Collagenous and Lymphocytic Colitis Clinical Presentation

  • Author: Eric Goosenberg, MD; Chief Editor: Julian Katz, MD   more...
 
Updated: Jan 5, 2012
 

History

  • A protracted course of nonbloody diarrhea occurs. Diarrhea may be of high volume; some patients may eliminate more than 1500 mL of fluid per day.
  • Symptoms may have been present from several months to 2-3 years before medical attention is sought and a diagnosis is made. In fact, perhaps half of patients proven to have microscopic colitis meet the Rome, Rome II, and Manning symptom-based criteria for diarrhea-predominant irritable bowel syndrome and may be so misdiagnosed until endoscopic biopsies of the colon are taken.
  • Less frequent complaints include abdominal cramping, fecal incontinence, and weight loss, although weight loss may be seen in 40% or more of patients with CC.
  • Incontinence is probably more a reflection of the advanced age of those individuals who are affected, and patients with this problem may do well if treated with antidiarrheal agents.
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Physical

  • Physical examination usually does not reflect specific abnormalities.
  • Severely affected individuals may show signs of dehydration, malnutrition, and weight loss.
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Causes

No definite etiology has been determined, but evidence now indicates that drug consumption may trigger underlying inflammatory factors in the colons of affected individuals, while others may exacerbate the diarrhea in patients with idiopathic microscopic colitis. While many drugs, either alone or in combination, may cause diarrhea as an adverse effect, nonsteroidal anti-inflammatory drugs (NSAIDs) show a strong trend (p=0.057) toward increasing the risk of CC, with rechallenge having been shown to cause recurrence of CC. Antidepressant selective serotonin reuptake inhibitors (SSRIs) as a group increase the risk of CC, but, among this class of medications, sertraline alone significantly increases the risk of LC. Anecdotal reports of of a large number of additional drugs have been associated with the onset of the microscopic colitides. Among these, ranitidine (confirmed by rechallenge), aspirin, acarbose, ticlopidine, and proton pump inhibitors have high-level evidenceofcausality,whileflutamide, simvastatin, carbamazepine and lisinopril have intermediate-level evidence.

  • Some patients have had histologic findings consistent with both CC and LC at different points during the course of disease. This raises the possibility that these may be different manifestations of the same medical condition or different points along a continuum.
  • Many case reports describe patients with preexisting presumed autoimmune conditions, such as celiac sprue, psoriasis and rheumatoid arthritis, who subsequently are diagnosed with microscopic colitis. Patients diagnosed with LC also have had uveitis, idiopathic pulmonary fibrosis, juvenile diabetes mellitus, pernicious anemia, autoimmune thyroid disease, and idiopathic thrombocytopenic purpura. Approximately 1/3 of patients with celiac disease have histologic findings consistent with microscopic colitis. For this reason microscopic colitis should be considered in patients diagnosed with celiac disease who have diarrhea that fails to respond to a gluten-free diet. Removal of gluten from the diet, however, is ineffective in treating microscopic colitis in the absence of celiac disease.
  • Microscopic colitis and inflammatory bowel disease (Crohn's disease or ulcerative colitis) have been diagnosed concurrently or sequentially in a small number of cases, with either diagnosis preceding the other. The two conditions may have similar histologic features, making the distinction between them difficult.
  • LC was diagnosed in a patient who failed to respond to antibiotic therapy for diarrhea associated with Campylobacter jejuni infection in the stool. The infection theoretically might have stimulated an autoimmune response that resulted in LC.
  • Increased mast cells in some LC patients might indicate that degranulation products could serve as a chemoattractant for inflammatory cells.
  • While only 14% of patients with LC were smoking actively when diagnosed, 23% were former smokers, suggesting that smoking may actually be protective against the development of LC. Excessive production of nitric oxide by inducible nitric oxide synthase (iNOS) may result in cytotoxicity through the generation of peroxynitrite that is formed when nitric oxide reacts with superoxide. Corticosteroids inhibit iNOS biosynthesis in some cells, and newer inhibitors of this enzyme may have a future role in the management of LC and other forms of colitis. Nitric oxide diffuses into cells and can induce inflammatory cell damage by causing nitration reactions. Increased nitric oxide generation has been reported in CC. The absence of nitrotyrosine staining, which is an indicator of active inflammation typically seen in ulcerative colitis, may correspond to the lesser degree of inflammation in CC compared with ulcerative colitis.[4]
  • Diarrhea associated with CC has been proven to be due to reduced net Na+ and Cl- absorption, with the thickened collagen layer serving as a diffusion barrier. The epithelium nearly completely loses its ability to absorb these ions. In fact, the shift in net chloride flux is to secretion rather than absorption.
  • Secretion of vascular endothelial growth factor, a fibrosis-enhancing peptide, is noted to be increased by the mucosa in some patients with CC. This may play a part in the pathogenesis.
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Contributor Information and Disclosures
Author

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.

Specialty Editor Board

Terence David Lewis, MBBS, FRACP, FRCPC, FACP  Program Director, Internal Medicine Residency, & Assistant Chairman, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, Loma Linda University Medical Center

Terence David Lewis, MBBS, FRACP, FRCPC, FACP is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, California Medical Association, Royal College of Physicians and Surgeons of Canada, and Sigma Xi

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous coauthor Arun Chaudhary, MD, to the development and writing of this article.

References

  1. 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.

  2. Mahajan D, Goldblum JR, Xiao SY, Shen B, Liu X. Lymphocytic colitis and collagenous colitis: a review of clinicopathologic features and immunologic abnormalities. Adv Anat Pathol. Jan 2012;19(1):28-38. [Medline].

  3. Bjørnbak C, Engel PJ, Nielsen PL, Munck LK. Microscopic colitis: clinical findings, topography and persistence of histopathological subgroups. Aliment Pharmacol Ther. Nov 2011;34(10):1225-34. [Medline].

  4. Yen EF, Pokhrel B, Du H, Nwe S, Bianchi L, Witt B, et al. Current and past cigarette smoking significantly increase risk for microscopic colitis. Inflamm Bowel Dis. Dec 6 2011;[Medline].

  5. [Best Evidence] Miehlke S, Madisch A, Karimi D, et al. Budesonide is effective in treating lymphocytic colitis: a randomized double-blind placebo-controlled study. Gastroenterology. Jun 2009;136(7):2092-100. [Medline].

  6. Baert F, Wouters K, D'Haens G, Hoang P, Naegels S, D'Heygere F, et al. Lymphocytic colitis: a distinct clinical entity? A clinicopathological confrontation of lymphocytic and collagenous colitis. Gut. Sep 1999;45(3):375-81. [Medline].

  7. Baum CA, Bhatia P, Miner PB Jr. Increased colonic mucosal mast cells associated with severe watery diarrhea and microscopic colitis. Dig Dis Sci. Sep 1989;34(9):1462-5. [Medline].

  8. Bo-Linn GW, Vendrell DD, Lee E, Fordtran JS. An evaluation of the significance of microscopic colitis in patients with chronic diarrhea. J Clin Invest. May 1985;75(5):1559-69. [Medline].

  9. Burgel N, Bojarski C, Mankertz J, Zeitz M, Fromm M, Schulzke JD. Mechanisms of diarrhea in collagenous colitis. Gastroenterology. Aug 2002;123(2):433-43. [Medline].

  10. Cappell MS. Colonic toxicity of administered drugs and chemicals. Am J Gastroenterol. May 2004;99(6):1175-90. [Medline].

  11. Chande N, MacDonald JK, McDonald JW. Interventions for treating microscopic colitis: a Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group systematic review of randomized trials. Am J Gastroenterol. Jan 2009;104(1):235-41; quiz 234, 242. [Medline].

  12. Chande N, McDonald JW, Macdonald JK. Interventions for treating collagenous colitis: a Cochrane Inflammatory Bowel Disease Group systematic review of randomized trials. Am J Gastroenterol. Dec 2004;99(12):2459-65. [Medline].

  13. 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. Feb 2007;102(2):324-30. [Medline].

  14. Fernandez-Banares F, Salas A, Esteve M, Espinos J, Forne M, Viver JM. Collagenous and lymphocytic colitis. evaluation of clinical and histological features, response to treatment, and long-term follow-up. Am J Gastroenterol. Feb 2003;98(2):340-7. [Medline].

  15. Fernandez-Banares F, Salas A, Forne M, Esteve M, Espinos J, Viver JM. Incidence of collagenous and lymphocytic colitis: a 5-year population-based study. Am J Gastroenterol. Feb 1999;94(2):418-23. [Medline].

  16. Freeman HJ. Collagenous mucosal inflammatory diseases of the gastrointestinal tract. Gastroenterology. Jul 2005;129(1):338-50. [Medline].

  17. Giardiello FM, Lazenby AJ. The atypical colitides. Gastroenterol Clin North Am. Jun 1999;28(2):479-90, x. [Medline].

  18. Giardiello FM, Lazenby AJ, Bayless TM. The new colitides, Collagenous, lymphocytic, and diversion colitis. Gastroenterol Clin North Am. Sep 1995;24(3):717-29. [Medline].

  19. Giardiello FM, Lazenby AJ, Yardley JH, Bias WB, Johnson J, Alianiello RG, et al. Increased HLA A1 and diminished HLA A3 in lymphocytic colitis compared to controls and patients with collagenous colitis. Dig Dis Sci. Apr 1992;37(4):496-9. [Medline].

  20. Limsui D, Pardi DS, Camilleri M, Loftus EV Jr, Kammer PP, Tremaine WJ, et al. Symptomatic overlap between irritable bowel syndrome and microscopic colitis. Inflamm Bowel Dis. Feb 2007;13(2):175-81. [Medline].

  21. Marshall JB, Singh R, Diaz-Arias AA. Chronic, unexplained diarrhea: are biopsies necessary if colonoscopy is normal?. Am J Gastroenterol. Mar 1995;90(3):372-6. [Medline].

  22. Maxson CJ, Klein HD, Rubin W. Atypical forms of inflammatory bowel disease. Med Clin North Am. Nov 1994;78(6):1259-73. [Medline].

  23. Miehlke S, Madisch A, Bethke B, Morgner A, Kuhlisch E, Henker C, et al. Oral budesonide for maintenance treatment of collagenous colitis: a randomized, double-blind, placebo-controlled trial. Gastroenterology. Nov 2008;135(5):1510-6. [Medline].

  24. Miehlke S, Madisch A, Karimi D, Wonschik S, Kuhlisch E, Beckmann R. Budesonide is effective in treating lymphocytic colitis: a randomized double-blind placebo-controlled study. Gastroenterology. Jun 2009;136(7):2092-2100. [Medline].

  25. Mosnier JF, Larvol L, Barge J, Dubois S, De La Bigne G, Henin D, et al. Lymphocytic and collagenous colitis: an immunohistochemical study. Am J Gastroenterol. Apr 1996;91(4):709-13. [Medline].

  26. Mullhaupt B, Guller U, Anabitarte M, Guller R, Fried M. Lymphocytic colitis: clinical presentation and long term course. Gut. Nov 1998;43(5):629-33. [Medline].

  27. Pardi DS. After budesonide, what next for collagenous colitis?. Gut. Jan 2009;58(1):3-4. [Medline].

  28. Pardi DS. Microscopic colitis. Gastroenterol & Hepatol. April 2009;5(4):283-288.

  29. Pardi DS. Microscopic colitis. Mayo Clin Proc. May 2003;78(5):614-6; quiz 616-7. [Medline].

  30. Pardi DS, Loftus EV Jr, Smyrk TC, Kammer PP, Tremaine WJ, Schleck CD, et al. The epidemiology of microscopic colitis: a population based study in Olmsted County, Minnesota. Gut. Apr 2007;56(4):504-8. [Medline].

  31. Pardi DS, Ramnath VR, Loftus EV Jr, Tremaine WJ, Sandborn WJ. Lymphocytic colitis: clinical features, treatment, and outcomes. Am J Gastroenterol. Nov 2002;97(11):2829-33. [Medline].

  32. Schiller LR. Chronic diarrhea. Gastroenterology. Jul 2004;127(1):287-93. [Medline].

  33. Shah V, Lyford G, Gores G, Farrugia G. Nitric oxide in gastrointestinal health and disease. Gastroenterology. Mar 2004;126(3):903-13. [Medline].

  34. Taha Y, Raab Y, Larsson A, Carlson M, Loof L, Gerdin B, et al. Vascular endothelial growth factor (VEGF)--a possible mediator of inflammation and mucosal permeability in patients with collagenous colitis. Dig Dis Sci. Jan 2004;49(1):109-15. [Medline].

  35. Zins BJ, Sandborn WJ, Tremaine WJ. Collagenous and lymphocytic colitis: subject review and therapeutic alternatives. Am J Gastroenterol. Sep 1995;90(9):1394-400. [Medline].

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