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 is seldom necessary.
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 lymphocytic colitis (LC) and collagenous colitis (CC).
Farrukh and Mayberry synthesized the work on the definition of microscopic colitis and the relationship between LC and CC, evaluated the international epidemiology and research on the etiology, and performed a systematic assessment of the available treatment options.  Among their findings: LC and CC have common clinical symptoms but are well defined histopathologically; these conditions are predominantly idiopathic and typically have a benign clinical course, although serious complications and death may occur. They noted a peak incidence at age 60 to 70 years and a female preponderance. There may be a relationship with autoimmune disorders and exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and proton-pump inhibitors (PPIs). Unfortunately, treatment is primarily based upon anecdotal evidence and findings from limited budesonide clinical trials; there are no well-established long-term follow-up of these patients.  Other reviewers have noted similar features of microscopic colitis. [15, 16]
A trial of dietary restriction and avoidance of potentially aggravating drugs (particularly NSAIDs) 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's condition is still not responding or if a patient has a more clinically 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.
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.
Miehlke et al evaluated the treatment of lymphocytic colitis with oral budesonide and found that 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. 
Miehlke et al also performed a phase 3, placebo-controlled, multicenter study to evaluate budesonide and mesalamine as short-term treatments for CC and noted that at week 8, a greater percentage of patients in the budesonide group were in clinical remission than in the placebo group: using the Hjortswang-Criteria, 80% of patients on budesonide and 44% of those on mesalamine achieved clinical remission compared with 37.8% of those given placebo. Budesonide was superior to mesalamine (P = .0035) and significantly improved stool consistency and mucosal histology, as well as relieved abdominal pain. The investigators concluded that short-term treatment of CC with oral budesonide (9 mg once daily) is safe and effective, whereas this was not true of short-term treatment with oral mesalamine (3 g once daily). 
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.
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