Approach

The main goals of treatment are to achieve clinical remission (i.e., <3 stools per day and a mean of <1 watery stool per day) and improve the patient's quality of life.[58]

Histologic remission does not need to be confirmed with repeat colonoscopy if the patient is in clinical remission.[1]

Where evidence for the medical treatment of microscopic colitis is lacking, recommendations are based on consensus expert opinion and/or the experience of the authors of this topic.

Lifestyle modification

Manage all patients with confirmed microscopic colitis with modification of factors contributing to symptoms including:[3]

  • Dietary modifications. For example, start patients with concomitant celiac disease on a gluten-free diet, and advise patients with lactose intolerance to eliminate lactose products or products with artificial sweeteners to minimize osmotic diarrhea. See Celiac disease and Lactase deficiency.

  • Avoiding/withdrawing nonsteroidal anti-inflammatory drugs (which are more strongly associated with microscopic colitis) and considering avoiding/withdrawing drugs such as proton-pump inhibitors, selective serotonin-reuptake inhibitors, statins, and H2 antagonists (which are less strongly associated with microscopic colitis), if feasible. The discontinuation of medication depends on medication indication, severity of underlying disease, and temporal association between medication start and onset of diarrhea.

  • Encouraging smokers to stop smoking.

Mild to moderate symptoms

Treatment should be guided by the severity of symptoms.[7]

For patients with mild symptoms (i.e., <3 stools per day), give antidiarrheal medications (e.g., loperamide, diphenoxylate/atropine).[7] Loperamide may be sufficient to control diarrhea.[7] If the patient has nocturnal symptoms, give loperamide at night to decrease their frequency.[59]

  • This recommendation is based on the experience of the topic authors. Regarding loperamide, its use in patients with mild symptoms is supported by the unanimous consensus opinion of the United European Gastroenterology Group and the European Microscopic Colitis Group, based on evidence for the effect of loperamide in patients with chronic diarrhea.[1][6]

  • The American Gastroenterology Association (AGA) does not address the use of antidiarrheals in its guideline on the medical management of microscopic colitis due to lack of evidence from clinical trials. Instead it recommends oral budesonide as first-line treatment for all patients with symptomatic microscopic colitis regardless of severity.[3]

For patients with moderate symptoms (ie., refractory to antidiarrheals), give bismuth subsalicylate (a colloidal bismuth salt with antidiarrheal and direct mucosal protective effects) for 6 to 8 weeks.[7][60][61] Long-term use of bismuth subsalicylate is not recommended due to the risk of neurotoxicity.[62]

  • In one open-label study, an 8-week treatment course of bismuth subsalicylate was associated with improvement in symptoms in 11 of 12 patients who completed the trial. Colitis resolved in 9 patients.[60] A subsequent preliminary trial of 14 patients randomly assigned to bismuth subsalicylate or placebo for 8 weeks showed similar results, with 11 of the 12 patients who completed the trial experiencing resolution of diarrhea and reduction in fecal weight.[61]

  • AGA guidelines recommend bismuth subsalicylate in patients with symptomatic microscopic colitis not responding to oral budesonide (which is recommended first line instead of antidiarrheals).[3]

  • European guidelines state that there is not enough evidence to recommend bismuth subsalicylate in patients with microscopic colitis.[6]

Give an 8-week course of oral budesonide if the patient does not respond to bismuth subsalicylate.[1][3][7]

Severe symptoms

In patients with severe symptoms (i.e., ≥3 watery stools per day), give an 8-week course of oral budesonide first line for induction of clinical remission.[1][3][6] In patients with contraindications to budesonide, give bismuth subsalicylate for 6 to 8 weeks.[3][61]

  • Budesonide is preferred over other oral corticosteroids such as prednisone given its high first-pass metabolism in the liver, with fewer systemic adverse effects.[63][64] After 8 weeks, budesonide can be discontinued or tapered, as both strategies appear effective.

  • Evidence suggests that budesonide may be an effective treatment for active collagenous colitis and lymphocytic colitis; however, the quality of the evidence is low.[65][66]

  • AGA guidelines recommend bismuth subsalicylate, prednisone, or mesalamine in patients with symptomatic disease and with contraindications to oral budesonide.[3] However, European guidelines recommended against the use of mesalamine, prednisone, or other corticosteroids except budesonide due to the limited evidence of their efficacy in inducing remission in patients with microscopic colitis.[6] The authors of this topic agree with the European guideline recommendation. Compared with budesonide, prednisone is associated with lower response rate (53% vs. 83%), more adverse effects, and higher risk of relapse when therapy is withdrawn.[63][64] Aminosalicylates including mesalamine appear to be ineffective in the treatment of collagenous colitis and lymphocytic colitis.[16][67]

In the absence of a formally validated criteria to measure disease activity, European guidelines recommend using the Hjortswang criteria, which define clinical remission as a mean of <3 stools/day and a mean <1 water stool/day during a 1‐week registration.[6]

Symptoms refractory to budesonide

Consider cholestyramine alone or in combination with loperamide for patients with mild, persistent diarrhea despite treatment with oral budesonide.[6] If there is an improvement in diarrhea, cholestyramine is typically continued until resolution of diarrhea.

  • Symptoms of microscopic colitis and bile acid diarrhea are indistinguishable.[6] Cholestyramine is a bile acid sequestrant used to treat diarrhea that is due to concurrent bile acid malabsorption, which is more common in patients with collagenous colitis.[39]

  • European guidelines recommend considering testing patients with mild symptoms who do not respond to oral budesonide for bile acid diarrhea using radiolabeled selenium homotaurocholic acid taurine (SeHCAT) testing.[6]

  • The AGA guideline does not address the use of cholestyramine in combination with loperamide or as monotherapy.[3] It recommends against combination therapy with cholestyramine and mesalamine over mesalamine alone for the induction of clinical remission.[3]

Re-evaluate any patient with inadequate response to oral budesonide, cholestyramine, antidiarrheals, and bismuth subsalicylate for other causes of diarrhea (e.g., celiac disease).[6]

In patients with severe symptoms refractory to oral budesonide, consider immunosuppressive agents such as thiopurines (e.g., azathioprine) or biologic agents such as tumor necrosis factor (TNF)-alpha inhibitors (e.g., adalimumab, infliximab), or vedolizumab (an integrin receptor antagonist monoclonal antibody).[1][3][6][68][69]

  • Limited evidence from small case series, retrospective studies, and a systematic review and meta-analysis suggest that TNF-alpha inhibitors and immunosuppressants induce remission in patients with refractory microscopic colitis.[69][70][71][72][73]

  • Vedolizumab has been shown to induce remission in selected patients with severe symptoms refractory to budesonide.[73][74][75][76]

  • European guidelines recommend against using methotrexate.[6]

No response to medical therapy may occur, but this is rare. Surgery including ileostomy with or without colectomy may be considered in selected patients following multiple re-treatment attempts.[1][6][77]

  • In one study, 1 out of 189 patients with lymphocytic colitis required surgery after all medical options had failed.[52]

Relapse after induction of remission

Despite high rates of response to an 8-week course of oral budesonide, relapse after discontinuation occurs in 60% to 80% of patients with variable time to relapse.[63][78] Risk factors for relapse after the discontinuation of budesonide include older age, longer duration of symptoms, and high stool frequency on presentation.[7]

Restart oral budesonide for maintenance of remission in patients who achieve clinical remission on budesonide but relapse after discontinuation. Prescribe the lowest effective dose that maintains resolution of symptoms. Consider stopping maintenance therapy after 6 to 12 months.[3][6]

  • General warnings and cautions concerning corticosteroids should be followed. Monitor patients with osteoporosis, diabetes, hypertension, peptic ulcer, or with any other condition where long-term corticosteroids may have unwanted effects.

  • Monitor patients on long-term oral budesonide for ophthalmologic disorders including glaucoma and cataracts.[7]

If the patient is intolerant to long-term oral budesonide or has chronic active disease refractory to long-term oral budesonide, consider:[6]

  • Cholestyramine alone or in combination with loperamide in patients with mild symptoms[39]

  • Azathioprine, adalimumab, infliximab, or vedolizumab in patients with severe symptoms.[69][70][71][72][73][74][75][76]

Surgery, including ileostomy with or without colectomy, may be considered in selected patients who relapse and do not respond to medical therapy, although this is rare.[1][6][77]

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