Microscopic Colitis (Collagenous and Lymphocytic Colitis) Workup

Updated: Mar 25, 2021
  • Author: Harika Balagoni, MD; Chief Editor: BS Anand, MD  more...
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Approach Considerations

A thorough history and physical examation with routine blood work including complete blood cell count, metabolic profile, thyroid profile, stool studies, and celiac serologies are indicated in patients with suspected microscopic colitis (MC). The presentation of irritable bowel syndrome-diarrhea predominant (IBS-D) is very similar to microscopic colitis. Multiple scoring systems have been proposed to noninvasively stratify such patients into one of these categories, but they are not yet validated. [33] Factors such as age over 50 years, female sex, weight loss, absence of abdominal pain, current smoking, nocturnal diarrhea, duration of diarrhea less than 6 months, and use of nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), and selective serotonin reuptake inhibitors (SSRIs) are all factored into these systems.

In the absence of a formally validated metric of disease activity, evaluate disease activity and clinical remission in microscopic colitis by the Hjortswang criteria (clinical remission: mean of < 3 stools per day and a mean < 1 watery stool per day during a 1-week registration). [10]

United European Gastroenterology (UEG) and the European Microscopic Colitis Group (EMCG) recommendations include the following [10] :

  • Ileocolonoscopy, with biopsies from at least the right and left colon

  • Not histologically monitoring patients with microscopic colitis

  • Fecal calprotectin is not useful for excluding or monitoring microscopic colitis

  • Screening for celiac disease in patients with microscopic colitis

  • Considering testing for bile acid diarrhea in those experiencing nonresponse to budesonide treatment


Laboratory Studies

Blood studies

Most of the blood test results in patients with microscopic colitis (MC) are usually within the reference range, but anemia, hypokalemia, hypoalbuminemia, elevation of the erythrocyte sedimentation rate, or a combination of these findings may be present.

Approximately 50% of patients with collagenous colitis (CC) and those with lymphocytic colitis (LC) may have circulating autoantibodies, especially rheumatoid factor (RF); antinuclear, antimitochondrial, antineutrophilic cytoplasmic antibodies (ANCA); and antiparietal cell, antithyroglobulin, and antimicrosomal antibodies. [34]

Stool studies

Increased levels of the stool inflammatory markers (eg, fecal calprotectin, leukocyte esterase) have been detected in stool from patients with collagenous colitis, whereas the levels of these markers in patients with irritable bowel syndrome (IBS) did not differ from healthy controls. [35]

On occasion, stool evaluation may show the presence of leukocytes and elevated fecal calprotectin. In these circumstances, the stool should be tested for enteric bacterial pathogens, ova and parasites, and C difficile.

It is also important to rule out bile acid malabsorption as well as steatorrhea. A prolonged (24-h to 72-h) stool collection occasionally may demonstrate steatorrhea in affected individuals. A finding of greater than 7 g of fecal fat excretion per 24 hours in an individual ingesting 100 g of fat per day is usually indicative of fat malabsorption, and, even if microscopic colitis is present, a diagnosis of concurrent sprue should be considered.

Other tests

Immunohistochemical studies of biopsies in lymphocytic colitis and collagenous colitis cases demonstrate abnormalities consistent with a mixed histocompatibility-restricted mechanism. [36]

The excessive intraepithelial lymphocytes observed in lymphocytic colitis are predominantly CD4+ T cells rather than CD8+.


Imaging Studies and Procedures

Imaging Studies

Findings on plain abdominal radiographs, barium enemas, and computed tomography (CT) scans are typically normal or nonspecific and show no evidence of colonic mucosal damage or wall abnormality in persons with microscopic colitis (MC).


Biopsies obtained by sigmoidoscopy or colonoscopy are necessary to diagnose lymphocytic colitis (LC) or collagenous colitis (CC). [3, 25, 37]  

If a colonoscopy is performed, multiple biopsies should be taken from different segments of the right and left side of the colon. Approximately 95% of patients with microscopic colitis will have diagnostic left colon biopsies [37] ; but, if these biopsies are nondiagnostic at sigmoidoscopy in a patient in whom clinical suspicion remains high, total colonoscopy for right-sided biopsies may confirm the diagnosis.

Although endoscopic findings are increasingly recognized in patients with microscopic colitis, they are nonspecific. [10] In individuals with lymphocytic or collagenous colitis, the mucosa appears normal endoscopically or occasionally mild mucosal edema may be seen. It does not show the more readily apparent changes of inflammatory bowel disease (IBD) such as friability, ulceration, and pseudopolyps. Most patients have similar degrees of histologic abnormality in the right and left sides of the colon.


Histologic Findings

Collagenous colitis (CC) demonstrates a thick colonic subepithelial collagenous deposit (≥10 μm) and an increased inflammatory infiltrate in the lamina propria, whereas lymphocytic colitis (LC) reveals a pronounced intraepithelial lymphocytic (IEL) inflammation (≥20 per 100 surface epithelial cells) and an increased inflammatory infiltrate in the lamina propria but in the absence of a thickened collagen band (< 10 μm). [10]

Incomplete microscopic colitis (MCi) comprises incomplete collagenous colitis (defined by a thickened subepithelial collagenous band >5 µm but < 10 µm) and incomplete lymphocytic colitis (defined by >10 IELs but < 20 IELs and a normal collagenous band). [10] Both types show a mild inflammatory infiltrate in the lamina propria. The criteria apply to hematoxylin and eosin (H&E)-stained slides.

In summary, histologic features of microscopic colitis include the following:

  • Surface epithelium shows a chronic inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils in the lamina propria.

  • Intraepithelial lymphocytosis, with more than 20 lymphocytes per 100 epithelial cells, is pathognomonic of the diagnosis of lymphocytic colitis (LC) (see the following image), although lesser numbers of IELs may be present in some patients with lymphocytic colitis.

    Microscopic Colitis (Collagenous and Lymphocytic C Microscopic Colitis (Collagenous and Lymphocytic Colitis). Lymphocytic colitis (LC) showing marked chronic inflammatory cell infiltrate of the surface epithelium (on right) with preservation of the crypt architecture. The subepithelial collagen layer is not thickened.
  • Epithelial cell damage is demonstrated by cell flattening, subepithelial blebs, and denuded epithelium. Fixed specimens may show epithelial loss and detachment.

  • Crypts may have minimal architectural distortion as in Crohn disease or ulcerative colitis. However, typically, evenly spaced parallel crypts of equal diameter are present.

  • Collagenous colitis shares the histologic features of lymphocytic colitis but additionally demonstrates a thickened subepithelial collagen layer (usually >10 µm) in the lamina propria, compared to a normal thickness of 5-7 µm.

  • For comparison, a representative biopsy of collagenous colitis is shown in the following image.

    Microscopic Colitis (Collagenous and Lymphocytic C Microscopic Colitis (Collagenous and Lymphocytic Colitis). Collagenous colitis (CC) showing similar inflammatory cell infiltration as in lymphocytic colitis (LC), with the characteristically thickened subepithelial collagen layer.
  • In some biopsy specimens, the surface epithelium may be denuded or partially detached from the collagen layer, even simulating pseudomembranes in rare cases. This either may be artifactual or may be due to a defect in adherence to the subepithelial membrane.