Skip to main content

Advertisement

SpringerLink
Log in

Celiac Disease Is Associated with Microscopic Colitis in Refractory Cases in Adults: A Systematic Review and Meta-Analysis of Observational Studies

  • Review
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Microscopic colitis and Celiac disease have been shown to occur concomitantly, but their relationship has yet to be systematically evaluated. Some patients with refractory microscopic colitis may have simultaneous celiac disease, and the converse is also true.

Aims

We performed a systematic review and meta-analysis of observational studies to assess the prevalence and possible association between these two conditions.

Methods

PubMed, Embase, Cochrane, Web of Science, SciELO, and CINAHL Plus were systematically searched through January 26, 2021, to include relevant observational studies assessing the prevalence of microscopic colitis in celiac disease population or vice versa. DerSimonian-Laird approach using random effects was used to pool data and compare outcomes. Pooled prevalence, 95% confidence interval (CI), and p values (where applicable) were calculated.

Results

Five studies (with 2589 patients, age range 39.5–52 years and females 66.6%) and 21 studies (with 7186 patients, age range 46.4–65.8 years and females 76.3%) were included assessing the prevalence of microscopic colitis in refractory celiac disease and celiac disease in refractory microscopic colitis cohort. The overall prevalence was 4.5% (2.6–6.3%) and 6.7% (5.2–8.1%), respectively. Five studies showed higher odds of celiac disease diagnosis in the refractory microscopic colitis population compared to the control group (OR 8.12, CI 4.92–13.41, p < 0.001).

Conclusion

Celiac disease and microscopic colitis are concomitantly prevalent in a subset of population with either refractory diagnosis. Clinicians should explore alternate diagnosis when one condition has been appropriately treated and patients continue to have refractory symptoms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

CC:

Collagenous colitis

CeD:

Celiac disease

CI:

Confidence interval

LC:

Lymphocytic colitis

MC:

Microscopic colitis

OR:

Odds ratio

References

  1. Pardi DS, Kelly CP. Microscopic colitis. Gastroenterology 2011;140:1155–1165.

    Article  PubMed  Google Scholar 

  2. Münch A, Aust D, Bohr J, Bonderup O, Fernández Bañares F, Hjortswang H et al. Microscopic colitis: current status, present and future challenges: statements of the European Microscopic Colitis Group. J Crohns Colitis 2012;6:932–945.

    Article  PubMed  Google Scholar 

  3. Park T, Cave D, Marshall C. Microscopic colitis: a review of etiology, treatment and refractory disease. World J Gastroenterol 2015;21:8804–8810.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Fasano A. Clinical presentation of celiac disease in the pediatric population. Gastroenterology 2005;128:S68-73.

    Article  PubMed  Google Scholar 

  5. De Re V, Magris R, Cannizzaro R. New insights into the pathogenesis of celiac disease. Front Med. 2017;4:137.

    Article  Google Scholar 

  6. Schumann M, Siegmund B, Schulzke JD, Fromm M. Celiac disease: role of the epithelial barrier. Cell Mol Gastroenterol Hepatol 2017;3:150–162.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Green PH, Cellier C. Celiac disease. N Engl J Med. 2007;357:1731–1743.

    Article  CAS  PubMed  Google Scholar 

  8. Leffler DA, Dennis M, Hyett B, Kelly E, Schuppan D, Kelly CP. Etiologies and predictors of diagnosis in nonresponsive celiac disease. Clin Gastroenterol Hepatol. 2007;5:445–450.

    Article  PubMed  Google Scholar 

  9. Hujoel IA, Murray JA. Refractory celiac disease. Curr Gastroenterol Rep 2020;22:18.

    Article  PubMed  Google Scholar 

  10. Rowinski SA, Christensen E. Epidemiologic and therapeutic aspects of refractory coeliac disease—a systematic review. Dan Med J 2016;63:A5307.

    PubMed  Google Scholar 

  11. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008–2012.

    Article  CAS  PubMed  Google Scholar 

  12. DerSimonian R, Laird N. Meta-analysis in clinical trials revisited. Contemp Clin Trials 2015;45:139–145.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Deeks JJ, Dinnes J, D’Amico R, Sowden AJ, Sakarovitch C, Song F et al. Evaluating non-randomised intervention studies. Health Technol Assess 2003;7:1–173.

    Article  Google Scholar 

  15. Dewar DH, Donnelly SC, McLaughlin SD, Johnson MW, Ellis HJ, Ciclitira PJ. Celiac disease: management of persistent symptoms in patients on a gluten-free diet. World J Gastroenterol 2012;18:1348–1356.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Green PH, Yang J, Cheng J, Lee AR, Harper JW, Bhagat G. An association between microscopic colitis and celiac disease. Clin Gastroenterol Hepatol 2009;7:1210–1216.

    Article  PubMed  Google Scholar 

  17. Leeds JS, Höroldt BS, Sidhu R, Hopper AD, Robinson K, Toulson B et al. Is there an association between coeliac disease and inflammatory bowel diseases? A study of relative prevalence in comparison with population controls. Scand J Gastroenterol 2007;42:1214–1220.

    Article  PubMed  Google Scholar 

  18. Spijkerman M, Tan IL, Kolkman JJ, Withoff S, Wijmenga C, Visschedijk MC et al. A large variety of clinical features and concomitant disorders in celiac disease—a cohort study in the Netherlands. Dig Liver Dis. 2016;48:499–505.

    Article  PubMed  Google Scholar 

  19. Stewart M, Andrews CN, Urbanski S, Beck PL, Storr M. The association of coeliac disease and microscopic colitis: a large population-based study. Aliment Pharmacol Ther 2011;33:1340–1349.

    Article  CAS  PubMed  Google Scholar 

  20. Armes J, Gee DC, Macrae FA, Schroeder W, Bhathal PS. Collagenous colitis: jejunal and colorectal pathology. J Clin Pathol 1992;45:784–787.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Freeman HJ. Collagenous colitis as the presenting feature of biopsy-defined celiac disease. J Clin Gastroenterol 2004;38:664–668.

    Article  PubMed  Google Scholar 

  22. Gillett HR, Freeman HJ. Prevalence of celiac disease in collagenous and lymphocytic colitis. Can J Gastroenterol 2000;14:919–921.

    Article  CAS  PubMed  Google Scholar 

  23. Green HD, Beaumont RN, Thomas A, Hamilton B, Wood AR, Sharp S et al. Genome-wide association study of microscopic colitis in the UK Biobank confirms immune-related pathogenesis. J Crohns Colitis. 2019;13:1578–1582.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Guagnozzi D, Lucendo AJ, Angueira T, González-Castillo S, Tenías JM. Drug consumption and additional risk factors associated with microscopic colitis: case–control study. Rev Esp Enferm Dig. 2015;107:347–353.

    CAS  PubMed  Google Scholar 

  25. Jobse P, Flens MJ, Loffeld RJ. Collagenous colitis: description of a single centre series of 83 patients. Eur J Intern Med. 2009;20:499–502.

    Article  CAS  PubMed  Google Scholar 

  26. Kao KT, Pedraza BA, McClune AC, Rios DA, Mao YQ, Zuch RH et al. Microscopic colitis: a large retrospective analysis from a health maintenance organization experience. World J Gastroenterol. 2009;15:3122–3127.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Koskela RM, Niemelä SE, Karttunen TJ, Lehtola JK. Clinical characteristics of collagenous and lymphocytic colitis. Scand J Gastroenterol 2004;39:837–845.

    Article  CAS  PubMed  Google Scholar 

  28. Larsson JK, Sjöberg K, Vigren L, Benoni C, Toth E, Olesen M. Chronic non-bloody diarrhoea: a prospective study in Malmö, Sweden, with focus on microscopic colitis. BMC Res Notes 2014;7:236.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Matteoni CA, Goldblum JR, Wang N, Brzezinski A, Achkar E, Soffer EE. Celiac disease is highly prevalent in lymphocytic colitis. J Clin Gastroenterol 2001;32:225–227.

    Article  CAS  PubMed  Google Scholar 

  30. Mellander MR, Ekbom A, Hultcrantz R, Löfberg R, Öst Å, Björk J. Microscopic colitis: a descriptive clinical cohort study of 795 patients with collagenous and lymphocytic colitis. Scand J Gastroenterol 2016;51:556–562.

    Article  PubMed  Google Scholar 

  31. O’Toole A, Coss A, Holleran G, Keegan D, Doherty G, Sheahan K et al. Microscopic colitis: clinical characteristics, treatment and outcomes in an Irish population. Int J Colorectal Dis 2014;29:799–803.

    Article  PubMed  Google Scholar 

  32. Olesen M, Eriksson S, Bohr J, Järnerot G, Tysk C. Lymphocytic colitis: a retrospective clinical study of 199 Swedish patients. Gut. 2004;53:536–541.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Pardi DS, Ramnath VR, Loftus EV Jr, Tremaine WJ, Sandborn WJ. Lymphocytic colitis: clinical features, treatment, and outcomes. Am J Gastroenterol 2002;97:2829–2833.

    Article  PubMed  Google Scholar 

  34. Simondi D, Pellicano R, Reggiani S, Pallavicino F, David E, Sguazzini C et al. A retrospective study on a cohort of patients with lymphocytic colitis. Rev Esp Enferm Dig 2010;102:381–384.

    Article  CAS  PubMed  Google Scholar 

  35. Sonnenberg A, Turner KO, Genta RM. Associations of microscopic colitis with other lymphocytic disorders of the gastrointestinal tract. Clin Gastroenterol Hepatol. 2018;16:1762–1767.

    Article  PubMed  Google Scholar 

  36. Svensson M, Bergman D, Olén O, Myrelid P, Bohr J, Wickbom A et al. Validating microscopic colitis (MC) in Swedish pathology registers. Scand J Gastroenterol 2018;53:1469–1475.

    Article  PubMed  Google Scholar 

  37. Verhaegh BPM, Pierik MJ, Goudkade D, Cuijpers Y, Masclee AAM, Jonkers D. Early life exposure, lifestyle, and comorbidity as risk factors for microscopic colitis: a case–control study. Inflamm Bowel Dis 2017;23:1040–1046.

    Article  PubMed  Google Scholar 

  38. Vigren L, Tysk C, Ström M, Kilander AF, Hjortswang H, Bohr J et al. Celiac disease and other autoimmune diseases in patients with collagenous colitis. Scand J Gastroenterol 2013;48:944–950.

    Article  PubMed  Google Scholar 

  39. Wickbom A, Nyhlin N, Montgomery SM, Bohr J, Tysk C. Family history, comorbidity, smoking and other risk factors in microscopic colitis: a case-control study. Eur J Gastroenterol Hepatol 2017;29:587–594.

    Article  PubMed  Google Scholar 

  40. Williams JJ, Kaplan GG, Makhija S, Urbanski SJ, Dupre M, Panaccione R et al. Microscopic colitis-defining incidence rates and risk factors: a population-based study. Clin Gastroenterol Hepatol. 2008;6:35–40.

    Article  PubMed  Google Scholar 

  41. Caio G, Volta U, Sapone A, Leffler DA, De Giorgio R, Catassi C et al. Celiac disease: a comprehensive current review. BMC Med 2019;17:142.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Di Sabatino A, Rosado MM, Cazzola P, Riboni R, Biagi F, Carsetti R et al. Splenic hypofunction and the spectrum of autoimmune and malignant complications in celiac disease. Clin Gastroenterol Hepatol 2006;4:179–186.

    Article  PubMed  Google Scholar 

  43. Malamut G, Afchain P, Verkarre V, Lecomte T, Amiot A, Damotte D et al. Presentation and long-term follow-up of refractory celiac disease: comparison of type I with type II. Gastroenterology 2009;136:81–90.

    Article  PubMed  Google Scholar 

  44. Freeman HJ. Complications of collagenous colitis. World J Gastroenterol 2008;14:1643–1645.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Freeman HJ, James D, Mahoney CJ. Spontaneous peritonitis from perforation of the colon in collagenous colitis. Can J Gastroenterol 2001;15:265–267.

    Article  CAS  PubMed  Google Scholar 

  46. Tong J, Zheng Q, Zhang C, Lo R, Shen J, Ran Z. Incidence, prevalence, and temporal trends of microscopic colitis: a systematic review and meta-analysis. Off J Am Coll Gastroenterol 2015;110:265.

    Article  Google Scholar 

  47. Singh P, Arora A, Strand TA, Leffler DA, Catassi C, Green PH et al. Global prevalence of celiac disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2018;16:823–36.e2.

    Article  PubMed  Google Scholar 

  48. Fernández-Bañares F, Esteve M, Farré C, Salas A, Alsina M, Casalots J et al. Predisposing HLA-DQ2 and HLA-DQ8 haplotypes of coeliac disease and associated enteropathy in microscopic colitis. Eur J Gastroenterol Hepatol 2005;17:1333–1338.

    Article  PubMed  Google Scholar 

  49. Tagkalidis PP, Gibson PR, Bhathal PS. Microscopic colitis demonstrates a T helper cell type 1 mucosal cytokine profile. J Clin Pathol 2007;60:382–387.

    Article  CAS  PubMed  Google Scholar 

  50. Mosnier JF, Larvol L, Barge J, Dubois S, De La Bigne G, Hénin D et al. Lymphocytic and collagenous colitis: an immunohistochemical study. Am J Gastroenterol 1996;91:709–713.

    CAS  PubMed  Google Scholar 

Download references

Funding

No funding was received for the preparation of this manuscript.

Author information

Author notes

  1. Muhammad Aziz and Hossein Haghbin have contributed equally to this work.

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, University of Toledo, Toledo, OH, USA

    Muhammad Aziz

  2. Department of Internal Medicine, University of Toledo, Toledo, OH, USA

    Hossein Haghbin

  3. Department of Internal Medicine, West Virginia University, Morgantown, WV, USA

    Raja Samir Khan

  4. Division of Gastroenterology and Hepatology, University of Texas at Houston, Houston, TX, USA

    Zubair Khan

  5. Department of Medicine, Hackensack University – Palisades Medical Center, North Bergen, NJ, USA

    Simcha Weissman

  6. Division of Gastroenterology, University of California, San Francisco, CA, USA

    Faisal Kamal

  7. University of Toledo Libraries, University of Toledo, Toledo, OH, USA

    Wade Lee-Smith

  8. Gastroenterology Unit, CHI Health Creighton University Medical Center, Omaha, NE, USA

    Saurabh Chandan

  9. Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Joseph D. Feuerstein

  10. Department of Gastroenterology, Centura Health, Center for Advanced Therapeutic Endoscopy, Denver, CO, USA

    Douglas G. Adler

Authors
  1. Muhammad Aziz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hossein Haghbin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raja Samir Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zubair Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Simcha Weissman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Faisal Kamal
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wade Lee-Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Saurabh Chandan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Joseph D. Feuerstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Douglas G. Adler
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.A.—planning and conducting the study, collecting, interpreting data, statistical analysis, drafting the manuscript. H.H., R.S.K.—Collecting data, interpreting data, drafting the manuscript. Z.K., S.W., F.K., S.C.—Interpreting data, drafting the manuscript. W.L.-S.—Search strategy and collected data, drafting the manuscript. J.D.F., D.G.A.—Study design and conception, critical revision of the manuscript.

Corresponding author

Correspondence to Douglas G. Adler.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal rights

No human subjects/animals were involved in this systematic review and meta-analysis.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file 1 (DOCX 49 KB)

Supplementary file 2 (DOCX 19 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aziz, M., Haghbin, H., Khan, R.S. et al. Celiac Disease Is Associated with Microscopic Colitis in Refractory Cases in Adults: A Systematic Review and Meta-Analysis of Observational Studies. Dig Dis Sci 67, 3529–3542 (2022). https://doi.org/10.1007/s10620-021-07232-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-021-07232-7

Keywords

Search

Navigation