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Microscopic Colitis: a Review for the Surgical Endoscopist

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Microscopic Colitis: a Review for the Surgical Endoscopist REVIEW • REVUE Microscopic colitis: a review for the surgical endoscopist Indraneel Datta, MD* Microscopic colitis (MC) is an inflammatory condition of the colon distinct from Savtaj S. Brar, MD* Crohn disease or ulcerative colitis that can cause chronic diarrhea as well as cramping and bloating. Although it was first described 30 years ago, awareness of this entity as a † Christopher N. Andrews, MD cause of diarrhea has only become more widespread recently. Up to 20% of adults Marc Dupre, MD‡ with chronic diarrhea who have an endoscopically normal colonoscopy may have MC. § Endoscopic and radiological examinations are usually normal, but histology reveals Chad G. Ball, MD increased lymphocytes in the colonic mucosa, which typically cause watery nonbloody W. Donald Buie, MD* diarrhea. Treatment is initially supportive but can include corticosteroids and Paul L. Beck MD, PhD† immunomodulatory therapy for resistant cases. Since surgeons perform a large num- ber of colonoscopies and sigmoidoscopies to assess diarrhea, it is important to be aware of this disease and to look for it with mucosal biopsy in appropriate patients. From the Divisions of *General Surgery and †Gastroenterology and the ‡Department of Pathology, University La colite microscopique (CM) est une inflammation du côlon différente de la maladie of Calgary, Calgary, Alta., and the de Crohn ou de la colite ulcéreuse, et qui peut causer une diarrhée chronique, des §Department of Surgery, Grady crampes et du ballonnement. Même si on l’a décrite pour la première fois il y a 30 ans, Memorial Hospital, Atlanta, Ga. la connaissance de cette entité comme cause de diarrhée ne s’est généralisée que récemment. Jusqu’à 20 % des adultes présentant une diarrhée chronique et dont la Accepted for publication coloscopie est normale sur le plan endoscopique peuvent être atteints de CM. L’endo- Jul. 21, 2008 scopie et la radiologie donnent habituellement des résultats normaux, mais l’histologie révèle une élévation des lymphocytes dans la muqueuse du côlon, ce qui cause typ- Correspondence to: iquement une diarrhée aqueuse non sanglante. Le traitement initial consiste à donner Dr. P.L. Beck du soutien, mais peut inclure l’administration de corticostéroïdes et d’immunomodu- Division of Gastroenterology, lateurs dans les cas résistants. Comme les chirurgiens pratiquent de nombreuses colo- University of Calgary scopies et sigmoïdoscopies pour évaluer la diarrhée, il importe d’être conscient de 3330 Hospital Dr NW, HSC 1725 cette maladie et de la rechercher par biopsie de la muqueuse chez les patients qui sem- Calgary AB blent présenter ce profil. T2N 4N1 [email protected] icroscopic colitis (MC) is a common and previously under- recognized cause of chronic diarrhea. In 1 study, MC was found in M 10% of all patients with nonbloody diarrhea referred for col on - oscopy and in almost 20% of those older than 70 years.1 Collagenous colitis (CC) and lymphocytic colitis (LC) are 2 morphologically distinct entities of MC. They are similar in presentation but differ histologically. The hallmark of diagnosis in MC is specific histological changes in the setting of colonic mucosa that appear to be endoscopically normal. Because these entities were only first described in the 1970s2,3 and because the main reports on incidence have only surfaced in the last few years, there is a concern that MC is not a commonly noted diagnosis. In addition, at least 1 study has shown that MC is diagnosed less commonly in smaller nonacademic centres.4 Consequently, the purpose of our review is to highlight the epidemiology, etiology, diagnosis and management of MC for the surgical endoscopist. EPIDEMIOLOGY The incidence of MC has been estimated to be 4.2–10.0 per 100 0001,5–8 (Table 1). Notably, 2 North American studies have incidence rates of 8.6 and 10.0 per 100 000, respectively, which may reflect a more accurate estimate for Canadian populations. The condition classically presents in adulthood, with © 2009 Canadian Medical Association Can J Surg, Vol. 52, No. 5, October 2009 E167 REVUE the peak age of onset being in the sixth to seventh decades more recent study showed that those with CC more com- of life.6,10,13 A female predominance has been described in monly consumed NSAIDs (46.2%v 23%, odds ratio [OR] several studies,6,10,14 and this appears to be stronger in CC 2.9, 95% confidence interval [CI] 1.3–6.4) and selective than LC. Rarely, MC can present in childhood.15–17 serotonin reuptake inhibitors (SSRIs; 18%v. 1%, OR 21, Studies from both Europe and North America have shown 95% CI 2.5–177), than controls, whereas those with LC an apparent increase in the incidence in MC over time.1,8 more commonly consumed SSRIs (28%v. 1%, OR 37.7, However, it is not clear whether this represents an escalating 95% CI 4.7–304), β-blockers (13 vs. 3%, OR 4.79, 95% CI awareness of the disease or intensified diagnostic efforts. 1.04–20), statins (13%vs 3%, OR 4.6, 95% CI 1.04–20) and biphosphonates (8%v. 0%).23 Other agents, including some ETIOLOGY proton pump inhibitors,24 ticlopidine14,25,26 and flutamide,14,26 have been linked with MC in case studies (Box 1). Although The mechanisms involved in the development of MC are there are a few reports of symptom improvement with ces- unknown. However, there seems to be an association with sation of NSAIDs,13,27,28 this has not been adequately studied bile acid malabsorption, infectious agents, nonsteroidal with the other agents mentioned. anti-inflammatory drugs (NSAIDs), other drugs, smoking Microscopic colitis is commonly seen in patients with and autoimmune conditions. It has been hypothesized that underlying autoimmune disease. Celiac disease, asthma, bile salts play a role in the development of MC. This was diabetes, thyroiditis and arthritis have all been associated based on some studies that suggested an increase in bile with MC.29–34 In 1 study, one-third of celiac disease patients malabsorption and that some patients report symptomatic have histological changes compatible with MC,35 and thus improvement with bile acid binding agents.18,19 Bile acid MC should be suspected in patients with celiac disease who malabsorption can occur following cholecystectomy,19,20 are not responding to a gluten-free diet. Those with and thus it has been hypothesized that it may be a risk fac- Hashimoto thyroiditis also have a marked increase risk of tor for MC. However, it is now evident that prior chole- MC, with one study reporting that 40% (20/50) of those cystectomy is not associated with MC. A recent case– with Hashimoto thyroiditis had histologic findings consis- control study compared 130 patients with MC and tent with LC.33 130 matched controls. The MC group had 12 patients with prior cholecystectomy compared with 17 in the con- NATURAL HISTORY trol group (p = 0.32).20 In the same study, there was no link found between previous appendectomies and MC.20 Fur- Microscopic colitis has a variable course. Symptoms of thermore, the degree of bile salt malabsorption does not diarrhea and abdominal pain may precede diagnosis appear to correlate well with the incidence of diarrhea for months. These symptoms are generally mild, and postcholecystectomy.21 most patients’ symptoms resolve spontaneously or with An infectious etiology has also been proposed for MC. medication. Historically, some patients report a preceding infectious Although controversial, there does not appear to be an enteropathy. Furthermore, some studies have reported a increased risk of progression to other inflammatory bowel substantial clinical response to antibiotics.13 No specific diseases or colorectal cancers in patients with MC.36,37 A infectious agent has been identified in patients with MC. small study of 24 patients showed no evidence of ulcerative Some studies have reported a significant association colitis or Crohn disease at a minimum follow-up of between the use of NSAIDs and MC. One such study 6years.37 Chan and colleagues38 identified 117 patients with showed 60% of patients with CC had substantial NSAID CC through the Johns Hopkins Registry and looked use compared with less than 15% of matched controls.22 A specifically at the possible risk of associated colorectal can- cer. No cases of colorectal cancer were identified, with follow-up ranging from 2 to 12 years.38 However, it is Table 1. Incidence rates of microscopic colitis reported in the literature Incidence per 100 000 Box 1. Drugs that have been associated with microsopic colitis Country Time period No. CC LC MC • Acarbose France9 1987–1992 22 0.6 — — • Acetylsalicylic acid (ASA) Sweden10 1984–1993 30 1.8 — — • Cirkan Sweden1 1993–1998 97 4.9 4.4 9.3 • Lansoprazole Spain6 1993–1997 60 1.1 3.1 4.2 • Nonsteroidal anti-inflammatory drugs 11 Iceland 1995–1999 125 5.2 4.0 9.2 (NSAIDs) 8 United States 1985–2001 130 3.1 5.5 8.6 • Ranitidine 12 Canada 2002–2004 164 4.6 5.4 10.0 • Sertraline CC = collagenous colitis; LC = lymphocytic colitis; MC = microscopic colitis. • Ticlopidine E168 J can chir, Vol. 52, No 5, octobre 2009 REVIEW difficult to draw definitive conclusions with these small lial collagen layer (Fig. 1).7 There is currently no consensus sample sizes, and larger population-based studies are war- on whether flexible sigmoidoscopy or colonoscopy is the ranted to further evaluate these questions. best first-line treatment.39 The benefits of flexible sigmoid - oscopy include time efficiency, cost savings, easier bowel DIAGNOSIS preparation and no sedation. Some studies state that biopsies of the left colon alone may be sufficient.40 Fine and col- Diagnosis of MC relies on a thorough history and ade- leagues40 reported on 809 patients evaluated for chronic diar- quate sampling of mucosa through colonic biopsy.
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