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Gastrointestinal Manifestations of Systemic Sclerosis

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Abstract

Systemic sclerosis is a chronic disorder of connective tissue that affects the gastrointestinal tract in more than 80% of patients. Changes in neuromuscular function with progressive fibrosis of smooth muscle within the muscularis propria impair normal motor function, which may secondarily alter transit and nutrient absorption. Esophageal manifestations with gastroesophageal reflux and dysphagia are the most common visceral manifestation of the disease, often requiring more intense acid-suppressive medication. Gastric involvement may lead to gastroparesis, which can be found in up to 50% of patients. Severe small bowel disease can present as chronic intestinal pseudo-obstruction with distended loops of small intestine, bacterial overgrowth, impaired absorption and progressive development of nutritional deficiencies. While not studied as extensively, systemic sclerosis often also affects colorectal function resulting in constipation, diarrhea or fecal incontinence. Nutritional support and prokinetics have been used with some success to manage gastric and small or large bowel involvement in patients with systemic sclerosis. Despite advances in management, significant gastrointestinal manifestations of systemic sclerosis still carry a poor prognosis with a five-year mortality exceeding 50%.

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References

  1. Krishnan E, Furst DE (2005) Systemic sclerosis mortality in the United States: 1979–1998. Eur J Epidemiol 20:855–861

    Article  PubMed  Google Scholar 

  2. Maricq HR, Weinrich MC, Keil JE, Smith EA, Harper FE, Nussbaum AI, LeRoy EC, McGregor AR, Diat F, Rosal EJ (1989) Prevalence of scleroderma spectrum disorders in the general population of South Carolina. Arthritis Rheum 32:998–1006

    Article  PubMed  CAS  Google Scholar 

  3. Szamosi S, Szekanecz Z, Szucs G (2006) Gastrointestinal manifestations in Hungarian scleroderma patients. Rheumatol Int 26:1120–1124

    Article  PubMed  Google Scholar 

  4. Weston S, Thumshirn M, Wiste J, Camilleri M (1998) Clinical and upper gastrointestinal motility features in systemic sclerosis and related disorders. Am J Gastroenterol 93:1085–1089. DOI:10.1111/j.1572–0241.1998.00334.x

    Article  PubMed  CAS  Google Scholar 

  5. Steen VD, Medsger TA (2000) Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum 43:2437–2444

    Article  PubMed  CAS  Google Scholar 

  6. LeRoy EC, Medsger TA (2001) Criteria for the classification of early systemic sclerosis. J Rheumatol 28:1573–1576

    PubMed  CAS  Google Scholar 

  7. Sjogren RW (1994) Gastrointestinal motility disorders in scleroderma. Arthritis Rheum 37:1265–1282

    Article  PubMed  CAS  Google Scholar 

  8. Greydanus MP, Camilleri M (1989) Abnormal postcibal antral and small bowel motility due to neuropathy or myopathy in systemic sclerosis. Gastroenterology 96:110–115

    PubMed  CAS  Google Scholar 

  9. Rees WD, Leigh RJ, Christofides ND, Bloom SR, Turnberg LA (1982) Interdigestive motor activity in patients with systemic sclerosis. Gastroenterology 83:575–580

    PubMed  CAS  Google Scholar 

  10. DeSchryver-Kecskemeti K, Clouse RE (1989) Perineural and intraneural inflammatory infiltrates in the intestines of patients with systemic connective-tissue disease. Arch Pathol Lab Med 113:394–398

    PubMed  CAS  Google Scholar 

  11. Malandrini A, Selvi E, Villanova M, Berti G, Sabadini L, Salvadori C, Gambelli S, De Stefano R, Vernillo R, Marcolongo R, Guazzi G (2000) Autonomic nervous system and smooth muscle cell involvement in systemic sclerosis: ultrastructural study of 3 cases. J Rheumatol 27:1203–1206

    PubMed  CAS  Google Scholar 

  12. Roberts CGP, Hummers LK, Ravich WJ, Wigley FM, Hutchins GM (2006) A case-control study of the pathology of oesophageal disease in systemic sclerosis (scleroderma). Gut 55:1697–1703

    Article  PubMed  CAS  Google Scholar 

  13. Arnett FC (2006) Is scleroderma an autoantibody mediated disease? Curr Opin Rheumatol 18:579–581

    Article  PubMed  CAS  Google Scholar 

  14. Howe S, Eaker EY, Sallustio JE, Peebles C, Tan EM, Williams RC (1994) Antimyenteric neuronal antibodies in scleroderma. J Clin Invest 94:761–770

    Article  PubMed  CAS  Google Scholar 

  15. Goldblatt F, Gordon TP and Waterman SA (2002) Antibody-mediated gastrointestinal dysmotility in scleroderma. Gastroenterology 123:1144–1150

    Article  PubMed  CAS  Google Scholar 

  16. Eaker EY, Kuldau JG, Verne GN, Ross SO, Sallustio JE (1999) Myenteric neuronal antibodies in scleroderma: passive transfer evokes alterations in intestinal myoelectric activity in a rat model. J Lab Clin Med 133:551–556

    Article  PubMed  CAS  Google Scholar 

  17. Denton CP, Black CM (2000) Scleroderma and related disorders: therapeutic aspects. Best Pract Res Clin Rheumatol 14:17–35

    Article  Google Scholar 

  18. Denton CP, Black CM, Abraham DJ (2006) Mechanisms and consequences of fibrosis in systemic sclerosis. Nat Clin Pract Rheumatol 2:134–144

    Article  PubMed  Google Scholar 

  19. Donato ML, Feasel AM, Weber DM, Prieto VG, Giralt SA, Champlin RE, Duvic M (2006) Scleromyxedema: role of high-dose melphalan with autologous stem cell transplantation. Blood 107:463–466

    Article  PubMed  CAS  Google Scholar 

  20. Farge D, Marolleau JP, Zohar S, Marjanovic Z, Cabane J, Mounier N, Hachulla E, Philippe P, Sibilia J, Rabian C, Chevret S, Gluckman E (2002) Autologous bone marrow transplantation in the treatment of refractory systemic sclerosis: early results from a French multicentre phase I-II study. Br J Haematol 119:726–739

    Article  PubMed  Google Scholar 

  21. McSweeney PA, Nash RA, Sullivan KM, Storek J, Crofford LJ, Dansey R, Mayes MD, McDonagh KT, Nelson JL, Gooley TA, Holmberg LA, Chen CS, Wener MH, Ryan K, Sunderhaus J, Russell K, Rambharose J, Storb R, Furst DE (2002) High-dose immunosuppressive therapy for severe systemic sclerosis: initial outcomes. Blood 100:1602–1610

    PubMed  CAS  Google Scholar 

  22. Nash RA, McSweeney PA, Crofford LJ, Abidi M, Chen C-S, Godwin JD, Gooley TA, Holmberg L, Henstorf G, LeMaistre CF, Mayes MD, McDonagh KT, McLaughlin B, Molitor JA, Nelson JL, Shulman H, Storb R, Viganego F, Wener MH, Seibold JR, Sullivan KM, Furst DE (2007) High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood 110:1388–1396

    Article  PubMed  CAS  Google Scholar 

  23. Soto-Rojas AE, Kraus A (2002) The oral side of Sjogren syndrome. Diagnosis and treatment. A review. Arch Med Res 33:95–106

    Article  PubMed  Google Scholar 

  24. Ostojic P, Damjanov N (2006) Different clinical features in patients with limited and diffuse cutaneous systemic sclerosis. Clin Rheumatol 25:453–457

    Article  PubMed  Google Scholar 

  25. Hamel-Roy J, Devroede G, Arhan P, Tetreault L, Duranceau A, Menard HA (1985) Comparative esophageal and anorectal motility in scleroderma. Gastroenterology 88:1–7

    PubMed  CAS  Google Scholar 

  26. Airo P, Della Casa D, Danieli E, Missale G, Cattaneo R, Cestari R (2005) Oesophageal manometry in early and definite systemic sclerosis. Clin Rheumatol 24:370–376

    Article  PubMed  Google Scholar 

  27. Bassotti G, Battaglia E, Debernardi V, Germani U, Quiriconi F, Dughera L, Buonafede G, Puiatti P, Morelli A, Spinozzi F, Mioli PR, Emanuelli G (1998) Esophageal dysfunction in scleroderma: relationship with disease subsets. Arthritis Rheum 40:2252–2259

    Article  Google Scholar 

  28. Wipff J, Allanore Y, Soussi F, Terris B, Abitbol V, Raymond J, Chaussade S, Kahan A (2005) Prevalence of Barrett’s esophagus in systemic sclerosis. Arthritis Rheum 52:2882–2888

    Article  PubMed  CAS  Google Scholar 

  29. Basilisco G, Carola F, Vanoli M, Bianchi P, Barbera R (1996) Oesophageal acid clearance in patients with systemic sclerosis: effect of body position. Eur J Gastroenterol Hepatol 8:205–209

    Article  PubMed  CAS  Google Scholar 

  30. Lock G, Zeuner M, Straub RH, Hein R, Lang B, Scholmerich J, Holstege A (1997) Esophageal manometry in systemic sclerosis: screening procedure or confined to symptomatic patients? Rheumatol Int 17:61–66

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  32. Johnson DA, Drane WE, Curran J, Benjamin SB, Chobanian SJ, Karvelis K, Cattau EL Jr (1987) Metoclopramide response in patients with progressive systemic sclerosis. Effect on esophageal and gastric motility abnormalities. Arch Intern Med 147:1597–1601

    Article  PubMed  CAS  Google Scholar 

  33. Mercado U, Arroyo de Anda R, Avendano L, Araiza-Casillas R, Avendano-Reyes M (2005) Metoclopramide response in patients with early diffuse systemic sclerosis. Effects on esophageal motility abnormalities. Clin Exp Rheumatol 23:685–688

    PubMed  CAS  Google Scholar 

  34. Richter JE, Sabesin SM, Kogut DG, Kerr RM, Wruble LD, Collen MJ (1996) Omeprazole versus ranitidine or ranitidine/metoclopramide in poorly responsive symptomatic gastroesophageal reflux disease. Am J Gastroenterol 91:1766–1772

    PubMed  CAS  Google Scholar 

  35. Wang SJ, La JL, Chen DY, Chen YH, Hsieh TY, Lin WY (2002) Effects of cisapride on oesophageal transit of solids in patients with progressive systemic sclerosis. Clin Rheumatol 21:43–45

    Article  PubMed  CAS  Google Scholar 

  36. Mansour KA, Malone CE (1995) Surgery for scleroderma of the esophagus: A 12-year experience. Ann Thorac Surg 60:227

    PubMed  CAS  Google Scholar 

  37. Orringer MB, Dabich L, Zarafonetis CJ, Sloan H (1976) Gastroesophageal reflux in esophageal scleroderma: diagnosis and implications. Ann Thorac Surg 22:120–130

    Article  PubMed  CAS  Google Scholar 

  38. Poirier NC, Taillefer R, Topart P, Duranceau A (1994) Antireflux operations in patients with scleroderma. Ann Thorac Surg 58:66–72

    Article  PubMed  CAS  Google Scholar 

  39. Watson DI, Jamieson GG, Bessell JR, Devitt PG (2006) Laparoscopic fundoplication in patients with an aperistaltic esophagus and gastroesophageal reflux. Dis Esophagus 19:94–98

    Article  PubMed  CAS  Google Scholar 

  40. Ebert EC (2006) Esophageal disease in scleroderma. J Clin Gastroenterol 40:769–775

    Article  PubMed  Google Scholar 

  41. Segel MC, Campbell WL, Medsger TA, Roumm AD (1985) Systemic sclerosis (scleroderma) and esophageal adenocarcinoma: is increased patient screening necessary? Gastroenterology 89:485–488

    PubMed  CAS  Google Scholar 

  42. Poelmans J, Tack J (2005) Extraoesophageal manifestations of gastro-oesophageal reflux. Gut 54:1492–1499

    Google Scholar 

  43. Kinuya K, Nakajima K, Kinuya S, Michigishi T, Tonami N, Takehara K (2001) Esophageal hypomotility in systemic sclerosis: close relationship with pulmonary involvement. Ann Nucl Med 15:97–101

    Article  PubMed  CAS  Google Scholar 

  44. Lock G, Pfeifer M, Straub RH, Zeuner M, Lang B, Scholmerich J, Holstege A (1998) Association of esophageal dysfunction and pulmonary function impairment in systemic sclerosis. Am J Gastroenterol 93:341–345

    Article  PubMed  CAS  Google Scholar 

  45. Marie I, Dominique S, Levesque H, Ducrotte P, Denis P, Hellot MF, Courtois H (2001) Esophageal involvement and pulmonary manifestations in systemic sclerosis. Arthritis Rheum 45:346–354

    Article  PubMed  CAS  Google Scholar 

  46. Troshinsky MB, Kane GC, Varga J, Cater JR, Fish JE, Jimenez SA, Castell DO (1994) Pulmonary function and gastroesophageal reflux in systemic sclerosis. Ann Intern Med 121:6–10

    PubMed  CAS  Google Scholar 

  47. Franck-Larsson K, Hedenstrom H, Dahl R, Ronnblom A (2003) 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

    Article  PubMed  CAS  Google Scholar 

  48. Marie I, Levesque H, Ducrotte P, Denis P, Hellot M-F, Benichou J, Cailleux N, Courtois H (2001) Gastric involvement in systemic sclerosis: a prospective study. Am J Gastroenterol 96:77–83

    Article  PubMed  CAS  Google Scholar 

  49. Sridhar KR, Lange RC, Magyar L, Soykan I, McCallum RW (1998) Prevalence of impaired gastric emptying of solids in systemic sclerosis: diagnostic and therapeutic implications. J Lab Clin Med 132:541–546

    Article  PubMed  CAS  Google Scholar 

  50. Talley NJ (2003) Diabetic gastropathy and prokinetics. Am J Gastroenterol 98:264–271

    Article  PubMed  Google Scholar 

  51. McNearney T, Lin X, Shrestha J, Lisse J, Chen JDZ (2002) Characterization of gastric myoelectrical rhythms in patients with systemic sclerosis using multichannel surface electrogastrography. Dig Dis Sci 47:690–698

    Article  PubMed  Google Scholar 

  52. Pfaffenbach B, Adamek RJ, Hagemann D, Busch S, Hoffmann K, Altmeyer P, Schaffstein J, Wegener M (1996) Effect of progressive systemic sclerosis on antral myoelectrical activity and gastric emptying. Z Gastroenterol 34:517–521

    PubMed  CAS  Google Scholar 

  53. Marie I, Levesque H, Ducrotté P, Denis P, Benichou J, Hellot MF, Cailleux N, Le Loët X, Joly P, Lauret P, Courtois H (1998) Manometry of the upper intestinal tract in patients with systemic sclerosis: a prospective study. Arthritis Rheum 41:1874–1883

    Article  PubMed  CAS  Google Scholar 

  54. Fiorucci S, Distrutti E, Bassotti G, Gerli R, Chiucchiu S, Betti C, Santucci L, Morelli A (1994) Effect of erythromycin administration on upper gastrointestinal motility in scleroderma patients. Scand J Gastroenterol 29:807–813

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  56. Horowitz M, Maddern GJ, Maddox A, Wishart J, Chatterton BE, Shearman DJ (1987) Effects of cisapride on gastric and esophageal emptying in progressive systemic sclerosis. Gastroenterology 93:311–315

    PubMed  CAS  Google Scholar 

  57. Linke R, Meier M, Muenzing W, Folwaczny C, Schnell O, Tatsch K (2005) Prokinetic therapy: what can be measured by gastric scintigraphy? Nucl Med Commun 26:527–233

    Article  PubMed  Google Scholar 

  58. Sebastian S, O’Morain CA, Buckley MJ (2003) Review article: current therapeutic options for gastric antral vascular ectasia. Aliment Pharmacol Ther 15:157–165

    Article  Google Scholar 

  59. Pickhardt PJ (1999) The “hide-bound” bowel sign. Radiology 213:837–838

    PubMed  CAS  Google Scholar 

  60. Shindo K, Machida M, Koide K, Fukumura M, Yamazaki R (1998) Deconjugation ability of bacteria isolated from the jejunal fluid of patients with progressive systemic sclerosis and its gastric pH. Hepatogastroenterology 45:1643–1650

    PubMed  CAS  Google Scholar 

  61. Kaye SA, Lim SG, Taylor M, Patel S, Gillespie S, Black CM (1995) Small bowel bacterial overgrowth in systemic sclerosis: detection using direct and indirect methods and treatment outcome. Rheumatology 34:265–269

    Article  CAS  Google Scholar 

  62. Wegener M, Adamek RJ, Wedmann B, Jergas M, Altmeyer P (1994) Gastrointestinal transit through esophagus, stomach, small and large intestine in patients with progressive systemic sclerosis. Dig Dis Sci 39:2209–2215

    Article  PubMed  CAS  Google Scholar 

  63. Stellaard F, Sauerbruch T, Luderschmidt CH, Leisner B, Paumgartner G (1987) Intestinal involvement in progressive systemic sclerosis detected by increased unconjugated serum bile acids. Gut 28:446–450

    Article  PubMed  CAS  Google Scholar 

  64. Emmanuel AV, Shand AG, Kamm MA (2004) Erythromycin for the treatment of chronic intestinal pseudo-obstruction: description of six cases with a positive response. Aliment Pharmacol Ther 19:687–694

    Article  PubMed  CAS  Google Scholar 

  65. Soudah HC, Hasler WL, Owyang C (1991) Effect of octreotide on intestinal motility and bacterial overgrowth in scleroderma. N Engl J Med 325:1461–1467

    Article  PubMed  CAS  Google Scholar 

  66. Verne GN, Eaker EY, Hardy E, Sninsky CA (1995) Effect of octreotide and erythromycin on idiopathic and scleroderma-associated intestinal pseudoobstruction. Dig Dis Sci 40:1892–1901

    Article  PubMed  CAS  Google Scholar 

  67. Perlemuter G, Cacoub P, Chaussade S, Wechsler B, Couturier D, Piette JC (1999) Octreotide treatment of chronic intestinal pseudoobstruction secondary to connective tissue diseases. Arthritis Rheum 42:1545–1549

    Article  PubMed  CAS  Google Scholar 

  68. Attar A, Flourié B, Rambaud J, Franchisseur C, Ruszniewski P, Bouhnik Y (1999) Antibiotic efficacy in small intestinal bacterial overgrowth–related chronic diarrhea: a crossover, randomized trial. Gastroenterology 117:794–797

    Article  PubMed  CAS  Google Scholar 

  69. Land MH, Rouster-Stevens K, Woods CR, Cannon ML, Cnota J, Shetty AK (2005) Lactobacillus sepsis associated with probiotic therapy. Pediatrics 115:178–181

    PubMed  Google Scholar 

  70. Grabowski G, Grant JP (1989) Nutritional support in patients with systemic scleroderma. J Parenter Enteral Nutr 13:147–151

    Article  CAS  Google Scholar 

  71. Quiroz ES, Flannery MT, Martinez EJ, Warner EA (1995) Pneumatosis cystoides intestinalis in progressive systemic sclerosis: a case report and literature review. Am J Med Sci 310:252–255

    PubMed  CAS  Google Scholar 

  72. Trezza M, Krogh K, Egekvist H, Bjerring P, Laurberg S (1999) Bowel problems in patients with systemic sclerosis. Scand J Gastroenterol 34:409–413

    Article  PubMed  CAS  Google Scholar 

  73. Engel A, Kamm M, Talbot I (1994) Progressive systemic sclerosis of the internal anal sphincter leading to passive faecal incontinence. Gut 35:857–859

    Article  PubMed  CAS  Google Scholar 

  74. deSouza N, Williams A, Wilson H, Gilderdale D, Coutts G, Black C (1998) Fecal incontinence in scleroderma: assessment of the anal sphincter with thin-section endoanal MR imaging. Radiology 208:529–535

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  76. Heyt GJ, Oh MK, Alemzadeh N, Rivera S, Jimenez SA, Rattan S, Cohen S, Dimarino AJ (2004) Impaired rectoanal inhibitory response in scleroderma (systemic sclerosis): an association with fecal incontinence. Dig Dis Sci 49:1040–1045

    Article  PubMed  Google Scholar 

  77. Boeckxstaens GE, Bartelsman JF, Lauwers L, Tytgat GN (2002) Treatment of GI dysmotility in scleroderma with the new enterokinetic agent prucalopride. Am J Gastroenterol 97:194–197

    Article  PubMed  CAS  Google Scholar 

  78. Wang SJ, Lan JL, Lan JL, Chen DY, Chen YH, Hsieh TY, Lin WY (2002) Effects of cisapride on colonic transit in patients with progressive systemic sclerosis. Clin Rheumatol 21:271–274

    Article  PubMed  Google Scholar 

  79. Chatoor DR, Taylor SJ, Cohen CR, Emmanuel AV (2007) Faecal incontinence. Br J Surg 94:134–144

    Article  PubMed  CAS  Google Scholar 

  80. Kenefick NJ, Vaizey CJ, Nicholls RJ, Cohen R, Kamm MA (2002) Sacral nerve stimulation for faecal incontinence due to systemic sclerosis. Gut 51:881–883

    Article  PubMed  CAS  Google Scholar 

  81. Norton C, Cody JD, Hosker G (2006) Biofeedback and/or sphincter exercises for the treatment of faecal incontinence in adults. Cochrane Database Syst Rev CD002111

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Domsic, R., Fasanella, K. & Bielefeldt, K. Gastrointestinal Manifestations of Systemic Sclerosis. Dig Dis Sci 53, 1163–1174 (2008). https://doi.org/10.1007/s10620-007-0018-8

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