Collagenous and Lymphocytic Colitis Workup

Updated: Jan 04, 2017
  • Author: Joyann A Kroser, MD, FACP, FACG, AGAF; Chief Editor: BS Anand, MD  more...
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Laboratory Studies

Blood studies

Results usually are within the reference range, but anemia, hypokalemia, hypoalbuminemia, elevation of the erythrocyte sedimentation rate, or a combination of these findings may be present.

Human leukocyte antigen (HLA)-A1 is more frequent in patients with lymphocytic colitis (LC) (67%) than in controls (28%) or in patients with collagenous colitis (CC) (26%). HLA-B3 has not been reported in patients with LC. A frequency of 26% is expected in controls and also is observed in patients with CC.

The HLA patterns observed in other gastrointestinal conditions, such as Crohn disease, have not been found in LC.

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

Stool studies

Increased levels of the stool inflammatory markers (eg, eosinophil protein X [EPX], myeloperoxidase [MPO], tryptase] have been detected in stool from patients with CC, whereas the levels of these markers in patients with irritable bowel syndrome did not differ from healthy controls. [12]

Some affected patients have a diminished ability to absorb water resulting from reduced colonic absorption of sodium and chloride. Chloride/bicarbonate exchange across the colonic mucosa also may be reduced.

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

A prolonged (24- 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 usually is 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 LC and CC cases demonstrate abnormalities consistent with a mixed histocompatibility-restricted mechanism. [13]

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


Imaging Studies and Procedures

Imaging Studies

Findings on plain abdominal radiograph, barium enemas, and computed tomography (CT) scans typically are normal or nonspecific and show no evidence of colonic mucosal damage or wall abnormality.


Biopsies obtained by sigmoidoscopy or colonoscopy are necessary to diagnose LC or CC. [1, 5]

If a colonoscopy is performed, biopsies should be taken from the rectosigmoid and possibly also from the right side of the colon. Approximately 95% of patients with microscopic colitis will have diagnostic left colon biopsies; 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.

In individuals with LC or CC, 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 such as friability, ulceration, and pseudopolyps. Most patients have similar degrees of histologic abnormality in the right and left sides of the colon.

CC demonstrates a thick colonic subepithelial collagenous deposit, whereas LC reveals a pronounced intraepithelial lymphocytic inflammation in the absence of a thickened collagen band. [1]


Histologic Findings

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

    Lymphocytic colitis (LC) showing marked chronic in Lymphocytic colitis (LC) showing marked chronic inflammatory cell infiltrate of the surface epithelium (on right) with preservation of crypt architecture. 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.

  • CC shares the histologic features of LC 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 CC is shown in the following image.

    Collagenous colitis (CC) showing similar inflammat 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.