Systemic sclerosis gastrointestinal dysmotility: risk factors, pathophysiology, diagnosis and management

Khanna, Dinesh; Kulkarni, Subhash; Chen, Joan; Chen, Jiande Z; Xavier, Ramnik J.; Pasricha, P. J.; Khanna, Dinesh

doi:10.1038/s41584-022-00900-6

Cited by 18 publications

(15 citation statements)

References 223 publications

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“…Furthermore, the present malabsorption of the mentioned saccharides was associated with increased gastrointestinal symptoms [29,30]. Malabsorption can be a result of multifactorial pathology of the affected intestinal wall, which includes fibrosis of the arterial tunica intima in the submucosal arteries of the small bowel, damage to the enteric nervous system, and marked fibrosis of the circular layer of the muscularis propria [31,32]. Available diagnostic methods for the involvement of the gastrointestinal tract are limited, complex, and expensive [31].…”

Section: Discussionmentioning

confidence: 92%

“…Malabsorption can be a result of multifactorial pathology of the affected intestinal wall, which includes fibrosis of the arterial tunica intima in the submucosal arteries of the small bowel, damage to the enteric nervous system, and marked fibrosis of the circular layer of the muscularis propria [31,32]. Available diagnostic methods for the involvement of the gastrointestinal tract are limited, complex, and expensive [31]. Since we observed a significantly lower LPS concentration in the patients with esophageal involvement compared to patients with normal esophageal motility, it could be hypothesized that the lower translocation of LPS in those patients may be due to decreased intestinal absorption of LPS.…”

Section: Discussionmentioning

confidence: 99%

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The Clinical Significance of Serum Biomarkers of the Intestinal Barrier in Systemic Sclerosis: A Cross-Sectional Study

Stec

Maciejewska

Zaremba

et al. 2023

JPM

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Systemic sclerosis (SSc) is an immune-mediated connective tissue disease. Recent studies reported differences in the composition of intestinal microbiota (dysbiosis) in patients with SSc compared to nonsclerodermic subjects. Dysbiosis may disrupt the intestinal barrier, which leads to immunological activation via microbial antigen and metabolite translocation. The study aimed to assess the differences in intestinal permeability between SSc patients and controls and to examine the correlation between intestinal permeability and complications of SSc. The study comprised 50 patients with SSc and 30 matched subjects. Serum intestinal permeability markers: intestinal fatty acid binding protein, claudin-3, and lipopolysaccharides (LPS) were determined using an enzyme-linked immunosorbent assay. SSc patients had a significantly increased concentration of LPS compared to control subjects (232.30 [149.00–347.70] versus 161.00 [83.92–252.20] pg/mL, p < 0.05). The patients with shorter SSc duration (≤6 years) had an increased concentration of LPS and claudin-3 compared to the subgroup with longer disease length: LPS (280.75 [167.30–403.40] versus 186.00 [98.12–275.90] pg/mL, p < 0.05), and claudin-3 (16.99 [12.41–39.59] versus 13.54 [10.29–15.47] ng/mL, p < 0.05). The patients with esophageal dysmotility had a decreased LPS level compared to those without this complication (188.05 [102.31–264.40] versus 283.95 [203.20–356.30] pg/mL, p < 0.05). Increased intestinal permeability in SSc may exacerbate the course of the disease and increase the risk of developing complications. Lower LPS levels in SSc might be a hallmark of esophageal dysmotility.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

The Clinical Significance of Serum Biomarkers of the Intestinal Barrier in Systemic Sclerosis: A Cross-Sectional Study

Stec

Maciejewska

Zaremba

et al. 2023

JPM

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“…Patients with SSc can have gastrointestinal involvement that can compromise nutrition through means of difficulty with intake (dysphagia), dysmotility or malabsorption [53]. Dietary protein ingestion is critical to maintaining the quality and quantity of skeletal muscle mass.…”

Section: What Is Systemic Sclerosis Associated Myopathy?mentioning

confidence: 99%

Myopathy in systemic sclerosis

Connolly,

Paik

2023

Current Opinion in Rheumatology

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Purpose of review Systemic sclerosis associated myopathy (SSc-AM) is a complex, heterogenous disease that is associated with poor outcomes. SSc-AM lacks a clear definition, and continues to be poorly recognized. The purpose of this review is to provide a contemporary overview of the clinical, serological and pathophysiologic findings in SSc-AM to guide optimal recognition and management of this challenging disease manifestation. Recent findings There have been several advances in diagnostic techniques to facilitate characterization of SSc-AM, including muscle MRI, in which findings were correlated to distinct histopathologic categories of muscle involvement in SSc, histopathologic findings of prominent fibrosis or inflammation on biopsy, and the identification of novel autoantibodies associated with SSc-AM, which may be associated with distinct clinical phenotypes. In one of the largest studies to date, 17% of a well phenotyped SSc cohort were found to have myopathy, which was an independent risk of death, even after adjusting for potential confounders, further highlighting the importance of timely recognistion and management of SSc-AM. Summary There is increasing recognition of the importance of SSc-AM. Novel diagnostic tools provide the opportunity for more detailed insights into pathophysiologic mechanisms, which may facilitate the development of a rigorous consensus definition of SSc-AM.

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“…7,8 However, other mechanisms are likely implicated (eg, autonomic dysfunction, dysmotility, and structural alterations to the esophagus). 9,10 Long-term uncontrolled GERD can also result in chronic inflammation of the GI tract, with potentially serious complications, 11 including stricture formation and malignant change. 12,13 Moreover, GERD and chronic microaspiration have been associated with interstitial lung disease (ILD) in SSc.…”

Section: Introductionmentioning

confidence: 99%

“…Hypotony and inefficacy of the lower esophageal sphincter is one of the most important factors leading to GERD in patients with SSc 7,8 . However, other mechanisms are likely implicated (eg, autonomic dysfunction, dysmotility, and structural alterations to the esophagus) 9,10 . Long‐term uncontrolled GERD can also result in chronic inflammation of the GI tract, with potentially serious complications, 11 including stricture formation and malignant change 12,13 .…”

Section: Introductionmentioning

confidence: 99%

A Multinational Survey Investigating the Unmet Needs and Patient Perspectives Concerning Proton Pump Inhibitors in Systemic Sclerosis

Bandini,

Alunno,

Pinheiro

et al. 2024

Arthritis Care & Research

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ObjectiveProton Pump Inhibitors (PPIs) are widely used to treat gastroesophageal reflux disease (GERD) in Systemic Sclerosis (SSc). However, not all patients adequately respond to the treatment, and there are frequent concerns about the safety of long‐term use of PPIs. Our aim was to identify the main problems/complaints of SSc patients on PPIs, as well as understand their unmet needs.MethodsSSc patients treated with PPIs were invited through international patient associations and social media to participate in an online survey.ResultsWe gathered 301 valid responses from 14 countries (UK 19.3% and US 70.4%). Multiple PPIs use (two: 30% and three: 21% in series) was common. The majority (89%) reported improvement in GI symptoms from PPIs. Side effects attributed to PPIs were uncommon (19%); however, most (79%) were potentially concerned. Around half (58%) had received lifestyle information and most (85%) had searched online for information about PPIs. Only in the minority (12%), had a surgical approach been discussed; however, half (46%) indicated that they would be willing to undergo surgery to resolve their GERD symptoms, but had important concerns.ConclusionDespite the frequent use of PPIs in SSc, there is significant heterogeneity in use, and combination therapy (PPIs plus other medication for acid reflux) is not uncommon (~40%). Patients have significant concerns about PPIs side effects. Education about PPIs is often neglected, and patients very frequently use online sources to obtain information on drug treatment. A surgical approach is infrequently discussed, and patients fear this potential therapeutic approach.This article is protected by copyright. All rights reserved.

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Systemic sclerosis gastrointestinal dysmotility: risk factors, pathophysiology, diagnosis and management

Cited by 18 publications

References 223 publications

The Clinical Significance of Serum Biomarkers of the Intestinal Barrier in Systemic Sclerosis: A Cross-Sectional Study

The Clinical Significance of Serum Biomarkers of the Intestinal Barrier in Systemic Sclerosis: A Cross-Sectional Study

Myopathy in systemic sclerosis

A Multinational Survey Investigating the Unmet Needs and Patient Perspectives Concerning Proton Pump Inhibitors in Systemic Sclerosis

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