Collagenous and Lymphocytic Colitis Treatment & Management
- Author: Joyann A Kroser, MD, FACP, FACG, AGAF; Chief Editor: BS Anand, MD more...
Evaluating treatment options is impaired by the fairly frequent occurrence of spontaneous remission of symptoms; however, positive placebo-controlled double-blind randomized trials of budesonide have been performed and reported in both LC and CC.
A trial of dietary restriction and avoidance of potentially aggravating drugs (particularly nonsteroidal anti-inflammatory drugs) may alleviate symptoms in some patients, but many will require medical therapy.
Treatment should be initiated with the least toxic regimen or medication, with stronger medication used only if the milder treatment fails. Generally, 4-6 weeks should be allowed before deeming a particular medication is ineffective in the treatment of CC or LC.
One possible treatment algorithm is as follows:
First line: Loperamide (Imodium AD) or diphoxylate/atropine (Lomotil) for mild diarrhea.
Second line: Bismuth subsalicylate, two or three 262 mg tab tid or qid for 1-2 months (effective in up to 90% of patients); mesalamine, 3 g/d for 8 wk; or cholestyramine (especially if bile acid malabsorption is documented), at a mean dose of 8 g/d in moderate disease.
Third line: If patient is still not responding or if a patient has clinically more severe colitis, a 6-week course of budesonide at the lowest effective dosage (usually 9 mg each morning) or a 2-week course of high-dose prednisone (60-80 mg/d) before tapering can be prescribed. Longer courses of budesonide may be beneficial, and, while systemic adverse effects may occur, little or no adrenal suppression should be anticipated. Recurrences after discontinuation of budesonide usually respond to reinstitution of the same medication. Longer courses of prednisone (up to 2 mo before tapering) may be needed in some patients, but recurrence is common after its discontinuation.In a randomized, double-blind, placebo-controlled study, Miehlke et al evaluated treatment of lymphocytic colitis with oral budesonide.  At week 6, remission was documented by colonoscopy and histology in 86% of the budesonide group compared with 48% of those administered placebo ( P = 0.01). Histologic remission was confirmed in 73% of those receiving budesonide and 31% of patients administered placebo ( P = 0.03).  Relapse during follow-up was evident in about 44% (15 patients), but 8 of those who had a relapse again had a response to budesonide. Clinical remission and improved histology is achieved in a majority of patients with lymphocytic colitis when treated with budesonide. 
Fourth line: Some refractory cases may benefit from azathioprine (approximately 2 g/kg/d) or 6-mercaptopurine, but responses often take months to occur. Methotrexate can alternatively be used in this setting.
Patients who respond to treatment, but experience a recurrence, will often respond again to the same previously effective medication.
There is no evidence of a benefit from probiotics.
Diet and activity
Patients should avoid or eliminate possible secretagogues, such as caffeine, and, when appropriate, lactose-containing products. A low-fat diet is advisable if steatorrhea is documented.
Consultation with a gastroenterologist often is needed to make the diagnosis and to work through the treatment algorithm.
If colitis is refractory to continued medical therapy or if effective medication cannot be tolerated, colectomy or ileostomy might be the only effective therapy; however, this seldom is necessary.
Jauregui-Amezaga A, Vermeire S, Geboes K. Contemporary methods for the diagnosis and treatment of microscopic colitis. Expert Rev Gastroenterol Hepatol. 2015 Oct 15. 1-15. [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.
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. 2012 Jan. 19(1):28-38. [Medline].
Bjornbak C, Engel PJ, Nielsen PL, Munck LK. Microscopic colitis: clinical findings, topography and persistence of histopathological subgroups. Aliment Pharmacol Ther. 2011 Nov. 34(10):1225-34. [Medline].
Villanueva MS, Alimi Y. Microscopic colitis (lymphocytic and collagenous), eosinophilic colitis, and celiac disease. Clin Colon Rectal Surg. 2015 Jun. 28 (2):118-26. [Medline].
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. 2011 Dec 6. [Medline].
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].
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].
Freeman HJ. Collagenous colitis as the presenting feature of biopsy-defined celiac disease. J Clin Gastroenterol. 2004 Sep. 38(8):664-8. [Medline].
Kingsmore SF, Kingsmore DB, Hall BD, Wilson JA, Gottfried MR, Allen NB. Cooccurrence of collagenous colitis with seronegative spondyloarthropathy: report of a case and literature review. J Rheumatol. 1993 Dec. 20(12):2153-7. [Medline].
Lettesjo H, Hansson T, Peterson C, et al. Detection of inflammatory markers in stools from patients with irritable bowel syndrome and collagenous colitis. Scand J Gastroenterol. 2006 Jan. 41(1):54-9. [Medline].
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].
Miehlke S, Madisch A, Karimi D, et al. Budesonide is effective in treating lymphocytic colitis: a randomized double-blind placebo-controlled study. Gastroenterology. 2009 Jun. 136(7):2092-100. [Medline].
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. 1999 Sep. 45(3):375-81. [Medline].
Baum CA, Bhatia P, Miner PB Jr. Increased colonic mucosal mast cells associated with severe watery diarrhea and microscopic colitis. Dig Dis Sci. 1989 Sep. 34(9):1462-5. [Medline].
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. 1985 May. 75(5):1559-69. [Medline].
Burgel N, Bojarski C, Mankertz J, Zeitz M, Fromm M, Schulzke JD. Mechanisms of diarrhea in collagenous colitis. Gastroenterology. 2002 Aug. 123(2):433-43. [Medline].
Cappell MS. Colonic toxicity of administered drugs and chemicals. Am J Gastroenterol. May 2004. 99(6):1175-90. [Medline].
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. 2009 Jan. 104(1):235-41; quiz 234, 242. [Medline].
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. 2004 Dec. 99(12):2459-65. [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].
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. 2003 Feb. 98(2):340-7. [Medline].
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. 1999 Feb. 94(2):418-23. [Medline].
Freeman HJ. Collagenous mucosal inflammatory diseases of the gastrointestinal tract. Gastroenterology. 2005 Jul. 129(1):338-50. [Medline].
Giardiello FM, Lazenby AJ. The atypical colitides. Gastroenterol Clin North Am. 1999 Jun. 28(2):479-90, x. [Medline].
Giardiello FM, Lazenby AJ, Bayless TM. The new colitides, Collagenous, lymphocytic, and diversion colitis. Gastroenterol Clin North Am. 1995 Sep. 24(3):717-29. [Medline].
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. 1992 Apr. 37(4):496-9. [Medline].
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. 2007 Feb. 13(2):175-81. [Medline].
Marshall JB, Singh R, Diaz-Arias AA. Chronic, unexplained diarrhea: are biopsies necessary if colonoscopy is normal?. Am J Gastroenterol. 1995 Mar. 90(3):372-6. [Medline].
Maxson CJ, Klein HD, Rubin W. Atypical forms of inflammatory bowel disease. Med Clin North Am. 1994 Nov. 78(6):1259-73. [Medline].
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. 2008 Nov. 135(5):1510-6. [Medline].
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. 2009 Jun. 136(7):2092-2100. [Medline].
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. 1996 Apr. 91(4):709-13. [Medline].
Mullhaupt B, Guller U, Anabitarte M, Guller R, Fried M. Lymphocytic colitis: clinical presentation and long term course. Gut. 1998 Nov. 43(5):629-33. [Medline].
Pardi DS. After budesonide, what next for collagenous colitis?. Gut. 2009 Jan. 58(1):3-4. [Medline].
Pardi DS. Microscopic colitis. Gastroenterol & Hepatol. April 2009. 5(4):283-288.
Pardi DS. Microscopic colitis. Mayo Clin Proc. 2003 May. 78(5):614-6; quiz 616-7. [Medline].
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. 2007 Apr. 56(4):504-8. [Medline].
Pardi DS, Ramnath VR, Loftus EV Jr, Tremaine WJ, Sandborn WJ. Lymphocytic colitis: clinical features, treatment, and outcomes. Am J Gastroenterol. 2002 Nov. 97(11):2829-33. [Medline].
Schiller LR. Chronic diarrhea. Gastroenterology. 2004 Jul. 127(1):287-93. [Medline].
Shah V, Lyford G, Gores G, Farrugia G. Nitric oxide in gastrointestinal health and disease. Gastroenterology. 2004 Mar. 126(3):903-13. [Medline].
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. 2004 Jan. 49(1):109-15. [Medline].
Zins BJ, Sandborn WJ, Tremaine WJ. Collagenous and lymphocytic colitis: subject review and therapeutic alternatives. Am J Gastroenterol. 1995 Sep. 90(9):1394-400. [Medline].
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 (11):1382-8. [Medline].