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Colonic and Anorectal Manifestations of Systemic Sclerosis

  • Beena Sattar
  • Reena V. ChokshiEmail author
Large Intestine (B Cash and R Chokshi, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Large Intestine

Abstract

Purpose of Review

Systemic sclerosis is a chronic autoimmune disorder commonly involving the gastrointestinal tract, including the colon and anorectum. In this review, we summarize major clinical manifestations and highlight recent developments in physiology, diagnostics, and treatment.

Recent Findings

The exact pathophysiology of systemic sclerosis is unclear and likely multifactorial. The role of the microbiome on gastrointestinal manifestations has led to a better understanding of potential pathogenic gut flora. Carbohydrate malabsorption is common. Evaluation using fecal calprotectin and high-resolution anorectal manometry may broaden our understanding of the etiologies of diarrhea and fecal incontinence and help with early recognition of pathology. Prucalopride, a high-affinity 5HT4 agonist, and pyridostigmine, an acetylcholinesterase inhibitor, may help improve colonic transit in patients with constipation. Intravenous immunoglobulins have been used to target muscarinic receptor antibodies that are believed to contribute to gastrointestinal dysmotility.

Summary

Colonic and anorectal manifestations of systemic sclerosis include constipation, diarrhea, and fecal incontinence, and can diminish quality of life for these patients. Recent studies regarding pathophysiology as well as diagnostic and treatment options are promising. Further targeted studies to facilitate early intervention and better management of refractory symptoms are still needed.

Keywords

Constipation Diarrhea Fecal incontinence Anorectal Scleroderma Systemic sclerosis 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Sallam H, McNearney TA, Chen JD. Systematic review: pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis (scleroderma). Aliment Pharmacol Ther. 2006 Mar 15;23(6):691–712.CrossRefGoogle Scholar
  2. 2.
    Nagaraja V, Hays RD, Khanna PP, Spiegel BMR, Chang L, Melmed GY, et al. Construct validity of the patient-reported outcomes measurement information system gastrointestinal symptom scales in systemic sclerosis. Arthritis Care Res. 2014 Nov;66(11):1725–30.CrossRefGoogle Scholar
  3. 3.
    Khanna D, Nagaraja V, Gladue H, Chey W, Pimentel M, Frech T. Measuring response in the gastrointestinal tract in systemic sclerosis. Curr Opin Rheumatol. 2013 Nov;25(6):700–6.CrossRefGoogle Scholar
  4. 4.
    Sakkas LI, Simopoulou T, Daoussis D, et al. Intestinal involvement in systemic sclerosis: a clinical review. Dig Dis Sci. 2018 Apr;63(4):833–4.CrossRefGoogle Scholar
  5. 5.
    Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017 Oct 7;390(10103):1685–99.CrossRefGoogle Scholar
  6. 6.
    Stern EP, Denton CP. The pathogenesis of systemic sclerosis. Rheum Dis Clin N Am. 2015 Aug;41(3):367–82.CrossRefGoogle Scholar
  7. 7.
    • McFarlane IM, Bhamra MS, Kreps A, et al. Gastrointestinal manifestations of systemic sclerosis. Rheumatology (Sunnyvale). 2018;8(1):235. Current review about the pathogenesis and GI clinical manifestations of systemic sclerosis. CrossRefGoogle Scholar
  8. 8.
    Furue M, Mitoma C, Mitoma H, Tsuji G, Chiba T, Nakahara T, et al. Pathogenesis of systemic sclerosis – current concept and emerging treatments. Immunol Res. 2017;65(4):790–7.CrossRefGoogle Scholar
  9. 9.
    Kumar S, Singh J, Kedika R, Mendoza F, Jimenez SA, Blomain ES, et al. Role of muscarinic-3 receptor antibody in systemic sclerosis: correlation with disease duration and effects of IVIG. Am J Physiol Gastrointest Liver Physiol. 2016;310(11):G1052–60.CrossRefGoogle Scholar
  10. 10.
    Steen VD, Medsger TA Jr. Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum. 2000;43(11):2437–44.CrossRefGoogle Scholar
  11. 11.
    Svegliati S, Spadoni T, Moroncini G, Gabrielli A. NADPH oxidase, oxidative stress and fibrosis in systemic sclerosis. Free Radic Biol Med. 2018;125:90–7.CrossRefGoogle Scholar
  12. 12.
    Vona R, Giovannetti A, Gambardella L, Malorni W, Pietraforte D, Straface E. Oxidative stress in the pathogenesis of systemic scleroderma: an overview. J Cell Mol Med. 2018;22(7):3308–14.CrossRefGoogle Scholar
  13. 13.
    Doridot L, Jeljeli M, Chene C, et al. Implication of oxidative stress in the pathogenesis of systematic sclerosis via inflammation, autoimmunity and fibrosis. Redox Biol. 2019;25:101122.CrossRefGoogle Scholar
  14. 14.
    • Bellochi C, Volkmann ER. Update on the gastrointestinal microbiome in systemic sclerosis. Curr Rheumatol Rep. 2018;20(8):49. Current review characterizing the role of the microbiome in systemic sclerosis. CrossRefGoogle Scholar
  15. 15.
    Patrone V, Puglisi E, Cardinali M, Schnitzler TS, Svegliati S, Festa A, et al. Gut microbiota profile in systemic sclerosis patients with and without clinical evidence of gastrointestinal involvement. Sci Rep. 2017;7(1):14874.CrossRefGoogle Scholar
  16. 16.
    Battle WM, Snape WJ Jr, Wright S, et al. Abnormal colonic motility in progressive systemic sclerosis. Ann Intern Med. 1981;94(6):749–52.CrossRefGoogle Scholar
  17. 17.
    • Vigone B, Caronni M, Severino A, Bellocchi C, Baldassarri AR, Fraquelli M, et al. Preliminary safety and efficacy profile of prucalopride in the treatment of systemic sclerosis (SSc)-related intestinal involvement: results from the open label cross-over PROGASS study. Arthritis Res Ther. 2017;19(1):145. Pivotal study examining prucalopride as a treatment option in systemic sclerosis patients. CrossRefGoogle Scholar
  18. 18.
    • Ahuja NK, Mische L, Clarke JO, et al. Pyridostigmine for the treatment of gastrointestinal symptoms in systemic sclerosis. Semin Arthritis Rheum. 2018;48(1):111–6. Pivotal study examining pyridostigmine as a treatment option in systemic sclerosis patients. CrossRefGoogle Scholar
  19. 19.
    Bharucha AE, Low PA, Camilleri M, Burton D, Gehrking TL, Zinsmeister AR. Pilot study of pyridostigmine in constipated patients with autonomic neuropathy. Clin Auton Res. 2008;18(4):194–202.CrossRefGoogle Scholar
  20. 20.
    Marie I, Leroi AM, Menard JF, Levesque H, Quillard M, Ducrotte P. Fecal calprotectin in systemic sclerosis and review of the literature. Autoimmun Rev. 2015;14(6):547–54.CrossRefGoogle Scholar
  21. 21.
    Zhong C, Qu C, Wang B, Liang S, Zeng B. Probiotics for preventing and treating small intestinal bacterial overgrowth: a meta-analysis and systematic review of current evidence. J Clin Gastroenterol. 2017;51(4):300–11.CrossRefGoogle Scholar
  22. 22.
    Frech TM, Khanna D, Maranian P, et al. Probiotics for the treatment of systemic sclerosis-associated gastrointestinal bloating/distension. Clin Exp Rheumatol. 2011;29(2 Suppl 65):S22–5.PubMedGoogle Scholar
  23. 23.
    • Smith E, Pauling JD. The efficacy of dietary intervention on gastrointestinal involvement in systemic sclerosis: a systematic literature review. Semin Arthitis Rheum. 2018. Comprehensive review of the evidence regarding dietary modification for gastrointestinal symptoms in systemic sclerosis. Google Scholar
  24. 24.
    Marie I, Leroi AM, Gourcerol G, Levesque H, Menard JF, Ducrotte P. Lactose malabsorption in systemic sclerosis. Aliment Pharmacol Ther. 2016;44(10):1123–33.CrossRefGoogle Scholar
  25. 25.
    Marie I, Leroi AM, Gourcerol G, Levesque H, Ménard JF, Ducrotte P. Fructose malabsorption in systemic sclerosis. Medicine (Baltimore). 2015;94(39):e1601.CrossRefGoogle Scholar
  26. 26.
    • Gomes JP, Santos L, Shoenfeld Y. Intravenous immunoglobulin (IVIG) in the vanguard therapy of systemic sclerosis. Clin Immunol. 2018. Current review regarding IVIG use in systemic sclerosis. Google Scholar
  27. 27.
    Sanges S, Riviere S, Mekinian A, et al. Intravenous immunoglobulins in systemic sclerosis: data from a French nationwide cohort of 46 patients and review of the literature. Autoimm Rev. 2017;16(4):377–84.CrossRefGoogle Scholar
  28. 28.
    Raja J, Nihtyanova SI, Murray CD, Denton CP, Ong VH. Rheumatology (Oxford). 2016;55(1):115–9.CrossRefGoogle Scholar
  29. 29.
    Bharadwaj S, Tandon P, Gohel T, Corrigan ML, Coughlin KL, Shatnawei A, et al. Gastrointestinal manifestations, malnutrition, and role of enteral and parenteral nutrition in patients with scleroderma. J Clin Gastroenterol. 2015;49(7):559–64.CrossRefGoogle Scholar
  30. 30.
    Preis E, Franz K, Siegert E, Makowka A, March C, Riemekasten G, et al. The impact of malnutrition on quality of life in patients with systemic sclerosis. Eur J Clin Nutr. 2018;72(4):504–10.CrossRefGoogle Scholar
  31. 31.
    Baron M, Hudson M, Steele R, et al. Malnutrition is common in systemic sclerosis: results from the Canadian scleroderma research group database. J Rheumatol. 2009;36(12):2737–43.CrossRefGoogle Scholar
  32. 32.
    Duchini A, Sessoms SL. Gastrointestinal hemorrhage in patients with systemic sclerosis and CREST syndrome. Am J Gastroenterol. 1998;93(9):1453–6.CrossRefGoogle Scholar
  33. 33.
    Jharap B, Koudstaal LG, Neefjes-Borst EA, et al. Colonic telangiectasias in progressive systemic sclerosis. Endoscopy. 2012;44(Suppl 2 UCTN):E42–3.PubMedGoogle Scholar
  34. 34.
    Wang YJ, Wang YM, Zheng YM, et al. Pneumatosis cystoides intestinalis: six case reports and a review of the literature. BMC Gastroenterol. 2018;18(1):100.CrossRefGoogle Scholar
  35. 35.
    Castro-Pocas R, Araujo T, Pedroto I. Endoscopic ultrasound of pneumatosis cystoides intestinalis. Endoscopy. 2015;47(Suppl 1 UCTN):E274.PubMedGoogle Scholar
  36. 36.
    Kaneko M, Sasaki S, Teruya S, et al. Pneumatosis cystoides intestinalis in patients with systemic sclerosis: a case report and review of 39 Japanese cases. Case Rep Gastrointest Med. 2016;2016:2474515.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Lepri G, Guiducci S, Bellando-Randome S, et al. Evidence for oesophageal and anorectal involvement in very early systemic sclerosis (VEDOSS): report from a single VEDOSS/EUSTAR centre. Ann Rheum Dis. 2015;74(1):124–8.CrossRefGoogle Scholar
  38. 38.
    Richard N, Hudson M, Gyger G, et al. Clinical correlates of faecal incontinence in systemic sclerosis: identifying therapeutic avenues. Rheumatology (Oxford). 2017;56(4):581–8.Google Scholar
  39. 39.
    Garros A, Marjoux S, Khouatra C, Coppere B, Grange C, Hot A, et al. Prevalence of fecal incontinence in a cohort of systemic sclerosis patients within a regional referral network. United European Gastroenterol J. 2017;5(7):1046–50.CrossRefGoogle Scholar
  40. 40.
    Omair MA, Lee P. Effect of gastrointestinal manifestations on quality of life in 87 consecutive patients with systemic sclerosis. J Rheumatol. 2012;39(5):992–6.CrossRefGoogle Scholar
  41. 41.
    Franck-Larsson K, Graf W, Ronnblom A. Lower gastrointestinal symptoms and quality of life in patients with systemic sclerosis: a population-based study. Eur J Gastroenterol Hepatol. 2009;21(2):176–82.CrossRefGoogle Scholar
  42. 42.
    Thoua NM, Schizas A, Forbes A, Denton CP, Emmanuel AV. Internal anal sphincter atrophy in patients with systemic sclerosis. Rheumatology (Oxford). 2011;50(9):1596–602.CrossRefGoogle Scholar
  43. 43.
    Heyt GJ, Oh MK, Alemzadeh N, Rivera S, Jimenez SA, Rattan S, et al. Impaired rectoanal inhibitory response in scleroderma (systemic sclerosis): an association with fecal incontinence. Dig Dis Sci. 2004;49(6):1040–5.CrossRefGoogle Scholar
  44. 44.
    Thoua NM, Abdel-Halin M, Forbes A, et al. Fecal incontinence in systemic sclerosis is secondary to neuropathy. Am J Gastroenterol. 2012;107(4):597–603.CrossRefGoogle Scholar
  45. 45.
    Luciano L, Granel B, Bernit E, et al. Esophageal and anorectal involvement in systemic sclerosis: a systematic assessment with high resolution manometry. Clin Exp Rheumatol. 2016;34 Suppl 100(5):63–9.PubMedGoogle Scholar
  46. 46.
    Kumar S, Singh J, Rattan S, DiMarino AJ, Cohen S, Jimenez SA. Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis. Aliment Pharmacol Ther. 2017;45(7):883–98.CrossRefGoogle Scholar
  47. 47.
    Pinsk I, Brown J, Phang PT. Assessment of sonographic quality of anal sphincter muscles in patients with faecal incontinence. Color Dis. 2009;11(9):933–40.CrossRefGoogle Scholar
  48. 48.
    • Collins J, Mazor Y, Jones M, et al. Efficacy of anorectal biofeedback in scleroderma patients with fecal incontinence: a case-control study. Scand J Gastroenterol. 2016;51(12):1433–8. Pivotal study supporting the use of biofeedback for fecal incontinence in systemic sclerosis patients. CrossRefGoogle Scholar
  49. 49.
    Kenefick NJ, Vaizey CJ, Nicholls RJ, Cohen R, Kamm MA. Sacral nerve stimulation for faecal incontinence due to systemic sclerosis. Gut. 2002;51(6):881–3.CrossRefGoogle Scholar
  50. 50.
    Butt SK, Alam A, Cohen R, Krogh K, Buntzen S, Emmanuel A. Lack of effect of sacral nerve stimulation for incontinence in patients with systemic sclerosis. Color Dis. 2015;17(10):903–7.CrossRefGoogle Scholar
  51. 51.
    Petersen S, Tobisch A, Puhl G, et al. Stubborn rectal prolapse in systemic sclerosis. Reumatologia. 2017;55(2):100–3.CrossRefGoogle Scholar
  52. 52.
    Leighton JA, Valdovinos MA, Pemberton JH, Rath DM, Camilleri M. Anorectal dysfunction and rectal prolapse in progressive systemic sclerosis. Dis Colon Rectum. 1993;36(2):182–5.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of MedicineUT HealthHoustonUSA
  2. 2.Section of Gastroenterology and HepatologyBaylor College of MedicineHoustonUSA

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