Current Approach to the Evaluation and Management of Microscopic Colitis

  • Thomas G. Cotter
  • Darrell S. PardiEmail author
Large Intestine (B Cash, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Large Intestine


Purpose of Review

Microscopic colitis is a common cause of chronic watery diarrhea, particularly in the elderly. The accompanying symptoms, which include abdominal pain and fatigue, can markedly impair patients’ quality of life. Diagnosis is based upon characteristic histologic findings of the colonic mucosa. This review focuses on the current approach to evaluation and management of patients with microscopic colitis.

Recent Findings

Although the incidence of microscopic colitis has been increasing over time, recent epidemiological studies show stabilization at 21.0–24.7 cases per 100,000 person-years. Recent research has further expanded our knowledge of the underlying pathophysiology and emphasized the entity of drug-induced microscopic colitis and the association with celiac disease. Two recent randomized studies have confirmed the effectiveness of oral budesonide for both induction and maintenance treatment of microscopic colitis and is now endorsed by the American Gastroenterological Association as first-line treatment.


The incidence of microscopic colitis has stabilized at just over 20 cases per 100,000 person-years. Celiac disease and drug-induced microscopic colitis should be considered in all patients diagnosed with microscopic colitis. There are a number of treatments available for patients with microscopic colitis; however, budesonide is the only option well studied in controlled trials and is effective for both induction and maintenance treatment.


Microscopic colitis Microscopic colitis treatment Microscopic colitis management Large intestine 


Compliance with Ethical Standards

Conflict of Interest

Thomas Cotter declares no conflict of interest. Darrell Pardi has served as a consultant to Salix, who markets Uceris.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: •Of importance, ••Of major importance

  1. 1.
    Pardi DS, Kelly CP. Microscopic colitis. Gastroenterology. 2011;140:1155–65.CrossRefPubMedGoogle Scholar
  2. 2.
    Gentile NM, Khanna S, Loftus Jr EV, et al. The epidemiology of microscopic colitis in Olmsted County from 2002 to 2010: a population-based study. Clin Gastroenterol Hepatol. 2014;12:838–42.CrossRefPubMedGoogle Scholar
  3. 3.
    Bonderup OK, Wigh T, Nielsen GL, et al. The epidemiology of microscopic colitis: a 10-year pathology-based nationwide Danish cohort study. Scand J Gastroenterol. 2015;50:393–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Nyhlin N, Wickbom A, Montgomery SM, et al. Long-term prognosis of clinical symptoms and health-related quality of life in microscopic colitis: a case-control study. Aliment Pharmacol Ther. 2014;39:963–72.CrossRefPubMedGoogle Scholar
  5. 5.
    Jessurun J, Yardley JH, Lee EL, et al. Microscopic and collagenous colitis: different names for the same condition? Gastroenterology. 1986;91:1583–4.CrossRefPubMedGoogle Scholar
  6. 6.
    Lazenby AJ, Yardley JH, Giardiello FM, et al. Lymphocytic ("microscopic") colitis: a comparative histopathologic study with particular reference to collagenous colitis. Hum Pathol. 1989;20:18–28.CrossRefPubMedGoogle Scholar
  7. 7.
    Pisani LF, Tontini GE, Vecchi M, et al. Microscopic colitis: what do we know about pathogenesis? Inflamm Bowel Dis. 2016;22:450–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Green PH, Yang J, Cheng J, et al. An association between microscopic colitis and celiac disease. Clin Gastroenterol Hepatol. 2009;7:1210–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Jarnerot G, Tysk C, Bohr J, et al. Collagenous colitis and fecal stream diversion. Gastroenterology. 1995;109:449–55.Google Scholar
  10. 10.
    • Verhaegh BP, de Vries F, Masclee AA, et al. High risk of drug-induced microscopic colitis with concomitant use of NSAIDs and proton pump inhibitors. Aliment Pharmacol Ther 2016;43(9):1004–13. This large case-control study showed that current use of NSAIDs, PPIs and SSRIs was all significantly associated with microscopic colitis, with a fivefold increased risk noted with concomitant PPI and NSAID use, emphasizing the importance of recognizing the entity of drug-induced microscopic colitis. This analysis also provided further insight into the potential pathophysiology of drug-induced microscopic colitis, including the hypothesis of PPI-induced intestinal dysbiosis related to acid suppression. Google Scholar
  11. 11.
    Roda G TJ, Hu J, et al. Genome-wide association identifies multiple collagenous colitis susceptibility loci. Gastroenterology. 2015;148(4) Suppl 1:S–875.Google Scholar
  12. 12.
    Burgel N, Bojarski C, Mankertz J, et al. Mechanisms of diarrhea in collagenous colitis. Gastroenterology. 2002;123:433–43.CrossRefPubMedGoogle Scholar
  13. 13.
    Fernandez-Banares F, Esteve M, Salas A, et al. Bile acid malabsorption in microscopic colitis and in previously unexplained functional chronic diarrhea. Dig Dis Sci. 2001;46:2231–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Magro F, Langner C, Driessen A, et al. European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis. 2013;7:827–51.CrossRefPubMedGoogle Scholar
  15. 15.
    Madisch A, Bethke B, Stolte M, et al. Is there an association of microscopic colitis and irritable bowel syndrome—a subgroup analysis of placebo-controlled trials. World J Gastroenterol. 2005;11:6409.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Abboud R, Pardi DS, Tremaine WJ, et al. Symptomatic overlap between microscopic colitis and irritable bowel syndrome: a prospective study. Inflamm Bowel Dis. 2013;19:550–3.CrossRefPubMedGoogle Scholar
  17. 17.
    Guagnozzi D, Arias A, Lucendo AJ. Systematic review with meta-analysis: diagnostic overlap of microscopic colitis and functional bowel disorders. Aliment Pharmacol Ther. 2016. doi: 10.1111/apt.13573.
  18. 18.
    Kane JS, Rotimi O, Everett SM, et al. Development and validation of a scoring system to identify patients with microscopic colitis. Clin Gastroenterol Hepatol. 2015;13:1125–31.CrossRefPubMedGoogle Scholar
  19. 19.
    Cotter TG, Binder M, Harper EP, et al. Optimization of a Scoring System to Predict Microscopic Colitis in a Cohort of Patients With Chronic Diarrhea. J Clin Gastroenterol. 2016. doi: 10.1097/MCG.0000000000000565.
  20. 20.
    Roth B, Gustafsson RJ, Ohlsson B. Auto-antibodies and their association with clinical findings in women diagnosed with microscopic colitis. PLoS One. 2013;8:e66088.CrossRefPubMedCentralGoogle Scholar
  21. 21.
    Pardi DS, Ramnath VR, Loftus Jr EV, et al. Lymphocytic colitis: clinical features, treatment, and outcomes. Am J Gastroenterol. 2002;97:2829–33.CrossRefPubMedGoogle Scholar
  22. 22.
    Kakar S, Pardi DS, Burgart LJ. Colonic ulcers accompanying collagenous colitis: implication of nonsteroidal anti-inflammatory drugs. Am J Gastroenterol. 2003;98:1834–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Ayata G, Ithamukkala S, Sapp H, et al. Prevalence and significance of inflammatory bowel disease-like morphologic features in collagenous and lymphocytic colitis. Am J Surg Pathol. 2002;26:1414–23.CrossRefPubMedGoogle Scholar
  24. 24.
    Cotter TG, Gurney M, Loftus CG. Gas and bloating-controlling emissions: a case-based review for the primary care provider. Mayo Clin Proc. 2016;91:1105–13.CrossRefPubMedGoogle Scholar
  25. 25.
    Cotter TG, Pardi DS. Editorial: additional evidence for drug-induced microscopic colitis. Aliment Pharmacol Ther. 2016;43:1343–4.CrossRefPubMedGoogle Scholar
  26. 26.
    Beaugerie L, Pardi DS. Review article: drug-induced microscopic colitis—proposal for a scoring system and review of the literature. Aliment Pharmacol Ther. 2005;22:277–84.CrossRefGoogle Scholar
  27. 27.
    Nguyen GC, Smalley WE, Vege SS, et al. American Gastroenterological Association Institute guideline on the medical management of microscopic colitis. Gastroenterology. 2016;150:242–6.CrossRefPubMedGoogle Scholar
  28. 28.
    •• Cotter TG, Binder M, Loftus EV, Jr., et al. Development of a Microscopic Colitis Disease Activity Index: a prospective cohort study. Gut. 2016. doi: 10.1136/gutjnl-2016-313051. This prospective cohort study developed the Microscopic Colitis Disease Activity Index (MCDAI) consisting of six patient-reported variables: unformed stools daily, nocturnal stools, abdominal pain, weight loss, faecal urgency and faecal incontinence. It is hoped that the MCDAI can be used to consistently score disease severity in clinical trials, enabling meaningful comparisons between different treatments in the future.
  29. 29.
    Olesen M, Eriksson S, Bohr J, et al. Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Orebro, Sweden, 1993-1998. Gut. 2004;53:346–50.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Bohr J, Tysk C, Eriksson S, et al. Collagenous colitis: a retrospective study of clinical presentation and treatment in 163 patients. Gut. 1996;39:846–51.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Fine KD, Lee EL. Efficacy of open-label bismuth subsalicylate for the treatment of microscopic colitis. Gastroenterology. 1998;114:29–36.CrossRefPubMedGoogle Scholar
  32. 32.
    Gentile NM KS, Loftus EV, et al. Outcomes of patients with microscopic colitis treated with bismuth subsalicylate. Gastroenterology 2015;148:S-483.Google Scholar
  33. 33.
    Colussi D, Salari B, Stewart KO, et al. Clinical characteristics and patterns and predictors of response to therapy in collagenous and lymphocytic colitis. Scand J Gastroenterol. 2015;50:1382–8.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Masannat Y, Nazer E. Pepto bismuth associated neurotoxicity: a rare side effect of a commonly used medication. W V Med J. 2013;109:32–4.PubMedGoogle Scholar
  35. 35.
    •• Miehlke S, Madisch A, Kupcinskas L, et al. Budesonide is more effective than mesalamine or placebo in short-term treatment of collagenous colitis. Gastroenterology 2014;146:1222-30 e1-2. This randomized placebo-controlled control trial showed oral budesonide (9 mg once daily) to be effective and safe for short-term treatment of collagenous colitis. Short-term treatment with oral mesalamine appeared to be ineffective. Google Scholar
  36. 36.
    Fernandez-Banares F, Salas A, Esteve M, et al. Collagenous and lymphocytic colitis. evaluation of clinical and histological features, response to treatment, and long-term follow-up. Am J Gastroenterol. 2003;98:340–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Bonderup OK, Hansen JB, Birket-Smith L, et al. Budesonide treatment of collagenous colitis: a randomised, double blind, placebo controlled trial with morphometric analysis. Gut. 2003;52:248–51.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Baert F, Schmit A, D’Haens G, et al. Budesonide in collagenous colitis: a double-blind placebo-controlled trial with histologic follow-up. Gastroenterology. 2002;122:20–5.CrossRefPubMedGoogle Scholar
  39. 39.
    Miehlke S, Heymer P, Bethke B, et al. Budesonide treatment for collagenous colitis: a randomized, double-blind, placebo-controlled, multicenter trial. Gastroenterology. 2002;123:978–84.CrossRefPubMedGoogle Scholar
  40. 40.
    Miehlke S, Madisch A, Karimi D, et al. Budesonide is effective in treating lymphocytic colitis: a randomized double-blind placebo-controlled study. Gastroenterology. 2009;136:2092–100.CrossRefPubMedGoogle Scholar
  41. 41.
    LE Pardi DS, Tremaine WJ, Sandborn WJ. A randomized, double-blind, placebo-controlled trial of budesonide for the treatment of active lymphocytic colitis. Gastroenterology. 2009;136:A519.CrossRefGoogle Scholar
  42. 42.
    Stewart MJ, Seow CH, Storr MA. Prednisolone and budesonide for short- and long-term treatment of microscopic colitis: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2011;9:881–90.CrossRefPubMedGoogle Scholar
  43. 43.
    Lichtenstein GR, Bengtsson B, Hapten-White L, et al. Oral budesonide for maintenance of remission of Crohn’s disease: a pooled safety analysis. Aliment Pharmacol Ther. 2009;29:643–53.CrossRefPubMedGoogle Scholar
  44. 44.
    Gentile NM, Abdalla AA, Khanna S, et al. Outcomes of patients with microscopic colitis treated with corticosteroids: a population-based study. Am J Gastroenterol. 2013;108:256–9.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Baert F, Wouters K, D’Haens G, et al. Lymphocytic colitis: a distinct clinical entity? a clinicopathological confrontation of lymphocytic and collagenous colitis. Gut. 1999;45:375–81.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Miehlke S, Hansen JB, Madisch A, et al. Risk factors for symptom relapse in collagenous colitis after withdrawal of short-term budesonide therapy. Inflamm Bowel Dis. 2013;19:2763–7.CrossRefPubMedGoogle Scholar
  47. 47.
    Pardi DS, Loftus Jr EV, Tremaine WJ, et al. Treatment of refractory microscopic colitis with azathioprine and 6-mercaptopurine. Gastroenterology. 2001;120:1483–4.CrossRefPubMedGoogle Scholar
  48. 48.
    Vennamaneni SR, Bonner GF. Use of azathioprine or 6-mercaptopurine for treatment of steroid-dependent lymphocytic and collagenous colitis. Am J Gastroenterol. 2001;96:2798–9.CrossRefPubMedGoogle Scholar
  49. 49.
    Riddell J, Hillman L, Chiragakis L, et al. Collagenous colitis: oral low-dose methotrexate for patients with difficult symptoms: long-term outcomes. J Gastroenterol Hepatol. 2007;22:1589–93.CrossRefPubMedGoogle Scholar
  50. 50.
    Miehlke S, Madisch A, Bethke B, et al. Oral budesonide for maintenance treatment of collagenous colitis: a randomized, double-blind, placebo-controlled trial. Gastroenterology. 2008;135:1510–6.CrossRefPubMedGoogle Scholar
  51. 51.
    Bonderup OK, Hansen JB, Teglbjaerg PS, et al. Long-term budesonide treatment of collagenous colitis: a randomised, double-blind, placebo-controlled trial. Gut. 2009;58:68–72.CrossRefPubMedGoogle Scholar
  52. 52.••
    Munch A, Bohr J, Miehlke S, et al. Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial. Gut. 2016;65:47–56. This randomized placebo-controlled trial revealed budesonide, at a mean dose of 4.5 mg/day, to be effective in maintaining clinical remission for 1 year in patients with collagenous colitis without safety concerns. This trial also suggested that treatment extension beyond 1 year may be beneficial, given the high relapse rate after budesonide discontinuation. CrossRefPubMedGoogle Scholar
  53. 53.
    Pardi DS. After budesonide, what next for collagenous colitis? Gut. 2009;58:3–4.CrossRefPubMedGoogle Scholar
  54. 54.
    Munch A, Fernandez-Banares F, Munck LK. Azathioprine and mercaptopurine in the management of patients with chronic, active microscopic colitis. Aliment Pharmacol Ther. 2013;37:795–8.CrossRefPubMedGoogle Scholar
  55. 55.
    Munch A, Bohr J, Vigren L, et al. Lack of effect of methotrexate in budesonide-refractory collagenous colitis. Clin Exp Gastroenterol. 2013;6:149–52.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Esteve M, Mahadevan U, Sainz E, et al. Efficacy of anti-TNF therapies in refractory severe microscopic colitis. J Crohns Colitis. 2011;5:612–8.CrossRefPubMedGoogle Scholar
  57. 57.
    Munch A, Ignatova S, Strom M. Adalimumab in budesonide and methotrexate refractory collagenous colitis. Scand J Gastroenterol. 2012;47:59–63.CrossRefPubMedGoogle Scholar
  58. 58.
    Pola S, Fahmy M, Evans E, et al. Successful use of infliximab in the treatment of corticosteroid dependent collagenous colitis. Am J Gastroenterol. 2013;108:857–8.CrossRefPubMedGoogle Scholar
  59. 59.
    Anderson RJ, Makins R. Successful use of adalimumab in patient with treatment-refractory microscopic colitis. BMJ Case Rep. 2016. doi: 10.1136/bcr-2016-215639.
  60. 60.
    Williams RA, Gelfand DV. Total proctocolectomy and ileal pouch anal anastomosis to successfully treat a patient with collagenous colitis. Am J Gastroenterol. 2000;95:2147.CrossRefPubMedGoogle Scholar
  61. 61.
    Varghese L, Galandiuk S, Tremaine WJ, et al. Lymphocytic colitis treated with proctocolectomy and ileal J-pouch-anal anastomosis: report of a case. Dis Colon Rectum. 2002;45:123–6.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Internal MedicineMayo ClinicRochesterUSA
  2. 2.Division of Gastroenterology and HepatologyMayo ClinicRochesterUSA

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