Abstract
Gastrointestinal (GI) involvement is frequent in scleroderma (systemic sclerosis [SSc]) and is the most frequent internal complication of the disease. Patients with GI involvement have impaired quality of life, and their prognosis may be one of severe impairment. Unfortunately, GI involvement is often noticed when severe complications have already occurred, is irreversible, and is difficult to manage. The past 2 to 3 years have been rich in exciting studies that we hope will help identify, prevent, treat, and monitor disease progression. Recent studies on the pathophysiology of GI tract disease could lead to advances in the treatment of GI tract involvement. The importance of treating gastroesophageal reflux (GER) has been reinforced by studies showing GER damage in almost all SSc patients, and the fact that GER damage is reversible if early treatment with proton pump inhibitors is introduced. Moreover, recent data showing a link between GER and interstitial lung disease in SSc underscore the importance of aggressive GER treatment in SSc patients. A novel lung pattern possibly related to GER also has been described. New, exciting data on gastric vascular antral ectasia have been published. Finally, malnutrition in SSc patients has been highlighted, and anorectal involvement has been emphasized.
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Ponge T, des Bruley SV. Atteintes digestives sclérodermiques. La Revue du Praticien. 2002;52:196–200.
Clements PJ, Becvar R, Drosos AA, et al. Assessment of gastrointestinal involvement. Clin Exp Rheumatol. 2003;21:S15–8.
Steen VD, Medsger Jr TA. Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum. 2000;43:2437–44.
Sjogren RW. Gastrointestinal motility disorders in scleroderma. Arthritis Rheum. 1994;37:1265–82.
Jaovisidha K, Csuka ME, Almagro UA, et al. Severe gastrointestinal involvement in systemic sclerosis: report of five cases and review of the literature. Semin Arthritis Rheum. 2005;34:689–702.
Forbes A, Marie I. Gastrointestinal complications: the most frequent internal complications of systemic sclerosis. Rheumatology (Oxford). 2009;48 Suppl 3:iii36–9.
Franck-Larsson K, Graf W, Rönnblom A. Lower gastrointestinal symptoms and quality of life in patients with systemic sclerosis: a population-based study. Eur J Gastroenterol Hepatol. 2009;21:m176–82.
Thombs BD, Hudson M, Taillefer SS, et al. Prevalence and clinical correlates of symptoms of depression in patients with systemic sclerosis. Arthritis Rheum. 2008;4:504–9.
Attar A. Atteintes digestives au cours de la sclérodermie. Ann Med Interne (Paris). 2002;153:260–4.
Savarino E, Bazzica M, Zentilin P, et al. Gastroesophageal reflux and pulmonary fibrosis in scleroderma. A study using pH-impedance monitoring. Am J Respir Crit Care Med. 2009;179:408–13.
Lock G, Holstege A, Lang B, et al. Gastrointestinal manifestations of progressive systemic sclerosis. Am J Gastroenterol. 1997;92:763–71.
Marie I, Lévesque H, Ducrotté P, et al. Atteinte de l’intestin grêle au cours de la sclérodermie systémique. Rev Med Interne. 1999;20:504–13.
D’Angelo WA, Fries JF, Masi AT, et al. Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med. 1969;46:428–40.
Sjogren RW. Gastrointestinal features of scleroderma. Curr Opin Rheumatol. 1996;8:569–75.
Hendel L, Kobayasi T, Petri M. Ultrastructure of the small intestinal mucosa in progressive systemic sclerosis (PSS). Acta Pathol Microbiol Immunol Scand A. 1987;95:41–6.
Denton CP, Black CM, Abraham DJ. Mechanisms and consequences of fibrosis in systemic sclerosis. Nat Clin Pract Rheumatol. 2006;2:134–44.
Hendel L, Ammitzboll T, Dirksen K, Petri M, et al. Collagen components in the duodenal and rectal mucosa in progressive systemic sclerosis and other diseases. Acta Derm Venereol. 1986;66:220–4.
Treacy WL, Baggenstoss AH, Slocumb CH, et al. Scleroderma of the esophagus. A correlation of histologic and physiologic findings. Ann Intern Med. 1963;59:351–6.
Howe S, Eaker EY, Sallustio JE, et al. Antimyenteric neuronal antibodies in scleroderma. J Clin Invest. 1994;94:761–70.
Eaker EY, Kuldau JG, Verne GN, et al. Myenteric neuronal antibodies in scleroderma: passive transfer evokes alterations in intestinal myoelectric activity in a rat model. J Lab Clin Med. 1999;133:551–6.
• Kawaguchi Y, Nakamura Y, Matsumoyo I, et al. Muscarinic-3 acetylcholine receptor autoantibody in patients with systemic sclerosis: contribution to severe gastrointestinal tract dysmotility. Ann Rheum Dis 2009, 68: 710–714. To clarify the pathogenesis of GI tract involvement in SSc, the occurrence of autoantibody for M3R was investigated in 14 SSc patients and 70 healthy controls. Anti-M3R antibody was found more frequently in patients with SSc, suggesting that M3R-mediated enteric cholinergic neurotransmission may provide a pathogenic mechanism for GI tract dysmotility in SSc.
•• Singh J, Mehendiratta V, Del Galdo F, et al. Immunoglobulins from scleroderma patients inhibit the muscarinic receptor activation in internal anal sphincter smooth muscle cells. Am J Physiol Gastrointest Liver Physiol 2009, 297: 206–213. This study determined the effect of SSc IgGs on the muscarinic receptor activation by bethanecol in smooth muscle cells and smooth muscle strips from rat IAS. The results suggest that SSc GI dysmotility may be caused by autoantibodies that inhibit the muscarinic neurotransmission in smooth muscle cells of the GI tract, opening a door for possible treatment of GI SSc disease directed at the removal or neutralization of the antibodies.
Ebert EC. Gastric and enteric involvement in progressive systemic sclerosis. J Clin Gastroenterol. 2008;42:5–12.
Poirier TJ, Rankin GB. Gastrointestinal manifestations of progressive systemic scleroderma based on a review of 364 cases. Am J Gastroenterol. 1972;58:30–44.
Thonhofer R, Siegel C, Trummer M, Graninger W. Early endoscopy in systemic sclerosis without gastrointestinal symptoms. Rheumatol Int. 2010 Aug 14. [Epub ahead of print].
Hendel L, Hage E, Hendel J, et al. Omeprazole in the long-term treatment of severe gastro-esophageal reflux disease in patients with systemic sclerosis. Aliment Pharmacol Ther. 1992;6:565–77.
Marie I, Ducrotte P, Denis P, et al. Oesophageal involvement in patients with systemic sclerosis receiving proton pump inhibitor therapy. Aliment Pharmacol Ther. 2006;24(11–12):1593–601.
Wipff J, Coriat R, Masciocchi M, et al. Outcome of Barrett’s oesophagus related to systemic sclerosis: a 3 year EULAR Scleroderma Trials and Research prospective follow-up study. Rheumatology. 2011;50(8):1440–4.
American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. Am J Resp Crit Care Med. 2000;161:646–64.
Raghu G, Freudenberg TD, Yang S, et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic fibrosis. Eur Respir J. 2006;27:136–42.
Appel 3rd JZ, Lee SM, Hartwig MG, et al. Characterization of the innate immune response to chronic aspiration in a novel rodent model. Respir Res. 2007;8:87.
•• Savarino E, Bazzica M, Zentilin P, et al. Gastroesophageal reflux and pulmonary fibrosis in scleroderma. A study using pH-impedance monitoring. Am J Respir Crit Care Med 2009, 179: 408–413. In this prospective study, 40 patients with SSc underwent pulmonary HRCT scan and 24-hour impedance pH monitoring off PPI therapy. Patients with ILD on HRCT had more reflux episodes and more reflux reaching the proximal esophagus, suggesting a relationship between GER and ILD. Whether the development of ILD in patients with SSc can be prevented via reflux-reducing treatments needs to be investigated.
•• Christmann RB, Wells AU, Capelozi VL, et al. Gastroesophageal reflux incites interstitial lung disease in systemic sclerosis: clinical, radiologic, histopathologic, and treatment evidence. Semin Arthritis Rheum 2010, 40:241–249. In this review, the authors summarize clinical, radiologic, histopathologic, and treatment aspects of GER in SSc-ILD. They describe the association of GER with SSc-ILD strongly supported by several studies. They recommend aggressive treatment for reflux in all patients with ILD, keeping in mind, however, that future studies need to be conducted to prove long-term benefit of GER treatment in ILD.
Raghu G, Yang ST, Spada C, et al. Sole treatment of acid gastroesophageal reflux in idiopathic fibrosis: a case series. Chest. 2006;129(3):794–800.
•• de Souza RBC, Borges CTL, Capelozzi VL, et al.: Centrilobular fibrosis: an underrecognized pattern in systemic sclerosis. Respiration 2009, 77: 389–397. In this prospective study, 28 patients with SSc-ILD went for open lung biopsy. A total of 21% of the patients had an isolated CLF, a novel histologic pattern described in idiopathic interstitial pneumonia. This pattern was also found in 84% of the patients with a predominant NSIP. A high frequency of esophageal abnormality was observed in both groups of CLF and NSIP, suggesting that the CLF pattern could be associated with GER.
De Carvalho ME, Kairalla RA, Capelozzi VL, et al. Centrilobular fibrosis: a novel histologic pattern of idiopathic interstitial pneumonia. Pathol Res Pract. 2002;198:577–83.
Brumit M, Carter E. Pathologic quiz case: patient with systemic sclerosis and anemia. Arch Pathol Lab Med. 2002;126:375–6.
Marie I, Ducrotte P, Antoinietti M, et al. Watermelon stomach in systemic sclerosis: its incidence and management. Aliment Pharmacol Ther. 2008;28:412–21.
• Ingraham KM, O’Brien MS, Shenn M, et al. Gastric antral vascular ectasia in systemic sclerosis: demographics and disease predictors. J Rheumatol 2010, 37:603–7. To date, general characteristics of patients with watermelon stomach have rarely been studied. In this retrospective study, it was found that GAVE was associated with early diffuse SSc, rapid skin progression, and anti-RNA pol III antibodies.
Sellinger CP, Ang YS. Gastric antral vascular ectasia (GAVE): an update on clinical presentation, pathophysiology and treatment. Digestion. 2008;77:131–7.
Schulz SW, O’Brien M, Maqsood M, et al. Improvement of severe systemic sclerosis-associated gastric antral vascular ectasia following immunosuppressive treatment with intravenous cyclophosphamide. J Rheumatol. 2009;36:1653–6.
Stratton RJ, King CL, Stroud MA, et al. ‘Malnutrition Universal Screening Tool’ predicts mortality and length of hospital stay in acutely ill elderly. Br J Nutr. 2006;95:325–30.
Baron M, Hudson M, Steele R. Malnutrition is common in systemic sclerosis: results from the Canadian Scleroderma Research Group Database. J Rheumatol. 2009;36:2737–43.
• Krause L, O Becker M, Brueckner CS, et al. Nutritional status as marker for disease activity and severity predicting mortality in patients with systemic sclerosis. Ann Rheum Dis 2010, 69: 1951–1957. This study showed that 55.7% of SSc patients had malnutrition, that the best predictors of malnutrition were low predicted forced vital capacity and high-NT–pro-BNP, and that malnutrition was associated with disease activity and severity. Also, severe malnutrition was a predictor of SSc-related mortality.
Jaffrin MY. Body composition determination by bioimpedance: an update. Curr Opin Clin Nutr Metab Care. 2009;12:482–6.
•• Baron M, Bernier P, Côté L-F, 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 2010, 28 (Suppl. 58): 42–46. This article is the result of a meeting between experts in areas of nutrition, speech pathology, oral health in SSc, and SSc and gastroenterology. Recommendations regarding screening of malnutrition, evaluation, interventions, and follow-up were made.
Khanna D, Hays RD, Maranian P, et al. Reliability and validity of the University of California, Los Angeles scleroderma clinical trial consortium gastrointestinal tract instrument. Arthritis Rheum. 2009;61:1257–63.
Perlemuter G, Cacoub P, Chaussade S, et al. Octreotide treatment of chronic intestinal pseudoobstruction secondary to connective tissue diseases. Arthritis Rheum. 1999;42:545–9.
Khanna D. Gastrointestinal involvement in systemic sclerosis. In: Font J, Ramos-Casals M, Rodés J, eds. Digestive Involvement in Systemic Autoimmune Diseases. New York: Elsevier:51–61.
Nikou GC, Toumpanakis C, Katsiari C, et al. Treatment of small intestinal disease in systemic sclerosis with octreotide: a prospective study in seven patients. J Clin Rheumatol. 2007;13:119–23.
Verne GN, Eaker EY, Hardy E, et al. Effect of octreotide and erythromycin on idiopathic and scleroderma-associated intestinal pseudoobstruction. Dig Dis Sci. 1995;40:1892–901.
Brown M, Teubner A, Shaffer J, et al. Home parenteral nutrition—an effective and safe long-term therapy for systemic sclerosis-related intestinal failure. Rheumatology (Oxford). 2008;47:176–9.
Mawdsley AH. Patient perception of UK scleroderma services—results of an anonymous questionnaire. Rheumatology. 2006;45:1573.
Engel AF, Kamm MA, Talbot IC. Progressive systemic sclerosis of the internal anal sphincter leading to passive faecal incontinence. Gut. 1994;35:857–9.
Thoua NM, Schizas A, Forbes A, et al. Internal anal sphincter atrophy in patients with systemic sclerosis. Rheumatology (Oxford). 2011 Apr 18. [Epub ahead of print].
Roberts CG, Hummers LK, Ravich WJ, et al. A case-control study of the pathology of oesophageal disease in systemic sclerosis (scleroderma). Gut. 2006;55:1697–703.
Thoua NM, Abdel-Halim M, Denton C, et al. Faecal incontinence in systemic sclerosis is related to sphincter atrophy and reflex dysfunction. Gut. 2009;58:A90.
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Gyger, G., Baron, M. Gastrointestinal Manifestations of Scleroderma: Recent Progress in Evaluation, Pathogenesis, and Management. Curr Rheumatol Rep 14, 22–29 (2012). https://doi.org/10.1007/s11926-011-0217-3
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DOI: https://doi.org/10.1007/s11926-011-0217-3