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%.








Similar content being viewed by others
References
Krishnan E, Furst DE (2005) Systemic sclerosis mortality in the United States: 1979–1998. Eur J Epidemiol 20:855–861
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
Szamosi S, Szekanecz Z, Szucs G (2006) Gastrointestinal manifestations in Hungarian scleroderma patients. Rheumatol Int 26:1120–1124
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
Steen VD, Medsger TA (2000) Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum 43:2437–2444
LeRoy EC, Medsger TA (2001) Criteria for the classification of early systemic sclerosis. J Rheumatol 28:1573–1576
Sjogren RW (1994) Gastrointestinal motility disorders in scleroderma. Arthritis Rheum 37:1265–1282
Greydanus MP, Camilleri M (1989) Abnormal postcibal antral and small bowel motility due to neuropathy or myopathy in systemic sclerosis. Gastroenterology 96:110–115
Rees WD, Leigh RJ, Christofides ND, Bloom SR, Turnberg LA (1982) Interdigestive motor activity in patients with systemic sclerosis. Gastroenterology 83:575–580
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
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
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
Arnett FC (2006) Is scleroderma an autoantibody mediated disease? Curr Opin Rheumatol 18:579–581
Howe S, Eaker EY, Sallustio JE, Peebles C, Tan EM, Williams RC (1994) Antimyenteric neuronal antibodies in scleroderma. J Clin Invest 94:761–770
Goldblatt F, Gordon TP and Waterman SA (2002) Antibody-mediated gastrointestinal dysmotility in scleroderma. Gastroenterology 123:1144–1150
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
Denton CP, Black CM (2000) Scleroderma and related disorders: therapeutic aspects. Best Pract Res Clin Rheumatol 14:17–35
Denton CP, Black CM, Abraham DJ (2006) Mechanisms and consequences of fibrosis in systemic sclerosis. Nat Clin Pract Rheumatol 2:134–144
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
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
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
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
Soto-Rojas AE, Kraus A (2002) The oral side of Sjogren syndrome. Diagnosis and treatment. A review. Arch Med Res 33:95–106
Ostojic P, Damjanov N (2006) Different clinical features in patients with limited and diffuse cutaneous systemic sclerosis. Clin Rheumatol 25:453–457
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
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
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
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
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
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
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
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
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
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
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
Mansour KA, Malone CE (1995) Surgery for scleroderma of the esophagus: A 12-year experience. Ann Thorac Surg 60:227
Orringer MB, Dabich L, Zarafonetis CJ, Sloan H (1976) Gastroesophageal reflux in esophageal scleroderma: diagnosis and implications. Ann Thorac Surg 22:120–130
Poirier NC, Taillefer R, Topart P, Duranceau A (1994) Antireflux operations in patients with scleroderma. Ann Thorac Surg 58:66–72
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
Ebert EC (2006) Esophageal disease in scleroderma. J Clin Gastroenterol 40:769–775
Segel MC, Campbell WL, Medsger TA, Roumm AD (1985) Systemic sclerosis (scleroderma) and esophageal adenocarcinoma: is increased patient screening necessary? Gastroenterology 89:485–488
Poelmans J, Tack J (2005) Extraoesophageal manifestations of gastro-oesophageal reflux. Gut 54:1492–1499
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
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
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
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
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
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
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
Talley NJ (2003) Diabetic gastropathy and prokinetics. Am J Gastroenterol 98:264–271
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
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
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
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
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
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
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
Sebastian S, O’Morain CA, Buckley MJ (2003) Review article: current therapeutic options for gastric antral vascular ectasia. Aliment Pharmacol Ther 15:157–165
Pickhardt PJ (1999) The “hide-bound” bowel sign. Radiology 213:837–838
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
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
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
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
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
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
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
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
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
Land MH, Rouster-Stevens K, Woods CR, Cannon ML, Cnota J, Shetty AK (2005) Lactobacillus sepsis associated with probiotic therapy. Pediatrics 115:178–181
Grabowski G, Grant JP (1989) Nutritional support in patients with systemic scleroderma. J Parenter Enteral Nutr 13:147–151
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
Trezza M, Krogh K, Egekvist H, Bjerring P, Laurberg S (1999) Bowel problems in patients with systemic sclerosis. Scand J Gastroenterol 34:409–413
Engel A, Kamm M, Talbot I (1994) Progressive systemic sclerosis of the internal anal sphincter leading to passive faecal incontinence. Gut 35:857–859
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
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
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
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
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
Chatoor DR, Taylor SJ, Cohen CR, Emmanuel AV (2007) Faecal incontinence. Br J Surg 94:134–144
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
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
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-007-0018-8