

Advanced Drug Delivery Reviews

312

275

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While vaccination remains the most cost effective strategy for disease prevention, communicable diseases persist as the second leading cause of death worldwide. There is a need to design safe, novel vaccine delivery methods to protect against unaddressed and emerging diseases. Development of vaccines administered orally is preferable to traditional injection-based formulations for numerous reasons including improved safety and compliance, and easier manufacturing and administration. Additionally, the oral route enables stimulation of humoral and cellular immune responses at both systemic and mucosal sites to establish broader and long-lasting protection. However, oral delivery is challenging, requiring formulations to overcome the harsh gastrointestinal (GI) environment and avoid tolerance induction to achieve effective protection. Here we address the rationale for oral vaccines, including key biological and physicochemical considerations for next-generation oral vaccine design.

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Mucosa: This is the surface layer of the GI tract and also responsible for mucus secretion.

…”

Section: The Oral Route: Physiology and Immunologymentioning

confidence: 99%

Current state and challenges in developing oral vaccines

Ramirez

Sharpe

Peppas

2017

Advanced Drug Delivery Reviews

312

275

View full text Add to dashboard Cite

show abstract

“…Diagnosis and management of GIT disease requires a collaborative and multidisciplinary approach . Once a rheumatologist confirms the diagnosis of SSc, the patient should be referred to a gastroenterologist even in the absence of GI symptoms .…”

Section: Resultsmentioning

confidence: 99%

Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis

Kumar

Singh

Rattan

et al. 2017

Aliment Pharmacol Ther

108

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SUMMARY Background Gastrointestinal tract involvement is a common cause of debilitating symptoms in patients with systemic sclerosis. There are no disease modifying therapies for this condition and the treatment remains symptomatic, largely owing to the lack of a clear understanding of its pathogenesis. Aim To investigate novel aspects of the pathogenesis of gastrointestinal involvement in systemic sclerosis To summarize existing knowledge regarding the cardinal clinical gastrointestinal manifestations of systemic sclerosis and its pathogenesis, emphasizing recent investigations that may be valuable in identifying potentially novel therapeutic targets. Methods Electronic (Pubmed/Medline) and manual Google search Results The gastrointestinal tract is the most common internal organ involved in systemic sclerosis. Any part of the gastrointestinal tract from the mouth to the anus can be affected. There is substantial variability in clinical manifestations and disease course and symptoms are non-specific and overlapping for a particular anatomical site. Gastrointestinal involvement can occur in the in the absence of cutaneous disease. Up to 8% of systemic sclerosis patients develop severe gastrointestinal tract symptoms. This subset of patients display increased mortality with only 15% survival at 9 years. Dysmotiity of the gastrointestinal tract causes the majority of symptoms. Recent investigations have identified a novel mechanism in the pathogenesis of gastrointestinal tract dysmotility mediated by functional anti-muscarinic receptor autoantibodies. Conclusion Despite extensive investigation the pathogenesis of gastrointestinal involvement in systemic sclerosis remains elusive. Although treatment currently remains symptomatic, an improved understanding of novel pathogenic mechanisms may allow the development of potentially highly effective approaches including intravenous immunoglobulin and microRNA based therapeutic interventions.

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“…This raises the possibility that motility changes may result from dysfunctions of neurons involved in the enteric nervous system, the vasculature, or elsewhere [19][20][21]. It is also possible that SSc GI damage occurring in such a case is a variation of AGID, considering that the anti-gAChR Abs might mediate autonomic dysfunction, contributing to the autoimmune mechanisms underlying these GI motility disorders [1,2,12,17]. Several reports have shown the occurrence of anti-M3R Abs correlating with GI dysmotility in SSc [32][33][34], as well as the efficacy of intravenous immunoglobulin (IVIg) due to antiidiotypic neutralization [34].…”

Section: Discussionmentioning

confidence: 99%

“…Systemic sclerosis (SSc), a multi-systemic disorder of the connective tissues, is characterized by widespread vascular damage and fibrosis of the skin and visceral organs [13,14] Gastrointestinal (GI) manifestations occur frequently in patients with SSc [15][16][17]. Pseudo-obstruction, malabsorption, gastroesophageal reflux disease (GERD), nausea, vomiting, constipation, and diarrhea are some of the GI complications that can occur in SSc [18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Detecting gastrointestinal manifestations in patients with systemic sclerosis using anti-gAChR antibodies

et al. 2020

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Background: Patients with systemic sclerosis (SSc) complicated by gastrointestinal dysmotility are difficult to treat and have high mortality. To clarify the pathogenesis of gastrointestinal manifestations, we aimed to demonstrate the association among the clinical features of SSc, the serological markers, the autoantibodies against nicotinic acetylcholine receptor at autonomic ganglia (gAChR). Methods: Fifty patients were enrolled and divided into two groups according to the presence or absence of gastrointestinal manifestations, and the characteristics were analyzed between these two groups. We measured biomarkers and the autoantibodies against two gAChRα3 and β4 subunits to test sera samples. Furthermore, patients were classified based on the presence or absence of anti-gAChR autoantibodies, and their clinical features were compared. Results: In patients with SSc and gastrointestinal manifestations, digital ulcers were more frequent (p = 0.050) and VEGF expression was significantly higher (p = 0.038). Seven subjects with SSc were seropositive for α3 subunit, whereas one patient was seropositive for β4 subunit. The mean level of anti-gAChRα3 autoantibodies in SSc patients with gastrointestinal manifestations was significantly higher than that in SSc patients without gastrointestinal manifestations (p = 0.001). The group of patients with SSc and gAChR autoantibodies had significantly higher endostatin levels (p = 0.046).Conclusions: This study is the first to demonstrate that clinical characteristics of SSc patients with seropositivity for gAChR autoantibodies. Patients with SSc have circulating autoantibodies against gAChR, which may contribute to gastrointestinal manifestations associated with this disease, suggesting that gAChR-mediated autonomic neurotransmission may provide a pathomechanism for gastrointestinal dysmotility in SSc.

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Current management of the gastrointestinal complications of systemic sclerosis

Cited by 67 publications

References 134 publications

Current state and challenges in developing oral vaccines

Current state and challenges in developing oral vaccines

Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis

Detecting gastrointestinal manifestations in patients with systemic sclerosis using anti-gAChR antibodies

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