Approach

Although microscopic colitis is not associated with increased mortality, symptoms can lead to a significantly impaired quality of life.[2][3] Most investigations are done to first rule out other causes of chronic diarrhea such as inflammatory bowel disease, celiac disease, or irritable bowel syndrome. See Differentials. Unlike Crohn disease and ulcerative colitis, the colonic mucosa in patients with microscopic colitis has a normal or near-normal appearance on colonoscopy.[9] However, biopsy of colonic mucosa demonstrates characteristic histopathologic features of collagenous colitis or lymphocytic colitis, which confirms the diagnosis.[8]

Clinical presentation

Suspect microscopic colitis in a patient presenting with chronic, nonbloody, watery diarrhea, particularly if they are ages >50 years and female.[2][6]​ These symptoms were reported by 85% to 100% of patients with microscopic colitis in 22 studies.[6] Patients usually report between 5 and 10 watery stools per day, but some may have 15 or more bowel movements per day.[12] Other symptoms may include any of fecal urgency, fecal incontinence, nocturnal stools, abdominal pain, weight loss, bloating, and fatigue.[6]

The clinical course is variable, with chronic or recurrent mild to severe symptoms persisting for months to years.[6]

History

Take a thorough history. Ask about:

  • Number of stools per day and whether the patient is experiencing night episodes.

  • Duration of symptoms.

  • Recent travel to endemic areas, to exclude gastrointestinal infection. Although infective pathogens typically cause acute or subacute diarrhea, some patients may present with chronic diarrhea.

  • Recent antibiotic exposure, as diarrhea can be an adverse effect of antibiotics.

  • Family history of autoimmune diseases, such as celiac disease, hypothyroidism, rheumatoid arthritis, hyperthyroidism, or Crohn disease. People with these disorders are at higher risk of developing microscopic colitis.[9][21]

  • Presence of bloody diarrhea, which may indicate a differential diagnosis such as food poisoning.

  • Relationship of abdominal pain and bowel movements. Some patients with microscopic colitis present with mild pain that is relieved after a bowel movement.

Ask about risk factors for microscopic colitis including cigarette smoking, presence of concomitant autoimmune diseases such as celiac disease, rheumatoid arthritis, and thyroid disorders, and use of certain medications (i.e., nonsteroidal anti-inflammatory drugs [NSAIDs], proton-pump inhibitors [PPIs], selective serotonin-reuptake inhibitors [SSRIs], statins, and H2 antagonists).[9][21][24][25][26][27][44][45] Note that the risk of developing microscopic colitis is higher in women than men.[10]

Physical exam

Physical exam is usually nonspecific and unlikely to further aid in refining the differential diagnosis in most patients.

Initial investigations

Order the following investigations in all patients to rule out other causes of chronic diarrhea:[6][7]

  • Serologic tests for celiac disease (i.e., immunoglobulin A-tissue transglutaminase [IgA-tTG] titer), a basic metabolic panel to assess dehydration in patients with severe disease, and complete blood count with inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) to rule out celiac disease and inflammatory bowel disease, respectively. Some patients with microscopic colitis may present with mild anemia.

  • Stool studies for Clostridium difficile toxin, routine stool cultures for Salmonella, Shigella, Campylobacter, and Yersinia; and specific testing for Escherichia coli O157:H7 to rule out gastrointestinal infection.

  • Stool microscopy for ova and parasites, and giardia stool antigen to rule out parasitic infections, particularly if the patient has recently traveled to an endemic area.

Ileocolonoscopy

Order an ileocolonoscopy with biopsies from at least the right and left colon if the initial investigations are negative.[6][48] Diagnosis is confirmed by the presence of characteristic pathohistologic findings.[5][6]

  • On endoscopic exam, findings are nonspecific. The colon typically appears completely normal, although mild erythema and edema may be seen.[6]

  • On histologic exam, distinct abnormalities are found that identify two major histologic subtypes:[6]

    • Collagenous colitis: characterized by a thickened subepithelial collagenous band ≥10 micrometers (normal <5 micrometers) combined with an increased inflammatory infiltrate in the lamina propria.

      [Figure caption and citation for the preceding image starts]: Biopsy demonstrating collagenous colitis with a thickened subepithelial collagen bandTome J et al. Microscopic Colitis: A Concise Review for Clinicians. Mayo Clin Proc. 2021 May;96(5):1302-8; used with permission [Citation ends].com.bmj.content.model.Caption@5f881f12

    • Lymphocytic colitis: characterized by an increased number of intraepithelial lymphocytes ≥20 per 100 surface epithelial cells (normal <5 micrometers) combined with an increased inflammatory infiltrate in the lamina propria and a not significantly thickened collagenous band (<10 micrometers).

      [Figure caption and citation for the preceding image starts]: Biopsy demonstrating lymphocytic colitis with intraepithelial lymphocytosis.Tome J et al. Microscopic Colitis: A Concise Review for Clinicians. Mayo Clin Proc. 2021 May;96(5):1302-8; used with permission [Citation ends].com.bmj.content.model.Caption@235556c7

    • There is a further subset of patients who do not meet the above histologic criteria. These patients may be diagnosed as microscopic colitis incomplete or microscopic colitis not otherwise specified. Microscopic colitis incomplete comprises incomplete collagenous colitis (defined by a thickened subepithelial collagenous band >5 micrometers but <10 micrometers) and incomplete lymphocytic colitis (defined by >10 but <20 intraepithelial lymphocytes per 100 epithelial cells and a normal collagenous band). Both types show a mild inflammatory infiltrate in the lamina propria.[6]

Other investigations

Flexible sigmoidoscopy

In patients who have recently undergone a colonoscopy for cancer screening, order flexible sigmoidoscopy for evaluation of microscopic colitis. This is a reasonable next test provided biopsies are obtained above the rectosigmoid colon.[1] Since most patients will have changes detectable in the distal colon, the diagnosis can be made from biopsies taken at flexible sigmoidoscopy.[5]

Fecal calprotectin

Fecal calprotectin testing is not recommended by guidelines to exclude or monitor microscopic colitis.[1]

  • Despite a few studies suggesting slightly elevated levels of fecal calprotectin in patients with microscopic colitis compared with patients without an organic cause of diarrhea and irritable bowel syndrome, its role in clinical practice is uncertain.[49][50]

  • Some centers may, however, include this test in the diagnostic workup as an elevated result indicates inflammation.

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