Review | Published:

Screening for Celiac Disease in Irritable Bowel Syndrome: An Updated Systematic Review and Meta-analysis

The American Journal of Gastroenterology volume 112, pages 6576 (2017) | Download Citation

Abstract

Objectives:

Celiac disease (CD) and irritable bowel syndrome (IBS) share similar symptoms, leading to confusion between the two and diagnostic delay. International guidelines recommend screening individuals with IBS for CD, via serological testing. However, studies published recently have cast doubt on the utility of this. We updated a previous meta-analysis examining this issue.

Methods:

MEDLINE, EMBASE, and EMBASE Classic were searched through to May 2016. Eligible studies recruited adults with IBS according to symptom-based criteria, physician’s opinion, or questionnaire data. Tests for CD included IgA-class antigliadin antibodies (AGA), endomysial antibodies (EMA), tissue transglutaminase antibodies (tTG), or duodenal biopsies following positive serology. The proportion of individuals meeting criteria for IBS testing positive for CD was combined to give a pooled prevalence for all studies, and compared between cases with IBS and, healthy controls without (where reported), using an odds ratio (OR) with a 95% confidence interval (CI).

Results:

There were 36 eligible studies, recruiting 15,256 individuals, of whom 9,275 (60.8%) met criteria for IBS. Pooled ORs for positive IgA AGAs, EMA and/or tTG, and biopsy-proven CD in IBS subjects vs. controls were 3.21 (95% CI 1.55–6.65), 2.75 (95% CI 1.35–5.61), and 4.48 (95% CI 2.33–8.60), respectively. There was no increase in ORs for any test for CD among cases with IBS in North American studies, and results were inconsistent in population-based studies. The prevalence of biopsy-proven CD was significantly higher across all subtypes of IBS. Limitations included heterogeneity in some analyses, and few North American studies.

Conclusions:

Overall, prevalence of positive celiac serology and biopsy-proven CD was significantly higher in subjects with symptoms suggestive of IBS vs. healthy controls. However, the utility of screening for CD in individuals with suspected IBS in North America or in the community is less clear.

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References

  1. 1.

    , , et al. Bowel disorders. Gastroenterology 2016;150:1393–1407.

  2. 2.

    , , et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology 2007;133:24–33.

  3. 3.

    , , . Quantitative meta-analysis identifies brain regions activated during rectal distension in irritable bowel syndrome. Gastroenterology 2011;140:91–100.

  4. 4.

    . Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut 1973;14:125–132.

  5. 5.

    , , et al. Increased proteasome-mediated degradation of occludin in irritable bowel syndrome. Am J Gastroenterol 2010;105:1181–1188.

  6. 6.

    , , et al. Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome. J Gastroenterol 2014;49:1467–1476.

  7. 7.

    , . Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol 2012;10:712–21.e4.

  8. 8.

    , , et al. Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut 2007;56:1770–1798.

  9. 9.

    , , et al. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol 2014;109 (Suppl 1): S2–26.

  10. 10.

    , , et al. Validation of the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care. Gastroenterology 2013;145:1262–70.e1.

  11. 11.

    , , . Coeliac disease. BMJ 2014;348:g1561.

  12. 12.

    , , et al. Screening for celiac disease in a North American population: sequential serology and gastrointestinal symptoms. Am J Gastroenterol 2011;106:1333–1339.

  13. 13.

    , , et al. The prevalence of celiac disease in Europe: results of a centralized, international mass screening project. Ann Med 2010;42:587–595.

  14. 14.

    , , et al. The prevalence of celiac disease in the United States. Am J Gastroenterol 2012;107:1538–1544.

  15. 15.

    , , et al. Undiagnosed coeliac disease at age seven: population based prospective birth cohort study. BMJ 2004;328:322–323.

  16. 16.

    , , et al. Association of adult coeliac disease with irritable bowel syndrome: a case-control study in patients fulfilling ROME II criteria referred to secondary care. Lancet 2001;358:1504–1508.

  17. 17.

    , , et al. A primary care cross-sectional study of undiagnosed adult coeliac disease. Eur J Gastroenterol Hepatol 2003;15:407–413.

  18. 18.

    , , . The incidence of other gastroenterological disease following diagnosis of irritable bowel syndrome in the UK: a cohort study. PLoS One 2014;9:e106478.

  19. 19.

    , , et al. Yield of diagnostic tests for celiac disease in individuals with symptoms suggestive of irritable bowel syndrome: systematic review and meta-analysis. Arch Intern Med 2009;169:651–658.

  20. 20.

    , . Serological testing for coeliac disease in patients with symptoms of irritable bowel syndrome: a cost-effectiveness analysis. Aliment Pharmacol Ther 2004;19:1199–1210.

  21. 21.

    , , et al. Testing for celiac sprue in irritable bowel syndrome with predominant diarrhea: a cost-effectiveness analysis. Gastroenterology 2004;126:1721–1732.

  22. 22.

    , , et al. Targeted screening for coeliac disease among irritable bowel syndrome patients: analysis of cost-effectiveness and value of information. Eur J Health Econ 2013;14:947–957.

  23. 23.

    , , et al. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 2013;108:656–676.

  24. 24.

    , , et al. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut 2014;63:1210–1228.

  25. 25.

    , , et al. Evidence against routine testing of patients with functional gastrointestinal disorders for celiac disease: a population-based study. Clin Gastroenterol Hepatol 2015;13:1937–1943.

  26. 26.

    , , et al. The prevalence of celiac disease among patients with nonconstipated irritable bowel syndrome is similar to controls. Gastroenterology 2011;141:1187–1193.

  27. 27.

    , , et al. Towards positive diagnosis of the irritable bowel. BMJ 1978;2:653–654.

  28. 28.

    , , . Identification of sub-groups of functional gastrointestinal disorders. Gastroenterology Int 1990;3:159–172.

  29. 29.

    , , et al. Functional bowel disorders. Gastroenterology 2006;130:1480–1491.

  30. 30.

    , , et al. Functional bowel disorders and functional abdominal pain. Gut 1999;45 (Suppl 2): Ii43–Ii47.

  31. 31.

    , , et al. A diagnostic score for the irritable bowel syndrome. Its value in the exclusion of organic disease. Gastroenterology 1984;87:1–7.

  32. 32.

    Institute TOHR. Newcastle-Ottawa quality assessment scale for case-control studies [Available from (accessed on 15 May 2016).

  33. 33.

    , . Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:1539–1558.

  34. 34.

    , . Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–188.

  35. 35.

    , , et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–634.

  36. 36.

    , , et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 2011;343:d4002.

  37. 37.

    , , et al. Immunological profile of coeliac disease in a subgroup of patients with symptoms of irritable bowel syndrome. Tunis Med 2008;86:802–805.

  38. 38.

    , , et al. Prevalence of celiac disease in patients with irritable bowel syndrome. Govaresh 2008;13:192–197.

  39. 39.

    , . Celiac disease in patients with presumed irritable bowel syndrome: a case-finding study. World J Gastroenterol 2009;15:5321–5325.

  40. 40.

    , , et al. Frequency of celiac disease and irritable bowel syndrome coexistance and its influence on the disease course. Przegl Lek 2009;66:126–129.

  41. 41.

    , , et al. Should we look for celiac disease in irritable bowel syndrome? Oman Med J 2011;26:59–60.

  42. 42.

    , , . Celiac disease rate increases in patients with irritable bowel syndrome–a community screen from West Virginia. Gastroenterology 2010;138:S309.

  43. 43.

    , , . How prevalent is celiac disease in IBS-D type among South Indians? Gastroenterology 2011;140:S441–S442.

  44. 44.

    , , et al. Coeliac disease in irritable bowel syndrome (Rome III) in Southeast Iran. Arab J Gastroenterol 2012;13:24–27.

  45. 45.

    , , et al. Celiac disease: serologic prevalence in patients with irritable bowel syndrome. J Res Med Sci 2012;17:839–842.

  46. 46.

    , , et al. A positive diagnostic strategy is noninferior to a strategy of exclusion for patients with irritable bowel syndrome. Clin Gastroenterol Hepatol 2013;11:956–62.e1.

  47. 47.

    , , et al. Prevalence of celiac disease in patients with irritable bowel syndrome in Ardabil-Iran (2009-10). J Gorgan Univ Med Sci 2013;14:129–133.

  48. 48.

    , , et al. The prevalence of celiac disease in patient with irritable bowel syndrome. Indian J Gastroenterol 2013;32 (suppl 1): A29.

  49. 49.

    , , et al. Is it reasonable to perform serological tests for celiac disease in patients with irritable bowel syndrome? Preglad Gastroenterol 2013;8:184–190.

  50. 50.

    , , et al. Remarkable prevalence of coeliac disease in patients with irritable bowel syndrome plus fibromyalgia in comparison with those with isolated irritable bowel syndrome: a case-finding study. Arthritis Res Ther 2013;15:R201.

  51. 51.

    , , et al. Celiac disease prevalence in the patients with irritable bowel syndrome in the Ilam province; a cross sectional study from Western Iran. J Clin Diagn Res 2014;8:Gc01–Gc03.

  52. 52.

    , , et al. Case-finding for coeliac disease in secondary care: a prospective multicentre UK study. Dig Liver Dis 2014;46:32–35.

  53. 53.

    , , et al. Prevalence of celiac disease in Iranian patients with irritable bowel syndrome: a cross-sectional study. J Dig Dis 2014;15:12–17.

  54. 54.

    , . Prevalence of celiac disease in patients with irritable bowel syndrome in Kerman, Iran. J Kerman Univ Med Sci 2015;22:319–327.

  55. 55.

    , , et al. Prevalence of celiac disease in Indian patients with irritable bowel syndrome and uninvestigated dyspepsia. J Dig Dis 2015;16:443–448.

  56. 56.

    , , et al. Serological screening for celiac disease in adult Chinese patients with diarrhea predominant irritable bowel syndrome. Medicine 2015;94:e1779.

  57. 57.

    , , et al. Prevalence of celiac disease and related antibodies in patients diagnosed with irritable bowel syndrome according to the Rome III criteria. A case-control study. Neurogastroenterol Motil 2016;28:994–1000.

  58. 58.

    , , et al. Screening for celiac sprue in patients with suspected irritable bowel syndrome: results form a prospective US multi-center trial. Gastroenterology 2007;132 (suppl 1): A147.

  59. 59.

    , , et al. Coeliac disease in primary care: case finding study. BMJ 1999;318:164–167.

  60. 60.

    , , et al. Endomysium antibodies are superior to gliadin antibodies in screening for coeliac disease in patients presenting supposed functional gastrointestinal symptoms. Scand J Prim Health Care 2000;18:105–110.

  61. 61.

    , , et al. Celiac disease-like abnormalities in a subgroup of patients with irritable bowel syndrome. Gastroenterology 2001;121:1329–1338.

  62. 62.

    , , et al. Prevalence of coeliac disease in IBS patients in Turin. Gastroenterology 2002;122 (suppl 4): A193.

  63. 63.

    , , et al. Coeliac disease presenting with symptoms of irritable bowel syndrome. Aliment Pharmacol Ther 2003;18:231–235.

  64. 64.

    , , et al. Low seroprevalence of celiac disease among patients with irritable bowel syndrome in Latvia. Gut 2004;53 (suppl VI): A198.

  65. 65.

    , , et al. Celiac disease serology in irritable bowel syndrome and dyspepsia: a population-based case-control study. Mayo Clin Proc 2004;79:476–482.

  66. 66.

    , , et al. Cognitive behavioural therapy in addition to antispasmodic therapy for irritable bowel syndrome in primary care: randomised controlled trial. Health Technol Assess 2006;10:1–67.

  67. 67.

    , , . Screening for coeliac disease in patients fulfilling the Rome II criteria for irritable bowel syndrome in a secondary care hospital in The Netherlands: a prospective observational study. Gut 2007;56:444–445.

  68. 68.

    , , et al. Detection of celiac disease in primary care: a multicenter case-finding study in North America. Am J Gastroenterol 2007;102:1454–1460.

  69. 69.

    , , et al. Association of gluten enteropathy and irritable bowel syndrome in adult Turkish population. Dig Dis Sci 2008;53:1852–1855.

  70. 70.

    , , et al. Ethnic variations in duodenal villous atrophy consistent with celiac disease in the United States. Clin Gastroenterol Hepatol 2016;14:1105–1111.

  71. 71.

    , , et al. Prevalence of adult celiac disease in India: regional variations and associations. Am J Gastroenterol 2016;111:115–123.

  72. 72.

    , , et al. Systematic review: worldwide variation in the frequency of coeliac disease and changes over time. Aliment Pharmacol Ther 2013;38:226–245.

  73. 73.

    , . Meta-analysis: deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac disease. Aliment Pharmacol Ther 2010;31:73–81.

  74. 74.

    . What are the sensitivity and specificity of serologic tests for celiac disease? Do sensitivity and specificity vary in different populations? Gastroenterology 2005;128 (4 Suppl 1): S25–S32.

  75. 75.

    , , et al. Irritable bowel syndrome in general practice: prevalence, characteristics, and referral. Gut 2000;46:78–82.

  76. 76.

    , , et al. Self-reported food-related gastrointestinal symptoms in IBS are common and associated with more severe symptoms and reduced quality of life. Am J Gastroenterol 2013;108:634–641.

  77. 77.

    , , et al. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol 2012;107:1898–1906.

  78. 78.

    , , et al. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology 2013145 2:e1–e3.

  79. 79.

    , . Suspected non-celiac gluten sensitivity confirmed in few patients after gluten challenge in double-blind, placebo-controlled trials. Clin Gastroenterol Hepatol 2016 doi:10.1016/j.cgh.2016.08.007.

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Acknowledgements

We are grateful to Dr Yuhong Yuan and Dr Noor Mohammed for their assistance with translation of foreign language articles.

Author information

Affiliations

  1. Leeds Gastroenterology Institute, St James’s University Hospital, Leeds, UK

    • Andrew J Irvine
    •  & Alexander C Ford
  2. Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK

    • Andrew J Irvine
    •  & Alexander C Ford
  3. Department of Internal Medicine, Division of Gastroenterology, University of Michigan Health System, Ann Arbor, Michigan, USA

    • William D Chey

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Competing interests

Guarantor of the article: Alexander C. Ford, MBChB, MD, FRCP.

Specific author contributions: Collected all data: Andrew J. Irvine and Alexander C. Ford. Analyzed and interpreted the data: Alexander C. Ford. All authors conceived and drafted the study, contributed to, and approved the final draft of the manuscript.

Financial support: None.

Potential competing interests: None.

Corresponding author

Correspondence to Alexander C Ford.

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DOI

https://doi.org/10.1038/ajg.2016.466

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