Journal of Gastroenterology and Hepatology 22 (2007) 809–814 © 2006 The Authors 809 Journal compilation © 2007 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd doi:10.1111/j.1440-1746.2006.04511.x Blackwell Publishing AsiaMelbourne, AustraliaJGHJournal of Gastroenterology and Hepatology0815 93192006 Blackwell Publishing Asia Pty Ltd2006226809814Original Article Treatment of microscopic colitisC Calabrese et al. GASTROENTEROLOGY Mesalazine with or without cholestyramine in the treatment of microscopic colitis: Randomized controlled trial Carlo Calabrese, Anna Fabbri, Alessandra Areni, Desiree Zahlane, Carlo Scialpi and Giulio Di Febo Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy Abstract Background: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflam- matory diseases of the colon with a benign and sometimes relapsing course. Frequency among patients with chronic diarrhea and normal looking colonoscopy is around 10–15%. To date, treatment of CC and LC is not well defined. Data about these conditions are mostly derived from retrospective studies. The aim of the present study was to evaluate the response to treatment and the clinical course of CC and LC in a large group of patients prospectively diagnosed. Methods and Results: A total of 819 patients underwent a colonoscopy because of chronic watery diarrhea and among them we found 41 patients with LC and 23 with CC. These patients were later randomized and assigned to treatment with mesalazine or mesalazine + cholestyramine for 6 months. Fifty-four patients (84.37%) had resolved diar- rhea in less than 2 weeks. After 6 months a colonoscopy with biopsies was repeated. Clinical and histological remission was achieved in 85.36% of patients with LC and in 91.3% with CC, with a better result in patients with CC treated with mesalazine + cholestyramine. During a mean period of 44.9 months, 13% of patients relapsed; four with LC and three with CC. They were retreated for another 6 months. At the end of this period one patient with CC was still symptomatic and persistence of CC was confirmed at histology. Conclusions: Treatment with mesalazine seems to be an effective therapeutic option for LC to date, while mesalazine + cholestyramine seems to be more useful in the treatment of CC. Introduction Microscopic colitis (MC) is a syndrome characterized by chronic watery diarrhea with normal radiological and endoscopic appear- ance and microscopic abnormalities of the colon. Incidence and prevalence of MC are not well defined. The annual incidence reported is 4.9/100 000 and 4.4/100 000 for CC and LC, respec- tively. Frequency among patients with chronic diarrhea and nor- mal looking colonoscopy is around 10–15%. 1,2 MC includes collagenous colitis (CC) and lymphocytic colitis (LC). 3,4 CC differs from LC by a specific histopathological feature consisting of the presence of a subepithelial collagen band (10 μm or more) adjacent to the basal membrane. Both diseases display inflammatory changes in lamina propria and superficial epithelial damage. They are considered benign chronic inflammatory dis- eases of the colon with a possible relapsing course. 5 The cause of MC is unknown. The identity of the inciting factors is uncertain although bile acids, toxins and infectious agents have been suggested. 6–8 In particular, intake of non- steroidal anti-inflammatory drugs (NSAIDs) or proton pump inhibitors (PPI) has been linked to MC as a possible cause. 6 The consequence of variable etiopathological factors seems to lead to an increased colonic permeability, allowing luminal anti- gens to enter the lamina propria and elicit an inflammatory response. 9,10 In this contest, a poorly regulated epithelial immune response to luminal or epithelial agents can be involved. 11 In fact, the prevalence of autoimmune disorders, such as arthritis, hyperthyroidism, diabetes mellitus, scleroderma and celiac disease, is increased in patients with MC. 12 Reports of accu- mulation in certain families suggest some degree of genetic susceptibility. 13 It has been suggested that a further mechanism in patients with LC is related to a decrease in active sodium absorption. In CC, a decreased Cl + /HCO 3 – exchange rate and increased electrogenic chloride secretion is suggested to be a coexistent pathway in the genesis of diarrhea. 14 The collagen deposition in CC is also unclear. In the normal colon, the epithelial basement membrane consists mainly of type IV collagen, whereas the collagen deposition in CC is of type VI. In addition, the subepithelial band contains significant amounts of the glycoprotein tenascin. 15 In both CC and LC the volume of diarrhea seems to be related to the intensity of lamina propria Key words cholestyramine, collagenous colitis, lymphocytic colitis, mesalazine, microscopic colitis. Accepted for publication 9 February 2006. Correspondence Carlo Calabrese, MD, PhD, Dipartimento di Medicina Interna e Gastroenterologia, Policlinico S. Orsola-Malpighi, Via Massarenti n. 9, 40138 Bologna, Italy. Email: calabrese.c@med.unibo.it