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Published in: Rheumatology International 5/2012

01-05-2012 | Original Article

Gastric dysmotility after liquid bolus ingestion in systemic sclerosis: an ultrasonographic study

Authors: Franco Cozzi, Giancarlo Parisi, Luca Ciprian, Arianna Bullo, Silvia Cardarelli, Michela Rizzo, Paolo Sfriso, Leonardo Punzi

Published in: Rheumatology International | Issue 5/2012

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Abstract

Gastric involvement appears quite commonly in systemic sclerosis (SSc). The aim of this study was to evaluate gastric wall motility using ultrasonography, a noninvasive method able to track both filling and emptying of fundus and antrum. The study was performed in 20 SSc patients and 20 healthy control subjects. Gastric filling and emptying were evaluated by transabdominal ultrasonography, measuring changes in fundus and antral areas over a 1-h period after ingestion of a liquid bolus (500 ml of mineral water). Areas of both gastric fundus and antrum at basal evaluation were found to be smaller in SSc patients than in healthy controls. Gastric filling was significantly reduced after ingestion of liquid bolus. Gastric emptying was delayed both in fundus and antrum. No significant differences of gastric wall motility have been observed in different subsets of SSc patients. Our findings show that gastric dysmotility is frequent and severe in SSc patients, contributing to the gastrointestinal disturbances which are very common in this disease.
Literature
1.
go back to reference Lock G, Holstege A, Lang B, Scholmerich J (1997) Gastrointestinal manifestations of progressive systemic sclerosis. Am J Gastroenterol 92:763–771PubMed Lock G, Holstege A, Lang B, Scholmerich J (1997) Gastrointestinal manifestations of progressive systemic sclerosis. Am J Gastroenterol 92:763–771PubMed
2.
go back to reference Weston S, Thumshirn M, Wiste J, Camilleri M (1998) Clinical and upper gastrointestinal motility features in systemic sclerosis and related disorders. Am J Gastroenterol 93:1085–1089PubMedCrossRef Weston S, Thumshirn M, Wiste J, Camilleri M (1998) Clinical and upper gastrointestinal motility features in systemic sclerosis and related disorders. Am J Gastroenterol 93:1085–1089PubMedCrossRef
3.
go back to reference Attar A (2002) Atteintes digestives au cours de la sclérodermie. Ann Med Interne 153:260–264 Attar A (2002) Atteintes digestives au cours de la sclérodermie. Ann Med Interne 153:260–264
4.
go back to reference Clements PJ, Becvar R, Drosos AA, Ghattas L, Gabrielli A (2003) Assessment of gastrointestinal involvement. Clin Exp Rheumatol 21(Suppl 29):S15–S18PubMed Clements PJ, Becvar R, Drosos AA, Ghattas L, Gabrielli A (2003) Assessment of gastrointestinal involvement. Clin Exp Rheumatol 21(Suppl 29):S15–S18PubMed
5.
go back to reference Forbes A, Marie I (2009) Gastrointestinal complications: the most frequent internal complications of systemic sclerosis. Rheumatology 48(Suppl 3):36–39 Forbes A, Marie I (2009) Gastrointestinal complications: the most frequent internal complications of systemic sclerosis. Rheumatology 48(Suppl 3):36–39
6.
go back to reference D’Angelo WA, Fries JF, Masi AT, Shulman LE (1969) Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med 46:428–440PubMedCrossRef D’Angelo WA, Fries JF, Masi AT, Shulman LE (1969) Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med 46:428–440PubMedCrossRef
7.
go back to reference Sjogren RW (1994) Gastrointestinal motility disorders in scleroderma. Arthritis Rheum 37:1265–1282PubMedCrossRef Sjogren RW (1994) Gastrointestinal motility disorders in scleroderma. Arthritis Rheum 37:1265–1282PubMedCrossRef
8.
go back to reference 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 39:2209–2215PubMedCrossRef 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 39:2209–2215PubMedCrossRef
9.
go back to reference Garrett JM, Winkelmann RK, Schlegel JF, Code CF (1971) Esophageal deterioration in scleroderma. Mayo Clin Proc 46:92–96PubMed Garrett JM, Winkelmann RK, Schlegel JF, Code CF (1971) Esophageal deterioration in scleroderma. Mayo Clin Proc 46:92–96PubMed
10.
go back to reference Bassotti G, Battaglia E, Debernardi V, Germani U, Quiriconi F, Dughera L et al (1997) Esophageal dysfunction in scleroderma: relationship with disease subsets. Arthritis Rheum 40:2252–2259PubMedCrossRef Bassotti G, Battaglia E, Debernardi V, Germani U, Quiriconi F, Dughera L et al (1997) Esophageal dysfunction in scleroderma: relationship with disease subsets. Arthritis Rheum 40:2252–2259PubMedCrossRef
11.
go back to reference Cozzi F, Zucchetta P, Durigon N, Marzola MC, Bullo A, Favaro M et al (2003) Alterazioni della peristalsi esofagea nelle diverse forme cliniche e specificità anticorpali della sclerodermia: studio scintigrafico in 100 pazienti. Reumatismo 55:86–92PubMed Cozzi F, Zucchetta P, Durigon N, Marzola MC, Bullo A, Favaro M et al (2003) Alterazioni della peristalsi esofagea nelle diverse forme cliniche e specificità anticorpali della sclerodermia: studio scintigrafico in 100 pazienti. Reumatismo 55:86–92PubMed
12.
go back to reference Abu-Shakra M, Guillemin F, Lee P (1994) Gastrointestinal manifestations of systemic sclerosis. Semin Arthritis Rheum 24:29–39PubMedCrossRef Abu-Shakra M, Guillemin F, Lee P (1994) Gastrointestinal manifestations of systemic sclerosis. Semin Arthritis Rheum 24:29–39PubMedCrossRef
13.
go back to reference Zamost BJ, Hirschberg J, Ippoliti AF, Furst DE, Clements PJ, Weinstein WM (1987) Esophagitis in scleroderma. Prevalence and risk factors. Gastroenterology 92:421–428PubMed Zamost BJ, Hirschberg J, Ippoliti AF, Furst DE, Clements PJ, Weinstein WM (1987) Esophagitis in scleroderma. Prevalence and risk factors. Gastroenterology 92:421–428PubMed
14.
go back to reference Maddern GJ, Horowitz M, Jamieson GG, Chatterton BE, Collins PJ, Roberts-Thomson P (1984) Abnormalities of esophageal and gastric emptying in progressive systemic sclerosis. Gastroenterology 87:922–926PubMed Maddern GJ, Horowitz M, Jamieson GG, Chatterton BE, Collins PJ, Roberts-Thomson P (1984) Abnormalities of esophageal and gastric emptying in progressive systemic sclerosis. Gastroenterology 87:922–926PubMed
15.
go back to reference Greydanus MP, Camilleri M (1989) Abnormal postcibal antral and small bowel motility due to neuropathy or myopathy in systemic sclerosis. Gastroenterology 96:110–115PubMed Greydanus MP, Camilleri M (1989) Abnormal postcibal antral and small bowel motility due to neuropathy or myopathy in systemic sclerosis. Gastroenterology 96:110–115PubMed
16.
go back to reference Marie I, Levesque H, Ducrotte P, Denis P, Benichou J, Hellot MF et al (1998) Manometry of the upper intestinal tract in patients with systemic sclerosis: a prospective study. Arthritis Rheum 41:1874–1883PubMedCrossRef Marie I, Levesque H, Ducrotte P, Denis P, Benichou J, Hellot MF et al (1998) Manometry of the upper intestinal tract in patients with systemic sclerosis: a prospective study. Arthritis Rheum 41:1874–1883PubMedCrossRef
17.
go back to reference Battle WM, Snape WJ Jr, Wright S, Sullivan MA, Cohen S, Meyers A et al (1981) Abnormal colonic motility in progressive systemic sclerosis. Ann Intern Med 94:749–752PubMed Battle WM, Snape WJ Jr, Wright S, Sullivan MA, Cohen S, Meyers A et al (1981) Abnormal colonic motility in progressive systemic sclerosis. Ann Intern Med 94:749–752PubMed
18.
go back to reference Wang SJ, Lan JL, Chen DY, Chen YH, Hsieh TY, Lin WY (2001) Colonic transit disorders in systemic sclerosis. Clin Rheumatol 20:251–254PubMedCrossRef Wang SJ, Lan JL, Chen DY, Chen YH, Hsieh TY, Lin WY (2001) Colonic transit disorders in systemic sclerosis. Clin Rheumatol 20:251–254PubMedCrossRef
19.
go back to reference Leighton JA, Valdovinos MA, Pemberton JH, Rath DM, Camilleri M (1993) Anorectal dysfunction and rectal prolapse in progressive systemic sclerosis. Dis Colon Rectum 36:182–185PubMedCrossRef Leighton JA, Valdovinos MA, Pemberton JH, Rath DM, Camilleri M (1993) Anorectal dysfunction and rectal prolapse in progressive systemic sclerosis. Dis Colon Rectum 36:182–185PubMedCrossRef
20.
go back to reference Heyt GJ, Oh MK, Alemzadeh N, Rivera S, Jimenez SA, Rattan S et al (2004) Impaired rectoanal inhibitory response in scleroderma (systemic sclerosis): an association with fecal incontinence. Dig Dis Sci 49:1040–1045PubMedCrossRef Heyt GJ, Oh MK, Alemzadeh N, Rivera S, Jimenez SA, Rattan S et al (2004) Impaired rectoanal inhibitory response in scleroderma (systemic sclerosis): an association with fecal incontinence. Dig Dis Sci 49:1040–1045PubMedCrossRef
21.
go back to reference Duan LP, Zheng ZT, Li YN (1993) A study of gastric emptying in non-ulcer dyspepsia using a new ultrasonographic method. Scand J Gastroenterol 28:355–360PubMedCrossRef Duan LP, Zheng ZT, Li YN (1993) A study of gastric emptying in non-ulcer dyspepsia using a new ultrasonographic method. Scand J Gastroenterol 28:355–360PubMedCrossRef
22.
go back to reference Kusunoki H, Haruma K, Hata J, Tani H, Okamoto E, Sumii K et al (2000) Real-time ultrasonographic assessment of antroduodenal motility after ingestion of solid and liquid meals by patients with functional dyspepsia. J Gastroenterol Hepatol 15:1022–1027PubMedCrossRef Kusunoki H, Haruma K, Hata J, Tani H, Okamoto E, Sumii K et al (2000) Real-time ultrasonographic assessment of antroduodenal motility after ingestion of solid and liquid meals by patients with functional dyspepsia. J Gastroenterol Hepatol 15:1022–1027PubMedCrossRef
23.
go back to reference Subcomittee for scleroderma criteria of the American Rheumatism Association Diagnostic, Theurapeutic Criteria Committee (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23:581–590CrossRef Subcomittee for scleroderma criteria of the American Rheumatism Association Diagnostic, Theurapeutic Criteria Committee (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23:581–590CrossRef
24.
go back to reference Le Roy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA et al (1988) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205 Le Roy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA et al (1988) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205
25.
go back to reference Bolondi L, Bortolotti M, Santi V, Calletti T, Gaiani S, Labò G (1985) Measurement of gastric emptying time by real-time ultrasonography. Gastroenterology 89:752–759PubMed Bolondi L, Bortolotti M, Santi V, Calletti T, Gaiani S, Labò G (1985) Measurement of gastric emptying time by real-time ultrasonography. Gastroenterology 89:752–759PubMed
26.
go back to reference Marzio L, Giacobbe A, Conoscitore P, Facciorusso D, Frusciante V, Modoni S (1989) Evaluation of the use of ultrasonography in the study of liquid gastric emptying. Am J Gastroenterol 84:496–500PubMed Marzio L, Giacobbe A, Conoscitore P, Facciorusso D, Frusciante V, Modoni S (1989) Evaluation of the use of ultrasonography in the study of liquid gastric emptying. Am J Gastroenterol 84:496–500PubMed
27.
go back to reference Sallam H, McNearny TA, Chen DZ (2006) Systematic review: pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis (scleroderma). Aliment Pharmacol Ther 23:691–712PubMedCrossRef Sallam H, McNearny TA, Chen DZ (2006) Systematic review: pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis (scleroderma). Aliment Pharmacol Ther 23:691–712PubMedCrossRef
28.
go back to reference Iovino P, Valentini G, Ciacci C, De Luca A, Tremolaterra F, Sabbatini F et al (2001) Proximal stomach function in systemic sclerosis: relationship with autonomic nerve function. Dig Dis Sci 46:723–730PubMedCrossRef Iovino P, Valentini G, Ciacci C, De Luca A, Tremolaterra F, Sabbatini F et al (2001) Proximal stomach function in systemic sclerosis: relationship with autonomic nerve function. Dig Dis Sci 46:723–730PubMedCrossRef
29.
go back to reference Bortolotti M, Turba E, Tosti A, Sarti P, Brunelli F, Del Campo L et al (1991) Gastric emptying and interdigestive antroduodenal motility in patients with esophageal scleroderma. Am J Gastroenterol 86:743–747PubMed Bortolotti M, Turba E, Tosti A, Sarti P, Brunelli F, Del Campo L et al (1991) Gastric emptying and interdigestive antroduodenal motility in patients with esophageal scleroderma. Am J Gastroenterol 86:743–747PubMed
30.
go back to reference Marycz T, Muehldorfer SM, Gruschwitz MS, Katalinic A, Herold C, Ell C et al (1999) Gastric involvement in progressive systemic sclerosis: electrogastrographic and sonographic findings. Eur J Gastroenterol Hepatol 11:1151–1156PubMedCrossRef Marycz T, Muehldorfer SM, Gruschwitz MS, Katalinic A, Herold C, Ell C et al (1999) Gastric involvement in progressive systemic sclerosis: electrogastrographic and sonographic findings. Eur J Gastroenterol Hepatol 11:1151–1156PubMedCrossRef
31.
go back to reference Marie I, Levesque H, Ducrotte P, Denis P, Hellot MF, Benichou J et al (2001) Gastric involvement in systemic sclerosis: a prospective study. Am J Gastroenterol 96:77–83PubMedCrossRef Marie I, Levesque H, Ducrotte P, Denis P, Hellot MF, Benichou J et al (2001) Gastric involvement in systemic sclerosis: a prospective study. Am J Gastroenterol 96:77–83PubMedCrossRef
32.
go back to reference McNearney T, Lin X, Shrestha J, Lisse J, Chen JD (2002) Characterization of gastric myoelectrical rhythms in patients with systemic sclerosis using multichannel surface electrogastrography. Dig Dis Sci 47:690–698PubMedCrossRef McNearney T, Lin X, Shrestha J, Lisse J, Chen JD (2002) Characterization of gastric myoelectrical rhythms in patients with systemic sclerosis using multichannel surface electrogastrography. Dig Dis Sci 47:690–698PubMedCrossRef
33.
go back to reference Madsen JL, Hendel L (1992) Gastrointestinal transit times of radiolabeled meal in progressive systemic sclerosis. Dig Dis Sci 37:1404–1408PubMedCrossRef Madsen JL, Hendel L (1992) Gastrointestinal transit times of radiolabeled meal in progressive systemic sclerosis. Dig Dis Sci 37:1404–1408PubMedCrossRef
34.
go back to reference Irvine EJ, Tougas G, Lappalainen R, Bathurst NC (1993) Reliability and interobserver variability of ultrasonographic measurement of gastric emptying rate. Dig Dis Sci 38:803–810PubMedCrossRef Irvine EJ, Tougas G, Lappalainen R, Bathurst NC (1993) Reliability and interobserver variability of ultrasonographic measurement of gastric emptying rate. Dig Dis Sci 38:803–810PubMedCrossRef
35.
go back to reference Hveem K, Jones KL, Chatterton BE, Horowitz M (1996) Scintigraphic measurement of gastric emptying and ultrasonographic assessment of antral area: relation to appetite. Gut 38:816–821PubMedCrossRef Hveem K, Jones KL, Chatterton BE, Horowitz M (1996) Scintigraphic measurement of gastric emptying and ultrasonographic assessment of antral area: relation to appetite. Gut 38:816–821PubMedCrossRef
36.
go back to reference Wedmann B, Wegener M, Adamek RJ, Gammal S (1994) Gastrobiliary motility after liquid fatty meal in progressive systemic sclerosis. A sonographic study. Dig Dis Sci 39:565–570PubMedCrossRef Wedmann B, Wegener M, Adamek RJ, Gammal S (1994) Gastrobiliary motility after liquid fatty meal in progressive systemic sclerosis. A sonographic study. Dig Dis Sci 39:565–570PubMedCrossRef
37.
go back to reference Di Ciaula A, Covelli M, Bernardino M, Wang DQ, Lapadula G, Palasciano G et al (2008) Gastrointestinal symptoms and motility disorders in patients with systemic scleroderma. BMC Gastroenterol 27:8–17 Di Ciaula A, Covelli M, Bernardino M, Wang DQ, Lapadula G, Palasciano G et al (2008) Gastrointestinal symptoms and motility disorders in patients with systemic scleroderma. BMC Gastroenterol 27:8–17
38.
go back to reference Manetti M, Neumann E, Milia AF, Tarner IH, Bechi P, Matucci-Cerinic M et al (2007) Severe fibrosis and increate expression of fibrogenic cytokines in the gastric wall of systemic sclerosis patients. Arthritis Rheum 56:3442–3447PubMedCrossRef Manetti M, Neumann E, Milia AF, Tarner IH, Bechi P, Matucci-Cerinic M et al (2007) Severe fibrosis and increate expression of fibrogenic cytokines in the gastric wall of systemic sclerosis patients. Arthritis Rheum 56:3442–3447PubMedCrossRef
39.
go back to reference Kahaleh MB, Matucci-Cerinic M (1995) Raynaud’s phenomenon, scleroderma dysregulated neuroendothelial control of vascular tone. Arthritis Rheum 38:1–4PubMedCrossRef Kahaleh MB, Matucci-Cerinic M (1995) Raynaud’s phenomenon, scleroderma dysregulated neuroendothelial control of vascular tone. Arthritis Rheum 38:1–4PubMedCrossRef
40.
go back to reference Kaye SA, Seifalian AM, Lim SG, Hamilton G, Black CM (1994) Ischaemia of the small intestine in patients with systemic sclerosis: Raynaud’s phenomenon or chronic vasculopathy. Q J Med 87:495–500 Kaye SA, Seifalian AM, Lim SG, Hamilton G, Black CM (1994) Ischaemia of the small intestine in patients with systemic sclerosis: Raynaud’s phenomenon or chronic vasculopathy. Q J Med 87:495–500
41.
go back to reference Bertinotti L, Bracci S, Nacci F, Colangelo N, Del Rosso A, Casale R et al (2004) The autonomic nervous system in systemic sclerosis. A review. Clin Rheumatol 23:1–5PubMedCrossRef Bertinotti L, Bracci S, Nacci F, Colangelo N, Del Rosso A, Casale R et al (2004) The autonomic nervous system in systemic sclerosis. A review. Clin Rheumatol 23:1–5PubMedCrossRef
42.
go back to reference Lock G, Straub RH, Zeuner M, Antoniou E, Holstege A, Scholmerich J et al (1998) Association of autonomic nervous dysfunction and esophageal dysmotility in systemic sclerosis. J Rheumatol 25:1330–1335PubMed Lock G, Straub RH, Zeuner M, Antoniou E, Holstege A, Scholmerich J et al (1998) Association of autonomic nervous dysfunction and esophageal dysmotility in systemic sclerosis. J Rheumatol 25:1330–1335PubMed
43.
go back to reference Ibba-Manneschi L, Del Rosso A, Pacini S, Tani A, Bechi P, Matucci Cerinic M (2002) Ultrastructural study of the muscle coat of the gastric wall in a case of systemic sclerosis. Ann Rheum Dis 61:754–756PubMedCrossRef Ibba-Manneschi L, Del Rosso A, Pacini S, Tani A, Bechi P, Matucci Cerinic M (2002) Ultrastructural study of the muscle coat of the gastric wall in a case of systemic sclerosis. Ann Rheum Dis 61:754–756PubMedCrossRef
44.
go back to reference Sogabe M, Okahisa T, Tsujigami K, Okita Y, Hayashi H, Taniki T et al (2005) Ultrasonographic assessment of gastric motility in diabetic gastroparesis before and after attaining glycemic control. J Gatroenterol 40:583–590CrossRef Sogabe M, Okahisa T, Tsujigami K, Okita Y, Hayashi H, Taniki T et al (2005) Ultrasonographic assessment of gastric motility in diabetic gastroparesis before and after attaining glycemic control. J Gatroenterol 40:583–590CrossRef
45.
go back to reference Szarka LA, Camilleri M (2010) Stomach dysfunction in diabetes mellitus: emerging technology and pharmacology. J Diabetes Sci Technol 4:180–189PubMed Szarka LA, Camilleri M (2010) Stomach dysfunction in diabetes mellitus: emerging technology and pharmacology. J Diabetes Sci Technol 4:180–189PubMed
46.
go back to reference Hata N, Murata S, Maeda J, Yatani H, Kohno Y, Yokono K, Okano H (2009) Predictors of gastric myoelectrical activity in type 2 diabetes mellitus. J Clin Gastroenterol 43:429–436PubMedCrossRef Hata N, Murata S, Maeda J, Yatani H, Kohno Y, Yokono K, Okano H (2009) Predictors of gastric myoelectrical activity in type 2 diabetes mellitus. J Clin Gastroenterol 43:429–436PubMedCrossRef
47.
go back to reference 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 32:348–355PubMedCrossRef 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 32:348–355PubMedCrossRef
Metadata
Title
Gastric dysmotility after liquid bolus ingestion in systemic sclerosis: an ultrasonographic study
Authors
Franco Cozzi
Giancarlo Parisi
Luca Ciprian
Arianna Bullo
Silvia Cardarelli
Michela Rizzo
Paolo Sfriso
Leonardo Punzi
Publication date
01-05-2012
Publisher
Springer-Verlag
Published in
Rheumatology International / Issue 5/2012
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-010-1779-5

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