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  • Review Article
  • Published:

Current management of the gastrointestinal complications of systemic sclerosis

Nature Reviews Gastroenterology & Hepatology volume 13, pages 461–472 (2016)Cite this article

Subjects

Key Points

  • Gut involvement in systemic sclerosis occurs more commonly in the diffuse than the limited cutaneous variant

  • Oesophageal involvement is the most common gastrointestinal manifestation of systemic sclerosis, with severe reflux disease and dysphagia as the main presentations

  • When treating small intestinal bacterial overgrowth in patients with systemic sclerosis, effectiveness of treatment and decisions about cyclical courses of antibiotic are best assessed by symptoms rather than breath testing

  • Malnutrition in patients with systemic sclerosis is associated with more aggressive disease progression, and the risk of developing malnutrition is related to both gut and extraintestinal factors

Abstract

Systemic sclerosis is a multisystem autoimmune disorder that involves the gastrointestinal tract in more than 90% of patients. This involvement can extend from the mouth to the anus, with the oesophagus and anorectum most frequently affected. Gut complications result in a plethora of presentations that impair oral intake and faecal continence and, consequently, have an adverse effect on patient quality of life, resulting in referral to gastroenterologists. The cornerstones of gastrointestinal symptom management are to optimize symptom relief and monitor for complications, in particular anaemia and malabsorption. Early intervention in patients who develop these complications is critical to minimize disease progression and improve prognosis. In the future, enhanced therapeutic strategies should be developed, based on an ever-improving understanding of the intestinal pathophysiology of systemic sclerosis. This Review describes the most commonly occurring clinical scenarios of gastrointestinal involvement in patients with systemic sclerosis as they present to the gastroenterologist, with recommendations for the suggested assessment protocol and therapy in each situation.

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Figure 1: Small intestinal involvement in systemic sclerosis is associated with marked physiological changes.
Figure 2
Figure 3: Proposed pathway for screening and managing malnutrition in patients with systemic sclerosis.

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References

  1. Allcock, R. J. et al. A study of the prevalence of systemic sclerosis in northeast england. Rheumatology (Oxford) 43, 596–602 (2004).

    CAS  Google Scholar 

  2. Chifflot, H. et al. Incidence and prevalence of systemic sclerosis: a systematic literature review. Semin. Arthritis Rheum. 37, 223–235 (2008).

    PubMed  Google Scholar 

  3. Andréasson, K. et al. Prevalence and incidence of systemic sclerosis in southern Sweden: population-based data with case ascertainment using the 1980 ARA criteria and the proposed ACR-EULAR classification criteria. Ann. Rheum. Dis. 73, 1788–1792 (2014).

    PubMed  Google Scholar 

  4. Mayes, M. D. et al. Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US population. Arthritis Rheum. 48, 2246–2255 (2003).

    PubMed  Google Scholar 

  5. Steen, V. D. & Medsger, T. A. Jr. Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum. 43, 2437–2444 (2000).

    CAS  PubMed  Google Scholar 

  6. Lock, G., Holstege, A., Lang, B. & Scholmerich, J. Gastrointestinal manifestations of progressive systemic sclerosis. Am. J. Gastroenterol. 92, 763–771 (1997).

    CAS  PubMed  Google Scholar 

  7. Attar, A. Digestive manifestations in systemic sclerosis. Ann. Med. Interne (Paris). 153, 260–264 (in French) (2002).

    PubMed  Google Scholar 

  8. Hunzelmann, N. et al. The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement. Rheumatology (Oxford) 47, 1185–1192 (2008).

    CAS  Google Scholar 

  9. Sjogren, R. W. Gastrointestinal features of scleroderma. Curr. Opin. Rheumatol. 8, 569–575 (1996).

    CAS  PubMed  Google Scholar 

  10. Malandrini, A. et al. Autonomic nervous system and smooth muscle cell involvement in systemic sclerosis: ultrastructural study of 3 cases. J. Rheumatol. 27, 1203–1206 (2000).

    CAS  PubMed  Google Scholar 

  11. Dessein, P. H. et al. Autonomic dysfunction in systemic sclerosis: sympathetic overactivity and instability. Am. J. Med. 93, 143–150 (1992).

    CAS  PubMed  Google Scholar 

  12. Eaker, E. Y. et al. Myenteric neuronal antibodies in scleroderma — passive transfer evokes alterations in intestinal myoelectric activity in a rat model. J. Lab. Clin. Med. 133, 551–556 (1999).

    CAS  PubMed  Google Scholar 

  13. Kawaguchi, Y. et al. Muscarinic-3 acetylcholine receptor autoantibody in patients with systemic sclerosis: contribution to severe gastrointestinal tract dysmotility. Ann. Rheum. Dis. 68, 710–714 (2009).

    CAS  PubMed  Google Scholar 

  14. Singh, J. et al. Immunoglobulins from scleroderma patients inhibit the muscarinic receptor activation in internal anal sphincter smooth muscle cells. Am. J. Physiol. Gastrointest. Liver Physiol. 297, 206–213 (2009).

    Google Scholar 

  15. Hendel, L., Kobayasi, T. & Petri, M. Ultrastructure of the small intestinal mucosa in progressive systemic sclerosis (PSS). Acta Pathol. Microbiol. Immunol. Scand. 95, 41–46 (1987).

    CAS  Google Scholar 

  16. Ponge, T. & Bruley des Varannes, S. Digestive involvement of scleroderma. Rev. Pract. 52, 1896–1900 (2002).

    Google Scholar 

  17. Poirier, T. J. & Rankin, G. B. Gastrointestinal manifestations of progressive systemic scleroderma based on a review of 364 cases. Am. J. Gastroenterol. 58, 30–44 (1972).

    CAS  PubMed  Google Scholar 

  18. Young, M. A., Rose, S. & Reynolds, J. C. Gastrointestinal manifestations of scleroderma. Rheum. Dis. Clin. North Am. 22, 797–823 (1996).

    CAS  PubMed  Google Scholar 

  19. Sallam, P. J. et al. Assessment of gastrointestinal involvement. Clin. Exp. Rheumatol. 21 (Suppl. 29), S15–S18 (2003).

    Google Scholar 

  20. Weber, P. et al. 24-h intraesophageal pH monitoring in children and adolescents with scleroderma and mixed connective tissue disease. J. Rheumatol. 27, 2692–2695 (2000).

    CAS  PubMed  Google Scholar 

  21. Thoua, N. et al. Assessment of gastrointestinal symptoms in patients with systemic slcerosis in a UK tertiary referral centre. Rheumatology (Oxford) 49, 1770–1775 (2010).

    Google Scholar 

  22. Harrison, E., Herrick, A. L., McLaughlin, J. T. & Lal, S. Malnutrition in systemic sclerosis. Rheumatology 51, 1747–1756 (2012).

    PubMed  Google Scholar 

  23. Hansi, N. et al. Consensus best practice pathway of the UK scleroderma study group: gastrointestinal manifestations of systemic sclerosis. Clin. Exp. Rheumatol. 32 (Suppl. 86), S-214–S-221 (2014).

    Google Scholar 

  24. Marshall, J. B. et al. Gastrointestinal manifestations of mixed connective tissue disease. Gastroenterology 98, 1232–1238 (1990).

    CAS  Google Scholar 

  25. Bestetti, A. et al. Esophageal scintigraphy with a semisolid meal to evaluate esophageal dysmotility in systemic sclerosis and Raynaud's phenomenon. J. Nucl. Med. 40, 77–84 (1999).

    CAS  PubMed  Google Scholar 

  26. Akesson, A. & Wollheim, F. A. Organ manifestations in 100 patients with progressive systemic sclerosis: a comparison between the CREST syndrome and diffuse scleroderma. Br. J. Rheumatol. 28, 281–286 (1989).

    CAS  PubMed  Google Scholar 

  27. Sallam, H., McNearney, T. A. & Chen, J. D. Z. Systematic review: pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis (scleroderma). Aliment. Pharmacol. Ther. 23, 691–712 (2006).

    CAS  PubMed  Google Scholar 

  28. Lepri, G. et al. Evidence for oesophageal and anorectal involvement in very early systemic sclerosis (VEDOSS): report from a single VEDOSS/EUSTAR centre. Ann. Rheum. Dis. 74, 124–128 (2015).

    PubMed  Google Scholar 

  29. Weston, S., Thumshirn, M., Wiste, J. & Carnilleri, M. Clinical and upper gastrointestinal motility features in systemic sclerosis and related disorders. Am. J. Gastroenterol. 93, 1085–1089 (1998).

    CAS  PubMed  Google Scholar 

  30. Roman, S. et al. Esophageal dysmotility associated with systemic sclerosis: a high-resolution manometry study. Dis. Esophagus 24, 299–304 (2011).

    CAS  PubMed  Google Scholar 

  31. Dantas, R. O. & Aprile, L. Esophageal striated muscle contractions in patients with gastroesophageal reflux symptoms. Dig. Dis. Sci. 47, 2586–2590 (2002).

    PubMed  Google Scholar 

  32. Emmanuel, A., Kamm, M. A., Roy, A. J. & Antonelli, K. Effect of a novel prokinetic drug, R093877, on gastrointestinal transit in healthy volunteers. Gut 42, 511–516 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Boeckxstaens, G. E., Bartelsman, J. F., Lauwers, L. & Tytgat, G. N. Treatment of GI dysmotility in scleroderma with the new enterokinetic agent prucalopride. Am. J. Gastroenterol. 97, 194–197 (2002).

    CAS  PubMed  Google Scholar 

  34. Maeda, M., Ichiki, Y., Sumi, A. & Mori, S. A trial of acupuncture for progressive systemic sclerosis. J. Dermatol. 15, 133–140 (1988).

    CAS  PubMed  Google Scholar 

  35. Mearin, F. et al. Effect of transcutaneous nerve stimulation on esophageal motility in patients with achalasia and scleroderma. Scand. J. Gastroenterol. 25, 1018–1023 (1990).

    CAS  PubMed  Google Scholar 

  36. Thonhofer, R., Siegel, C., Trummer, M. & Graninger, W. Early endoscopy in systemic sclerosis without gastrointestinal symptoms. Rheumatol. Int. 32, 165–168 (2012).

    PubMed  Google Scholar 

  37. Zamost, B. J. et al. Esophagitis in scleroderma. Prevalence and risk factors. Gastroenterology 92, 421–428 (1987).

    CAS  PubMed  Google Scholar 

  38. Marie, I. et al. Gastric involvement in systemic sclerosis — a prospective study. Am. J. Gastroenterol. 96, 77–83 (2001).

    CAS  PubMed  Google Scholar 

  39. Katzka, D. A. et al. Barrett's metaplasia and adenocarcinoma of the esophagus in scleroderma. Am. J. Med. 82, 46–52 (1987).

    CAS  PubMed  Google Scholar 

  40. Domsic, R., Fasanella, K. & Bielefeldt, K. Gastrointestinal manifestations of systemic sclerosis. Dig. Dis. Sci. 53, 1163–1174 (2008).

    PubMed  Google Scholar 

  41. McMahan, Z. H. & Hummers, L. K. Systemic sclerosis — challenges for clinical practice. Nat. Rev. Rheumatol. 9, 90–100 (2003).

    Google Scholar 

  42. Nagaraja, V., McMahan, Z. H., Getzug, T. & Khanna, D. Management of gastrointestinal involvement in scleroderma. Curr. Treatm. Opt. Rheumatol. 1, 82–105 (2015).

    PubMed  PubMed Central  Google Scholar 

  43. Shoenut, J. P., Wieler, J. A. & Micflikier, A. B. The extent and pattern of gastro-oesophageal reflux in patients with scleroderma oesophagus: the effect of low-dose omeprazole. Aliment. Pharmacol. Ther. 7, 509–513 (1993).

    CAS  PubMed  Google Scholar 

  44. Hendel, L., Hage, E., Hendel, J. & Stentoft, P. Omeprazole in the long-term treatment of severe gastro-oesophageal reflux disease in patients with systemic sclerosis. Aliment. Pharmacol. Ther. 6, 565–577 (1992).

    CAS  PubMed  Google Scholar 

  45. Corleto, V. D., Festa, S., Di Giulio, E. & Annibale, B. Proton pump inhibitor therapy and potential long-term harm. Curr. Opin. Endocrinol. Diabetes Obes. 21, 3–8 (2014).

    CAS  PubMed  Google Scholar 

  46. Abraham, N. S. Proton pump inhibitors: potential adverse effects. Curr. Opin. Gastroenterol. 28, 615–620 (2012).

    CAS  PubMed  Google Scholar 

  47. Petrokubi, R. J. & Jeffries, G. H. Cimetidine versus antacid in scleroderma with reflux esophagitis. A randomized double-blind controlled study. Gastroenterology 77, 691–695 (1979).

    CAS  PubMed  Google Scholar 

  48. Wang, Y., Pan, T., Wang, Q. & Guo, Z. Additional bedtime H2-receptor antagonist for the control of nocturnal management of gastric acid breakthrough. Cochrane Database Syst Rev. 4, CD004275 (2009).

    Google Scholar 

  49. Zuccaro, G. Esophagoscopy and endoscopic esophageal ultrasound in the assessment of esophageal function. Semin. Thorac. Cardiovasc. Surg. 13, 226–233 (2001).

    PubMed  Google Scholar 

  50. Wipff, J. et al. Outcomes of Barrett's oesophagus related to systemic sclerosis: a 3-year EULAR Scleroderma Trials and Research prospective follow-up study. Rheumatology 50, 1440–1444 (2011).

    PubMed  Google Scholar 

  51. Conio, M. et al. Long-term endoscopic surveillance of patients with Barrett's esophagus. Incidence of dysplasia and adenocarcinoma: a prospective study. Am. J. Gastroenterol. 98, 1931–1939 (2003).

    PubMed  Google Scholar 

  52. Appel, J. Z. 3rd et al. Characterization of the innate immune response to chronic aspiration in a novel rodent model. Respir. Res. 8, 87–90 (2007).

    PubMed  PubMed Central  Google Scholar 

  53. Savarino, E. et al. Gastroesophageal reflux and pulmonary fibrosis in scleroderma. A study using pH-impedance monitoring. Am. J. Respir. Crit. Care Med. 179, 408–413 (2009).

    PubMed  Google Scholar 

  54. Gilson, M. et al. Prognostic factors for lung function in systemic sclerosis: prospective study of 105 cases. Eur. Respir. J. 35, 112–117 (2010).

    CAS  PubMed  Google Scholar 

  55. Christmann, R. B. et al. Gastroesophageal reflux incites interstitial lung disease in systemic sclerosis: clinical, radiologic, histopathologic, and treatment evidence. Semin. Arthritis Rheum. 40, 241–249 (2010).

    PubMed  Google Scholar 

  56. de Souza, R. B. C. et al. Centrilobular fibrosis: an underrecognized pattern in systemic sclerosis. Respiration 77, 389–397 (2009).

    PubMed  Google Scholar 

  57. Madsen, J. L. & Hendel, L. Gastrointestinal transit times of radiolabeled meal in progressive systemic sclerosis. Dig. Dis. Sci. 37, 1404–1408 (1992).

    CAS  PubMed  Google Scholar 

  58. Cozzi, F. et al. Gastric dysmotility after liquid bolus ingestion in systemic sclerosis: an ultrasonographic study. Rheumatol. Int. 32, 1219–1223 (2012).

    PubMed  Google Scholar 

  59. Franck-Larsson, K., Hedenstrom, H., Dahl, R. & Ronnblom, A. Delayed gastric emptying in patients with diffuse versus limited systemic sclerosis, unrelated to gastrointestinal symptoms and myoelectric gastric activity. Scand. J. Rheumatol. 32, 348–355 (2003).

    CAS  PubMed  Google Scholar 

  60. Tack, J., Carbone, F. & Rotondo, A. Gastroparesis. Curr. Opin. Gastroenterol. 31, 499–505 (2015).

    CAS  PubMed  Google Scholar 

  61. Fiorucci, S., Distrufti, V., Gerli, R. & Morelli, A. Effect of erythromycin on gastric and gallbladder emptying and gastrointestinal symptoms in scleroderma patients is maintained medium term. Am. J. Gastroenterol. 89, 550–555 (1994).

    CAS  PubMed  Google Scholar 

  62. Verne, G. N., Eaker, E. Y., Hardy, E. & Sninsky, C. A. Effect of octreotide and erythromycin on idiopathic and scleroderma-associated intestinal pseudoobstruction. Dig. Dis. Sci. 40, 1892–1901 (1995).

    CAS  PubMed  Google Scholar 

  63. Edmunds, M. C. et al. Effect of octreotide on gastric and small bowel motility in patients with gastroparesis. Aliment. Pharmacol. Ther. 12, 167–174 (1998).

    CAS  PubMed  Google Scholar 

  64. Murray, C., Kamm, M., Bloom, S. & Emmanuel, A. Ghrelin for the gastroenterologist: history and potential. Gastroenterology 125, 1492–1502 (2003).

    CAS  PubMed  Google Scholar 

  65. Ariyasu, H. et al. Clinical effects of ghrelin on gastrointestinal involvement in patients with systemic sclerosis. Endocr. J. 61, 735–742 (2014).

    CAS  PubMed  Google Scholar 

  66. McCallum, R. et al. Clinical response to gastric electrical stimulation in patients with postsurgical gastroparesis. Clin. Gastroenterol. Hepatol. 3, 49–54 (2005).

    PubMed  Google Scholar 

  67. Sallam, H., Doshi, D., McNearney, T. & Chen, J. D. Z. Transcutaneous electrical nerve stimulation improves gastric motility, dyspeptic symptoms and physical functioning in patients with systemic sclerosis by balancing the sympathovagal activity. Gastroenterology 128, A-468 (2005).

    Google Scholar 

  68. Oiwa, H. et al. A case of systemic sclerosis sine scleroderma associated with perforation of an afferent loop after subtotal gastrectomy with Bilroth 2 anastomosis for its severe gastrointestinal involvement. Mod. Rheumatol. 15, 371–373 (2005).

    PubMed  Google Scholar 

  69. You, C. H. et al. Gastric and small intestinal myoelectrical dysrhythmia associated with chronic intractable nausea and vomiting. Ann. Int. Med. 95, 449–451 (1981).

    CAS  PubMed  Google Scholar 

  70. Ghoshal, U. C., Srivastava, D., Ghoshal, U. & Misra, A. Breath tests in the diagnosis of small intestinal bacterial overgrowth in patients with irritable bowel syndrome in comparison with quantitative upper gut aspirate culture. Eur. J. Gastroenterol. Hepatol. 26, 753–760 (2014).

    CAS  PubMed  Google Scholar 

  71. Simrén, M. & Stotzer, P. O. Use and abuse of hydrogen breath tests. Gut 55, 297–303 (2006).

    PubMed  PubMed Central  Google Scholar 

  72. Quigley, E. M. Small intestinal bacterial overgrowth: what it is and what it is not. Curr. Opin. Gastroenterol. 30, 141–146 (2014).

    PubMed  Google Scholar 

  73. Quigley, E. M. & Quera, R. Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics. Gastroenterology 130 (Suppl. 1), S78–S90 (2006).

    CAS  PubMed  Google Scholar 

  74. Parodi, A. et al. Small intestinal bacterial overgrowth in patients suffering from scleroderma: clinical effectiveness of its eradication. Am. J. Gastroenterol. 103, 1257–1262 (2008).

    PubMed  Google Scholar 

  75. Shah, S. C., Day, L. W., Somsouk, M. & Sewell, J. L. Metaanalysis: antibiotic therapy for small intestinal bacterial overgrowth. Aliment. Pharmacol. Ther. 38, 925–934 (2013).

    CAS  PubMed  Google Scholar 

  76. Gyger, G. & Baron, M. Gastrointestinal manifestations of scleroderma: recent progress in evaluation, pathogenesis and management. Curr. Rheumatol. Rep. 14, 22–29 (2012).

    PubMed  Google Scholar 

  77. Baron, M. et al. Screening and management for malnutrition and related gastro-intestinal disorders in systemic sclerosis: recommendations of a North American expert panel. Clin. Exp. Rheumatol. 28 (Suppl. 58), 42–46 (2010).

    Google Scholar 

  78. Soifer, L. O., Peralta, D., Dima, G. & Besasso, H. Comparative clinical efficacy of a probiotic versus an antibiotic in the treatment of patients with intestinal bacterial overgrowth and chronic abdominal functional distension: a pilot study. Acta Gastroenterol. Latinoam. 40, 323–327 (in Spanish) (2010).

    PubMed  Google Scholar 

  79. Frech, T. M. et al. Probiotics for the treatment of systemic sclerosis-associated gastrointestinal bloating/distention. Clin. Exp. Rheumatol. 29, S22–S25 (2011).

    PubMed  Google Scholar 

  80. Forbes, A. & Marie, I. Gastrointestinal complications: the most frequent internal complications of systemic sclerosis. Rheumatology 48, 36–39 (2009).

    Google Scholar 

  81. da Silva Fink, J., Daniel de Mello, P. & Daniel de Mello, E. Subjective global assessment of nutritional status — a systematic review of the literature. Clin. Nutr. 34, 785–792 (2015).

    PubMed  Google Scholar 

  82. Baron, M. et al. Malnutrition is common in systemic sclerosis: results from the Canadian scleroderma research group database. J. Rheumatol. 36, 2737–2743 (2009).

    PubMed  Google Scholar 

  83. Khanna, D. et al. Reliability and validity of the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument. Arthritis Rheum. 61, 1257–1263 (2009).

    PubMed  PubMed Central  Google Scholar 

  84. Krause, L. et al. Nutritional status as marker for disease activity and severity predicting mortality in patients with systemic sclerosis. Ann. Rheum. Dis. 69, 1951–1957 (2010).

    PubMed  Google Scholar 

  85. Brown, M. et al. Home parenteral nutrition — an effective and safe long-term therapy for systemic sclerosisrelated intestinal failure. Rheumatology (Oxford) 47, 176–179 (2008).

    CAS  Google Scholar 

  86. Mann, S. D., Debinski, H. S. & Kamm, M. A. Clinical characteristics of chronic idiopathic intestinal pseudo-obstruction in adults. Gut 41, 675–681 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Stanghellini, V. et al. Natural history of intestinal failure induced by chronic idiopathic intestinal pseudo-obstruction. Transplant. Proc. 42, 15–18 (2010).

    CAS  PubMed  Google Scholar 

  88. Lindberg, G., Iwarzon, M. & Tornblom, H. Clinical features and long-term survival in chronic intestinal pseudo-obstruction and enteric dysmotility. Scand. J. Gastroenterol. 44, 692–699 (2009).

    PubMed  Google Scholar 

  89. Mecoli, C., Purohit, S., Sandorfi, N. & Derk, C. T. Mortality, recurrence, and hospital course of patients with systemic sclerosis-related acute intestinal pseudoobstruction. J. Rheumatol. 41, 2049–2054 (2014).

    PubMed  Google Scholar 

  90. Lauro, A., De Giorgio, R. & Pinna, A. D. Advancement in the clinical management of intestinal pseudo-obstruction. Expert. Rev. Gastroenterol. Hepatol. 9, 197–208 (2015).

    CAS  PubMed  Google Scholar 

  91. Emmanuel, A. V., Shand, A. & Kamm, M. A. Erythromycin for the treatment of chronic intestinal pseudo-obstruction: description of six cases with positive response. Aliment. Pharmacol. Ther. 19, 687–694 (2004).

    CAS  PubMed  Google Scholar 

  92. Emmanuel, A. V. et al. Randomised clinical trial: the efficacy of prucalopride in patients with chronic intestinal pseudo-obstruction — a double-blind, placebo-controlled, cross-over, multiple n = 1 study. Aliment. Pharmacol. Ther. 35, 48–55 (2012).

    CAS  PubMed  Google Scholar 

  93. Camilleri, M. et al. American College of Gastroenterology Clinical guideline: management of gastroparesis. Am. J. Gastroenterol. 108, 18–37 (2013).

    CAS  PubMed  Google Scholar 

  94. Ponec, R. J., Saunders, M. D. & Kimmey, M. B. Neostigmine for the treatment of acute colonic pseudo-obstruction. N. Engl. J. Med. 341, 137–141 (1999).

    CAS  PubMed  Google Scholar 

  95. Nikou, G. C. et al. Effect of octreotide on intestinal motility and bacterial overgrowth in scleroderma. N. Engl. J. Med. 325, 1461–1467 (1991).

    Google Scholar 

  96. Perlemuter, G. et al. Octreotide treatment of chronic intestinal pseudoobstruction secondary to connective tissue diseases. Arthritis Rheum. 42, 1545–1549 (1999).

    CAS  PubMed  Google Scholar 

  97. Charalambopoulos, D. & Sfikakis, P. P. Treatment of small intestinal disease in systemic sclerosis with octreotide: a prospective study in seven patients. J. Clin. Rheumatol. 13, 119–123 (2007).

    PubMed  Google Scholar 

  98. Klein-Weigel, P., Opitz, C. & Riemekasten, G. Systemic sclerosis — a systematic overview: part 1 — disease characteristics and classification, pathophysiologic concepts, and recommendations for diagnosis and surveillance. Vasa 40, 6–19 (2011).

    CAS  PubMed  Google Scholar 

  99. Ruiter, G. et al. Iron deficiency in systemic sclerosis patients with and without pulmonary hypertension. Rheumatology (Oxford) 53, 285–292 (2014).

    CAS  Google Scholar 

  100. Ghrénassia, E. et al. Prevalence, correlates and outcomes of gastric antral vascular ectasia in systemic sclerosis: a EUSTAR case–control study. J. Rheumatol. 41, 99–105 (2014).

    PubMed  Google Scholar 

  101. Marie, I. et al. Watermelon stomach in systemic sclerosis: its incidence and management. Aliment. Pharmacol. Ther. 28, 412–421 (2008).

    CAS  PubMed  Google Scholar 

  102. Ingraham, K. M. et al. Gastric antral vascular ectasia in systemic sclerosis: demographics and disease predictors. J. Rheumatol. 37, 603–607 (2010).

    PubMed  Google Scholar 

  103. Sellinger, C. P. & Ang, Y. S. Gastric antral vascular ectasia (GAVE): an update on clinical presentation, pathophysiology and treatment. Digestion 77, 131–137 (2008).

    Google Scholar 

  104. Gostout, C. J. et al. Endoscopic laser therapy for watermelon stomach. Gastroenterology 96, 1462–1465 (1989).

    CAS  PubMed  Google Scholar 

  105. Shibukawa, G. et al. Gastric antral vascular ectasia (GAVE) associated with systemic sclerosis: relapse after endoscopic treatment by argon plasma coagulation. Intern. Med. 46, 279–283 (2007).

    PubMed  Google Scholar 

  106. Swanson, E., Mahgoub, A., MacDonald, R. & Shaukat, A. Medical and endoscopic therapies for angiodysplasia and gastric antral vascular ectasia: a systematic review. Clin. Gastroenterol. Hepatol. 12, 571–582 (2014).

    PubMed  Google Scholar 

  107. Wells, C. D. et al. Treatment of gastric antral vascular ectasia (watermelon stomach) with endoscopic band ligation. Gastrointest. Endosc. 68, 231–236 (2008).

    PubMed  Google Scholar 

  108. Watson, M. et al. Gastric antral vascular ectasia (watermelon stomach) in patients with systemic sclerosis. Arthritis Rheum. 39, 341–346 (1996).

    CAS  PubMed  Google Scholar 

  109. Cho, S. et al. Endoscopic cryotherapy for the management of gastric antral vascular ectasia. Gastrointest. Endosc. 68, 895–902 (2008).

    PubMed  Google Scholar 

  110. Schulz, S. W. et al. Improvement of severe systemic sclerosis-associated gastric antral vascular ectasia following immunosuppressive treatment with intravenous cyclophosphamide. J. Rheumatol. 36, 1653–1656 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Sebastian, S., O'Morain, C. A. & Buckley, M. J. Review article: current therapeutic options for gastric antral vascular ectasia. Aliment. Pharmacol. Ther. 18, 157–165 (2003).

    CAS  PubMed  Google Scholar 

  112. van Laar, J. M. et al. Autologous hematopoietic stem cell transplantation versus intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA 311, 2490–2498 (2014).

    CAS  PubMed  Google Scholar 

  113. Bhattacharyya, A. et al. Autologous hematopoietic stem cell transplant for systemic sclerosis improves anemia from gastric antral vascular ectasia. J. Rheumatol. 42, 554–555 (2015).

    PubMed  Google Scholar 

  114. Battle, W. M. et al. Abnormal colonic motility in progressive systemic sclerosis. Ann. Intern. Med. 94, 749–752 (1981).

    CAS  PubMed  Google Scholar 

  115. Sacher, P., Buchmann, P. & Burger, H. Stenosis of the large intestine complicating scleroderma and mimicking a sigmoid carcinoma. Dis. Colon Rectum 26, 347–348 (1983).

    CAS  PubMed  Google Scholar 

  116. Wang, S. J. et al. Colonic transit disorders in systemic sclerosis. Clin. Rheumatol. 20, 251–254 (2001).

    CAS  PubMed  Google Scholar 

  117. Whitehead, W. E., Taitelbaum, G., Wigley, F. M. & Schuster, M. M. Rectosigmoid motility and myoelectric activity in progressive systemic sclerosis. Gastroenterology 96, 428–432 (1989).

    CAS  PubMed  Google Scholar 

  118. Emmanuel, A., Tack, J., Quigley, E. & Talley, N. Pharmacological management of constipation. Neurogastroenterol. Motility 21 (Suppl. 2), 41–54 (2009).

    CAS  Google Scholar 

  119. Butt, S. & Emmanuel, A. Systemic sclerosis and the gut. Expert Rev. Gastroenterol. Hepatol. 7, 331–339 (2013).

    CAS  PubMed  Google Scholar 

  120. Folwaczny, C. et al. Effects of various prokinetic drugs on gastrointestinal transit times in patients with progressive systemic scleroderma. Z. Gastroenterol. 35, 905–912 (in German) (1997).

    CAS  PubMed  Google Scholar 

  121. Lindsey, I., Farmer, C. R. & Cunningham, I. G. Subtotal colectomy and cecosigmoid anastomosis for colonic systemic sclerosis: report of a case and review of the literature. Dis. Colon Rectum 46, 1706–1711 (2003).

    PubMed  Google Scholar 

  122. Davis, R. P., Hines, J. R. & Flinn, W. R. Scleroderma of the colon with obstruction: report of a case. Dis. Colon Rectum 19, 256–259 (1976).

    CAS  PubMed  Google Scholar 

  123. Shafik, A., Shafik, A. A., El-Sibai, O. & Ahmed, I. Colonic pacing: a therapeutic option for the treatment of constipation due to total colonic inertia. Arch. Surg. 139, 775–779 (2004).

    PubMed  Google Scholar 

  124. Thaha, M. A. et al. Sacral nerve stimulation for faecal incontinence and constipation in adults. Cochrane Database Syst. Rev. 8, CD004464 (2015).

    Google Scholar 

  125. Balbir-Gurman, A., Brook, O. R., Chermesh, I. & Braun-Moscovici, Y. Pneumatosis cystoides intestinalis in scleroderma-related conditions. Intern. Med. J. 42, 323–329 (2012).

    CAS  PubMed  Google Scholar 

  126. Wu, L. L., Yang, Y. S., Dou, Y. & Liu, Q. S. A systematic analysis of pneumatosis cystoids intestinalis. World J. Gastroenterol. 19, 4973–4978 (2013).

    PubMed  PubMed Central  Google Scholar 

  127. Vischio, J., Matlyuk-Urman, Z. & Lakshminarayanan, S. Benign spontaneous pneumoperitoneum in systemic sclerosis. J. Clin. Rheumatol. 16, 379–381 (2010).

    PubMed  Google Scholar 

  128. Andréasson, K. et al. Faecal levels of calprotectin in systemic sclerosis are stable over time and are higher compared to primary Sjögren's syndrome and rheumatoid arthritis. Arthritis Res. Ther. 16, R46 (2014).

    PubMed  PubMed Central  Google Scholar 

  129. Pazzi, P. et al. Bile acid malabsorption in progressive systemic sclerosis. Gut 29, 552–553 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Staudacher, H. M., Irving, P. M., Lomer, M. C. & Whelan, K. Mechanisms and efficacy of dietary FODMAP restriction in IBS. Nat. Rev. Gastroenterol. Hepatol. 11, 256–266 (2014).

    CAS  PubMed  Google Scholar 

  131. Muir, J. G. & Gibson, P. R. The low FODMAP diet for treatment of irritable bowel syndrome and other gastrointestinal disorders. Gastroenterol. Hepatol. 9, 450–445 (2013).

    Google Scholar 

  132. 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. 21, 176–182 (2009).

    PubMed  Google Scholar 

  133. Clements, P. J., Becvar, R., Drosos, A. A., Ghattas, L. & Gabrielli, A. Assessment of gastrointestinal involvement. Clin. Exp. Rheumatol. 21, S15–S18 (2003).

    CAS  PubMed  Google Scholar 

  134. Mawdsley, A. H. Patient perception of UK scleroderma services — results of an anonymous questionnaire. Rheumatology 45, 1573 (2006).

    CAS  PubMed  Google Scholar 

  135. Thoua, N. et al. Internal anal sphincter atrophy in patients with systemic sclerosis. Rheumatology 50, 1596–1602 (2011).

    PubMed  Google Scholar 

  136. Fynne, L. et al. Distensibility of the anal canal in patients with systemic sclerosis: a study with the functional lumen imaging probe. Colorectal Dis. 15, e40–e47 (2013).

    CAS  PubMed  Google Scholar 

  137. Thoua, N. M., Abdel-Halim, M., Forbes, A., Denton, C. P. & Emmanuel, A. V. Fecal incontinence in systemic sclerosis is secondary to neuropathy. Am. J. Gastroenterol. 107, 597–603 (2011).

    PubMed  Google Scholar 

  138. Chiou, A. W., Lin, J. K. & Wang, F. M. Anorectal abnormalities in progressive systemic sclerosis. Dis. Colon Rectum 32, 417–421 (1989).

    CAS  PubMed  Google Scholar 

  139. Leighton, J. A. et al. Anorectal dysfunction and rectal prolapse in progressive systemic sclerosis. Dis. Colon Rectum 36, 182–185 (1993).

    CAS  PubMed  Google Scholar 

  140. Jaffin, B. W., Chang, P. & Spiera, H. Fecal incontinence in scleroderma. Clinical features, anorectal manometric findings, and their therapeutic implications. J. Clin. Gastroenterol. 25, 513–517 (1997).

    CAS  PubMed  Google Scholar 

  141. Denton, C. & Black, C. Scleroderma — clinical and pathological advances. Best Pract. Res. Clin. Rheumatol. 18, 271–290 (2004).

    CAS  PubMed  Google Scholar 

  142. Sporbeck, B. et al. Effect of biofeedback and deep oscillation on Raynaud's phenomenon secondary to systemic sclerosis: results of a controlled prospective randomized clinical trial. Rheumatol. Int. 32, 1469–1473 (2012).

    PubMed  Google Scholar 

  143. Kenefick, N. J. et al. Sacral nerve stimulation for faecal incontinence due to systemic sclerosis. Gut 51, 881–883 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Butt, S. et al. Lack of effect of sacral nerve stimulation for incontinence in patients with systemic sclerosis. Colorectal Dis. 17, 903–907 (2015).

    CAS  PubMed  Google Scholar 

  145. Butt, S. K. et al. Preliminary significant findings from a randomised controlled trial of posterior tibial nerve stimulation in systemic sclerosis associated faecal incontinence. UEG J. 2 (1 Suppl. 1), A407 (2014).

    Google Scholar 

  146. Bae, S. et al. Associations between a scleroderma specific gastrointestinal instrument and objective tests of upper gastrointestinal involvements in systemic sclerosis. Clin. Exp. Rheumatol. 31 (Suppl. 76), 57–63 (2013).

    PubMed  Google Scholar 

  147. Alrubaiy, L. et al. Systematic review of health-related quality of life measures for inflammatory bowel disease. J. Crohns Colitis 9, 284–292 (2015).

    PubMed  Google Scholar 

  148. Spiegel, B. M. et al. Development of the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) gastrointestinal symptom scales. Am. J. Gastroenterol. 109, 1804–1814 (2014).

    PubMed  PubMed Central  Google Scholar 

  149. Nagaraja, V. et al. Construct validity of the Patient-Reported Outcomes Measurement Information System gastrointestinal symptom scales in systemic sclerosis. Arthritis Care Res. (Hoboken) 66, 1725–1730 (2014).

    Google Scholar 

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Acknowledgements

The author is supported by the National Institute of Health Research, University College London Hospitals Biomedical Research Centre.

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    Anton Emmanuel

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Emmanuel, A. Current management of the gastrointestinal complications of systemic sclerosis. Nat Rev Gastroenterol Hepatol 13, 461–472 (2016). https://doi.org/10.1038/nrgastro.2016.99

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