Laboratory Studies
Laboratory studies to be considered include the following:
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Complete blood count (CBC) - This will reveal leukocytosis, with the white blood cell (WBC) count in the range of 10,000-50,000/μL
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Blood chemistry - Hypoalbuminemia is common
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Fecal leukocytes - Positive tests for fecal leukocytes (3-5 leukocytes per high-power field [HPF]) excludes benign diarrhea; however, a negative result does not exclude colitis
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Stool culture - Culture of C difficile is relatively demanding, with low predictive value because of the large number of asymptomatic carriers; many laboratories do not perform this test
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Stool assay for C difficile toxins (mostly toxin B) - This test requires 2 days and is considered positive when cultured cells undergo cytopathic changes when exposed to stool, with the result then confirmed by neutralizing these toxins with specific antitoxins; although this is the criterion standard test (sensitivity is 95% in patients with antibiotic-induced diarrhea and increases with the severity of the colitis), results are negative in 5-10% of patients with endoscopic evidence of pseudomembranous colitis
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Enzyme-linked immunoabsorbent assay (ELISA) for toxin A - This test is less expensive than stool assay for C difficile toxins and is completed in 2.5 hours; however, sensitivity (75-85%) is lower
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Latex agglutination test - This test has poor sensitivity and specificity
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Polymerase chain reaction (PCR) - The PCR test is expensive but fast and highly sensitive and specific; it is currently used only as a research tool in laboratories for detecting C difficile toxin genes A and B in fecal specimens [10]
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Glutamate dehydrogenase - This enzyme (also referred to as the common antigen [10] ) is expressed at high levels by all strains of C difficile; ELISA screening tests are highly sensitive, simple, and cost-effective for detecting it; although none of these screening tests specifically identify toxigenic strains, since the enzyme is produced by toxigenic and nontoxigenic strains, they have negative predictive values of roughly 99%, which supports their value for ruling specimens negative for C difficile [10]
Imaging Studies
Plain abdominal radiography may show mucosal edema and abnormal haustral pattern (see the image below). Ileus pattern was described in 28% of the patients. It is useful for ruling out toxic megacolon or perforation.
Frontal abdominal radiograph in a patient with proved pseudomembranous colitis. Note the nodular haustral thickening, most pronounced in the transverse colon.
Air contrast barium enema study can outline the mucosal abnormalities further; however, these are late and nonspecific findings. This procedure is not recommended, because it carries the risk of perforation and may precipitate toxic megacolon.
Computed tomography (CT) may show distention and diffuse and focal thickening of the wall of the colon, along with pericolonic inflammation.
Indium-labeled leukocyte scans will show nonspecific inflammation of the colonic mucosa.
Other Tests
Pseudomembranous colitis is uncommon in infants and young children. They commonly harbor C difficile and its toxins in their stool, which makes it difficult to diagnose the disease in this age group. A therapeutic trial with vancomycin may be the only way to confirm the clinical significance of the positive toxins in the stool.
Rigid proctosigmoidoscopy is diagnostic in 77% of patients. Endoscopic visualization of the pseudomembranes characteristic of the disease (see the images below) is the most rapid and definitive diagnostic method. When the pseudomembranes are manipulated, ulcerated mucosa is uncovered. In early stages of the disease, lesions may be confused with Crohn disease, Behçet disease, and viral colitis.
Colonic pseudomembranes of pseudomembranous colitis. Photographs courtesy of Eric M. Osgard, MD.
Endoscopic visualization of pseudomembranous colitis, a characteristic manifestation of full-blown Clostridium difficile colitis. Classic pseudomembranes are visible as raised yellow plaques, which range from 2-10 mm in diameter and are scattered over the colorectal mucosa. Courtesy of Gregory Ginsberg, MD, University of Pennsylvania.
Flexible sigmoidoscopy is diagnostic in 91% of the patients.
Colonoscopy may be required in 10% of the cases where the disease is localized to the cecum or transverse colon with rectal sparing. It is a hazardous procedure in patients with toxic megacolon.
Histologic Findings
Gross pathologic analysis reveals raised exudative plaques 2-5 mm in size, the coalescence of which gives rise to yellowish pseudomembranes lining the colonic mucosa (see the images below).
Gross pathology specimen from a case of pseudomembranous colitis revealing characteristic yellowish plaques.
Gross pathology specimen from a case of pseudomembranous colitis, again demonstrating characteristic yellowish plaques.
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Colonic pseudomembranes of pseudomembranous colitis. Photographs courtesy of Eric M. Osgard, MD.
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Endoscopic visualization of pseudomembranous colitis, a characteristic manifestation of full-blown Clostridium difficile colitis. Classic pseudomembranes are visible as raised yellow plaques, which range from 2-10 mm in diameter and are scattered over the colorectal mucosa. Courtesy of Gregory Ginsberg, MD, University of Pennsylvania.
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Gross pathology specimen from a case of pseudomembranous colitis revealing characteristic yellowish plaques.
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Gross pathology specimen from a case of pseudomembranous colitis, again demonstrating characteristic yellowish plaques.
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Frontal abdominal radiograph in a patient with proved pseudomembranous colitis. Note the nodular haustral thickening, most pronounced in the transverse colon.
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Barium enema demonstrating typical serrated appearance of the barium column (resulting from trapped barium between the edematous mucosal folds and the plaquelike membranes of pseudomembranous colitis).
