Diagnostic Considerations

Rule out microscopic colitis (MC) in those who fulfill the criteria for functional bowel disease, especially in the presence of risk factors for microscopic colitis and/or in the absence of response to therapy for irritable bowel syndrome (IBS).

Microscopic colitis should be considered as a differential diagnosis in the workup of chronic diarrhea, especially in the elderly population. In addition, microscopic colitis should be considered in patients diagnosed with celiac disease who have diarrhea that fails to respond to a gluten-free diet.

Differential diagnosis

Different small bowel diseases and conditions may mimic microscopic colitis, including the following:

Concurrent lymphocytic colitis (LC) and lymphocytic gastritis^[31]
Celiac disease: Collagenous colitis (CC) may represent a diffuse manifestation of gluten sensitivity; therefore, it is reasonable to evaluate patients for celiac disease^[32]
Infectious colitis (other than Clostridium difficile infection)
Ischemic colitis
Laxative abuse
Bile acid malabsorption

Important considerations

Patients whose condition fails to respond to reasonable medical therapy should be evaluated for other conditions that may clinically mimic lymphocytic colitis and collagenous colitis.

The adverse effects of corticosteroids and immunosuppressants/immunomodulators may be serious. Such drugs would be difficult to justify in a patient later found to have an irritable bowel syndrome (IBS) or infectious or other causes of colitis or enteritis that should have been treated differently.

Performing a colonoscopy on patients with chronic diarrhea is commonly accepted and widely practiced, but performing biopsies in all such individuals has a low yield, even with normal findings on endoscopy. Patients clinically assessed as having diarrhea-predominant IBS (IBS-D) in whom conventional medical therapy is refractory may in fact have microscopic colitis, and these patients may benefit from colonoscopy with biopsies.

Limit biopsies to those subgroups of patients in whom microscopic colitis is most likely, such as patients with watery, severe, debilitating, or nocturnal diarrhea; substantial weight loss; an elevated erythrocyte sedimentation rate; or patients who are immunosuppressed.

Special concerns

As with the management of inflammatory bowel disease (IBD), antidiarrheal and nonimmunosuppressive medications have an acceptable risk in pregnant patients when clinical symptoms are significant and might threaten the pregnancy.

Methotrexate may induce spontaneous abortion and is contraindicated during pregnancy. 6-Mercaptopurine and azathioprine may cause fetal harm but so may refractory colitis. Consequently, the risk versus benefit considerations must be carefully discussed before prescribing these medications to a pregnant patient.

Differential Diagnoses

Workup

Tulassay Z, Mihaly E, Herszényi L. Microscopic colitis: a challenging disorder. Dig Dis. 2020. 38 (2):117-21. [Medline]. [Full Text].
Guagnozzi D, Landolfi S, Vicario M. Towards a new paradigm of microscopic colitis: incomplete and variant forms. World J Gastroenterol. 2016 Oct 14. 22(38):8459-71. [Medline]. [Full Text].
Genta RM, Sonnenberg A. The yield of colonic biopsy in the evaluation of chronic unexplained diarrhea. Eur J Gastroenterol Hepatol. 2015 Aug. 27(8):963-7. [Medline].
Park T, Cave D, Marshall C. Microscopic colitis: a review of etiology, treatment and refractory disease. World J Gastroenterol. 2015 Aug 7. 21(29):8804-10. [Medline]. [Full Text].
Pardi DS. Diagnosis and management of microscopic colitis. Am J Gastroenterol. 2017 Jan. 112(1):78-85. [Medline].
Lindstrom CG. 'Collagenous colitis' with watery diarrhoea--a new entity?. Pathol Eur. 1976. 11 (1):87-9. [Medline].
Freeman HJ, Weinstein WM, Shnitka TK, et al. Watery diarrhea syndrome associated with a lesion of the colonic basement membrane (CD)-lamina propria (LP) interface. Ann R Coll Phys Surg Can. 1976. 9:45.
Read NW, Krejs GJ, Read MG, Santa Ana CA, Morawski SG, Fordtran JS. Chronic diarrhea of unknown origin. Gastroenterology. 1980 Feb. 78 (2):264-71. [Medline].
Lazenby AJ, Yardley JH, Giardiello FM, Jessurun J, Bayless TM. Lymphocytic ("microscopic") colitis: a comparative histopathologic study with particular reference to collagenous colitis. Hum Pathol. 1989 Jan. 20 (1):18-28. [Medline].
[Guideline] Miehlke S, Guagnozzi D, Zabana Y, et al. European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations. United European Gastroenterol J. 2021 Feb 22. [Medline]. [Full Text].
Pisani LF, Tontini GE, Vecchi M, Pastorelli L. Microscopic colitis: What do we know about pathogenesis?. Inflamm Bowel Dis. 2016 Feb. 22(2):450-8. [Medline].
Fine KD, Do K, Schulte K, et al. High prevalence of celiac sprue-like HLA-DQ genes and enteropathy in patients with the microscopic colitis syndrome. Am J Gastroenterol. 2000 Aug. 95(8):1974-82. [Medline].
Fernandez-Banares F, Esteve M, Farre C, et al. Predisposing HLA-DQ2 and HLA-DQ8 haplotypes of coeliac disease and associated enteropathy in microscopic colitis. Eur J Gastroenterol Hepatol. 2005 Dec. 17(12):1333-8. [Medline].
Sikander A, Sinha SK, Prasad KK, Rana SV. Association of serotonin transporter promoter polymorphism (5-HTTLPR) with microscopic colitis and ulcerative colitis. Dig Dis Sci. 2015 Apr. 60(4):887-94. [Medline].
Koskela RM, Karttunen TJ, Niemela SE, Lehtola JK, Bloigu RS, Karttunen RA. Cytokine gene polymorphism in microscopic colitis association with the IL-6-174 GG genotype. Eur J Gastroenterol Hepatol. 2011 Jul. 23(7):607-13. [Medline].
Fernandez-Banares F, Esteve M, Espinos JC, Rosinach M, Forne M, Salas A, et al. Drug consumption and the risk of microscopic colitis. Am J Gastroenterol. 2007 Feb. 102(2):324-30. [Medline].
Cappell MS. Colonic toxicity of administered drugs and chemicals. Am J Gastroenterol. 2004 Jun. 99(6):1175-90. [Medline].
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 Sep. 45(3):375-81. [Medline]. [Full Text].
Al Momani L, Balagoni H, Alomari M, et al. The association between smoking and both types of microscopic colitis: A systematic review and meta-analysis. Arab J Gastroenterol. 2020 Mar. 21(1):9-18. [Medline].
Yen EF, Pokhrel B, Du H, et al. Current and past cigarette smoking significantly increase risk for microscopic colitis. Inflamm Bowel Dis. 2012 Oct. 18(10):1835-41. [Medline].
Fernndez-Baares F, de Sousa MR, Salas A, et al, for the RECOMINA Project, GETECCU (Grupo Español de Enfermedades de Crohn y Colitis Ulcerosa). Impact of current smoking on the clinical course of microscopic colitis. Inflamm Bowel Dis. 2013 Jun. 19(7):1470-6. [Medline].
Roth B, Gustafsson RJ, Jeppsson B, Manjer J, Ohlsson B. Smoking- and alcohol habits in relation to the clinical picture of women with microscopic colitis compared to controls. BMC Womens Health. 2014 Jan 23. 14:16. [Medline]. [Full Text].
Munch A, Tysk C, Bohr J, et al. Smoking status influences clinical outcome in collagenous colitis. J Crohns Colitis. 2016 Apr. 10(4):449-54. [Medline]. [Full Text].
Kandemir O, Utas C, Gonen O, et al. Colonic subepithelial collagenous thickening in diabetic patients. Dis Colon Rectum. 1995 Oct. 38(10):1097-100. [Medline].
Langner C, Aust D, Ensari A, et al, for the Working Group of Digestive Diseases of the European Society of Pathology (ESP) and the European Microscopic Colitis Group (EMCG). Histology of microscopic colitis-review with a practical approach for pathologists. Histopathology. 2015 Apr. 66(5):613-26. [Medline].
Beaugerie L, Pardi DS. Review article: drug-induced microscopic colitis - proposal for a scoring system and review of the literature. Aliment Pharmacol Ther. 2005 Aug 15. 22(4):277-84. [Medline]. [Full Text].
Masclee GM, Coloma PM, Kuipers EJ, Sturkenboom MC. Increased risk of microscopic colitis with use of proton pump inhibitors and non-steroidal anti-inflammatory drugs. Am J Gastroenterol. 2015 May. 110(5):749-59. [Medline].
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. Am J Gastroenterol. 2015 Feb. 110(2):265-76; quiz 277. [Medline].
Townsend T, Campbell F, O'Toole P, Probert C. Microscopic colitis: diagnosis and management. Frontline Gastroenterol. 2019 Oct. 10(4):388-93. [Medline]. [Full Text].
Bohr J, Tysk C, Eriksson S, Abrahamsson H, Jarnerot G. Collagenous colitis: a retrospective study of clinical presentation and treatment in 163 patients. Gut. 1996 Dec. 39(6):846-51. [Medline]. [Full Text].
Christ AD, Meier R, Bauerfeind P, Wegmann W, Gyr K. [Simultaneous occurrence of lymphocytic gastritis and lymphocytic colitis with transition to collagenous colitis] [German]. Schweiz Med Wochenschr. 1993 Jul 31. 123(30):1487-90. [Medline].
O'Mahony S, Nawroz IM, Ferguson A. Coeliac disease and collagenous colitis. Postgrad Med J. 1990 Mar. 66(773):238-41. [Medline]. [Full Text].
Cotter TG, Binder M, Harper EP, Smyrk TC, Pardi DS. Optimization of a scoring system to predict microscopic colitis in a cohort of patients with chronic diarrhea. J Clin Gastroenterol. 2017 Mar. 51(3):228-34. [Medline].
Holstein A, Burmeister J, Plaschke A, Rosemeier D, Widjaja A, Egberts EH. Autoantibody profiles in microscopic colitis. J Gastroenterol Hepatol. 2006 Jun. 21(6):1016-20. [Medline].
von Arnim U, Wex T, Ganzert C, Schulz C, Malfertheiner P. Fecal calprotectin: a marker for clinical differentiation of microscopic colitis and irritable bowel syndrome. Clin Exp Gastroenterol. 2016. 9:97-103. [Medline]. [Full Text].
Gunaltay S, Kumawat AK, Nyhlin N, et al. Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment. Mediators Inflamm. 2015. 2015:132458. [Medline]. [Full Text].
Fine KD, Seidel RH, Do K. The prevalence, anatomic distribution, and diagnosis of colonic causes of chronic diarrhea. Gastrointest Endosc. 2000 Mar. 51(3):318-26. [Medline].
[Guideline] Nguyen GC, Smalley WE, Vege SS, et al, for the Clinical Guidelines Committee. American Gastroenterological Association institute guideline on the medical management of microscopic colitis. Gastroenterology. 2016 Jan. 150(1):242-6; quiz e17-8. [Medline]. [Full Text].
American Gastroenterological Association. AGA Institute guideline on the management of microscopic colitis: clinical decision support tool. Gastroenterology. 2016 Jan. 150 (1):276. [Medline].
Pardi DS, Loftus EV Jr, Tremaine WJ, Sandborn WJ. Treatment of refractory microscopic colitis with azathioprine and 6-mercaptopurine. Gastroenterology. 2001 May. 120(6):1483-4. [Medline].
Esteve M, Mahadevan U, Sainz E, Rodriguez E, Salas A, Fernandez-Banares F. Efficacy of anti-TNF therapies in refractory severe microscopic colitis. J Crohns Colitis. 2011 Dec. 5(6):612-8. [Medline]. [Full Text].
Munch A, Ignatova S, Strom M. Adalimumab in budesonide and methotrexate refractory collagenous colitis. Scand J Gastroenterol. 2012 Jan. 47(1):59-63. [Medline].

Media Gallery

Microscopic Colitis (Collagenous and Lymphocytic Colitis). Lymphocytic colitis (LC) showing marked chronic inflammatory cell infiltrate of the surface epithelium (on right) with preservation of the crypt architecture. The subepithelial collagen layer is not thickened.
Microscopic Colitis (Collagenous and Lymphocytic Colitis). Collagenous colitis (CC) showing similar inflammatory cell infiltration as in lymphocytic colitis (LC), with the characteristically thickened subepithelial collagen layer.

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Author

Harika Balagoni, MD Fellow, Department of Gastroenterology, Ascension Providence-Providence Park Hospital, Michigan State University College of Human Medicine

Harika Balagoni, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, Crohn's and Colitis Foundation of America

Disclosure: Nothing to disclose.

Coauthor(s)

Michael H Piper, MD Clinical Assistant Professor, Department of Internal Medicine, Division of Gastroenterology, Wayne State University School of Medicine; Consulting Staff, Digestive Health Associates, PLC

Michael H Piper, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Gastroenterology, American College of Physicians, Michigan State Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Additional Contributors

Joyann A Kroser, MD, FACP, FACG, AGAF Adjunct Clinical Associate Professor of Medicine, Gastroenterology, and Hepatology, Drexel University College of Medicine; Adjunct Professor of Medicine, Temple University School of Medicine

Joyann A Kroser, MD, FACP, FACG, AGAF is a member of the following medical societies: American College of Physicians, Alpha Omega Alpha, Crohn's and Colitis Foundation of America, American College of Gastroenterology, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Pennsylvania Medical Society, Phi Beta Kappa, Philadelphia County Medical Society

Disclosure: Nothing to disclose.

Amandeep Singh, MBBS Resident Physician, Department of Internal Medicine, Crozer Chester Medical Center

Amandeep Singh, MBBS is a member of the following medical societies: American Academy of Family Physicians, American College of Gastroenterology, American College of Physicians

Disclosure: Nothing to disclose.

Acknowledgements

Arun Chaudhary, MD Consulting Staff, Department of Internal Medicine, Wentworth-Douglass Hospital

Disclosure: Nothing to disclose.

Eric Goosenberg, MD Assistant Professor of Medicine, Temple University School of Medicine

Eric Goosenberg, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, and Bockus International Society of Gastroenterology

Disclosure: Nothing to disclose.

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of GI, Hepatology, and Nutrition at North Shore University Hospital/Long Island Jewish Medical Center; Professor, Department of Medicine, Hofstra North Shore-LIJ School of Medicine

Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, and American Gastroenterological Association

Disclosure: Novartis Grant/research funds Other; Bayer Grant/research funds Other; Otsuka Grant/research funds None; Bristol Myers Squibb Grant/research funds Other; Scynexis None None; Salix Grant/research funds Other; MannKind Other