Overview

Microscopic colitis is a chronic inflammatory disease of the colon that is characterized by chronic, watery, non-bloody diarrhea. It typically occurs in middle-aged patients and has a female preponderance. The colon appears typically normal or almost normal on colonoscopy in patients with microscopic colitis. The diagnosis is established by biopsy of the colonic mucosa demonstrating characteristic histologic changes. Microscopic colitis, first described in 1980, has two main histologic subtypes [1]

lymphocytic colitis, more specifically defined in 1989
collagenous colitis

Risk factors

Medications

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been implicated as being causative or triggering flares of microscopic colitis. Several other drugs have also been implicated as potential causes of microscopic colitis, including proton pump inhibitors (PPIs), specifically lansoprazole, statins, selective serotonin reuptake inhibitors and other drugs, (eg, pembrolizumab). Concomitant use of PPIs and NSAIDs may increase the risk even further. However, convincing pathophysiologic evidence is still lacking, and most of the drugs that have been associated with microscopic colitis are also known to be associated with the development of chronic diarrhea as a side effect. [1]

Microscopic colitis can be idiopathic, but medications, including NSAIDs, proton pump inhibitors, and selective serotonin reuptake inhibitors, have been associated with its development. Management of microscopic colitis starts with discontinuation of potentially causative medications, [2]

Smoking

Smoking may play a role in the development of microscopic colitis and the clinical outcome. In a case-control study that included 340 patients with microscopic colitis, cigarette smoking (past or present) was associated with a significantly increased risk of microscopic colitis (odds ratio 2.1, 95% CI 1.6-2.9). On average, smokers also develop microscopic colitis more than 10 years earlier than non-smokers. [1]

Tests

Treatment

Active disease is defined ≥3 stools daily or ≥1 watery stool daily

Antidiarrheals

Loperamide HS and prn.

Glucocorticoids

Budesonide

In patients with active disease (≥3 stools daily or ≥1 watery stool daily) or diarrhea that persists despite the use of antidiarrheals, add oral budesonide (9 mg daily for six to eight weeks). Budesonide is a locally active corticosteroid with extensive first-pass metabolism in the liver and low systemic exposure. Symptomatic improvement can be seen within a few days. However, complete resolution usually requires six to eight weeks or longer. We continue budesonide for at least eight weeks and then gradually taper budesonide in patients in clinical remission (<3 stools daily and no watery stools). We taper oral budesonide to 6 mg for two weeks, followed by 3 mg for another two weeks, and then discontinue therapy. In patients who are not in clinical remission at eight weeks, or if symptoms recur on tapering, the budesonide dose of 9 mg can be continued for 12 weeks or longer before tapering the dose. Randomized trials in patients with collagenous colitis suggest that budesonide is effective for short-term treatment of microscopic colitis and can improve quality of life. A meta-analysis of eight randomized trials that included 248 patients randomized to glucocorticoids versus placebo found that short-term clinical response rates were significantly higher with budesonide, as compared with placebo (risk ratio 3.1, 95% CI 2.1-4.6). Budesonide has also demonstrated efficacy in inducing clinical and histologic remission in patients with lymphocytic colitis. In a meta-analysis of two randomized trials (only one of which was published) that included 57 patients with lymphocytic colitis assigned to budesonide or placebo, treatment with budesonide resulted in an improvement in diarrhea and microscopic inflammation as compared with placebo (88 versus 38 percent, and 78 versus 33 percent, respectively). In a subsequent randomized trial, 57 patients with active lymphocytic colitis were assigned to budesonide (9 mg daily), mesalazine (3 g daily), or placebo for eight weeks. Clinical and histologic remission rates at week 8 were higher in patients treated with budesonide as compared with placebo (79 versus 42 percent and 68 versus 21 percent, respectively). However, there was no statistically significant difference in clinical remission rates between the mesalamine and placebo groups (63 versus 42 percent). Rates of drug-related adverse events were not significantly different between the three groups. Of the 27 patients in clinical remission at the end of the eight weeks, seven (26 percent) had a relapse in the 16-week treatment free follow-up. Of note, the study excluded patients with suspected drug-induced lymphocytic colitis and those with mild symptoms. The placebo group had a higher proportion of smokers and a longer duration of symptoms as compared with the treatment groups, both of which may be a source of potential bias, however, these results are consistent with prior studies.[1]

Prednisone

Reserve the use of prednisone or prednisolone for the treatment of microscopic colitis in patients in whom budesonide therapy is not feasible. While indirect evidence suggests that prednisone should induce clinical remission, its efficacy has not been demonstrated. In addition, systemic glucocorticoids have a higher risk of adverse events. In a randomized clinical trial in which 12 patients with microscopic colitis were assigned to prednisone or placebo for two weeks, there was no difference in the clinical remission rates. Prednisone lead to a reduction in colonic inflammation, but not in the thickness of the collagen band. As compared with budesonide, prednisone is associated with a lower response rate (53 versus 83 percent), more side effects, and a higher risk of relapse when therapy is withdrawn. [1]

Microscopic colitis