Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

mild to moderate disease

1st line – antidiarrheal

Back
ACUTE
|
mild to moderate disease
1st line – 

antidiarrheal

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 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]

Primary options

loperamide: 4 mg orally initially, followed by 2 mg after each loose stool, reduce dose according to response after symptom control is achieved, maximum 16 mg/day

Secondary options

diphenoxylate/atropine: 5 mg (diphenoxylate)/0.05 mg (atropine) orally four times daily initially, reduce dose according to response after symptom control is achieved, maximum 20 mg (diphenoxylate)/day

Plus – lifestyle modification

Back
ACUTE
|
mild to moderate disease
Plus – 

lifestyle modification

Treatment recommended for ALL patients in selected patient group

Manage all patients 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.

2nd line – bismuth subsalicylate

Back
ACUTE
|
mild to moderate disease
2nd line – 

bismuth subsalicylate

For patients with moderate symptoms (i.e., 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]

  • American Gastroenterology Association 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]

Primary options

bismuth subsalicylate: 524 mg orally every hour when required (or four times daily), maximum 4200 mg/day

Plus – lifestyle modification

Back
ACUTE
|
mild to moderate disease
Plus – 

lifestyle modification

Treatment recommended for ALL patients in selected patient group

Manage all patients 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.

3rd line – budesonide

Back
ACUTE
|
mild to moderate disease
3rd line – 

budesonide

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

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

Primary options

budesonide: 9 mg (extended-release) orally once daily in the morning for 8 weeks

Plus – lifestyle modification

Back
ACUTE
|
mild to moderate disease
Plus – 

lifestyle modification

Treatment recommended for ALL patients in selected patient group

Manage all patients 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.

4th line – cholestyramine ± loperamide

Back
ACUTE
|
mild to moderate disease
4th line – 

cholestyramine ± loperamide

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 American Gastroenterology Association guideline does not address the use of cholestyramine in combination with loperamide or in 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 cholestyramine, oral budesonide, antidiarrheals, and bismuth subsalicylate for other causes of diarrhea (e.g., celiac disease).[6]

Primary options

cholestyramine: 2-4 g orally two to four times daily, maximum 16 g/day

OR

cholestyramine: 2-4 g orally two to four times daily, maximum 16 g/day

and

loperamide: 4 mg orally initially, followed by 2 mg after each loose stool, reduce dose according to response after symptom control is achieved, maximum 16 mg/day

Plus – lifestyle modification

Back
ACUTE
|
mild to moderate disease
Plus – 

lifestyle modification

Treatment recommended for ALL patients in selected patient group

Manage all patients 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.

severe disease

1st line – budesonide or bismuth subsalicylate

Back
ACUTE
|
severe disease
1st line – 

budesonide or bismuth subsalicylate

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]

  • American Gastroenterology Association guidelines recommend bismuth subsalicylate, prednisone, or mesalamine in patients with symptomatic disease 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]

Primary options

budesonide: 9 mg (extended-release) orally once daily in the morning for 8 weeks

Secondary options

bismuth subsalicylate: 524 mg orally every hour when required (or four times daily), maximum 4200 mg/day

Plus – lifestyle modification

Back
ACUTE
|
severe disease
Plus – 

lifestyle modification

Treatment recommended for ALL patients in selected patient group

Manage all patients 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.

2nd line – immunosuppressant or biologic

Back
ACUTE
|
severe disease
2nd line – 

immunosuppressant or biologic

In patients with severe symptoms refractory to oral budesonide, consider immunosuppressants such as thiopurines (e.g., azathioprine), and 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 one 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.[74][75][76]

  • European guidelines recommend against using methotrexate.[6]

Use azathioprine with caution in patients with thiopurine methyltransferase and/or nucleotide diphosphatase (NUDT15) deficiency. There is a risk of serious infections and malignancy with azathioprine and biologic agents.

Primary options

azathioprine: 50 mg orally once daily initially, increase gradually according to response, maximum 2.5 mg/kg/day

OR

adalimumab: 160 mg subcutaneously as a single dose initially (or 80 mg once daily for 2 days), followed by 80 mg on day 15, then 40 mg every 2 weeks starting on day 29

OR

infliximab: 5 mg/kg intravenously at weeks 0, 2, and 6, followed by 5 mg/kg every 8 weeks

OR

vedolizumab: 300 mg intravenously at weeks 0, 2, and 6, followed by 300 mg every 8 weeks

Plus – lifestyle modification

Back
ACUTE
|
severe disease
Plus – 

lifestyle modification

Treatment recommended for ALL patients in selected patient group

Manage all patients 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.

3rd line – surgery

Back
ACUTE
|
severe disease
3rd line – 

surgery

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]

Plus – lifestyle modification

Back
ACUTE
|
severe disease
Plus – 

lifestyle modification

Treatment recommended for ALL patients in selected patient group

Manage all patients 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.

ONGOING

relapse after induction of remission

1st line – budesonide

Back
ONGOING
|
relapse after induction of remission
1st line – 

budesonide

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 budesonide for ophthalmologic disorders including glaucoma and cataracts.[7]

Primary options

budesonide: 9 mg (extended-release) orally once daily in the morning for 8 weeks initially, reduce dose according to response, usual maintenance dose 3-6 mg/day

More

Plus – lifestyle modification

Back
ONGOING
|
relapse after induction of remission
Plus – 

lifestyle modification

Treatment recommended for ALL patients in selected patient group

Continue managing patients 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.

2nd line – cholestyramine ± loperamide

Back
ONGOING
|
relapse after induction of remission
2nd line – 

cholestyramine ± loperamide

If the patient is intolerant to long-term oral budesonide or has mild symptoms despite long-term oral budesonide, consider cholestyramine alone or in combination with loperamide.[6][39]

Primary options

cholestyramine: 2-4 g orally two to four times daily, maximum 16 g/day

OR

cholestyramine: 2-4 g orally two to four times daily, maximum 16 g/day

and

loperamide: 4 mg orally initially, followed by 2 mg after each loose stool, reduce dose according to response after symptom control is achieved, maximum 16 mg/day

Plus – lifestyle modification

Back
ONGOING
|
relapse after induction of remission
Plus – 

lifestyle modification

Treatment recommended for ALL patients in selected patient group

Continue managing patients 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.

2nd line – immunosuppressant or biologic

Back
ONGOING
|
relapse after induction of remission
2nd line – 

immunosuppressant or biologic

If the patient is intolerant to long-term oral budesonide or has severe symptoms refractory to long-term oral budesonide, consider immunosuppressants such as thiopurines (e.g., azathioprine), and biologic agents such as tumor necrosis factor (TNF)-alpha inhibitors (e.g., adalimumab, infliximab), or vedolizumab (an integrin receptor antagonist monoclonal antibody).[6][69][70][71][72][73][74][75][76]

Use azathioprine with caution in patients with thiopurine methyltransferase and/or nucleotide diphosphatase (NUDT15) deficiency. There is a risk of serious infections and malignancy with azathioprine and biologic agents.

Primary options

azathioprine: 50 mg orally once daily initially, increase gradually according to response, maximum 2.5 mg/kg/day

OR

adalimumab: 160 mg subcutaneously as a single dose initially (or 80 mg once daily for 2 days), followed by 80 mg on day 15, then 40 mg every 2 weeks starting on day 29

OR

infliximab: 5 mg/kg intravenously at weeks 0, 2, and 6, followed by 5 mg/kg every 8 weeks

OR

vedolizumab: 300 mg intravenously at weeks 0, 2, and 6, followed by 300 mg every 8 weeks

Plus – lifestyle modification

Back
ONGOING
|
relapse after induction of remission
Plus – 

lifestyle modification

Treatment recommended for ALL patients in selected patient group

Continue managing patients 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.

3rd line – surgery

Back
ONGOING
|
relapse after induction of remission
3rd line – 

surgery

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

Plus – lifestyle modification

Back
ONGOING
|
relapse after induction of remission
Plus – 

lifestyle modification

Treatment recommended for ALL patients in selected patient group

Continue managing patients 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.

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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