Gastrointestinal Involvement in Systemic Sclerosis

Introduction: The gastrointestinal tract (GI) is the second most affected organ system in systemic sclerosis or systemic/localized scleroderma (SSc) and is an important topic for research. Approximately 90% of patients with scleroderma exhibit pathology of the GI tract. The systemic scleroderma has the potential to impact any part of the gastrointestinal tract, between the oral cavity and anorectum. The pathological complications of scleroderma adversely impact the health-related quality of life of the affected patients and increase the treatment burden of patients and medical professionals. Study Aim: We summarized the epidemiology, commonly reported clinical manifestations, complications, and available therapies for treating the GI pathology in systemic scleroderma patients. Methodology: We performed a literature review using the keywords "systemic sclerosis," "scleroderma," "GI manifestations in scleroderma," and "GI complications of scleroderma" across databases, including Google Scholar, Medline, Embase, and PubMed. We also analyzed a range of case reports concerning scleroderma manifestations and treatment modalities. Results: Our research revealed the annual incidence of SSc attributing to19.3 cases per million adults in the United States. We found the highest incidence of systemic scleroderma in patients within the age range of 44-55 years. Our results affirmed 5:1 incidence of systemic scleroderma that confirmed the higher impact of this disease condition in females than male populations. We found that the gastrointestinal manifestations of systemic scleroderma predominantly elevate the morbidity and mortality incidence among the affected patients. Esophageal and intestinal manifestations impact 90% and 40-70% of patients with systemic scleroderma. The small bowel hypomotility and small intestinal bacterial overgrowth (SIBO) in systemic scleroderma cases trigger the episodes of malabsorption and malnutrition that eventually add to 50% of the mortality rate. Systemic sclerosis is associated with the high incidence of fecal incontinence that triggers depression and its deleterious mental health manifestations in many clinical scenarios. Conclusion: The gastrointestinal complications in systemic sclerosis potentially deteriorate the daily living activities of the affected patients. The systematic management of the gastrointestinal complications of systemic scleroderma warrants multidisciplinary approaches. Prospective studies should focus on developing targeted therapies for improving the recovery patterns and prognostic outcomes in systemic scleroderma cases.

Download Full-text

Systemic sclerosis and localized scleroderma: Where are we now?

Bőrgyógyászati és Venerológiai Szemle ◽

10.7188/bvsz.2021.97.3.2 ◽

2021 ◽

Vol 97 (3) ◽

pp. 129-143

Author(s):

Gábor Bali ◽

◽

Bernadett Hidvégi ◽

Miklós Sárdy

Keyword(s):

Systemic Sclerosis ◽

Cannabinoid Receptor ◽

Treatment Options ◽

Immunosuppressive Treatment ◽

Treatment Modalities ◽

Localized Scleroderma ◽

Digital Ulcers ◽

Internal Organs ◽

Cannabinoid Receptor 2 ◽

Pulmonary Arterial

Systemic sclerosis is a collagen vascular disease which could lead to fibrosis of the skin and internal organs. It is characterized by a high disease burden and mortality. The 2013 classification criteria system helps to recognize the disease early, which allows prompt intervention and a better survival. In the past few year the recognition of the association between the presence of RNA polimerase III antibodies and malignancies was important. Treatment options of SSc have been improved. Early, intensive immunosuppressive treatment (cyclophosphamide, mycophenolate mofetil) of interstitial lung disease inhibits progression. There are several treatment modalities for the treatment of pulmonary arterial hypertension and digital ulcers (endothelin receptor antagonists, phosphodiesterase 5 inhibitors, prostaglandin analogues). Antifibrotic drugs (nintedanib, riociguate) are also available among former immunosuppressive and vasoactive agents. Lenabasum is a new promising selective cannabinoid receptor 2 agonist, which inhibits inflammation and fibrosis. Localized scleroderma presents a diverse clinical picture. The disease leads to fibrosis of the skin but it is not accompanied with serious inner organ involvement typically seen in systemic sclerosis. Capillaroscopy abnormalities, sclerodactyly and SSc specific antibodies are absent in localized scleroderma . The 2017 EDF guideline formulates a very useful classification, checkup and treatment recommendations.

Download Full-text

Clinical Manifestations of Scleroderma

Pediatrics in Review ◽

10.1542/pir.16.2.49 ◽

1995 ◽

Vol 16 (2) ◽

pp. 49-49

Author(s):

Patricia L. Haber

Keyword(s):

Systemic Sclerosis ◽

Connective Tissue ◽

Clinical Manifestations ◽

Skin Lesions ◽

Localized Scleroderma ◽

Unknown Etiology ◽

Collagen Deposition ◽

Muscle Fibrosis ◽

Favorable Prognosis ◽

Organ Systems

Scleroderma is a connective tissue disease of unknown etiology. Its most characteristic feature is thickening of the skin due to increased collagen deposition. However, the disease may involve multiple other organ systems. Two broad categories of scleroderma have been defined: localized and systemic. Although all forms of scleroderma are rare, localized scleroderma occurs more frequently than systemic sclerosis and has a more favorable prognosis. Several types of localized scleroderma exist. Morphea is characterized by the presence of one or more patches of hard, ivory-colored skin lesions. They begin with erythema and progress to nonpitting edema before becoming sclerotic. The margins of active lesions often have a violaceous hue. Underlying muscle fibrosis and atrophy may occur.

Download Full-text

SAT0283 SOLUBLE GUANYLATE CYCLASE REDUCED THE GASTROINTESTINAL FIBROSIS IN BLEOMYCIN-INDUCED MOUSE MODEL OF SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2768 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1086.1-1086

Author(s):

Y. Yamamoto ◽

T. Okano ◽

T. Nagamoto ◽

Y. Fujikawa ◽

Y. Ichise ◽

...

Keyword(s):

Systemic Sclerosis ◽

Gastrointestinal Tract ◽

Histological Examination ◽

Guanylate Cyclase ◽

Soluble Guanylate Cyclase ◽

Skin Fibrosis ◽

Vascular Lesions ◽

Muscularis Mucosa ◽

Gastrointestinal Complications ◽

Peristaltic Movement

Background:Systemic scleroderma (SSc) is a chronic autoimmune-mediated connective tissue disorder. Although the etiology of the disease remains undermined, SSc is characterized by fibrosis and proliferative vascular lesions of the skin and internal organs. SSc involves the gastrointestinal tract in more than 90% of patients1. Soluble guanylate cyclase (sGC) is used to treat pulmonary artery hypertension (PAH), and has been shown to inhibit experimental skin fibrosis2.Objectives:The aim of this study is to investigate whether bleomycin (BLM)-treated mice show gastrointestinal fibrosis, and find a therapeutic strategy to the lesion.Methods:Female C57BL/6J mice were treated with BLM or normal saline by subcutaneous implantation of osmotic minipump. These mice were sacrificed on day 28 or day 42. Gastrointestinal pathologies were examined by Masson Trichrome staining. The expression of fibrosis-related genes in gastrointestinal tract were analyzed by real-time PCR, and the levels of collagen in the tissue was measured by Sircol collagen assay. To evaluate peristaltic movement, the small intestinal transport (ITR%) was calculated as [Dyeing distance×(Duodenum- Appendix)] -1 ×100 (%). We treated BLM-treated mice with soluble guanylate cyclase (sGC) or DMSO orally and analyzed them on day 42.Results:Histological examination revealed that fibrosis from lamina propria to muscularis mucosa in the esophagus was significantly increased in BLM-treated mice, suggesting that BLM induces esophageal fibrosis in C57BL/6J mice. In addition, the levels of Col3a1 and CTGF were significantly increased in BLM-treated mice. More severe fibrosis was observed in the mice sacrificed on day 42 than the mice sacrificed on day 28. The ITR% was found to be significantly lower in BLM-treated mice, suggesting that gastrointestinal peristaltic movement was reduced in BLM-treated mice. Furthermore, we demonstrated that sGC treatment significantly reduced fibrosis of esophagus and intestine in BLM-treated mice, by histological examination and Sircol collagen assay.Esophagus (Masson’s trichrome stain×100)* One way ANOVA Newman-KeulsConclusion:These findings suggest that BLM induces gastrointestinal fibrosis in C57BL/6J mice, and treatment with sGC improves the BLM-induced gastrointestinal lesion.References:[1]Anton Emmanuel. Current management of the gastrointestinal complications of systemic sclerosis. Nat Rev Gastroenterol Hepatol. 2016; 13: 461-472.[2]Clara Dees, et al. Stimulators of Soluble Guanylate Cyclase (sGC) Inhibit experimental Skin Fibrosis of Different Aetiologies. Ann Rheum Dis. 2015;74 (8): 1621-5.Acknowledgments: :None.Disclosure of Interests:None declared

Download Full-text

Anti-RNA Polymerase III Antibody Prevalence and Associated Clinical Manifestations in a Large Series of French Patients with Systemic Sclerosis: A Cross-sectional Study

The Journal of Rheumatology ◽

10.3899/jrheum.090677 ◽

2009 ◽

Vol 37 (1) ◽

pp. 125-130 ◽

Cited By ~ 41

Author(s):

OLIVIER MEYER ◽

LUC DE CHAISEMARTIN ◽

PASCALE NICAISE-ROLAND ◽

JEAN CABANE ◽

FLORENCE TUBACH ◽

...

Keyword(s):

Systemic Sclerosis ◽

Rna Polymerase ◽

Topoisomerase I ◽

Rna Polymerase Iii ◽

Laboratory Data ◽

Clinical Manifestations ◽

The United States ◽

Cutaneous Disease ◽

Polymerase Iii ◽

Renal Crisis

Objective.To determine the prevalence of anti-RNA polymerase III autoantibodies in French patients with systemic sclerosis (SSc) and to identify the associated clinical manifestations.Methods.Consecutive patients with SSc seen in 3 tertiary centers in Paris were included. Sera samples were collected together with the relevant clinical and immunological data. Anti-RNA polymerase III antibodies were detected by ELISA at a central laboratory. Data on other antibodies were abstracted from the medical records.Results.We included 319 patients: 84% women, 36% with a diffuse cutaneous subtype, 44% with pulmonary fibrosis, 5% with pulmonary hypertension, 4% with renal crisis, among whom 29 (9.4%) had anti-RNA polymerase III antibodies. These antibodies were more prevalent in patients with diffuse than with limited cutaneous disease (14.3% vs 6.0%; OR 2.6, 95% CI 1.2–5.48, p = 0.016). Renal crisis was more prevalent in patients with than in those without anti-RNA polymerase III antibodies (14% vs 3%; OR 5.0, 95% CI 1.4–17.3, p = 0.012). Renal crisis occurred in 2.2% of patients with anti-topoisomerase I and 3.9% of patients with anticentromere antibodies. Of the patients with anti-RNA polymerase III antibodies, 24 (83%) had no other systemic sclerosis-specific autoantibodies.Conclusion.The prevalence of anti-RNA polymerase III antibodies in French patients appeared to be lower than in the United States and similar to that in continental Europe. These antibodies were consistently associated with diffuse cutaneous disease and were the most common immunological marker for renal crisis. Anti-RNA polymerase III determination can help to risk-stratify SSc patients at high risk for this severe manifestation.

Download Full-text

Diagnostics and treatment of foreign bodies in the gastrointestinal tract in children. A literature review

Russian Journal of Pediatric Surgery ◽

10.18821/1560-9510-2020-24-3-198-204 ◽

2020 ◽

Vol 24 (3) ◽

pp. 198-204

Author(s):

H. A. Akilov ◽

Donier R. Asadullaev

Keyword(s):

Gastrointestinal Tract ◽

Foreign Body ◽

Literature Review ◽

Digestive Tract ◽

Foreign Bodies ◽

Surgical Intervention ◽

Treatment Modalities ◽

Clinical Scenarios ◽

Life Threatening ◽

Delay In Treatment

Foreign bodies in the gastrointestinal tract in children is one of the most challenging clinical scenarios which pediatric surgeons and gastroenterologists face. Previously published materials demonstrate that 80% of foreign bodies pass spontaneously through the gastrointestinal digestive tract without any harm to the child’s health, while 20% require endoscopic and/or surgical intervention, since delay in treatment can cause serious life-threatening complications. The present review discusses prevalence of foreign body ingestion in children. It also describes in detail controversial aspects of current diagnostic and treatment modalities.

Download Full-text

Small intestinal bacterial overgrowth in systemic sclerosis

Journal of Scleroderma and Related Disorders ◽

10.1177/2397198319863953 ◽

2019 ◽

Vol 5 (1) ◽

pp. 33-39

Author(s):

Kathleen Morrisroe ◽

Murray Baron ◽

Tracy Frech ◽

Mandana Nikpour

Keyword(s):

Systemic Sclerosis ◽

Gastrointestinal Tract ◽

Clinical Symptoms ◽

Bacterial Overgrowth ◽

Intestinal Bacteria ◽

Small Intestinal Bacterial Overgrowth ◽

Therapeutic Trial ◽

Hydrogen Breath Test ◽

Intestinal Bacterial Overgrowth ◽

Small Intestinal

Systemic sclerosis is a multi-organ autoimmune disease characterized by vasculopathy and fibrosis, and it is arguably the most devastating of the rheumatological diseases. The gastrointestinal tract is the most commonly involved internal organ in systemic sclerosis. Gastrointestinal tract involvement is reported in up to 90% of SSc patients, is the leading cause of morbidity, and is the third most common cause of mortality in this disease. Among all gastrointestinal tract manifestations, small intestinal bacterial overgrowth is one manifestation that may be ameliorated and even eradicated with appropriate treatment, if recognized early. Small intestinal bacterial overgrowth occurs with a prevalence of approximately 39% in systemic sclerosis and presents with a range of non-specific gastrointestinal tract symptoms, including diarrhea, flatulence, abdominal pain, bloating, and early satiety. These manifestations occur due to an alteration and overgrowth of small intestinal bacteria occurring in the setting of gastrointestinal tract dysmotility and slow transit time. The clinical diagnosis of small intestinal bacterial overgrowth is commonly based on the presence of characteristic clinical symptoms together with a positive hydrogen breath test and response to a therapeutic trial of oral antibiotics used sequentially. Almost two-thirds of systemic sclerosis patients with small intestinal bacterial overgrowth have an improvement in their gastrointestinal tract symptoms with rotating antibiotics. Untreated small intestinal bacterial overgrowth can lead to malnutrition, and thus an important aspect of treatment is the identification and treatment of any associated vitamin and mineral deficiencies. This article focuses on small intestinal bacterial overgrowth, an important and understudied area in systemic sclerosis that remains a diagnostic and therapeutic challenge for both patients and clinicians alike.

Download Full-text

A Case of Ulcerated Gastric Mass and Anemia due to Strongyloidiasis

Case Reports in Gastrointestinal Medicine ◽

10.1155/2020/8885990 ◽

2020 ◽

Vol 2020 ◽

pp. 1-3

Author(s):

Monjur Ahmed ◽

Kristen Singer ◽

Cecilia Kelly ◽

Brian O’hara ◽

Curtis Alloy

Keyword(s):

United States ◽

Clinical Practice ◽

Gastrointestinal Tract ◽

Clinical Manifestations ◽

The United States ◽

Review Of The Literature ◽

Intestinal Infection ◽

Disseminated Strongyloidiasis ◽

Gastric Mass

Strongyloidiasis is an intestinal infection caused by the nematode Strongyloides, and it is rarely seen in our clinical practice in the United States. Although it remains localized to the gastrointestinal tract most of the time, it can disseminate to other organs when it causes autoinfection in the setting of immunosuppression. The clinical manifestations vary depending on the involved organ. A case of disseminated strongyloidiasis presenting as a case of ulcerated gastric mass and anemia is described here along with a review of the literature on this condition.

Download Full-text

Antifibrillarin Antibodies Are Associated with Native North American Ethnicity and Poorer Survival in Systemic Sclerosis

The Journal of Rheumatology ◽

10.3899/jrheum.160574 ◽

2017 ◽

Vol 44 (6) ◽

pp. 799-805 ◽

Cited By ~ 9

Author(s):

Carolina Mejia Otero ◽

Shervin Assassi ◽

Marie Hudson ◽

Maureen D. Mayes ◽

Rosa Estrada-Y-Martin ◽

...

Keyword(s):

Native American ◽

Systemic Sclerosis ◽

North American ◽

Cox Regression ◽

Bacterial Overgrowth ◽

Demographic Factors ◽

The United States ◽

Cox Regression Analysis ◽

Native North American ◽

American Ethnicity

Objective.To examine the clinical correlates and survival in patients with antifibrillarin antibodies (AFA) in a large international study population consisting of well-characterized systemic sclerosis (SSc) cohorts from Canada, Australia, and the United States.Methods.Baseline clinical data from the prospective cohorts (Canadian Scleroderma Research Group, the Australian Scleroderma Cohort Study, and the American Genetics versus Environment in Scleroderma Outcome Study) were investigated. Clinical variables were harmonized and sera were tested for AFA using a commercially available SSc profile line immunoassay, regardless of the immunofluorescence staining pattern. Association of demographic and clinical features with AFA was investigated by logistic or linear regression. Further, a survival analysis was performed by Cox regression analysis.Results.A total of 1506 patients with SSc with complete serological profiles were included in the study. Fifty-two patients (3.5%) had antibodies detected against fibrillarin. Patients of African descent and Native North American ethnicity were more likely to be AFA-positive compared with other ethnicities. After adjustment for demographic factors, diffuse involvement, and intestinal bacterial overgrowth requiring antibiotics, gastrointestinal reflux disease showed a trend for association with AFA. Further, AFA positivity was associated with shorter survival independently of demographic factors and disease type (HR 1.76, 95% CI 1.11–2.79, p = 0.016).Conclusion.In this large multinational SSc cohort, AFA was associated with Native American ethnicity and was an independent predictor of mortality.

Download Full-text