eMedicine Specialties > Gastroenterology > Colon

Collagenous and Lymphocytic Colitis: Differential Diagnoses & Workup

Author: Eric Goosenberg, MD, Clinical Assistant Professor, Department of Medicine, Drexel University School of Medicine
Contributor Information and Disclosures

Updated: Jul 15, 2009

Differential Diagnoses

Celiac Sprue
Irritable Bowel Syndrome
Crohn Disease
Ulcerative Colitis
Giardiasis
Hyperthyroidism
Inflammatory Bowel Disease

Other Problems to Be Considered

Infectious colitis (other than Clostridium difficile infection)
Ischemic colitis
Laxative abuse

Workup

Laboratory Studies

  • Blood studies
    • Results usually are within the reference range, but anemia, hypokalemia, hypoalbuminemia, elevation of the erythrocyte sedimentation rate, or a combination of these findings may be present.
    • HLA-A1 is more frequent in patients with LC (67%) than in controls (28%) or in patients with CC (26%).
    • HLA-B3 has not been reported in patients with LC. A frequency of 26% is expected in controls and also is observed in patients with CC.
    • The HLA patterns observed in other gastrointestinal conditions, such as Crohn disease, have not been found in LC.
    • Approximately 50% of both patients with CC and patients with LC may have circulating autoantibodies, especially antiparietal cell, antithyroglobulin, and antimicrosomal antibodies.
  • Stool studies
    • Some affected patients have a diminished ability to absorb water resulting from reduced colonic absorption of sodium and chloride. Chloride/bicarbonate exchange across the colonic mucosa also may be reduced.
    • Stool evaluation on occasion may show the presence of leukocytes. In these circumstances, the stool should be tested for enteric bacterial pathogens, ova and parasites, and C difficile.
    • A prolonged (24- to 72-h) stool collection occasionally may demonstrate steatorrhea in affected individuals. A finding of greater than 7 g of fecal fat excretion per 24 hours in an individual ingesting 100 g of fat per day usually is indicative of fat malabsorption, and, even if microscopic colitis is present, a diagnosis of concurrent sprue should be considered.

Imaging Studies

  • Findings on plain abdominal radiograph, barium enemas, and CT scans typically are normal or nonspecific and show no evidence of colonic mucosal damage or wall abnormality.

Other Tests

  • Immunohistochemical studies of biopsies in LC and CC cases demonstrate abnormalities consistent with a mixed histocompatibility-restricted mechanism.
  • The excessive intraepithelial lymphocytes observed in LC are predominantly CD4+ T cells rather than CD8+.

Procedures

  • Biopsies obtained by sigmoidoscopy or colonoscopy are necessary to diagnose LC or CC.
  • If a colonoscopy is performed, biopsies should be taken from the rectosigmoid and possibly also from the right side of the colon. Approximately 95% of patients with microscopic colitis will have diagnostic left colon biopsies; but, if these biopsies are nondiagnostic at sigmoidoscopy in a patient in whom clinical suspicion remains high, total colonoscopy for right-sided biopsies may confirm the diagnosis.
  • In individuals with LC or CC, the mucosa appears normal endoscopically or occasionally mild mucosal edema may be seen. It does not show the more readily apparent changes of inflammatory bowel disease such as friability, ulceration, and pseudopolyps. Most patients have similar degrees of histologic abnormality in the right and left sides of the colon.

Histologic Findings

  • Surface epithelium shows a chronic inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils in the lamina propria.
  • Intraepithelial lymphocytosis, with greater than 20 lymphocytes per 100 epithelial cells, is pathognomonic of the diagnosis of LC (see Media file 1),  although lesser numbers of IEL may be present in some patients with LC.
  • Epithelial cell damage is demonstrated by cell flattening, subepithelial blebs, and denuded epithelium. Fixed specimens may show epithelial loss and detachment.
  • Crypts may have minimal architectural distortion as in Crohn's disease or ulcerative colitis. However, typically, evenly spaced parallel crypts of equal diameter are present.
  • CC shares the histologic features of LC but additionally demonstrates a thickened subepithelial collagen layer (usually >10 µm) in the lamina propria, compared to a normal thickness of 5-7 µm.
  • For comparison, a representative biopsy of CC is shown in Media file 2.
  • In some biopsy specimens, the surface epithelium may be denuded or partially detached from the collagen layer, even simulating pseudomembranes in rare cases. This either may be artifactual or may be due to a defect in adherence to the subepithelial membrane.

More on Collagenous and Lymphocytic Colitis

Overview: Collagenous and Lymphocytic Colitis
Differential Diagnoses & Workup: Collagenous and Lymphocytic Colitis
Treatment & Medication: Collagenous and Lymphocytic Colitis
Follow-up: Collagenous and Lymphocytic Colitis
Multimedia: Collagenous and Lymphocytic Colitis
References
[ CLOSE WINDOW ]

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. [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].

  3. 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].

  4. 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].

  5. 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].

  6. 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].

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

  8. 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].

  9. 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].

  10. 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].

  11. 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].

  12. 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].

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

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

  15. 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].

  16. 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].

  17. 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].

  18. 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].

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

  20. 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].

  21. 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].

  22. 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].

  23. 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].

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

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

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

  27. 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].

  28. 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].

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

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

  31. 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].

  32. 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].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

collagenous colitis, CC, lymphocytic colitis, LC, microscopic colitis

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Eric Goosenberg, MD, Clinical Assistant Professor, Department of Medicine, Drexel University School of Medicine
Eric Goosenberg, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Douglas M Heuman, MD, FACP, FACG, AGAF, Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University 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: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, 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; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
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 and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.