|
1
|
Ezquerra-Durán A, Alcala-Gonzalez LG, Guillen-del-Castillo A, Simeón-Aznar CP, Barba E, Malagelada C, Hughes M, McMahan ZH. The role of prokinetics in managing gastrointestinal involvement in SSc: a systematic literature review. Rheumatology (Oxford) 2025; 64:3266-3279. [PMID: 39909554 PMCID: PMC12107030 DOI: 10.1093/rheumatology/keaf064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 01/20/2025] [Accepted: 01/23/2025] [Indexed: 02/07/2025] Open
Abstract
OBJECTIVES Gastrointestinal involvement (GI) in SSc is frequent and heterogeneous, manifesting with different degrees of dysmotility. This systematic literature review aimed to summarize evidence on prokinetics for treating SSc-related GI dysmotility. METHODS Studies investigating the effects of prokinetic agents on GI function and/or GI symptoms in patients with SSc were systematically identified on PubMed and Embase. A qualitative data synthesis was conducted, given the (anticipated) wide heterogeneity in study designs, interventions and outcomes. RESULTS Twenty-one studies evaluating the effects of prokinetics in patients with SSc were included. Thirteen studies focused on GI motility using objective tests, eight assessed clinical responses, and six evaluated both. Cisapride (n = 5 studies), metoclopramide (n = 7 studies), octreotide (n = 4 studies) and prucalopride (n = 1 study) were among the most studied prokinetics, with varying effects on different GI anatomical regions. While metoclopramide consistently improved overall GI motility, other prokinetics provided selective benefits; cisapride improved gastric emptying and colonic motility, but not oesophageal motility, and octreotide improved small bowel motility but delayed gastric emptying. Regarding symptomatic improvement, only prucalopride was evaluated using a validated patient questionnaire, showing improvement in both upper and lower GI symptoms. CONCLUSION Prokinetic drugs may improve GI motility and symptoms in patients with SSc. There is an unmet need for future well-designed studies to refine patient stratification and optimize treatment outcomes.
Collapse
Affiliation(s)
- Alberto Ezquerra-Durán
- Neurogastroenterology and Motility Unit, Gastroenterology Department, Hospital Clinic of Barcelona, Barcelona, Spain
| | - Luis G Alcala-Gonzalez
- Digestive System Research Unit, Department of Digestive Diseases, Vall d’Hebron University Hospital, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Alfredo Guillen-del-Castillo
- Systemic Autoimmune Diseases Unit, Internal Medicine Department, Vall d’Hebron University Hospital, Barcelona, Spain
| | - Carmen P Simeón-Aznar
- Systemic Autoimmune Diseases Unit, Internal Medicine Department, Vall d’Hebron University Hospital, Barcelona, Spain
| | - Elizabeth Barba
- Neurogastroenterology and Motility Unit, Gastroenterology Department, Hospital Clinic of Barcelona, Barcelona, Spain
| | - Carolina Malagelada
- Digestive System Research Unit, Department of Digestive Diseases, Vall d’Hebron University Hospital, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Instituto de Salud Carlos III, Madrid, Spain
- Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Michael Hughes
- Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
- Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Salford, United Kingdom
| | - Zsuzsanna H McMahan
- Department of Medicine, Division of Rheumatology, UTHealth Houston, Houston, TX, United States
| |
Collapse
|
|
2
|
Bandini G, Campochiaro C, Ciuti G, Baccellieri D, Ardita V, Bellando Randone S, El Aoufy K, Giuggioli D, Orlandi M, Dagna L, Chiesa R, Matucci Cerinic M, Moggi Pignone A. Doppler ultrasound unveils splanchnic arteries ischemia allowing early successful revascularization in symptomatic systemic sclerosis patients. Eur J Intern Med 2025; 135:126-129. [PMID: 40140335 DOI: 10.1016/j.ejim.2025.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 03/15/2025] [Accepted: 03/17/2025] [Indexed: 03/28/2025]
Abstract
BACKGROUND Systemic sclerosis (SSc) is characterized by macro and microvasculopathy, including splanchnic circulation. Chronic mesenteric ischemia (CMI) is a potentially severe condition which can complicate SSc gastrointestinal vasculopathy. Doppler ultrasound (DUS) may be a non-invasive procedure for identifying CMI in symptomatic SSc patients. OBJECTIVES To investigate the capacity of DUS to detect early CMI and the effect of the endovascular approach on CMI-related symptoms. METHODS DUS of splanchnic arteries was performed in symptomatic SSc patients, during routinary outpatient visits. RESULTS In 6 out of 72 SSc symptomatic patients, DUS suggested a splanchnic vessels stenosis which was confirmed by computed tomography angiography (CTA). After multidisciplinary evaluation in 3 patients a revascularization was performed. Three-monthly clinical and DUS follow-up was negative in all patients. CONCLUSION CDU is a useful screening tool for CMI in SSc patients. Revascularization of stenotic mesenteric arteries seems to be a safe and effective procedure.
Collapse
Affiliation(s)
- Giulia Bandini
- Department of Experimental and Clinical Medicine, Division of Internal Medicine, University of Florence, AOUC, Firenze, Italy.
| | - Corrado Campochiaro
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UniRAR) & Inflammation, Fibrosis and Aging Initiative (INFLAGE), IRCCS Ospedale San Raffaele, Milano, Italy. Vita Salute University San Raffaele, Milano, Italy
| | - Gabriele Ciuti
- Department of Experimental and Clinical Medicine, Division of Internal Medicine, University of Florence, AOUC, Firenze, Italy
| | - Domenico Baccellieri
- Department of Vascular Surgery, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
| | - Vincenzo Ardita
- Department of Vascular Surgery, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
| | - Silvia Bellando Randone
- Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy
| | - Khadija El Aoufy
- Department of Health Science, University of Florence, Florence, Italy
| | - Dilia Giuggioli
- Rheumatology Unit, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena and Reggio Emilia School of Medicine, Italy
| | - Martina Orlandi
- Rheumatology Unit, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena and Reggio Emilia School of Medicine, Italy
| | - Lorenzo Dagna
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UniRAR) & Inflammation, Fibrosis and Aging Initiative (INFLAGE), IRCCS Ospedale San Raffaele, Milano, Italy. Vita Salute University San Raffaele, Milano, Italy
| | - Roberto Chiesa
- Department of Vascular Surgery, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
| | - Marco Matucci Cerinic
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UniRAR) & Inflammation, Fibrosis and Aging Initiative (INFLAGE), IRCCS Ospedale San Raffaele, Milano, Italy. Vita Salute University San Raffaele, Milano, Italy
| | - Alberto Moggi Pignone
- Department of Experimental and Clinical Medicine, Division of Internal Medicine, University of Florence, AOUC, Firenze, Italy
| |
Collapse
|
|
3
|
Chandradevan R, Handley J, Rao S. Bidirectional endoscopic and pharmacological approach for the treatment of severe right-sided colonic stool impaction. BMJ Case Rep 2025; 18:e263383. [PMID: 40306749 PMCID: PMC12049734 DOI: 10.1136/bcr-2024-263383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 04/11/2025] [Indexed: 05/02/2025] Open
Abstract
A female patient in her 40s with scleroderma and Behçet's disease presented with dehydration, weight loss, fever and stool impaction. She failed aggressive laxatives and rectal enemas and was referred for colectomy. Abdominal X-ray revealed severe proximal colonic faecal impaction. We used a bidirectional approach to stimulate laxation composed of jejunal infusion of magnesium citrate using enteroscopy, gastrografin infusion into the right colon using colonoscopy, and intravenous neostigmine to stimulate peristalsis. This novel, three-pronged, outpatient approach using osmotic laxatives and peristaltic stimulants facilitated successful disimpaction over 36 hours, preventing possible colonic perforation or colectomy in a complex patient with right-sided stool impaction and comorbidities. This is a single case report that does not provide evidence for the safety or efficacy of a new treatment strategy.
Collapse
Affiliation(s)
- Raguraj Chandradevan
- Gastroenterology/Hepatology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
| | - Judith Handley
- Anesthesiology, Medical College of Georgia, Augusta University, Augusta, GA, USA
| | - Satish Rao
- Gastroenterology/Hepatology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
| |
Collapse
|
|
4
|
Quinlivan A, Hansen D, Stevens W, Ross L, Ferdowsi N, Proudman SM, Walker JG, Sahhar J, Ngian G, Apostolopoulos D, Host LV, Major G, Basnayake C, Morrisroe K, Nikpour M. Prevalence and Outcomes of Gastrointestinal Manifestations in an Australian Scleroderma Cohort. Arthritis Care Res (Hoboken) 2024; 76:1686-1695. [PMID: 39245927 PMCID: PMC11605790 DOI: 10.1002/acr.25426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 08/21/2024] [Accepted: 08/28/2024] [Indexed: 09/10/2024]
Abstract
OBJECTIVE The gastrointestinal tract (GIT) is the most commonly affected internal organ in systemic sclerosis (SSc). We sought to determine the prevalence and impact of GIT symptoms on survival and patient-reported outcomes. METHODS A total of 907 consecutive patients from the Australian Scleroderma Cohort Study who had prospectively completed the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 Questionnaire (UCLA GIT) between 2015 and 2021 were included. The associations between UCLA GIT scores and physical function (Scleroderma Health Assessment Questionnaire), quality of life (QoL; Short Form 36), mood (Patient-Reported Outcomes Measurement Information System [PROMIS] anxiety and depression domains), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue score), and employment were investigated using multivariable population-averaged panel models using generalized estimating equations (GEEs). Kaplan-Meier curves and multivariable Cox proportional hazard regression models were used to evaluate survival according to total UCLA GIT scores. RESULTS GIT symptoms were reported in 87% of participants, with 46% to 52% reporting moderate to very severe symptoms of reflux, distension, diarrhea, and constipation. Higher total UCLA GIT scores were associated with worse QoL, physical function, fatigue, anxiety, and depression (P < 0.001). In the multivariable GEE analysis, moderate and severe to very severe total scores, reflux scores, and distension scores were associated with worse physical function, QoL, fatigue, anxiety, and depression compared to mild scores (P < 0.05). Patients with severe total scores and diarrhea scores were more likely to be unemployed compared to those with mild scores (P < 0.05). UCLA GIT total scores were not independently associated with death in our cohort. CONCLUSION GIT manifestations are common in SSc and negatively impact QoL, physical function, and employment but are not directly associated with increased death.
Collapse
Affiliation(s)
- Alannah Quinlivan
- St. Vincent's Hospital Melbourne, Fitzroy, and The University of MelbourneMelbourneVictoriaAustralia
| | - Dylan Hansen
- St. Vincent's Hospital MelbourneFitzroyVictoriaAustralia
| | - Wendy Stevens
- St. Vincent's Hospital MelbourneFitzroyVictoriaAustralia
| | - Laura Ross
- St. Vincent's Hospital Melbourne, Fitzroy, and The University of MelbourneMelbourneVictoriaAustralia
| | - Nava Ferdowsi
- St. Vincent's Hospital Melbourne, Fitzroy, and The University of MelbourneMelbourneVictoriaAustralia
| | - Susanna M. Proudman
- Royal Adelaide Hospital and the University of AdelaideAdelaideSouth AustraliaAustralia
| | - Jennifer G. Walker
- Royal Adelaide Hospital and Flinders University, Adelaide, Flinders Medical CentreBedford ParkSouth AustraliaAustralia
| | - Joanne Sahhar
- Monash Health and Monash UniversityClaytonVictoriaAustralia
| | | | | | | | - Gabor Major
- John Hunter Hospital, New Lambton Heights, University of NewcastleCallaghanNew South WalesAustralia
| | - Chamara Basnayake
- St. Vincent's Hospital Melbourne, Fitzroy, and The University of MelbourneMelbourneVictoriaAustralia
| | - Kathleen Morrisroe
- St. Vincent's Hospital Melbourne, Fitzroy, and The University of MelbourneMelbourneVictoriaAustralia
| | - Mandana Nikpour
- St. Vincent's Hospital Melbourne, Fitzroy, The University of Melbourne, Melbourne, Victoria, and the University of Sydney and Royal Prince Alfred HospitalCamperdownNew South WalesAustralia
| |
Collapse
|
|
5
|
Hughes M, Harrison E, Herrick AL, Lal S, McLaughlin JT. An evaluation of autonomic and gastrointestinal symptoms, and gastric emptying, in patients with systemic sclerosis. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2024:23971983241288039. [PMID: 39544898 PMCID: PMC11559523 DOI: 10.1177/23971983241288039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 09/13/2024] [Indexed: 11/17/2024]
Abstract
Objective Assessment of gastrointestinal and autonomic symptoms in patients with systemic sclerosis, and possible associations with gastric emptying rate. Methods Participant and patient disease-related characteristics were collected. Gastrointestinal and autonomic symptoms were assessed by the UCLA-SCTC GIT 2.0 and COMPASS-31 questionnaires, respectively. Potentially confounding gastrointestinal medications were discontinued where possible. Gastric emptying was assessed using a non-radioactive 13C sodium acetate isotope, end-expiratory breath samples collected at baseline and then serial timepoints up to 120 min. Results In total, 49 participants were studied: 17 with systemic sclerosis with variable gastrointestinal involvement, and healthy matched (n = 17) and non-matched controls (n = 15), the last to control for the impact of age rather than disease on gastric emptying and autonomic function. The total mean (range) UCLA GIT 2.0 questionnaire for patients with systemic sclerosis was 0.63 (0.0-1.5) and for both healthy matched and non-matched controls was 0.04 (0.0-0.2), and was higher in patients with systemic sclerosis across all domains. The total mean (range) COMPASS-31 score for patients with systemic sclerosis patients was 32.2 (0.0-54.9) and for healthy matched- and non-matched controls: 7.45 (0.0-24.9) and 4.25 (0.0-2.1), respectively, again higher for patients with systemic sclerosis across all domains. No association was observed between patients' UCLA GIT 2.0 total score (s = -0.039, p = 0.38), total COMPASS 31 score (s = -0.108, p = 0.68), or COMPASS-31 GI domain (s = -0.051, p = 0.85) and gastric emptying rates. Conclusion Gastrointestinal and autonomic symptoms are overrepresented in patients with systemic sclerosis but did not associate with gastric emptying rates.
Collapse
Affiliation(s)
- Michael Hughes
- Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | | | - Ariane L Herrick
- Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - Simon Lal
- Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine and Health, The University of Manchester, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Manchester, UK
- Intestinal Failure Unit, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Salford, UK
| | - John T McLaughlin
- Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine and Health, The University of Manchester, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Manchester, UK
| |
Collapse
|
|
6
|
Park D, Kővári B, Shimizu M. Miscellaneous conditions of the stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:347-358. [DOI: 10.1002/9781119423195.ch16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
7
|
Ranjbar M, Naeini F, Rostamian A, Djafarian K, Mohammadi H. Effects of probiotics supplementation in gastrointestinal complications and quality of life of patients with systemic sclerosis: A systematic review. Heliyon 2024; 10:e36230. [PMID: 39247342 PMCID: PMC11379610 DOI: 10.1016/j.heliyon.2024.e36230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 08/07/2024] [Accepted: 08/12/2024] [Indexed: 09/10/2024] Open
Abstract
Background Systemic sclerosis (SSc), as an autoimmune rheumatic disease characterized by immune dysregulation and vasculopathy, affects multiple organs. Due to the high burden of its symptoms on the health care system, this study aims to investigate the effects of probiotic supplements in patients with SSc. Methods We searched electronic databases with predefined search terms in PubMed, Scopus, and ISI Web of Science up to June 2023. Randomized controlled trials that evaluated the effects of probiotic supplementation in adult patients suffering from SSc were included in the study. Results of the included studies were reported as weighted mean difference (WMD) with a 95 % confidence interval (CI). Results Four studies met the inclusion criteria and were included in the meta-analysis. There was a total of 176 SSc patients. The results show a significant effect of probiotics supplementation on gastrointestinal (GI) symptoms containing reflux (WMD: -0.36, 95 % CI: -0.51 to -0.22, p-value <0.001), gas and bloating (WMD: -0.88, 95 % CI: -1.05 to -0.7, p-value<0.001). However, the results for constipation (WMD: -0.12, 95 % CI: -0.27 to 0.04, p-value = 0.13), diarrhea (WMD: -0.14, 95 % CI: -0.31 to 0.03, p-value = 0.10), and fecal incontinence (WMD: 0.04, 95 % CI: -0.06 to 0.15, p-value = 0.43) were insignificant. Conclusion Supplementing with probiotics may alleviate a few numbers of GI complications in SSc. Nevertheless, due to the limited number of studies, more well-designed studies are needed to strengthen these results.
Collapse
Affiliation(s)
- Mahsa Ranjbar
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science, Tehran, Iran
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Naeini
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science, Tehran, Iran
| | | | - Kurosh Djafarian
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science, Tehran, Iran
- Neuroscience Institute, Sports Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamed Mohammadi
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science, Tehran, Iran
| |
Collapse
|
|
8
|
Takahashi T, Takahashi T, Ikawa T, Terui H, Takahashi T, Segawa Y, Sumida H, Yoshizaki A, Sato S, Asano Y. Serum levels of AGGF1: Potential association with cutaneous and cardiopulmonary involvements in systemic sclerosis. J Dermatol 2024; 51:1083-1090. [PMID: 38619119 DOI: 10.1111/1346-8138.17233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 03/09/2024] [Accepted: 03/31/2024] [Indexed: 04/16/2024]
Abstract
Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, aberrant immune activation, and extensive tissue fibrosis of the skin and internal organs. Because of the complicated nature of its pathogenesis, the underlying mechanisms of SSc remain incompletely understood. Angiogenic factor with a G-patch domain and a Forkhead-associated domain 1 (AGGF1) is a critical factor in angiogenesis expressed on vascular endothelial cells, associated with inflammatory and fibrotic responses. To elucidate the possible implication of AGGF1 in SSc pathogenesis, we investigated the association between serum AGGF1 levels and clinical manifestations in SSc patients. We conducted a cross-sectional analysis of AGGF1 levels in sera from 60 SSc patients and 19 healthy controls with enzyme-linked immunosorbent assay. Serum AGGF1 levels in SSc patients were significantly higher than those in healthy individuals. In particular, diffuse cutaneous SSc patients with shorter disease duration had higher levels compared to those with longer disease duration and limited cutaneous SSc patients. Patients with higher serum AGGF1 levels had a higher incidence of digital ulcers, higher modified Rodnan Skin Scores (mRSS), elevated serum Krebs von den Lungen-6 (KL-6) levels, C-reactive protein levels, and right ventricular systolic pressures (RVSP) on the echocardiogram, whereas they had reduced percentage of vital capacity (%VC) and percentage of diffusing capacity of the lungs for carbon monoxide (%DLCO) in pulmonary functional tests. In line, serum AGGF1 levels were significantly correlated with mRSS, serum KL-6 and surfactant protein D levels, RVSP, and %DLCO. These results uncovered notable correlations between serum AGGF1 levels and key cutaneous and vascular involvements in SSc, suggesting potential roles of AGGF1 in SSc pathogenesis.
Collapse
Affiliation(s)
- Takuya Takahashi
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takehiro Takahashi
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tetsuya Ikawa
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hitoshi Terui
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Toshiya Takahashi
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yuichiro Segawa
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hayakazu Sumida
- Department of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
- Scleroderma Center, The University of Tokyo Hospital, Tokyo, Japan
| | - Ayumi Yoshizaki
- Department of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | - Shinichi Sato
- Department of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | - Yoshihide Asano
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| |
Collapse
|
|
9
|
Stamm L, Garaiman A, Becker MO, Bruni C, Dobrota R, Elhai M, Ismail S, Jordan S, Zampatti N, Tatu AM, Distler O, Mihai C. Does therapy with immunosuppressive drugs improve gastrointestinal symptoms in patients with systemic sclerosis? RMD Open 2024; 10:e004333. [PMID: 39053950 PMCID: PMC11284906 DOI: 10.1136/rmdopen-2024-004333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 06/24/2024] [Indexed: 07/27/2024] Open
Abstract
OBJECTIVES While important progress was made regarding the treatment of systemic sclerosis (SSc), there is still no evidence-based disease-modifying treatment available for SSc-related gastrointestinal (GI) manifestations. We aimed to identify an association between immunosuppressive therapy and the the severity of GI symptoms, measured by the University of California at Los Angeles/Scleroderma Clinical Trial Consortium Gastro-Intestinal Tract instrument 2.0 (GIT). METHODS We selected patients with SSc who had at least two visits (further referred to as 'baseline' and 'follow-up') with completed GITs, within an interval of 12±3 months. The study outcome was the GIT score at follow-up. We used multivariable linear regression with the following covariates: immunosuppressive therapy during observation, immunosuppressive therapy before baseline, baseline GIT and several baseline parameters selected by clinical judgement as potentially influencing GI symptoms. RESULTS We included 209 SSc patients (82.3% female, median age 59.0 years, median disease duration 6.0 years, 40 (19.1%) diffuse cutaneous SSc, median baseline GIT 0.19). Of these, 71 were exposed to immunosuppressive therapy during the observation period, and, compared with unexposed patients, had overall more severe SSc and a higher prevalence of treatment with proton pump inhibitors. In multivariable linear regression, immunosuppressive therapy during the period of observation and lower baseline GIT scores were significantly associated with lower (better) GIT scores at follow-up. CONCLUSION Immunosuppressive treatment was associated with lower GIT scores in our cohort, which suggests the potential effects of immunosuppressants on GI manifestations in patients with SSc, requiring confirmation in prospective randomised clinical trials.
Collapse
Affiliation(s)
- Lea Stamm
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Alexandru Garaiman
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Mike Oliver Becker
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Cosimo Bruni
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Rucsandra Dobrota
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Muriel Elhai
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Sherif Ismail
- Department of Internal Medicine, National Research Center, Cairo, Egypt
| | - Suzana Jordan
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Norina Zampatti
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Aurora Maria Tatu
- Department of Gastroenterology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Oliver Distler
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Carina Mihai
- Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| |
Collapse
|
|
10
|
Roszkowska P, Klimczak E, Ostrycharz E, Rączka A, Wojciechowska-Koszko I, Dybus A, Cheng YH, Yu YH, Mazgaj S, Hukowska-Szematowicz B. Small Intestinal Bacterial Overgrowth (SIBO) and Twelve Groups of Related Diseases-Current State of Knowledge. Biomedicines 2024; 12:1030. [PMID: 38790992 PMCID: PMC11117733 DOI: 10.3390/biomedicines12051030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 05/01/2024] [Accepted: 05/03/2024] [Indexed: 05/26/2024] Open
Abstract
The human gut microbiota creates a complex microbial ecosystem, characterized by its high population density, wide diversity, and complex interactions. Any imbalance of the intestinal microbiome, whether qualitative or quantitative, may have serious consequences for human health, including small intestinal bacterial overgrowth (SIBO). SIBO is defined as an increase in the number of bacteria (103-105 CFU/mL), an alteration in the bacterial composition, or both in the small intestine. The PubMed, Science Direct, Web of Science, EMBASE, and Medline databases were searched for studies on SIBO and related diseases. These diseases were divided into 12 groups: (1) gastrointestinal disorders; (2) autoimmune disease; (3) cardiovascular system disease; (4) metabolic disease; (5) endocrine disorders; (6) nephrological disorders; (7) dermatological diseases; (8) neurological diseases (9); developmental disorders; (10) mental disorders; (11) genetic diseases; and (12) gastrointestinal cancer. The purpose of this comprehensive review is to present the current state of knowledge on the relationships between SIBO and these 12 disease groups, taking into account risk factors and the causal context. This review fills the evidence gap on SIBO and presents a biological-medical approach to the problem, clearly showing the groups and diseases having a proven relationship with SIBO, as well as indicating groups within which research should continue to be expanded.
Collapse
Affiliation(s)
- Paulina Roszkowska
- Department of Diagnostic Immunology, Pomeranian Medical University, st. Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (P.R.); (I.W.-K.)
| | - Emilia Klimczak
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
| | - Ewa Ostrycharz
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
- Doctoral School, University of Szczecin, st. A. Mickiewicz 16, 71-412 Szczecin, Poland
- Molecular Biology and Biotechnology Center, University of Szczecin, st. Wąska 13, 71-412 Szczecin, Poland
| | - Aleksandra Rączka
- Department of Genetics, West Pomeranian University of Technology, st. Aleja Piastów 45, 70-311 Szczecin, Poland; (A.R.); (A.D.)
| | - Iwona Wojciechowska-Koszko
- Department of Diagnostic Immunology, Pomeranian Medical University, st. Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (P.R.); (I.W.-K.)
| | - Andrzej Dybus
- Department of Genetics, West Pomeranian University of Technology, st. Aleja Piastów 45, 70-311 Szczecin, Poland; (A.R.); (A.D.)
| | - Yeong-Hsiang Cheng
- Department of Biotechnology and Animal Science, National Ilan University, Yilan 26047, Taiwan; (Y.-H.C.); (Y.-H.Y.)
| | - Yu-Hsiang Yu
- Department of Biotechnology and Animal Science, National Ilan University, Yilan 26047, Taiwan; (Y.-H.C.); (Y.-H.Y.)
| | - Szymon Mazgaj
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
| | - Beata Hukowska-Szematowicz
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
- Molecular Biology and Biotechnology Center, University of Szczecin, st. Wąska 13, 71-412 Szczecin, Poland
| |
Collapse
|
|
11
|
Suzon B, Louis-Sidney F, Abel A, Moinet F, Bagoée C, Henry K, Coco-Viloin I, Cougnaud R, Wolff S, Guilpain P, Rivière S, Flori N, Deligny C, Maria A. [Severe small bowel involvement and chronic intestinal pseudo-obstruction in systemic sclerosis (scleroderma): Pathophysiological, diagnostic and therapeutic basis, including parenteral nutrition]. Rev Med Interne 2024; 45:147-155. [PMID: 38388303 DOI: 10.1016/j.revmed.2024.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 01/15/2024] [Accepted: 02/03/2024] [Indexed: 02/24/2024]
Abstract
Gastrointestinal involvement in systemic sclerosis can be severe, reaching the critical point of chronic intestinal pseudo-obstruction, secondary to major disorders of small bowel motility. It is associated with some clinical and biological characteristics, in particular the positivity of anti-fibrillarin/U3RNP antibodies. Chronic intestinal pseudo-obstruction (CIPO) is complicated by a small intestinal bacterial overgrowth that requires cyclic antibiotic therapy. CIPO leads to a reduction of the food intake, due to painful symptoms, nausea and vomiting caused by meals, and ultimately to severe malnutrition. Meal splitting is often transiently effective and patients require exogenous nutritional support, mostly parenteral. Systemic sclerosis is not an obstacle to initiation and long-term continuation of parenteral nutrition and central venous catheter implantation is not associated with an increased risk of cutaneous or infectious complications. However, continuation of long-term parenteral nutrition requires monitoring in an expert nutrition center in order to adapt nutritional volumes and intakes and to limit potentially fatal cardiac and hepatobiliary complications. In addition to nutrition, prokinetic treatments, whose side effects must be known, can be associated. Invasive procedures, whose risk-benefit ratio must be carefully assessed, can also be used to treat symptoms exclusively.
Collapse
Affiliation(s)
- B Suzon
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique; Unité EpiCliV, Université des Antilles, Fort-de-France, Martinique.
| | - F Louis-Sidney
- Unité EpiCliV, Université des Antilles, Fort-de-France, Martinique; Rhumatologie, CHU de Martinique, Fort-de-France, Martinique
| | - A Abel
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique
| | - F Moinet
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique
| | - C Bagoée
- Médecine interne et polyvalente, Centre hospitalier territorial Gaston-Bourret, Nouméa, Nouvelle-Calédonie
| | - K Henry
- Maladies infectieuses et tropicales, Centre hospitalier de Cayenne, Cayenne, Guyane
| | - I Coco-Viloin
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique
| | - R Cougnaud
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique
| | - S Wolff
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique
| | - P Guilpain
- Médecine interne et maladies multi-organiques, Hôpital Saint Eloi, CHU de Montpellier, Montpellier, France; Institut de médecine régénérative et biothérapies, Inserm U1183, Montpellier, France; Faculté de médecine, Université de Montpellier, Montpellier, France
| | - S Rivière
- Médecine interne et maladies multi-organiques, Hôpital Saint Eloi, CHU de Montpellier, Montpellier, France
| | - N Flori
- Centre expert régional de nutrition, ICM, Montpellier, France
| | - C Deligny
- Médecine Interne, CHU de Martinique, Fort-de-France, Martinique; Unité EpiCliV, Université des Antilles, Fort-de-France, Martinique
| | - A Maria
- Institut de médecine régénérative et biothérapies, Inserm U1183, Montpellier, France; Faculté de médecine, Université de Montpellier, Montpellier, France; Médecine interne et immuno-oncologie (MedI2O), Hôpital Saint-Eloi, CHU de Montpellier, Montpellier, France
| |
Collapse
|
|
12
|
Binda M, Moccaldi B, Civieri G, Cuberli A, Doria A, Tona F, Zanatta E. Autoantibodies Targeting G-Protein-Coupled Receptors: Pathogenetic, Clinical and Therapeutic Implications in Systemic Sclerosis. Int J Mol Sci 2024; 25:2299. [PMID: 38396976 PMCID: PMC10889602 DOI: 10.3390/ijms25042299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 02/11/2024] [Accepted: 02/13/2024] [Indexed: 02/25/2024] Open
Abstract
Systemic sclerosis (SSc) is a multifaceted connective tissue disease whose aetiology remains largely unknown. Autoimmunity is thought to play a pivotal role in the development of the disease, but the direct pathogenic role of SSc-specific autoantibodies remains to be established. The recent discovery of functional antibodies targeting G-protein-coupled receptors (GPCRs), whose presence has been demonstrated in different autoimmune conditions, has shed some light on SSc pathogenesis. These antibodies bind to GPCRs expressed on immune and non-immune cells as their endogenous ligands, exerting either a stimulatory or inhibitory effect on corresponding intracellular pathways. Growing evidence suggests that, in SSc, the presence of anti-GPCRs antibodies correlates with specific clinical manifestations. Autoantibodies targeting endothelin receptor type A (ETAR) and angiotensin type 1 receptor (AT1R) are associated with severe vasculopathic SSc-related manifestations, while anti-C-X-C motif chemokine receptors (CXCR) antibodies seem to be predictive of interstitial lung involvement; anti-muscarinic-3 acetylcholine receptor (M3R) antibodies have been found in patients with severe gastrointestinal involvement and anti-protease-activated receptor 1 (PAR1) antibodies have been detected in patients experiencing scleroderma renal crisis. This review aims to clarify the potential pathogenetic significance of GPCR-targeting autoantibodies in SSc, focusing on their associations with the different clinical manifestations of scleroderma. An extensive examination of functional autoimmunity targeting GPCRs might provide valuable insights into the underlying pathogenetic mechanisms of SSc, thus enabling the development of novel therapeutic strategies tailored to target GPCR-mediated pathways.
Collapse
Affiliation(s)
- Marco Binda
- Rheumatology Unit, Department of Medicine-DIMED, Padova University Hospital, 35128 Padova, Italy; (M.B.)
| | - Beatrice Moccaldi
- Rheumatology Unit, Department of Medicine-DIMED, Padova University Hospital, 35128 Padova, Italy; (M.B.)
| | - Giovanni Civieri
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
| | - Anna Cuberli
- Rheumatology Unit, Department of Medicine-DIMED, Padova University Hospital, 35128 Padova, Italy; (M.B.)
| | - Andrea Doria
- Rheumatology Unit, Department of Medicine-DIMED, Padova University Hospital, 35128 Padova, Italy; (M.B.)
| | - Francesco Tona
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
| | - Elisabetta Zanatta
- Rheumatology Unit, Department of Medicine-DIMED, Padova University Hospital, 35128 Padova, Italy; (M.B.)
| |
Collapse
|
|
13
|
Clarke JO, Ahuja NK. Upper Gastrointestinal Tract: Manifestations of Systemic Sclerosis. SCLERODERMA 2024:477-493. [DOI: 10.1007/978-3-031-40658-4_31] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
14
|
Shah AA, Wigley FM. Overlooked Manifestations. SCLERODERMA 2024:587-611. [DOI: 10.1007/978-3-031-40658-4_38] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
15
|
McMahan ZH, Kulkarni S, Chen J, Chen JZ, Xavier RJ, Pasricha PJ, Khanna D. Systemic sclerosis gastrointestinal dysmotility: risk factors, pathophysiology, diagnosis and management. Nat Rev Rheumatol 2023; 19:166-181. [PMID: 36747090 DOI: 10.1038/s41584-022-00900-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2022] [Indexed: 02/08/2023]
Abstract
Nearly all patients with systemic sclerosis (SSc) are negatively affected by dysfunction in the gastrointestinal tract, and the severity of gastrointestinal disease in SSc correlates with high mortality. The clinical complications of this dysfunction are heterogeneous and include gastro-oesophageal reflux disease, gastroparesis, small intestinal bacterial overgrowth, intestinal pseudo-obstruction, malabsorption and the requirement for total parenteral nutrition. The abnormal gastrointestinal physiology that promotes the clinical manifestations of SSc gastrointestinal disease throughout the gastrointestinal tract are diverse and present a range of therapeutic targets. Furthermore, the armamentarium of medications and non-pharmacological interventions that can benefit affected patients has substantially expanded in the past 10 years, and research is increasingly focused in this area. Here, we review the details of the gastrointestinal complications in SSc, tie physiological abnormalities to clinical manifestations, detail the roles of standard and novel therapies and lay a foundation for future investigative work.
Collapse
Affiliation(s)
| | - Subhash Kulkarni
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Joan Chen
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA
| | - Jiande Z Chen
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA
| | - Ramnik J Xavier
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
- Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - P Jay Pasricha
- Division of Gastroenterology, Johns Hopkins University, Baltimore, MD, USA
- Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA
| | - Dinesh Khanna
- Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA.
- University of Michigan Scleroderma Program, Ann Arbor, MI, USA.
| |
Collapse
|
|
16
|
Carroll-Portillo A, Rumsey KN, Braun CA, Lin DM, Coffman CN, Alcock JA, Singh SB, Lin HC. Mucin and Agitation Shape Predation of Escherichia coli by Lytic Coliphage. Microorganisms 2023; 11:microorganisms11020508. [PMID: 36838472 PMCID: PMC9966288 DOI: 10.3390/microorganisms11020508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 02/15/2023] [Accepted: 02/15/2023] [Indexed: 02/19/2023] Open
Abstract
The ability of bacteriophage (phage), abundant within the gastrointestinal microbiome, to regulate bacterial populations within the same micro-environment offers prophylactic and therapeutic opportunities. Bacteria and phage have both been shown to interact intimately with mucin, and these interactions invariably effect the outcomes of phage predation within the intestine. To better understand the influence of the gastrointestinal micro-environment on phage predation, we employed enclosed, in vitro systems to investigate the roles of mucin concentration and agitation as a function of phage type and number on bacterial killing. Using two lytic coliphage, T4 and PhiX174, bacterial viability was quantified following exposure to phages at different multiplicities of infection (MOI) within increasing, physiological levels of mucin (0-4%) with and without agitation. Comparison of bacterial viability outcomes demonstrated that at low MOI, agitation in combination with higher mucin concentration (>2%) inhibited phage predation by both phages. However, when MOI was increased, PhiX predation was recovered regardless of mucin concentration or agitation. In contrast, only constant agitation of samples containing a high MOI of T4 demonstrated phage predation; briefly agitated samples remained hindered. Our results demonstrate that each phage-bacteria pairing is uniquely influenced by environmental factors, and these should be considered when determining the potential efficacy of phage predation under homeostatic or therapeutic circumstances.
Collapse
Affiliation(s)
- Amanda Carroll-Portillo
- Division of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, NM 87131, USA
- Correspondence:
| | - Kellin N. Rumsey
- Statistical Sciences, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
| | - Cody A. Braun
- Biomedical Research Institute of New Mexico, Albuquerque, NM 87108, USA
| | - Derek M. Lin
- Biomedical Research Institute of New Mexico, Albuquerque, NM 87108, USA
| | | | - Joe A. Alcock
- Department of Emergency Medicine, University of New Mexico, Albuquerque, NM 87131, USA
| | - Sudha B. Singh
- Biomedical Research Institute of New Mexico, Albuquerque, NM 87108, USA
| | - Henry C. Lin
- Division of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, NM 87131, USA
- Medicine Service, New Mexico VA Health Care System, Albuquerque, NM 87108, USA
| |
Collapse
|
|
17
|
Abstract
The upper gastrointestinal (GI) tract is frequently involved in systemic sclerosis (SSc) and may impact quality of life, physical function and survival. Although we are currently very proactive in terms of screening for heart and lung involvement, patients with SSc are not routinely screened for GI involvement. This review details the available investigations for common upper GI symptoms in SSc, including dysphagia, reflux and bloating and provides advice as to how to integrate these investigations into current clinical care.
Collapse
|
|
18
|
Sroka N, Rydzewska-Rosołowska A, Kakareko K, Rosołowski M, Głowińska I, Hryszko T. Show Me What You Have Inside-The Complex Interplay between SIBO and Multiple Medical Conditions-A Systematic Review. Nutrients 2022; 15:nu15010090. [PMID: 36615748 PMCID: PMC9824151 DOI: 10.3390/nu15010090] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/18/2022] [Accepted: 12/20/2022] [Indexed: 12/28/2022] Open
Abstract
The microbiota, as a complex of microorganisms in a particular ecosystem, is part of the wider term-microbiome, which is defined as the set of all genetic content in the microbial community. Imbalanced gut microbiota has a great impact on the homeostasis of the organism. Dysbiosis, as a disturbance in bacterial balance, might trigger or exacerbate the course of different pathologies. Small intestinal bacterial overgrowth (SIBO) is a disorder characterized by differences in quantity, quality, and location of the small intestine microbiota. SIBO underlies symptoms associated with functional gastrointestinal disorders (FGD) as well as may alter the presentation of chronic diseases such as heart failure, diabetes, etc. In recent years there has been growing interest in the influence of SIBO and its impact on the whole human body as well as individual systems. Therefore, we aimed to investigate the co-existence of SIBO with different medical conditions. The PubMed database was searched up to July 2022 and we found 580 original studies; inclusion and exclusion criteria let us identify 112 eligible articles, which are quoted in this paper. The present SIBO diagnostic methods could be divided into two groups-invasive, the gold standard-small intestine aspirate culture, and non-invasive, breath tests (BT). Over the years scientists have explored SIBO and its associations with other diseases. Its role has been confirmed not only in gastroenterology but also in cardiology, endocrinology, neurology, rheumatology, and nephrology. Antibiotic therapy could reduce SIBO occurrence resulting not only in the relief of FGD symptoms but also manifestations of comorbid diseases. Although more research is needed, the link between SIBO and other diseases is an important pathway for scientists to follow.
Collapse
Affiliation(s)
- Natalia Sroka
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
- Correspondence:
| | - Alicja Rydzewska-Rosołowska
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
| | - Katarzyna Kakareko
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
| | - Mariusz Rosołowski
- Department of Internal Medicine and Hypertension, Medical University of Białystok, 15-540 Białystok, Poland
| | - Irena Głowińska
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
| | - Tomasz Hryszko
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
| |
Collapse
|
|
19
|
Liu P, Chai J, Dai L, Chen B, Zhao J, Lu M, Zeng L, Xia Z, Mu R. Development of a Diagnostic Model Focusing on Esophageal Dysmotility in Patients with Systemic Sclerosis. Diagnostics (Basel) 2022; 12:diagnostics12123142. [PMID: 36553149 PMCID: PMC9776849 DOI: 10.3390/diagnostics12123142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/06/2022] [Accepted: 12/11/2022] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE Esophageal dysmotility is a common and neglected complication of systemic sclerosis (SSc) associated with poor prognosis, while the assessment remains a challenge. We aimed to develop a diagnostic model for esophageal dysmotility in SSc patients that provides individualized risk estimates. METHODS Seventy-five SSc patients who underwent high-resolution manometry (HRM) were included in the study. Esophageal widest diameter (WED) was measured on a chest CT scan. Esophageal parameters between patients with and without esophageal dysmotility were compared. Multivariate logistic regression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to fit the model. The diagnostic model was evaluated by discrimination and calibration. Internal validation was estimated using the enhanced bootstrap method with 1000 repetitions. RESULTS Sixty-one systemic sclerosis patients (81.3%) were diagnosed with esophageal dysmotility according to the Chicago Classification v 3.0. The diagnostic model for evaluating the probability of esophageal dysmotility integrated clinical and imaging features, including disease duration, ILD, and WED. The model displayed good discrimination with an area under the curve (AUC) of 0.923 (95% CI: 0.837-1.000), a Brier score of 0.083, and good calibration. A high AUC value of 0.911 could still be achieved in the internal validation. CONCLUSION The diagnostic model, which combines the disease duration, ILD, and imaging feature (WED), is an effective and noninvasive method for predicting esophageal dysmotility in SSc patients.
Collapse
Affiliation(s)
- Peiling Liu
- Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing 100191, China
| | - Jing Chai
- Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing 100191, China
| | - Liyi Dai
- Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing 100191, China
| | - Beidi Chen
- Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing 100191, China
| | - Jinxia Zhao
- Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing 100191, China
| | - Ming Lu
- Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China
- Department of Infectious Diseases, Peking University Third Hospital, Beijing 100191, China
| | - Lin Zeng
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
| | - Zhiwei Xia
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Rong Mu
- Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing 100191, China
- Correspondence:
| |
Collapse
|
|
20
|
Volkmann ER, McMahan Z. Gastrointestinal involvement in systemic sclerosis: pathogenesis, assessment and treatment. Curr Opin Rheumatol 2022; 34:328-336. [PMID: 35993874 PMCID: PMC9547962 DOI: 10.1097/bor.0000000000000899] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW The majority of patients with systemic sclerosis (SSc) will experience involvement of their gastrointestinal over the course of their disease. Despite the high prevalence of gastrointestinal involvement in SSc, the strategies pertaining to the assessment and treatment for this clinical dimension of SSc have historically been limited. However, the present review highlights recent research contributions that enhance our understanding of SSc-GI patient subsets and provides updates on pathogenic mechanisms of disease, assessment and symptom-directed management. RECENT FINDINGS In the past few years, several studies have identified risk factors for more severe gastrointestinal disease in SSc and have provided insight to optimize diagnosis and management of SSc-GI symptoms. This article also provides a review of currently available investigations and therapies for individual SSc-GI disease manifestations and reflects on actively evolving areas of research, including our understanding the role of the gut microbiome in SSc. SUMMARY Here, we provide important updates pertaining to the risk stratification, assessment, diagnosis and management of SSc patients with gastrointestinal symptoms. These findings provide opportunities to enhance patient care and highlight exciting opportunities for future research.
Collapse
Affiliation(s)
- Elizabeth R. Volkmann
- Division of Rheumatology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Zsuzsanna McMahan
- Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
21
|
Keane N, Ghannam A, Konstantinos C. Fragkos, Rahman F. Oral, Enteral and Parenteral Nutritional Therapies in Scleroderma: a Systematic Review. Clin Nutr ESPEN 2022; 51:174-184. [DOI: 10.1016/j.clnesp.2022.06.108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 06/16/2022] [Accepted: 06/28/2022] [Indexed: 11/17/2022]
|
|
22
|
Marabotto E, Savarino V, Savarino E. Towards a more precise classification of esophageal motility disorders in patients with systemic sclerosis. Neurogastroenterol Motil 2022; 34:e14416. [PMID: 35593267 DOI: 10.1111/nmo.14416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 04/21/2022] [Accepted: 05/04/2022] [Indexed: 02/08/2023]
Abstract
Systemic sclerosis (SSc) is a chronic and generalized disease affecting the connective tissue of the skin and many internal organs, in particular the gastrointestinal tract. The esophagus is involved in up to 80% of the cases and represents a major cause of serious morbidities that deeply impact on the quality of life and survival of patients. Indeed, the presence of esophageal dysfunction is a good prognostic indicator in SSc, primarily due to its impact on pulmonary disease. Thus, the detection of esophageal motility alterations plays a critical role to prevent the development of both esophageal and pulmonary complications and to improve the survival of these patients. Currently, this diagnostic work-up has been limited to the use of esophageal manometry, which is considered the gold standard for the evaluation of motor physiology and pathophysiology of this organ in different clinical situations. However, in recent years, new equipments such as high-resolution (-impedance) manometry and functional luminal imaging probe have been developed and used in many esophageal clinical settings, including SSc. In this mini-review, we summarize current evidence regarding esophageal dysmotility, in the light of new data on secondary peristalsis published in this issue of the journal.
Collapse
Affiliation(s)
- Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.,Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| |
Collapse
|
|
23
|
Carlson DA, Prescott JE, Germond E, Brenner D, Carns M, Correia CS, Tetreault MP, McMahan ZH, Hinchcliff M, Kou W, Kahrilas PJ, Perlman HR, Pandolfino JE. Heterogeneity of primary and secondary peristalsis in systemic sclerosis: A new model of "scleroderma esophagus". Neurogastroenterol Motil 2022; 34:e14284. [PMID: 34709690 PMCID: PMC9046463 DOI: 10.1111/nmo.14284] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 09/27/2021] [Accepted: 10/12/2021] [Indexed: 12/10/2022]
Abstract
BACKGROUND Although esophageal dysmotility is common in systemic sclerosis (SSc)/scleroderma, little is known regarding the pathophysiology of motor abnormalities driving reflux severity and dysphagia. This study aimed to assess primary and secondary peristalsis in SSc using a comprehensive esophageal motility assessment applying high-resolution manometry (HRM) and functional luminal imaging probe (FLIP) Panometry. METHODS A total of 32 patients with scleroderma (28 female; ages 38-77; 20 limited SSc, 12 diffuse SSc) completed FLIP Panometry and HRM. Secondary peristalsis, i.e., contractile responses (CR), was classified on FLIP Panometry by pattern of contractility as normal (NCR), borderline (BCR), impaired/disordered (IDCR), or absent (ACR). Primary peristalsis on HRM was assessed according to the Chicago classification. RESULTS The manometric diagnoses were 56% (n = 18) absent contractility, 22% (n = 7) ineffective esophageal motility (IEM), and 22% (n = 7) normal motility. Secondary peristalsis (CRs) included 38% (n = 12) ACR, 38% (n = 12) IDCR, 19% (n = 6) BCR, and 15% (n = 5) NCR. The median (IQR) esophagogastric junction (EGJ) distensibility index (DI) was 5.8 mm2 /mmHg (4.8-10.1) mm2 /mmHg; EGJ-DI was >8.0 mm2 /mmHg in 31%, and >2.0 mm2 /mmHg in 100% of patients. Among 18 patients with absent contractility on HRM, 11 had ACR, 5 had IDCR, and 2 had BCR. Among 7 patients with IEM, 1 had ACR, 5 had IDCR, and 1 NCR. All of the patients with normal peristalsis had NCR or BCR. CONCLUSIONS This was the first study assessing combined HRM and FLIP Panometry in a cohort of SSc patients, which demonstrated heterogeneity in primary and secondary peristalsis. This complementary approach facilitates characterizing esophageal function in SSc, although future study to examine clinical outcomes remains necessary.
Collapse
Affiliation(s)
- Dustin A. Carlson
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Jacqueline E Prescott
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Emma Germond
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Darren Brenner
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Mary Carns
- Department of Medicine, Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Chase S. Correia
- Department of Medicine, Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Marie-Pier Tetreault
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Zsuzsanna H. McMahan
- Department of Medicine, Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Monique Hinchcliff
- Department of Internal Medicine, Division of Rheumatology, Allergy, and Immunology, Yale School of Medicine, New Haven, CT, USA
| | - Wenjun Kou
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Peter J Kahrilas
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Harris R. Perlman
- Department of Medicine, Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - John E. Pandolfino
- Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| |
Collapse
|
|
24
|
Emil NS, Vondenberg JA, Waters YM, Muruganandam M, Ariza-Hutchinson A, Patel RA, Nunez SE, Gibb JI, McElwee MK, Poole JL, O'Sullivan FX, Fields RA, Sibbitt WL. Systemic sclerosis in Native Americans of the American Southwest. Int J Rheum Dis 2022; 25:916-925. [PMID: 35699136 DOI: 10.1111/1756-185x.14367] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 05/27/2022] [Accepted: 05/30/2022] [Indexed: 11/28/2022]
Abstract
OBJECTIVE Many indigenous non-Caucasian populations, including Native Americans, have been reported to have higher rates, distinct clinical phenotypes, increased complications, and greater severity of systemic sclerosis (SSc). However, little is known of SSc specifically in Native Americans of the American Southwest. This study compared the clinical and serologic manifestations and outcomes of SSc in Native Americans and non-Native Americans (non-Natives) of this region. METHODS This cross-sectional retrospective study included 137 SSc patients (109 [80%] were non-Native and 28 [20%] were Native Americans) followed over a mean of 11.5 ± 7.6 years. Participants were repetitively evaluated with medical history, physical examination, echocardiography, chest imaging, and serologic testing. Disease characteristics and outcomes were statistically compared between Native Americans and non-Native patients. RESULTS The estimated prevalence of SSc in Native Americans was 40.0 cases/100 000 vs 17.1 cases/100 000 for non-Natives (odds ratio 2.34, 95% confidence interval [CI] 1.55-3.55, P < .001). The cohorts were similar in terms age, age of onset, limited vs diffuse cutaneous SSc, telangiectasias, gastroesophageal reflux disease, Raynaud phenomenon, serologies, interstitial lung disease, pulmonary arterial hypertension, scleroderma renal crisis, cancer prevalence, and overall mortality (all P > .05). However, for Native Americans, mortality specifically from fatal infections was 3.94-fold that of non-Natives (hazard ratio 6.88, 95% CI 1.37-34.64; P < .001). CONCLUSION In Native Americans of the American Southwest, SSc is increased in prevalence but is phenotypically similar to SSc in non-Natives. However, mortality due specifically to infection is increased in Native Americans with SSc.
Collapse
Affiliation(s)
- N Suzanne Emil
- Division of Rheumatology and School of Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Jaime A Vondenberg
- Department of Medicine, Rheumatology/Immunology, Cleveland Clinic, Cleveland, Ohio, USA
| | - Yvonne M Waters
- Division of Rheumatology and School of Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Maheswari Muruganandam
- Division of Rheumatology and School of Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Angie Ariza-Hutchinson
- Division of Rheumatology and School of Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Rosemina A Patel
- Division of Rheumatology and School of Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Sharon E Nunez
- Division of Rheumatology and School of Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - James I Gibb
- Division of Rheumatology and School of Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Matthew K McElwee
- Division of Rheumatology and School of Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Janet L Poole
- Division of Rheumatology and School of Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Frank X O'Sullivan
- Division of Rheumatology and School of Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Roderick A Fields
- Division of Rheumatology and School of Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Wilmer L Sibbitt
- Division of Rheumatology and School of Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| |
Collapse
|
|
25
|
Bandini G, Cometi L, Accogli E, Domanico A, Tofani L, Bruni C, Bellando-Randone S, Lepri G, Orlandi M, Guiducci S, El-Aoufy K, Ciuti G, Fabbri A, Matucci-Cerinic M, Moggi-Pignone A. Ultrasound evaluation of bowel vasculopathy in systemic sclerosis. Eur J Intern Med 2022; 100:62-68. [PMID: 35058148 DOI: 10.1016/j.ejim.2022.01.026] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 01/05/2022] [Accepted: 01/13/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastrointestinal (GI) manifestations are frequent in systemic sclerosis (SSc) with an impact on quality of life and morbidity. Bowel vasculopathy is a key pathogenetic factor responsible for GI involvement. OBJECTIVES To compare abdominal ultrasound (US) and Color Doppler Ultrasonography (CDU) features of splanchnic vessels of SSc patients with healthy controls. METHODS The charts of SSc patients who underwent an abdominal US and CDU study were retrospectively analyzed. For Superior Mesenteric Artery (SMA) and Inferior Mesenteric Artery (IMA) caliber, Peak Systolic Velocity (PSV), Reverse Velocity (RV), End-Diastolic Velocity (EDV), Mean Velocity (mV), Blood-flow, Resistive Index (RI) and Pulsatility Index (PI) were recorded. RESULTS 28 SSc patients and 28 controls were enrolled. In SSc, caliber of SMA was significantly smaller than in controls (5.75 ± 0.62 mm vs. 6.45 ± 0.60 mm, p < 0.0001 - p adj =0.0002). The flow study of SMA and IMA showed a significant reduction of RV (SMA: 7.25 ± 6.37 cm/s vs. 18.52 ± 6.16 cm/s, p < 0.0001 - p adj <0.0001; IMA: 2.69 ± 6.10 cm/s vs. 17.06 ± 5.75 cm/s, p < 0.0001 - p adj <0.0001) and PI (SMA: 3.33 ± 0.75 vs. 4.53 ± 1.03, p < 0.0001 - p adj =0.0002; IMA: 3.54 ± 0.95 vs. 6.08 ± 1.53, p < 0.0001 - p adj <0.0001) in SSc patients than controls. CONCLUSION involvement of splanchnic vessels in SSc may be non-invasively investigated with abdominal US and CDU. Morphological and functional changes of Doppler parameters observed in SMA and IMA clearly demonstrate that these vessels are affected by SSc vasculopathy.
Collapse
Affiliation(s)
- Giulia Bandini
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Internal Medicine AOUC, Viale San Luca, Florence 50134, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy.
| | - Laura Cometi
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Esterita Accogli
- Department of Internal Medicine, Centre of Research and Learning in Ultrasound, Maggiore Hospital, Bologna, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Andrea Domanico
- Department of Internal Medicine, Centre of Research and Learning in Ultrasound, Maggiore Hospital, Bologna, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Lorenzo Tofani
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Cosimo Bruni
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Silvia Bellando-Randone
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Gemma Lepri
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Martina Orlandi
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Serena Guiducci
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Khadija El-Aoufy
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Gabriele Ciuti
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Internal Medicine AOUC, Viale San Luca, Florence 50134, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Alessia Fabbri
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Internal Medicine AOUC, Viale San Luca, Florence 50134, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Marco Matucci-Cerinic
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC, Florence, Italy; Unit of Immunology, Rheumatology, Allergy and Rare diseases (UnIRAR), IRCCS San Raffaele Hospital, Milan, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| | - Alberto Moggi-Pignone
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Internal Medicine AOUC, Viale San Luca, Florence 50134, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy; Interventional and Structural Cardiology, Heart, Lung and Vessels Department, AOU Careggi, Italy
| |
Collapse
|
|
26
|
Kobayashi S, Nagafuchi Y, Shoda H, Fujio K. The Pathophysiological Roles of Regulatory T Cells in the Early Phase of Systemic Sclerosis. Front Immunol 2022; 13:900638. [PMID: 35686127 PMCID: PMC9172592 DOI: 10.3389/fimmu.2022.900638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 04/26/2022] [Indexed: 11/13/2022] Open
Abstract
Systemic sclerosis (SSc) is an autoimmune disease that is characterized by vascular damage and fibrosis. Both clinical manifestations and immunological disturbances are diverse according to the disease duration. Particularly, changes in immunological processes are prominent in the early phase of SSc. The orchestration of several subsets of immune cells promotes autoimmune responses and inflammation, and eventually stimulates pro-fibrotic processes. Many reports have indicated that CD4+ T cells play pivotal roles in pathogenesis in the early phase of SSc. In particular, the pathogenic roles of regulatory T (Treg) cells have been investigated. Although the results were controversial, recent reports suggested an increase of Treg cells in the early phase of SSc patients. Treg cells secrete transforming growth factor-β (TGF-β), which promotes myofibroblast activation and fibrosis. In addition, the dysfunction of Treg cells in the early phase of SSc was reported, which results in the development of autoimmunity and inflammation. Notably, Treg cells have the plasticity to convert to T-helper17 (Th17) cells under pro-inflammatory conditions. Th17 cells secrete IL-17A, which could also promote myofibroblast transformation and fibrosis and contributes to vasculopathy, although the issue is still controversial. Our recent transcriptomic comparison between the early and late phases of SSc revealed a clear difference of gene expression patterns only in Treg cells. The gene signature of an activated Treg cell subpopulation was expanded in the early phase of SSc and the oxidative phosphorylation pathway was enhanced, which can promote Th17 differentiation. And this result was accompanied by the increase in Th17 cells frequency. Therefore, an imbalance between Treg and Th17 cells could also have an important role in the pathogenesis of the early phase of SSc. In this review, we outlined the roles of Treg cells in the early phase of SSc, summarizing the data of both human and mouse models. The contributions of Treg cells to autoimmunity, vasculopathy, and fibrosis were revealed, based on the dysfunction and imbalance of Treg cells. We also referred to the potential development in treatment strategies in SSc.
Collapse
Affiliation(s)
- Satomi Kobayashi
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan
- Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Japan
| | - Yasuo Nagafuchi
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan
- Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan
| | - Hirofumi Shoda
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan
| | - Keishi Fujio
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan
| |
Collapse
|
|
27
|
Snyder DL, Katzka DA. Complex Gastroesophageal Reflux Disease. GASTRO HEP ADVANCES 2022; 1:420-430. [PMID: 39131678 PMCID: PMC11307939 DOI: 10.1016/j.gastha.2022.02.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 02/15/2022] [Indexed: 08/13/2024]
Abstract
Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disorder posing diagnostic and therapeutic challenges. Diagnosis should be objectively defined with endoscopy and pH testing, while novel metrics may augment diagnosis for inconclusive GERD cases, including the postreflux swallow-induced peristaltic wave index and esophageal mucosal impedance. Conditions that overlap with or mimic GERD should be considered such as achalasia, rumination, and eosinophilic esophagitis. Genetic testing for proton pump inhibitor metabolism is an option for precision therapy in complex persistent GERD. Proton pump inhibitor refractory GERD may require medical, surgical, or endoscopic therapies. The presence of GERD should be objectively evaluated in achalasia patients treated with peroral endoscopic myotomy, and further studies are needed to determine timing of this evaluation. Patients with scleroderma are at a high risk for GERD owing to abnormal esophageal motility and should be managed with aggressive medical therapy and lifestyle changes given the high prevalence of esophagitis and Barrett's esophagus in this population. Further studies are needed to understand the complex mechanisms of GERD in idiopathic pulmonary fibrosis and lung transplantation.
Collapse
|
|
28
|
McMahan ZH, Tucker AE, Perin J, Volkmann ER, Kulkarni S, Ziessman HA, Pasricha PJ, Wigley FM. Relationship Between Gastrointestinal Transit, Medsger Gastrointestinal Severity, and University of California-Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 Symptoms in Patients With Systemic Sclerosis. Arthritis Care Res (Hoboken) 2022; 74:442-450. [PMID: 33064934 PMCID: PMC8050123 DOI: 10.1002/acr.24488] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 09/22/2020] [Accepted: 10/13/2020] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Systemic sclerosis (SSc)-associated gastrointestinal (GI) complications are attributed to a variety of factors, including diet, microbiota dysbiosis, or GI transit abnormalities. Our objective was to examine the contribution of abnormal GI transit to SSc Medsger GI severity scores and/or University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA GIT) 2.0 symptoms. METHODS Patients with SSc and GI symptoms (n = 71) and healthy controls (n = 18) underwent whole gut transit (WGT) scintigraphy to assess transit from the esophagus to the colon. The presence of delayed transit and percent emptying in each GI region were measured. We compared the WGT measurements between categories of the Medsger GI severity score (0-4) and across UCLA GIT 2.0 domains and total score (0-3). RESULTS A total of 88% of patients had >1 abnormal region of the gut on WGT scintigraphy. All patients requiring total parenteral nutrition had delayed small bowel transit, compared to only approximately 11% of patients in other Medsger GI severity groups (P ≤ 0.01). Severe colonic transit delays were more likely in patients with Medsger GI scores of 3 (pseudo-obstruction and/or malabsorption) compared to other Medsger GI groups (P = 0.02). Seventy-percent of these patients had ≤30% colonic emptying at 72 hours. Modest associations were noted between gastroesophageal reflux disease symptoms and delayed esophageal (r = -0.31, P = 0.05) and gastric emptying (r = -0.32, P = 0.05). CONCLUSION These data are important in providing evidence that SSc bowel disease affects transit of GI content and that delay in transit accounts in part for both bowel symptoms and Medsger GI severity. Prospective studies examining the benefit of early therapeutic intervention targeting GI transit abnormalities in patients at high risk for severe GI complications are needed.
Collapse
Affiliation(s)
| | - Ana E Tucker
- Johns Hopkins Bayview Medical Center, Baltimore, Maryland
| | - Jamie Perin
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | | | | | | | | | | |
Collapse
|
|
29
|
Cardoneanu A, Burlui AM, Macovei LA, Bratoiu I, Richter P, Rezus E. Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6? Biomedicines 2022; 10:318. [PMID: 35203527 PMCID: PMC8869570 DOI: 10.3390/biomedicines10020318] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/25/2022] [Accepted: 01/26/2022] [Indexed: 12/04/2022] Open
Abstract
Systemic sclerosis (SS) is a chronic autoimmune disorder, which has both cutaneous and systemic clinical manifestations. The disease pathogenesis includes a triad of manifestations, such as vasculopathy, autoimmunity, and fibrosis. Interleukin-6 (IL-6) has a special role in SS development, both in vascular damage and in the development of fibrosis. In the early stages, IL-6 participates in vascular endothelial activation and apoptosis, leading to the release of damage-associated molecular patterns (DAMPs), which maintain inflammation and autoimmunity. Moreover, IL-6 plays an important role in the development of fibrotic changes by mediating the transformation of fibroblasts into myofibroblasts. All of these are associated with disabling clinical manifestations, such as skin thickening, pulmonary fibrosis, pulmonary arterial hypertension (PAH), heart failure, and dysphagia. Tocilizumab is a humanized monoclonal antibody that inhibits IL-6 by binding to the specific receptor, thus preventing its proinflammatory and fibrotic actions. Anti-IL-6 therapy with Tocilizumab is a new hope for SS patients, with data from clinical trials supporting the favorable effect, especially on skin and lung damage.
Collapse
Affiliation(s)
- Anca Cardoneanu
- Department of Rheumatology, University of Medicine and Pharmacy “Grigore T Popa”, 700115 Iasi, Romania; (A.M.B.); (L.A.M.); (I.B.); (P.R.); (E.R.)
- Rehabilitation Hospital, 700661 Iasi, Romania
| | - Alexandra Maria Burlui
- Department of Rheumatology, University of Medicine and Pharmacy “Grigore T Popa”, 700115 Iasi, Romania; (A.M.B.); (L.A.M.); (I.B.); (P.R.); (E.R.)
- Rehabilitation Hospital, 700661 Iasi, Romania
| | - Luana Andreea Macovei
- Department of Rheumatology, University of Medicine and Pharmacy “Grigore T Popa”, 700115 Iasi, Romania; (A.M.B.); (L.A.M.); (I.B.); (P.R.); (E.R.)
- Rehabilitation Hospital, 700661 Iasi, Romania
| | - Ioana Bratoiu
- Department of Rheumatology, University of Medicine and Pharmacy “Grigore T Popa”, 700115 Iasi, Romania; (A.M.B.); (L.A.M.); (I.B.); (P.R.); (E.R.)
- Rehabilitation Hospital, 700661 Iasi, Romania
| | - Patricia Richter
- Department of Rheumatology, University of Medicine and Pharmacy “Grigore T Popa”, 700115 Iasi, Romania; (A.M.B.); (L.A.M.); (I.B.); (P.R.); (E.R.)
- Rehabilitation Hospital, 700661 Iasi, Romania
| | - Elena Rezus
- Department of Rheumatology, University of Medicine and Pharmacy “Grigore T Popa”, 700115 Iasi, Romania; (A.M.B.); (L.A.M.); (I.B.); (P.R.); (E.R.)
- Rehabilitation Hospital, 700661 Iasi, Romania
| |
Collapse
|
|
30
|
Showalter K, Hoffmann A, Richardson C, Aaby D, Lee J, Dematte J, Agrawal R, Savas H, Wu X, Chang RW, Hinchcliff M. Esophageal Dilation and Other Clinical Factors Associated With Pulmonary Function Decline in Patients With Systemic Sclerosis. J Rheumatol 2021; 48:1830-1838. [PMID: 34266985 PMCID: PMC8985598 DOI: 10.3899/jrheum.210533] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2021] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To identify clinical factors, including esophageal dilation on chest high-resolution computed tomography (HRCT), that are associated with pulmonary function decline in patients with systemic sclerosis (SSc). METHODS Patients fulfilled 2013 SSc criteria and had ≥ 1 HRCT and ≥ 2 pulmonary function tests (PFTs). According to published methods, widest esophageal diameter (WED) and radiographic interstitial lung disease (ILD) were assessed, and WED was dichotomized as dilated (≥ 19 mm) vs not dilated (< 19 mm). Clinically meaningful PFT decline was defined as % predicted change in forced vital capacity (FVC) ≥ 5 and/or diffusion capacity for carbon monoxide (DLCO) ≥ 15. Linear mixed effects models were used to model PFT change over time. RESULTS One hundred thirty-eight patients with SSc met the study criteria: 100 (72%) had radiographic ILD; 49 (35%) demonstrated FVC decline (median follow-up 2.9 yrs). Patients with antitopoisomerase I (Scl-70) autoantibodies had 5-year FVC% predicted decline (-6.33, 95% CI -9.87 to -2.79), whereas patients without Scl-70 demonstrated 5-year FVC stability (+1.78, 95% CI -0.59 to 4.15). Esophageal diameter did not distinguish between those with vs without FVC decline. Patients with esophageal dilation had statistically significant 5-year DLCO% predicted decline (-5.58, 95% CI -10.00 to -1.15), but this decline was unlikely clinically significant. Similar results were observed in the subanalysis of patients with radiographic ILD. CONCLUSION In patients with SSc, Scl-70 positivity is a risk factor for FVC% predicted decline at 5 years. Esophageal dilation on HRCT was associated with a minimal, nonclinically significant decline in DLCO and no change in FVC during the 5-year follow-up. These results have prognostic implications for SSc-ILD patients with esophageal dilation.
Collapse
Affiliation(s)
- Kimberly Showalter
- K. Showalter, MD, Northwestern University Feinberg School of Medicine, Department of Medicine, Chicago, Illinois, and Hospital for Special Surgery, Department of Medicine, Division of Rheumatology, New York, New York
| | - Aileen Hoffmann
- A. Hoffmann, MS, Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, Illinois
| | - Carrie Richardson
- C. Richardson, MD, Northwestern University Feinberg School of Medicine, Department of Medicine, Chicago, Illinois
| | - David Aaby
- D. Aaby, MS, Northwestern University Feinberg School of Medicine, Department of Preventive Medicine, Chicago, Illinois
| | - Jungwha Lee
- J. Lee, PhD, MPH, Northwestern University Feinberg School of Medicine, Department of Preventive Medicine, and Institute for Public Health and Medicine, Chicago, Illinois
| | - Jane Dematte
- J. Dematte, MD, MBA, Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Chicago, Illinois
| | - Rishi Agrawal
- R. Agrawal, MD, H. Savas, MD, Northwestern University Feinberg School of Medicine, Department of Radiology, Chicago, Illinois
| | - Hatice Savas
- R. Agrawal, MD, H. Savas, MD, Northwestern University Feinberg School of Medicine, Department of Radiology, Chicago, Illinois
| | - Xiaoping Wu
- X. Wu, MD, MS, New York Presbyterian/Weill Cornell, Department of Medicine, Division of Pulmonary and Critical Care Medicine, New York, New York
| | - Rowland W Chang
- R.W. Chang, MD, MPH, Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Department of Preventive Medicine, and Institute for Public Health and Medicine, Chicago, Illinois
| | - Monique Hinchcliff
- M. Hinchcliff, MD, MS, Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, Illinois, and Yale School of Medicine, Department of Medicine, Section of Rheumatology, Allergy & Immunology, New Haven, Connecticut, USA.
| |
Collapse
|
|
31
|
Abstract
The gastrointestinal tract is the second largest organ system in the body and is often affected by connective tissue disorders. Scleroderma is the classic rheumatologic disease affecting the esophagus; more than 90% of patients with scleroderma have esophageal involvement. This article highlights esophageal manifestations of scleroderma, focusing on pathogenesis, clinical presentation, diagnostic considerations, and treatment options. In addition, this article briefly reviews the esophageal manifestations of other key connective tissue disorders, including mixed connective tissue disease, myositis, Sjogren syndrome, systemic lupus erythematosus, fibromyalgia, and Ehlers-Danlos syndrome.
Collapse
Affiliation(s)
- Nitin K Ahuja
- Division of Gastroenterology and Hepatology, University of Pennsylvania, 3400 Civic Center Boulevard 7 South Pavilion, Philadelphia, PA 19104, USA
| | - John O Clarke
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 430 Broadway Street, Pavilion C, 3rd Floor, C-343, Redwood City, CA 94063-6341, USA.
| |
Collapse
|
|
32
|
Voulgaris TA, Karamanolis GP. Esophageal manifestation in patients with scleroderma. World J Clin Cases 2021; 9:5408-5419. [PMID: 34307594 PMCID: PMC8281422 DOI: 10.12998/wjcc.v9.i20.5408] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/22/2021] [Accepted: 05/10/2021] [Indexed: 02/06/2023] Open
Abstract
The esophagus is the most commonly affected part of the gastrointestinal system in patients with systemic sclerosis (SSc). Esophageal involvement may lead to a significant reduction in patient quality of life. The exact pathophysiology is complex and not yet fully elucidated. Ultimately, esophageal smooth muscle becomes atrophied and replaced by fibrous tissue leading to severe motility disturbance of the distal esophagus. Symptoms are mainly attributed to gastroesophageal reflux disease and to esophageal dysmotility. Compelling evidence has correlated esophageal involvement to the severity of pulmonary disease. No formed guidelines exist about the diagnostic modalities used to assess esophageal disease in patients with SSc, though upper gastrointestinal endoscopy is the first and most important modality used as it can reveal alterations commonly observed in patients with SSc. Further exploration can be made by high resolution manometry and pH-impedance study. Proton pump inhibitors remain the mainstay of treatment, while prokinetic agents are commonly used as add-on therapy in patients with symptoms attributed to gastroesophageal reflux disease not responding to standard therapy as well as to motility disturbances. Gastroesophageal reflux disease symptoms in patients with SSc are frequently difficult to manage, and new therapeutic modalities are emerging. The role of surgical treatment is restricted and should only be preserved for resistant cases.
Collapse
Affiliation(s)
- Theodoros A Voulgaris
- Department of Gastroenterology and Hepatology, Laiko General Hospital, National and Kapodistian University of Athens, Athens 11527, Greece
| | - Georgios P Karamanolis
- Department of Gastroenterology and Hepatology, Laiko General Hospital, National and Kapodistian University of Athens, Athens 11527, Greece
| |
Collapse
|
|
33
|
Delaney FT, Fenlon HM, Buckley B, Welaratne I, Cronin CG. Multimodality imaging of the gastrointestinal manifestations of scleroderma. Clin Radiol 2021; 76:640-649. [PMID: 34108098 DOI: 10.1016/j.crad.2021.04.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 04/21/2021] [Indexed: 11/29/2022]
Abstract
Scleroderma is a complex multisystem connective tissue disorder. Early visceral disease, such as gastrointestinal (GI) involvement, is associated with significant morbidity and a poorer prognosis. Prompt diagnosis is crucial to allow disease modifying therapies be initiated early in the course of the disease. The primary underlying pathophysiology in the GI tract is dysmotility, muscular atrophy, and fibrosis, and this is reflected in the imaging features. In this paper, we demonstrate the imaging appearances of involvement of the GI tract and describe the use of advanced imaging with magnetic resonance enterography (MRE). A multimodal imaging approach is required to identify both characteristic features of scleroderma and potential complications. Traditional fluoroscopic contrast (barium) studies are still commonly performed for assessment of the oesophagus. More recent advances in cross-sectional imaging allow for thorough three-dimensional assessment of the entire GI tract. MRE is particularly useful for small bowel evaluation while also allowing "pseudodynamic" functional imaging and concomitant assessment of the other abdominal viscera and structures.
Collapse
Affiliation(s)
- F T Delaney
- Radiology Department, Mater Misericordiae University Hospital, Dublin, Ireland.
| | - H M Fenlon
- Radiology Department, Mater Misericordiae University Hospital, Dublin, Ireland
| | - B Buckley
- Radiology Department, Mater Misericordiae University Hospital, Dublin, Ireland
| | - I Welaratne
- Radiology Department, Mater Misericordiae University Hospital, Dublin, Ireland
| | - C G Cronin
- Radiology Department, Mater Misericordiae University Hospital, Dublin, Ireland
| |
Collapse
|
|
34
|
Galli J, Marchese MR, De Canio C, Mandiello M, Mangone GM, Padula AA, Abignano G, Santandrea L, Paludetti G. Upper dysphagia in patients affected by systemic sclerosis: prevalence and features. ACTA ACUST UNITED AC 2021; 40:204-210. [PMID: 32773782 PMCID: PMC7416371 DOI: 10.14639/0392-100x-n0477] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 03/20/2020] [Indexed: 12/27/2022]
Abstract
Herein, we describe the prevalence and features of dysphagia in patients affected by systemic sclerosis (SS). We analysed the data of 19 patients obtained by administering the M.D. Anderson Dysphagia Inventory (MDADI) scale that measures dysphagia symptoms and by physical assessment consisting of judging specific lip, mandible and tongue performances (scale 0-3) and diadochokinesis, respiratory and phonatory functions (scale “poor”, “fair”, “good”, “normal”) according to Robertson’s method. Subjects also underwent flexible endoscopic examination of swallowing. MDADI showed that 74% of answers were included in “mild” class of disability, 21% as “moderate” and 5% as “severe”. The performance of lips, mandible and tongue that most frequently scored 1 were the opening (52.6% for the lips and 47.4% for the mandible) and the pop of the tongue (52.7%). The percentage of compromised respiratory, phonatory and diadochokinesis tests (“poor” or “fair”) was 81%, 70.1% and 74%, respectively. Flexible endoscopic examination of swallowing revealed pharyngolaryngeal sensory deficit and signs of oropharyngeal dysphagia in more than half of cases (58% and 53%, respectively). This study highlights the presence of dysphagia in SS patients and demonstrates the importance of a multidimensional approach that includes subjective and objective evaluation to characterise specific features of swallowing alterations that have a high-impact on upper dysphagia.
Collapse
Affiliation(s)
- Jacopo Galli
- Department of Aging, Neuroscience, Orthopedics and Head and Neck Sciences, UOC of Otorhinolaryngology, Istituto di Otorinolaringoiatria "Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore", Roma, Italy
| | - Maria Raffaella Marchese
- Department of Aging, Neuroscience, Orthopedics and Head and Neck Sciences, UOC of Otorhinolaryngology, "Fondazione Policlinico Universitario A. Gemelli IRCCS", Roma, Italy
| | | | | | | | - Angela Anna Padula
- Rheumatology Institute of Lucania (IReL) and Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, Italy
| | - Giuseppina Abignano
- Rheumatology Institute of Lucania (IReL) and Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, Italy
| | | | - Gaetano Paludetti
- Department of Aging, Neuroscience, Orthopedics and Head and Neck Sciences, UOC of Otorhinolaryngology, Istituto di Otorinolaringoiatria "Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore", Roma, Italy
| |
Collapse
|
|
35
|
Ma L, Zhu Q, Zhang Y, Li J, Jiang Y, Xu D, Zeng X, Hou Y, Liu H. Esophagus involvement in systemic sclerosis: ultrasound parameters and association with clinical manifestations. Arthritis Res Ther 2021; 23:122. [PMID: 33882993 PMCID: PMC8059267 DOI: 10.1186/s13075-021-02505-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 04/06/2021] [Indexed: 11/16/2022] Open
Abstract
Background The esophagus involvement in systemic sclerosis (SSc) is very common yet underestimated due to the lack of suitable screening tools. This study aims to explore the usefulness of ultrasound (US) in the assessment of esophagus involvement and to identify its relationship with clinical and CT manifestations. Methods We performed transabdominal esophageal US in 38 SSc patients and 38 controls. US parameters including the abdominal esophagus length, esophagus wall thickness, shear-wave elastography, gastro-esophageal (His) angle, and reflux were compared. Relationships between distinguishable US parameters and clinical/CT parameters, such as gastro-esophageal reflux disease questionnaire (GERDQ), modified Rodnan skin score (mRSS), interstitial lung disease (ILD) score, the largest esophagus diameter (Dmax), and esophagus dilation percentage (%Eop), were evaluated. Results Abdominal esophagus length was shorter in the SSc group than the control group (2.69 cm vs 3.06 cm, P = 0.018), whereas His angle and the angle change before and after drinking water were larger in the SSc group than the control group (121° vs 108°, P < 0.001; 7.97° vs 2.92°, P = 0.025). Reflux was more frequently seen in the SSc group than the control group (7/38 vs 0/38; P = 0.017). As for correlation with clinical and CT parameters, His angle was higher in patients with GERDQ ≥ 8 than GERDQ < 8 (116.5° vs 125.6°, P = 0.035). Patients with reflux showed higher ILD score than patients without (15.8 vs 9.6, P = 0.043). Furthermore, abdominal esophagus length was negatively correlated with %Eop and Dmax (r = − 0.573, P < 0.001; r = − 0.476, P = 0.003). Conclusion US parameters of the esophagus can distinguish SSc patients from controls, as well as have correlations with clinical and CT characteristics. Our pilot study first shows that US can be used as a noninvasive and convenient method to evaluate the esophagus involvement in SSc.
Collapse
Affiliation(s)
- Li Ma
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Qingli Zhu
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Yan Zhang
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Jianchu Li
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Yuxin Jiang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Dong Xu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China
| | - Yong Hou
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China.
| | - He Liu
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Street, Dongcheng District, Beijing, 100730, China.
| |
Collapse
|
|
36
|
Prevalence of Barrett's Esophagus in Female Patients With Scleroderma. Am J Gastroenterol 2021; 116:517-521. [PMID: 33657040 DOI: 10.14309/ajg.0000000000001109] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Accepted: 11/17/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Systemic sclerosis or scleroderma (SSc) is a chronic autoimmune disease that renders the esophagus prone to significant gastroesophageal reflux due to impaired esophageal clearance and reduced lower esophageal sphincter pressure. The reported prevalence of Barrett's esophagus (BE) in women with SSc varies from 2% to 37% and is derived from older studies with small sample sizes. We aimed to assess the prevalence of BE in a large cohort of women with SSc. METHODS Women with SSc referred from the Mayo Clinic Arizona Rheumatology Clinic who completed esophagogastroduodenoscopy between 2002 and 2020 were included. Demographic and high-resolution manometry data were evaluated. The diagnosis of scleroderma was confirmed by an expert rheumatologist. The BE diagnosis was confirmed by an expert gastrointestinal pathologist. RESULTS There were 235 women with SSc who underwent EGD. High-resolution manometry (HRM) was completed in 172 patients. Women with SSc with BE were significantly more likely to have scleroderma esophagus (absent contractility with hypotensive lower esophageal sphincter) on HRM than women with SSc without BE (P = 0.018). There were 30 patients with SSc (12.8%) with histologically proven BE. Dysplasia was found in 13 (43.3%): 4 with indefinite, 7 with low grade, and 2 with adenocarcinoma. The incidence of any dysplasia was 5.3% per year (0.9% per year for adenocarcinoma). DISCUSSION This the largest study on prevalence of BE in women with SSc, yielding a prevalence of 12.8%. Women with SSc with BE were significantly more likely to have absent contractility with hypotensive lower esophageal sphincter findings on HRM. The high prevalence and incidence of dysplasia found suggest that women with SSc should be included in the screening recommendations for BE.
Collapse
|
|
37
|
Abignano G, Mennillo GA, Lettieri G, Karadag DT, Carriero A, Padula AA, Del Galdo F, Khanna D, D’Angelo S. UCLA Scleroderma Clinical Trials Consortium Gastrointestinal Tract (GIT) 2.0 Reflux Scale Correlates With Impaired Esophageal Scintigraphy Findings in Systemic Sclerosis. J Rheumatol 2021; 48:1422-1426. [PMID: 33452163 PMCID: PMC10374195 DOI: 10.3899/jrheum.201283] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2020] [Indexed: 12/15/2022]
Abstract
ObjectiveThe University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (GIT 2.0) instrument is a self-report tool measuring gastrointestinal (GI) quality of life in patients with systemic sclerosis (SSc). Scarce data are available on the correlation between patient-reported GI symptoms and motility dysfunction as assessed by esophageal transit scintigraphy (ETS).MethodsWe evaluated the GIT 2.0 reflux scale in patients with SSc admitted to our clinic and undergoing ETS, and correlated their findings.ResultsThirty-one patients with SSc undergoing ETS were included. Twenty-seven were female, and 9 had diffuse cutaneous SSc. Twenty-six of 31 (84%) patients had a delayed transit and an abnormal esophageal emptying activity (EA); they also had a higher GIT 2.0 reflux score (P = 0.04). Mean EA percentage was higher in patients with none to mild GIT 2.0 reflux score (81.1 [SD 11.5]) than in those with moderate (55.7 [SD 17.8], P = 0.003) and severe to very severe scores (55.8 [SD 19.7], P = 0.002). The percentage of esophageal EA negatively correlated with the GIT 2.0 reflux score (r = –0.68, P < 0.0001), but it did not correlate with the other GIT 2.0 scales and the total GIT 2.0 score.ConclusionSSc patients with impaired ETS findings have a higher GIT 2.0 reflux score. The GIT 2.0 is a complementary tool for objective measurement of esophageal involvement that can be easily administered in day-to-day clinical assessment.
Collapse
|
|
38
|
Imaging in Diagnosis of Systemic Sclerosis. J Clin Med 2021; 10:jcm10020248. [PMID: 33445449 PMCID: PMC7827740 DOI: 10.3390/jcm10020248] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 12/28/2020] [Accepted: 01/08/2021] [Indexed: 12/27/2022] Open
Abstract
Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis in skin and internal organs, progressive vascular obliteration, and the production of autoantibodies. Diagnostic imaging is irreplaceable in both diagnosing and monitoring patients suffering from systemic sclerosis. In addition to routinely used methods, such as comparative X-ray of the hands or a contrast-enhanced examination of the upper gastrointestinal tract or chest, there is an array of less widespread examinations, with an emphasis on magnetic resonance imaging (MRI) and ultrasonography, not only in the evaluation of the musculoskeletal system. This article will review the various imaging modalities available for SSc imaging and assessment, focusing on their utility as tissue-specific diagnosis and treatment monitoring.
Collapse
|
|
39
|
Akiyama J, Sumida J, Nakagawa K, Masamune A, Issariyakulkarn N, Patcharatrakul T, Shetler K, Kuribayashi S, Uraoka T, Triadafilopoulos G. New developments in esophageal function testing and esophageal manifestations of connective tissue disorders. Ann N Y Acad Sci 2020; 1481:170-181. [DOI: 10.1111/nyas.14424] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 05/25/2020] [Accepted: 06/09/2020] [Indexed: 12/31/2022]
Affiliation(s)
- Junichi Akiyama
- Division of Gastroenterology and Hepatology National Center for Global Health and Medicine Tokyo Japan
| | - Junko Sumida
- Division of Gastroenterology and Hepatology National Center for Global Health and Medicine Tokyo Japan
| | - Kenichiro Nakagawa
- Division of Gastroenterology Tohoku University Graduate School of Medicine Sendai Japan
| | - Atsushi Masamune
- Division of Gastroenterology Tohoku University Graduate School of Medicine Sendai Japan
| | - Navapan Issariyakulkarn
- Division of Gastroenterology King Chulalongkorn Memorial Hospital Thai Red Cross Society Bangkok Thailand
| | - Tanisa Patcharatrakul
- Division of Gastroenterology King Chulalongkorn Memorial Hospital Thai Red Cross Society Bangkok Thailand
- Center of Excellence in Neurogastroenterology and Motility, Department of Medicine, Faculty of Medicine Chulalongkorn University Bangkok Thailand
| | - Katerina Shetler
- Department of Gastroenterology Palo Alto Medical Foundation Mountain View California
| | - Shiko Kuribayashi
- Department of Gastroenterology and Hepatology Gunma University Graduate School of Medicine Maebashi Japan
| | - Toshio Uraoka
- Department of Gastroenterology and Hepatology Gunma University Graduate School of Medicine Maebashi Japan
| | - George Triadafilopoulos
- Division of Gastroenterology and Hepatology Stanford University School of Medicine Stanford California
| |
Collapse
|
|
40
|
Suliman Y, Kafaja S, Oh SJ, Alemam M, Bagnato G, Abignano G, Singh RR, Barlow G, Liu X, Valera I, Morales W, Rezaie A, Pimentel M, Del Galdo F, Furst DE. Anti-vinculin antibodies in scleroderma (SSc): a potential link between autoimmunity and gastrointestinal system involvement in two SSc cohorts. Clin Rheumatol 2020; 40:2277-2284. [PMID: 33231773 DOI: 10.1007/s10067-020-05479-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 10/11/2020] [Accepted: 10/26/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Systemic sclerosis (SSc) is an autoimmune disorder and commonly presents with vascular system involvement and motility disorders in the gastrointestinal (GI) tract. Vinculin is a cytoskeletal protein that plays major roles in cell-cell adhesion and is expressed in the neuromuscular apparatus of the gut. Antibodies to vinculin have been identified as a biomarker of irritable bowel syndrome (IBS). Our aim was to evaluate serum anti-vinculin antibodies in patients with SSc. METHODS Patients were recruited from two SSc centers: group I (GI-enriched group), University of Leeds, UK, and Group II (vascular predominant), University of California, Los Angeles. Serum samples of patients recruited from two SSc centres, Group I ( GI enriched group), University of Leeds, UK and Group II (Vascular predominant), University of California, Los Angeles) were collected. Samples from age- and sex-matched healthy volunteers (N = 88) were used as controls. RESULTS Group I (GI-enriched group, N = 83) patients were 58 [50-67] years old; 83% were females with a median body mass index (BMI) of 20.3 (21.2 ± 4.5) [18-23]. Group II (vascular-enriched group, N = 72) patients were 58 [50-67] years old; 80% were female, and BMI was 23.9 (21.3-26.9). More subjects in group I had prominent GI involvement (N = 55, 66%) than group II (12, 16%), p ˂ 0.0001. Anti-vinculin antibody levels in SSc group I (1.3 [0.9]) were significantly higher than in HC (0.7 [0.8]; p = 0.002). When pooled, circulating anti-vinculin levels in both SSc groups remained significantly higher than in the HC group (p = 0.02). Higher anti-vinculin levels were associated with higher GI-visual analogue scale (GI-VAS) scores and specifically with GI-VAS scores of ≥ 4 (p < 0.0001). CONCLUSION This study demonstrates that elevated anti-vinculin antibody levels are common in SSc and suggests a potential link between increased anti-vinculin levels and GI tract symptoms. KEY POINTS • Anti-vinculin antibodies are elevated in systemic sclerosis and are relatively common. • In these SSc patients, anti-vinculin antibodies are associated with higher levels of GI symptoms in SSc. • A potential link between anti-vinculin antibodies and vascular system involvement was shown.
Collapse
Affiliation(s)
- Yossra Suliman
- Division of Rheumatology, Department of Internal Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.,Rheumatology and Rehabilitation Department, Assiut University Hospital, Assiut, Egypt
| | - Suzanne Kafaja
- Division of Rheumatology, Department of Internal Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Sunny J Oh
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Mohamed Alemam
- Clinical Pathology and Laboratory Medicine Department, Qena faculty of Medicine, South Valley University, Qena, Egypt
| | - Gianluca Bagnato
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Giuseppina Abignano
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.,San Carlo Hospital, Rheumatology Institute of Lucania (IReL), Potenza, Italy
| | - Ram Raj Singh
- Division of Rheumatology, Department of Internal Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Gillian Barlow
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Xiaochen Liu
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Isela Valera
- Division of Rheumatology, Department of Internal Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Walter Morales
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Ali Rezaie
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Mark Pimentel
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Francesco Del Galdo
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Daniel E Furst
- Division of Rheumatology, Department of Internal Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. .,Division of Rheumatology, University of Washington, Seattle, WA, USA. .,Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy.
| |
Collapse
|
|
41
|
Kaniecki T, Abdi T, McMahan ZH. Clinical Assessment of Gastrointestinal Involvement in Patients with Systemic Sclerosis. ACTA ACUST UNITED AC 2020; 8. [PMID: 34337149 DOI: 10.18103/mra.v8i10.2252] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Systemic sclerosis (SSc) has the potential to affect any component of the gastrointestinal (GI) tract. GI involvement in SSc is a leading cause of morbidity and overall decreased quality of life in this patient population, identifying a need for a concise approach to work-up. This literature review aims to present a systematic, anatomical approach and differential diagnosis of GI involvement in SSc for the general internist and rheumatologist. Each component of the luminal GI tract has its own specified section, beginning with a review of a clinical approach to diagnosis that includes a differential for clinicians to consider, followed by a discussion of the literature surrounding objective evaluation of these conditions (i.e. serologic studies, imaging, endoscopy). Additionally there is a focused discussion on an approach to GI bleeding in the patient with SSc.
Collapse
Affiliation(s)
| | - Tsion Abdi
- Johns Hopkins University, Division of Gastroenterology
| | | |
Collapse
|
|
42
|
Comparing Clinical, Imaging, and Physiological Correlates of Intestinal Pseudo-Obstruction: Systemic Sclerosis vs Amyloidosis and Paraneoplastic Syndrome. Clin Transl Gastroenterol 2020; 11:e00206. [PMID: 32931184 PMCID: PMC7410023 DOI: 10.14309/ctg.0000000000000206] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Intestinal pseudo-obstruction is characterized by impaired transit and luminal dilation in the absence of mechanical obstruction. Our study aims to describe the clinical, radiographic, and physiological findings in pseudo-obstruction associated with systemic sclerosis (SSc), amyloidosis, and paraneoplastic syndrome. METHODS A retrospective cohort of patients evaluated at our institution between January 1, 2008, and August 1, 2018, was assembled. Clinical, imaging, and physiological characteristics were abstracted from electronic medical records. RESULTS We identified 100 cases of pseudo-obstruction (55 SSc, 27 amyloidosis, and 18 paraneoplastic). Female population predominance was seen in SSc (71%) vs male population in amyloidosis (74%). Most common symptom was abdominal bloating in all 3 groups. Vomiting was more common in SSc than amyloidosis (73% vs 46%, P = 0.02). Diarrhea was more common in amyloidosis and SSc compared with paraneoplastic (81% and 67% vs 28%, P < 0.01). Weight loss (>5%) was more common in SSc compared with amyloidosis and paraneoplastic (78% vs 31% and 17%, P < 0.0001). Only small bowel dilation was seen in 79%, 40%, and 44% and only large bowel dilation in 2%, 44%, and 44% of patients in SSc, amyloidosis, and paraneoplastic, respectively. Five of 8 SSc patients had myopathic and 3 of 5 paraneoplastic had neuropathic involvement on gastroduodenal manometry. DISCUSSION SSc-associated pseudo-obstruction demonstrates female population predominance and presents with vomiting, diarrhea, and weight loss. Amyloidosis-associated pseudo-obstruction shows male population predominance. Small bowel is more commonly involved than large bowel on both imaging and transit studies in SSc. Myopathic involvement was more common in SSc, contrary to neuropathic in paraneoplastic syndrome.
Collapse
|
|
43
|
Nicola S, Rolla G, Bucca C, Geronazzo G, Ridolfi I, Ferraris A, Fusaro E, Peroni CL, Dughera L, Brussino L. Gastric Juice Expression of Th-17 and T-Reg Related Cytokines in Scleroderma Esophageal Involvement. Cells 2020; 9:E2106. [PMID: 32947843 PMCID: PMC7564480 DOI: 10.3390/cells9092106] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 09/07/2020] [Accepted: 09/11/2020] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Systemic sclerosis (SSc) is a connective tissue disorder which key feature is a fibrotic process. The role of Endothelin-1 (ET-1) and T-helper (Th)-1 cells in lung and skin fibrosis is well known, although Th17- and Treg-cells were found to be involved. However, no studies analyzed cytokines expression in gastric-juice of SSc patients. Our study aimed to evaluate proinflammatory and profibrotic cytokines in gastric-juice of SSc patients and to investigate their correlations with esophageal dysmotility. METHODS Patients performed upper-gastrointestinal-endoscopy with gastric-juice collection, esophageal manometry and thoracic CT-scan. GM-CSF, ET-1, Th-1 (IFN-γ, IL-1β, TNF-α, IL-2, IL-6, IL-9), Th-17 (IL-17, IL-21, IL-22, IL-23) and T-reg (IL-10, TGF-β) related cytokines were measured in 29 SSc-patients and 20 healthy-controls. RESULTS Patients showed significant lower levels of IL-6, IL-17, IL-22 and ET-1 (p < 0.005) compared with controls. Patients with atrophic gastritis presented significant lower levels of IL-2, IL-9, IL-6, TGF-β, GM-CSF, IL-17 and ET-1 (p < 0.005) compared to patients without gastritis. Increased values of IL-2, IL-9, IL-1β, IL-17, ET-1 and GM-CSF (p < 0.005) were observed in patients with esophageal impairment. This is the first report of cytokines measurement in gastric juice of patients with SSc. The high IL-17 concentrations in gastric-juice of scleroderma patients with esophageal dysmotility support the signature of Th-17 cells in scleroderma esophageal fibrosis.
Collapse
Affiliation(s)
- Stefania Nicola
- Department of Medical Sciences, Allergy and Clinical Immunology Unit, University of Torino & Mauriziano Hospital, 10128 Turin, Italy; (S.N.); (G.R.); (C.B.); (G.G.); (I.R.)
| | - Giovanni Rolla
- Department of Medical Sciences, Allergy and Clinical Immunology Unit, University of Torino & Mauriziano Hospital, 10128 Turin, Italy; (S.N.); (G.R.); (C.B.); (G.G.); (I.R.)
| | - Caterina Bucca
- Department of Medical Sciences, Allergy and Clinical Immunology Unit, University of Torino & Mauriziano Hospital, 10128 Turin, Italy; (S.N.); (G.R.); (C.B.); (G.G.); (I.R.)
| | - Giada Geronazzo
- Department of Medical Sciences, Allergy and Clinical Immunology Unit, University of Torino & Mauriziano Hospital, 10128 Turin, Italy; (S.N.); (G.R.); (C.B.); (G.G.); (I.R.)
| | - Irene Ridolfi
- Department of Medical Sciences, Allergy and Clinical Immunology Unit, University of Torino & Mauriziano Hospital, 10128 Turin, Italy; (S.N.); (G.R.); (C.B.); (G.G.); (I.R.)
| | - Andrea Ferraris
- Division of Diagnostic Imaging, Department of Surgical Sciences, Città della Salute e della Scienza Hospital, University of Turin, 10126 Turin, Italy;
| | - Enrico Fusaro
- Rheumatology Department, Azienda Ospedaliera Città della Salute e della Scienza di Torino, 10126 Turin, Italy; (E.F.); (C.L.P.)
| | - Clara Lisa Peroni
- Rheumatology Department, Azienda Ospedaliera Città della Salute e della Scienza di Torino, 10126 Turin, Italy; (E.F.); (C.L.P.)
| | - Luca Dughera
- Unit of Digestive Motility and Endoscopy, Department of Medicine, Città della Salute e della Scienza, 10126 Turin, Italy;
| | - Luisa Brussino
- Department of Medical Sciences, Allergy and Clinical Immunology Unit, University of Torino & Mauriziano Hospital, 10128 Turin, Italy; (S.N.); (G.R.); (C.B.); (G.G.); (I.R.)
| |
Collapse
|
|
44
|
Intestinal hypomotility in systemic sclerosis: a histological study into the sequence of events. Clin Rheumatol 2020; 40:981-990. [PMID: 32812181 PMCID: PMC7895795 DOI: 10.1007/s10067-020-05325-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 07/16/2020] [Accepted: 08/04/2020] [Indexed: 10/30/2022]
Abstract
OBJECTIVES The pathogenesis of intestinal involvement in systemic sclerosis (SSc) is thought to be a sequential process (vascular, neuronal, and consecutive muscular impairment), but understanding of the underlying histological changes and how they translate to symptoms, is still lacking. Therefore, we systematically investigated histological characteristics of SSc in the intestines, compared to controls. METHODS Autopsy material from the small bowel and colon was used for histological semiquantitative evaluation of the vasculature, enteric nervous system, interstitial cells of Cajal (ICC), and muscle layers, using a combination of histochemical and immunohistochemical stainings, according to guidelines of the Gastro 2009 International Working Group. RESULTS Vascular changes were most frequently encountered, represented by intima fibrosis in both arteries and small vessels, and represented by venous dilatation. Second, generalized fibrosis of the circular muscle layer was significantly more found in SSc patients than in controls. Third, reduction of submucosal nerve fibers and myenteric neurons was shown in the colon of four SSc patients, which may explain severe symptoms of intestinal dysmotility. The density of myenteric ICC network was decreased in the small bowel of SSc patients. CONCLUSIONS The postulated sequential processes of intestinal involvement in SSc could not be supported by our histological evaluation. The interpatient diversity suggests that parallel processes occur, explaining the variety of histological features and clinical symptoms. Key Points • Histological analysis showed vascular changes, fibrosis in the muscularis propria, and reduction of the ENS and ICC network in the intestines of SSc patients. • Pathophysiological mechanisms leading to intestinal dysmotility in SSc may be parallel rather than sequential. • The interpatient diversity suggests parallel pathophysiological processes, explaining the variety of histological features and clinical symptoms.
Collapse
|
|
45
|
Worsening of esophageal dilatation is associated with increase in a high-resolution computed tomography (HRCT) score in early systemic sclerosis-associated interstitial lung disease (SSc-ILD). Clin Rheumatol 2020; 40:955-963. [PMID: 32803568 DOI: 10.1007/s10067-020-05346-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 08/05/2020] [Accepted: 08/11/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Data regarding longitudinal association between changes (Δ: time2-time1) in the widest esophageal diameter (WED) and Δ HRCT score in early SSc-ILD patients is limited. We therefore investigated the association of ΔWED with Δ HRCT score and predictors of a worse Δ HRCT score in those patients. METHODS We used an inception cohort of early SSc-ILD patients with availability for two HRCT records at enrollment and 1-year follow-up.The extent of ground glass, reticulation, bronchiectasis, and honeycombing was scored and then aggregated to produce a total HRCT score. The WED was measured at four levels and the maximum value was used. The Δ maximum WED, Δ mean WED, and Δ tHRCT score were analyzed. RESULTS We recruited 75 early SSc-ILD patients and found a significant correlation of Δ tHRCT score with a Δ maximum WED (rho = 0.34, p < 0.01) and Δ mean WED (rho = 0.26, p < 0.05). There were 34 patients with a worsening Δ tHRCT (Δ > 0), 17 with stability (Δ = 0), and 24 with improvement (Δ < 0). Patients with a worsening ILD had a significantly shorter disease duration, lower prevalence of tendon friction rub, higher cumulative prednisolone dose, and larger ΔWED than those with stable and improved Δ tHRCT scores. Multivariate ordinal logistic regression identified a larger Δ mean WED (OR 1.21, 95% CI 1.03-1.42, p = 0.02) as a predictor of worsening HRCT score, while presence of tendon friction rub was associated with a lower risk (OR 0.18, 95% CI 0.04-0.77, p = 0.021). CONCLUSION Our study cohort found that a worsening esophageal diameter was a predictor of progression of lung fibrosis determined by HRCT score in early SSc-ILD. A further study regarding esophageal dilation progression different in early versus longstanding SSc-ILD is needed. Key Points •In early SSc-ILD patients, we demonstrated that a worsening esophageal diameter was a predictor of progression of HRCT score at 1-year follow-up. •Further study regarding the association of worsening of the esophageal dilatation with the progression of ILD comparing between early versus late SSc-ILD is needed.
Collapse
|
|
46
|
Pauling JD, Caetano J, Campochiaro C, De Luca G, Gheorghiu AM, Lazzaroni MG, Khanna D. Patient-reported outcome instruments in clinical trials of systemic sclerosis. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2020; 5:90-102. [PMID: 35382020 PMCID: PMC8922614 DOI: 10.1177/2397198319886496] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 10/04/2019] [Indexed: 09/01/2023]
Abstract
Patient-reported outcome instruments provide valuable insight into disease-related morbidity known only to the patient and complement more objective outcome tools in the clinical trial setting. They are of particular importance in systemic sclerosis owing to the challenges around defining disease activity, the episodic nature of many disease-specific manifestations and the paucity of validated objective surrogate outcome measures for use in clinical trials. Early clinical trials of systemic sclerosis often incorporated legacy patient-reported outcome instruments, but the last 20 years has witnessed the emergence of several scleroderma-specific instruments that are now being routinely used alongside other outcomes in systemic sclerosis clinical trials. More recently, the value of patient-reported outcomes has been highlighted by their prominence in the American College of Rheumatology Combined Response Index for Systemic Sclerosis that has been utilized as the primary endpoint of recent clinical trials of early diffuse systemic sclerosis. This review considers the role and performance of the various patient-reported outcome instruments utilized in systemic sclerosis clinical trials, the current positioning of patient-reported outcome instruments within clinical trial endpoint models across the range of systemic sclerosis disease manifestations and, where applicable, we shall highlight areas for future research.
Collapse
Affiliation(s)
- John D Pauling
- Royal National Hospital for Rheumatic Diseases, Bath, UK
- Department of Pharmacy & Pharmacology, University of Bath, Bath, UK
| | - Joana Caetano
- Systemic Immune-Mediated Diseases Unit, Department of Medicine IV, Fernando Fonseca Hospital, Amadora, Portugal
| | - Corrado Campochiaro
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
| | - Giacomo De Luca
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
| | - Ana Maria Gheorghiu
- Internal Medicine and Rheumatology, Cantacuzino Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Maria Grazia Lazzaroni
- Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia, Brescia, Italy
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | - Dinesh Khanna
- Scleroderma Program, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA
| |
Collapse
|
|
47
|
Richard N, Hudson M, Wang M, Gyger G, Proudman S, Stevens W, Nikpour M, Baron M. Severe gastrointestinal disease in very early systemic sclerosis is associated with early mortality. Rheumatology (Oxford) 2020; 58:636-644. [PMID: 30517716 DOI: 10.1093/rheumatology/key350] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Accepted: 09/23/2018] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES To examine the incidence, predictors and outcomes associated with severe gastrointestinal (GI) disease in a large inception SSc cohort. METHODS SSc subjects with <2 years of disease duration were identified from two multicentre cohorts. Severe GI disease was defined as: malabsorption, hyperalimentation, pseudo-obstruction and/or ⩾10% weight loss in association with the use of antibiotics for bacterial overgrowth or oesophageal stricture. Kaplan-Meier, multivariate logistic regression and Cox proportional hazard analyses were performed to determine the cumulative incidence rate, independent clinical correlates and mortality rate associated with severe GI disease. A longitudinal mixed model was used to assess the impact of severe GI disease on the Short Form Health Survey. RESULTS In this inception SSc cohort, the probability of developing severe GI disease was estimated at 9.1% at 2 years and 16.0% at 4 years. In multivariate analysis, severe GI disease was associated with inflammatory myositis (odds ratio 4.68, 95% CI 1.65, 13.24), telangiectasias (odds ratio 2.45, 95% CI 1.19, 5.04) and modified Rodnan skin score (odds ratio 1.03, 95% CI 1.01, 1.07). Severe GI disease was associated with a >2-fold increase in the risk of death (hazard ratio 2.27, 95% CI 1.27, 4.09) and worse health-related quality of life [Short Form Health Survey physical (β = -2.37, P = 0.02) and mental (β = -2.86, P = 0.01) component summary scores]. CONCLUSION Severe GI disease is common in early SSc and is associated with significant morbidity and increased mortality. More research is needed to understand, prevent and mitigate severe GI disease in SSc.
Collapse
Affiliation(s)
- Nicolas Richard
- Division of Rheumatology, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.,Department of Medicine, McGill University, Montreal, Quebec, Canada
| | - Marie Hudson
- Department of Medicine, McGill University, Montreal, Quebec, Canada.,Division of Rheumatology, Jewish General Hospital, Montreal, Quebec, Canada.,Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
| | - Mianbo Wang
- Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
| | - Geneviève Gyger
- Department of Medicine, McGill University, Montreal, Quebec, Canada.,Division of Rheumatology, Jewish General Hospital, Montreal, Quebec, Canada
| | - Susanna Proudman
- Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia.,Discipline of Medicine, University of Adelaide, Adelaide, South Australia
| | - Wendy Stevens
- Department of Rheumatology, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - Mandana Nikpour
- Department of Rheumatology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, University of Melbourne at St Vincent's Hospital, Melbourne, Victoria, Australia
| | | | | | - Murray Baron
- Department of Medicine, McGill University, Montreal, Quebec, Canada.,Division of Rheumatology, Jewish General Hospital, Montreal, Quebec, Canada.,Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
| |
Collapse
|
|
48
|
Gatti M, Allois L, Carisio A, Dianzani C, Garcia Martinez M, Ruggirello I, Varello S, Darvizeh F, Faletti R. Magnetic resonance enterography. MINERVA GASTROENTERO 2019; 65:319-334. [PMID: 31760740 DOI: 10.23736/s1121-421x.19.02639-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Crohn's disease is a condition of chronic inflammation that may involve any part of the gastrointestinal tract, although it more frequently affects the terminal ileum. Longstanding inflammation may lead to several bowel complications including obstruction, stricture, fistula and abscesses which often necessitate surgery. Cross-sectional imaging methods such as computed tomography and magnetic resonance imaging are being utilized more frequently to assess mural and extramural inflammatory bowel disease manifestations. Magnetic resonance enterography (MRE) for assessment of small bowel is optimal because of absence of ionizing radiation, better soft tissue contrast, development of motion-free sequences and high resolution images. A typical protocol includes pre and postcontrast sequences utilizing an enteric contrast agent for adequate bowel distention and an antiperistaltic agent. Overall, MRE allows the evaluation of disease activity, extraenteric complication and response to therapy with a great impact on patient management. In this review we discuss the features of MRE from patient's preparation and exam protocol to pathological findings.
Collapse
Affiliation(s)
- Marco Gatti
- Department of Diagnostic and Interventional Radiology, University of Turin, Turin, Italy -
| | - Luca Allois
- Department of Diagnostic and Interventional Radiology, University of Turin, Turin, Italy
| | - Andrea Carisio
- Department of Diagnostic and Interventional Radiology, University of Turin, Turin, Italy
| | - Chiara Dianzani
- Department of Diagnostic and Interventional Radiology, University of Turin, Turin, Italy
| | - Maria Garcia Martinez
- Department of Diagnostic and Interventional Radiology, University of Turin, Turin, Italy
| | - Irene Ruggirello
- Department of Diagnostic and Interventional Radiology, University of Turin, Turin, Italy
| | - Sara Varello
- Department of Diagnostic and Interventional Radiology, University of Turin, Turin, Italy
| | - Fatemeh Darvizeh
- Department of Diagnostic and Interventional Radiology, University of Turin, Turin, Italy
| | - Riccardo Faletti
- Department of Diagnostic and Interventional Radiology, University of Turin, Turin, Italy
| |
Collapse
|
|
49
|
Jubran BB, Bolduc J, Eng A, Stapleton M, Wilson BJ. Off‐label use of aprepitant for scleroderma‐associated nausea and vomiting: A case report. J Clin Pharm Ther 2019; 44:805-808. [DOI: 10.1111/jcpt.12851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 02/22/2019] [Accepted: 04/29/2019] [Indexed: 11/30/2022]
Affiliation(s)
| | | | - Amy Eng
- Peter Lougheed Centre Calgary Alberta Canada
| | - Melanie Stapleton
- University of Calgary Calgary Alberta Canada
- Program of Adult GI Training at the University of Calgary Calgary Alberta Canada
| | - Ben J. Wilson
- General Internal Medicine at the University of Calgary Calgary Alberta Canada
| |
Collapse
|
|
50
|
Smith E, Pauling JD. The efficacy of dietary intervention on gastrointestinal involvement in systemic sclerosis: A systematic literature review. Semin Arthritis Rheum 2019; 49:112-118. [DOI: 10.1016/j.semarthrit.2018.12.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 12/03/2018] [Indexed: 12/19/2022]
|