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Managing Gastrointestinal Complications in Patients With Systemic Sclerosis

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Abstract

Objective

We sought to critically evaluate the literature published over the past 3 years on the management of gastrointestinal complications in systemic sclerosis (SSc). We emphasize interesting and important new findings to bring the reader up-to-date. We also discuss controversial discoveries and hypotheses currently of interest.

Methods

We conducted a literature search on PubMed over the last 3 years using the keywords “systemic sclerosis,” “gastrointestinal,” “scleroderma,” and “treatment.” We also screened clinicaltrials.gov for ongoing trials relevant to the gastrointestinal complications of SSc. Reference lists from recent reviews on the management of gastrointestinal complications of SSc to identify articles that might have been missed in the initial search.

Results

One hundred three publications and ongoing clinical trials were identified. We eliminated all case reports and review articles. Ultimately, we had 58 articles remaining and we prioritized what we found to be the strongest and/or novel findings to discuss in this review.

Conclusions

Advances in the management of gastrointestinal disease in SSc continue to evolve. The application of novel therapies and the repurposing of existing therapies for the management of gastrointestinal involvement are shaping the therapeutic arsenal so that we can more effectively manage these complex patients.

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References and Recommended Reading

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

  1. Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med. 2009;360(19):1989–2003. https://doi.org/10.1056/NEJMra0806188.

    Article  CAS  PubMed  Google Scholar 

  2. Nagaraja V, McMahan ZH, Getzug T, Khanna D. Management of gastrointestinal involvement in scleroderma. Curr Treatm Opt Rheumatol. 2015;1(1):82–105. https://doi.org/10.1007/s40674-014-0005-0.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Jaovisidha K, Csuka ME, Almagro UA, Soergel KH. Severe gastrointestinal involvement in systemic sclerosis: report of five cases and review of the literature. Semin Arthritis Rheum. 2005;34(4):689–702. https://doi.org/10.1016/j.semarthrit.2004.08.009.

    Article  PubMed  Google Scholar 

  4. Dein E, Kuo PL, Hong YS, Hummers LK, Mecoli CA, McMahan ZH. Evaluation of risk factors for pseudo-obstruction in systemic sclerosis. Semin Arthritis Rheum. 2019;49(3):405–10. https://doi.org/10.1016/j.semarthrit.2019.05.005.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Volkmann ER, Chang YL, Barroso N, Furst DE, Clements PJ, Gorn AH, et al. Association of systemic sclerosis with a unique colonic microbial consortium. Arthritis Rheumatol. 2016;68(6):1483–92. https://doi.org/10.1002/art.39572.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Marie I, Leroi AM, Gourcerol G, Levesque H, Menard JF, Ducrotte P. Fructose malabsorption in systemic sclerosis. Medicine (Baltimore). 2015;94(39):e1601. https://doi.org/10.1097/MD.0000000000001601.

    Article  CAS  Google Scholar 

  7. Volkmann ER, Hoffmann-Vold AM. Gastrointestinal tract microbiota modifications in systemic sclerosis. Eur J Rheumatol. 2019:1–8. https://doi.org/10.5152/eurjrheum.2019.19103.

  8. Volkmann ER, Hoffmann-Vold AM, Chang YL, Jacobs JP, Tillisch K, Mayer EA, et al. Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts. BMJ Open Gastroenterol. 2017;4(1):e000134. https://doi.org/10.1136/bmjgast-2017-000134. The first multi-centered study evaluating the GI microbiome in SSc.

  9. Gyger G, Baron M. Systemic sclerosis: gastrointestinal disease and its management. Rheum Dis Clin N Am. 2015;41(3):459–73. https://doi.org/10.1016/j.rdc.2015.04.007.

    Article  Google Scholar 

  10. Kawaguchi Y, Nakamura Y, Matsumoto I, Nishimagi E, Satoh T, Kuwana M, et al. Muscarinic-3 acetylcholine receptor autoantibody in patients with systemic sclerosis: contribution to severe gastrointestinal tract dysmotility. Ann Rheum Dis. 2009;68(5):710–4. doi: https://doi.org/10.1136/ard.2008.096545. Important study reporting anti-muscarinic 3 antibodies in SSc patients with severe GI dysmotility.

  11. 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. https://doi.org/10.1152/ajpgi.00034.2016.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Smirani R, Truchetet ME, Poursac N, Naveau A, Schaeverbeke T, Devillard R. Impact of systemic sclerosis oral manifestations on patients’ health-related quality of life: a systematic review. J Oral Pathol Med. 2018;47(9):808–15. https://doi.org/10.1111/jop.12739.

    Article  PubMed  Google Scholar 

  13. Shah AA, Wigley FM. Often forgotten manifestations of systemic sclerosis. Rheum Dis Clin N Am. 2008;34(1):221–38; ix. https://doi.org/10.1016/j.rdc.2007.10.002.

  14. Thonhofer R, Siegel C, Trummer M, Graninger W. Early endoscopy in systemic sclerosis without gastrointestinal symptoms. Rheumatol Int. 2012;32(1):165–8. https://doi.org/10.1007/s00296-010-1595-y.

    Article  PubMed  Google Scholar 

  15. Braddom CL. The ethics of research. Am J Phys Med Rehabil. 1990;69(3):170–1. https://doi.org/10.1097/00002060-199006000-00012.

    Article  CAS  PubMed  Google Scholar 

  16. Matsuda R, Yamamichi N, Shimamoto T, Sumida H, Takahashi Y, Minatsuki C, et al. Gastroesophageal reflux disease-related disorders of systemic sclerosis based on the analysis of 66 patients. Digestion. 2018;98(4):201–8. https://doi.org/10.1159/000489848.

    Article  CAS  PubMed  Google Scholar 

  17. Strek ME. Systemic sclerosis-associated interstitial lung disease: role of the oesophagus in outcomes. Respirology. 2018;23(10):885–6. https://doi.org/10.1111/resp.13335.

    Article  PubMed  Google Scholar 

  18. Salaffi F, Di Carlo M, Carotti M, Fraticelli P, Gabrielli A, Giovagnoni A. Relationship between interstitial lung disease and oesophageal dilatation on chest high-resolution computed tomography in patients with systemic sclerosis: a cross-sectional study. Radiol Med. 2018;123(9):655–63. https://doi.org/10.1007/s11547-018-0894-3.

    Article  PubMed  Google Scholar 

  19. Furnari M, Savarino V, de Bortoli N, Savarino E. Interstitial lung disease in systemic sclerosis patients may benefit more from anti-reflux therapies than from immunosuppressants. Autoimmun Rev. 2016;15(12):1208–9. https://doi.org/10.1016/j.autrev.2016.09.025.

    Article  PubMed  Google Scholar 

  20. Smith E, Pauling JD. The efficacy of dietary intervention on gastrointestinal involvement in systemic sclerosis: a systematic literature review. Semin Arthritis Rheum. 2019;49(1):112–8. https://doi.org/10.1016/j.semarthrit.2018.12.001.

    Article  PubMed  Google Scholar 

  21. Foocharoen C, Chunlertrith K, Mairiang P, Mahakkanukrauh A, Suwannaroj S, Namvijit S, et al. Prevalence and predictors of proton pump inhibitor partial response in gastroesophageal reflux disease in systemic sclerosis: a prospective study. Sci Rep. 2020;10(1):769. https://doi.org/10.1038/s41598-020-57636-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Foocharoen C, Chunlertrith K, Mairiang P, Mahakkanukrauh A, Suwannaroj S, Namvijit S, et al. Effectiveness of add-on therapy with domperidone vs alginic acid in proton pump inhibitor partial response gastro-oesophageal reflux disease in systemic sclerosis: randomized placebo-controlled trial. Rheumatology (Oxford). 2017;56(2):214–22. https://doi.org/10.1093/rheumatology/kew216.

    Article  CAS  Google Scholar 

  23. Karamanolis GP, Panopoulos S, Denaxas K, Karlaftis A, Zorbala A, Kamberoglou D, et al. The 5-HT1A receptor agonist buspirone improves esophageal motor function and symptoms in systemic sclerosis: a 4-week, open-label trial. Arthritis Res Ther. 2016;18:195. https://doi.org/10.1186/s13075-016-1094-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Weston S, Thumshirn M, Wiste J, Camilleri M. Clinical and upper gastrointestinal motility features in systemic sclerosis and related disorders. Am J Gastroenterol. 1998;93(7):1085–9. https://doi.org/10.1111/j.1572-0241.1998.00334.x.

    Article  CAS  PubMed  Google Scholar 

  25. Carbone F, Van den Houte K, Clevers E, Andrews CN, Papathanasopoulos A, Holvoet L, et al. Prucalopride in Gastroparesis: a randomized placebo-controlled crossover study. Am J Gastroenterol. 2019;114(8):1265-74. https://doi.org/10.14309/ajg.0000000000000304. The first RCT evaluating the effects of prucalopride in patients with gastroparesis.

  26. 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. https://doi.org/10.1186/s13075-017-1340-y. First study in SSc evaluating the efficacy of prucalopride for lower bowel disease.

  27. Messerli M, Aschwanden R, Buslau M, Hersberger KE, Arnet I. Swallowing difficulties with medication intake assessed with a novel self-report questionnaire in patients with systemic sclerosis - a cross-sectional population study. Patient Prefer Adherence. 2017;11:1687–99. https://doi.org/10.2147/PPA.S142653.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Sallam H, McNearney TA, Chen JD. Systematic review: pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis (scleroderma). Aliment Pharmacol Ther. 2006;23(6):691–712. https://doi.org/10.1111/j.1365-2036.2006.02804.x.

    Article  CAS  PubMed  Google Scholar 

  29. Polkowska-Pruszynska B, Gerkowicz A, Szczepanik-Kulak P, Krasowska D. Small intestinal bacterial overgrowth in systemic sclerosis: a review of the literature. Arch Dermatol Res. 2019;311(1):1–8. https://doi.org/10.1007/s00403-018-1874-0.

    Article  PubMed  Google Scholar 

  30. Domsic R, Fasanella K, Bielefeldt K. Gastrointestinal manifestations of systemic sclerosis. Dig Dis Sci. 2008;53(5):1163–74. https://doi.org/10.1007/s10620-007-0018-8.

    Article  PubMed  Google Scholar 

  31. Ebert EC. Gastric and enteric involvement in progressive systemic sclerosis. J Clin Gastroenterol. 2008;42(1):5–12. https://doi.org/10.1097/MCG.0b013e318042d625.

    Article  PubMed  Google Scholar 

  32. Tauber M, Avouac J, Benahmed A, Barbot L, Coustet B, Kahan A, et al. Prevalence and predictors of small intestinal bacterial overgrowth in systemic sclerosis patients with gastrointestinal symptoms. Clin Exp Rheumatol. 2014;32(6 Suppl 86):S-82-7.

  33. Roland BC, Ciarleglio MM, Clarke JO, Semler JR, Tomakin E, Mullin GE, et al. Small intestinal transit time is delayed in small intestinal bacterial overgrowth. J Clin Gastroenterol. 2015;49(7):571-6. https://doi.org/10.1097/MCG.0000000000000257. Important study demonstrating that delayed small bowel transit is associated with bacterial overgrowth.

  34. Parodi A, Sessarego M, Greco A, Bazzica M, Filaci G, Setti M, et al. Small intestinal bacterial overgrowth in patients suffering from scleroderma: clinical effectiveness of its eradication. Am J Gastroenterol. 2008;103(5):1257–62. https://doi.org/10.1111/j.1572-0241.2007.01758.x.

    Article  PubMed  Google Scholar 

  35. Manini ML, Camilleri M, Grothe R, Di Lorenzo C. Application of pyridostigmine in pediatric gastrointestinal motility disorders: a case series. Paediatr Drugs. 2018;20(2):173–80. https://doi.org/10.1007/s40272-017-0277-6.

    Article  PubMed  Google Scholar 

  36. Ahuja NK, Mische L, Clarke JO, Wigley FM, McMahan ZH. Pyridostigmine for the treatment of gastrointestinal symptoms in systemic sclerosis. Semin Arthritis Rheum. 2018;48(1):111–6. https://doi.org/10.1016/j.semarthrit.2017.12.007.

    Article  CAS  PubMed  Google Scholar 

  37. Robinson-Papp J, Nmashie A, Pedowitz E, George MC, Sharma S, Murray J, et al. The effect of pyridostigmine on small intestinal bacterial overgrowth (SIBO) and plasma inflammatory biomarkers in HIV-associated autonomic neuropathies. J Neuro-Oncol. 2019;25(4):551–9. https://doi.org/10.1007/s13365-019-00756-9.

    Article  CAS  Google Scholar 

  38. Pasha SF, Lunsford TN, Lennon VA. Autoimmune gastrointestinal dysmotility treated successfully with pyridostigmine. Gastroenterology. 2006;131(5):1592–6. https://doi.org/10.1053/j.gastro.2006.06.018.

    Article  PubMed  Google Scholar 

  39. Soudah HC, Hasler WL, Owyang C. Effect of octreotide on intestinal motility and bacterial overgrowth in scleroderma. N Engl J Med. 1991;325(21):1461–7. doi: https://doi.org/10.1056/NEJM199111213252102. Landmark paper demonstrating the efficacy of octreotide in SSc patients with intestinaly dysmotility.

  40. H. F, O M, A HT, H D, T G, E B, et al. Fecal microbiota transplantation in patients with systemic sclerosis- a pilot study. Arthritis Rheumatol.2018.

  41. Khanna D, Furst DE, Maranian P, Seibold JR, Impens A, Mayes MD, et al. Minimally important differences of the UCLA scleroderma clinical trial consortium gastrointestinal tract instrument. J Rheumatol. 2011;38(9):1920–4. https://doi.org/10.3899/jrheum.110225.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Garcia-Collinot G, Madrigal-Santillan EO, Martinez-Bencomo MA, Carranza-Muleiro RA, Jara LJ, Vera-Lastra O, et al. Effectiveness of Saccharomyces boulardii and metronidazole for small intestinal bacterial overgrowth in systemic sclerosis. Dig Dis Sci. 2020;65(4):1134-43. Doi: https://doi.org/10.1007/s10620-019-05830-0. Study demonstrating the benefits of Saccharomyces boulardii treatment in patients in SSc and SIBO.

  43. Brandler JB, Sweetser S, Khoshbin K, Babameto M, Prokop LJ, Camilleri M. Colonic manifestations and complications are relatively under-reported in systemic sclerosis: a systematic review. Am J Gastroenterol. 2019;114(12):1847–56. https://doi.org/10.14309/ajg.0000000000000397.

    Article  PubMed  Google Scholar 

  44. Battle WM, Snape WJ Jr, Wright S, Sullivan MA, Cohen S, Meyers A, et al. Abnormal colonic motility in progressive systemic sclerosis. Ann Intern Med. 1981;94(6):749–52. https://doi.org/10.7326/0003-4819-94-6-749.

    Article  CAS  PubMed  Google Scholar 

  45. Boeckxstaens GE, Bartelsman JF, Lauwers L, Tytgat GN. Treatment of GI dysmotility in scleroderma with the new enterokinetic agent prucalopride. Am J Gastroenterol. 2002;97(1):194–7. https://doi.org/10.1111/j.1572-0241.2002.05396.x.

    Article  CAS  PubMed  Google Scholar 

  46. Quigley EM. Prokinetics in the management of functional gastrointestinal disorders. J Neurogastroenterol Motil. 2015;21(3):330–6. https://doi.org/10.5056/jnm15094.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Dein E CJ, Wigley F, McMahan Z. Linaclotide for the treatment of gastrointestinal symptoms in systemic sclerosis [abstract]. Arthritis Rheumatol. 2019;71.

  48. Clark KE, Etomi O, Denton CP, Ong VH, Murray CD. Intravenous immunogobulin therapy for severe gastrointestinal involvement in systemic sclerosis. Clin Exp Rheumatol. 2015;33(4 Suppl 91):S168–70.

    PubMed  Google Scholar 

  49. Raja J, Nihtyanova SI, Murray CD, Denton CP, Ong VH. Sustained benefit from intravenous immunoglobulin therapy for gastrointestinal involvement in systemic sclerosis. Rheumatology (Oxford). 2016;55(1):115–9. https://doi.org/10.1093/rheumatology/kev318.

    Article  Google Scholar 

  50. Richard N, Hudson M, Gyger G, Baron M, Sutton E, Khalidi N, et al. Clinical correlates of faecal incontinence in systemic sclerosis: identifying therapeutic avenues. Rheumatology (Oxford). 2017;56(4):581–8. https://doi.org/10.1093/rheumatology/kew441.

    Article  CAS  Google Scholar 

  51. Thoua NM, Abdel-Halim M, Forbes A, Denton CP, Emmanuel AV. Fecal incontinence in systemic sclerosis is secondary to neuropathy. Am J Gastroenterol. 2012;107(4):597-603. https://doi.org/10.1038/ajg.2011.399. Important manscript providing data supporting the etiology of fecal incontinence in SSc being associated with a neuropathy.

  52. Collins J, Mazor Y, Jones M, Kellow J, Malcolm A. Efficacy of anorectal biofeedback in scleroderma patients with fecal incontinence: a case-control study. Scand J Gastroenterol. 2016;51(12):1433–8. https://doi.org/10.1080/00365521.2016.1218537.

    Article  PubMed  Google Scholar 

  53. Al Asari S, Meurette G, Mantoo S, Kubis C, Wyart V, Lehur PA. Percutaneous tibial nerve stimulation vs sacral nerve stimulation for faecal incontinence: a comparative case-matched study. Color Dis. 2014;16(11):O393–9. https://doi.org/10.1111/codi.12680.

    Article  Google Scholar 

  54. 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. https://doi.org/10.1111/codi.12969.

    Article  CAS  Google Scholar 

  55. Fernandez-Codina A, Walker KM, Pope JE, Scleroderma Algorithm G. Treatment algorithms for systemic sclerosis according to experts. Arthritis Rheumatol. 2018;70(11):1820-8. https://doi.org/10.1002/art.40560. Updated treatment algorithms for managing SSc GI disease.

  56. Roberts CG, Hummers LK, Ravich WJ, Wigley FM, Hutchins GM. A case-control study of the pathology of oesophageal disease in systemic sclerosis (scleroderma). Gut. 2006;55(12):1697–703. https://doi.org/10.1136/gut.2005.086074.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Miller JB, Gandhi N, Clarke J, McMahan Z. Gastrointestinal involvement in systemic sclerosis: an update. J Clin Rheumatol. 2018;24(6):328–37. https://doi.org/10.1097/RHU.0000000000000626.

    Article  PubMed  Google Scholar 

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Funding

NIH/NIAMS K23 AR071473 to ZM; Scleroderma Research Foundation to ZM; National Institute of Arthritis and Musculoskeletal and Skin Diseases grants K24-AR-063120 and R01-AR-07047 to Dr. Khanna.

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Authors and Affiliations

  1. Division of Rheumatology, Johns Hopkins University, 5200 Eastern Avenue, Suite 5200, Mason F. Lord Building, Center Tower, Baltimore, MD, 21224, USA

    Z. H. McMahan MD, MHS & D. Khanna MBBS, MSc

  2. Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA

    Z. H. McMahan MD, MHS

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  1. Z. H. McMahan MD, MHS
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  2. D. Khanna MBBS, MSc
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Correspondence to Z. H. McMahan MD, MHS.

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Conflict of interest

Consultant: Acceleron, Actelion, Amgen, Bayer, Blade Therapeutics, Boehringer Ingelheim, CSL Behring, Corbus, Cytori, Galapagos, Genentech/Roche, GSK, Horizon, Merck, Mitsubishi Tanabe Pharma, Regeneron, Sanofi-Aventis, and United Therapeutics; CME programs: Impact PH; Stocks: Eicos Sciences, Inc.; Leadership/Equity position -Medical lead, Scleroderma Development, CiviBioPharma/Eicos Sciences, Inc.

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McMahan, Z.H., Khanna, D. Managing Gastrointestinal Complications in Patients With Systemic Sclerosis. Curr Treat Options Gastro 18, 531–544 (2020). https://doi.org/10.1007/s11938-020-00314-x

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