Practice Essentials
Pseudomembranous colitis is an acute inflammatory disease of the colon that in mild cases may appear as minimal inflammation or edema of the colonic mucosa. In more severe cases, the mucosa often is covered with loosely adherent nodular or diffuse exudates. These raised exudative plaques are 2-5 mm in size. Coalescence of these plaques generates an endoscopic appearance of yellowish pseudomembranes lining the colonic mucosa.
In the late 1800s, before the availability of antibiotics, Finney reported the first case of pseudomembranous colitis, calling it "diphtheritic colitis." [1] Hall and O'Toole first described Clostridium difficile in 1935. [2] (The organism is now known as Clostridioides difficile.) C difficile was first implicated as a causative factor in pseudomembranous colitis in the 1970s. Over the past 100 years, pseudomembranous colitis has changed from a fatal disease caused by a postoperative event to, in the era of antibiotics, a commonly occurring complication of antibiotic use that may lead to serious morbidity but that usually is treated easily. [3]
In mild or moderate cases, supportive therapy alone is sufficient. Such therapy includes the following:
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Discontinuing or changing the offending antibiotics
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Avoiding narcotics and antidiarrheal agents
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Maintaining fluid and electrolyte intake
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Employing enteric isolation
In fulminant or intractable cases, hospitalization for intravenous (IV) hydration will be necessary. Two thirds of patients with toxic megacolon require surgical intervention.
See Can't-Miss Gastrointestinal Diagnoses, a Critical Images slideshow, to help diagnose the potentially life-threatening conditions that present with gastrointestinal symptoms.
Pathophysiology
Pseudomembranous colitis is an inflammatory disease of the colon. In some cases (5-19%), the disease is localized to the cecum and the proximal colon.
The antibiotic-induced change in the balance of normal gut flora allows overgrowth of C difficile. [4] Colitis results from the bacterial production of large amount of toxins. The most important toxins are toxin A (enterotoxin) and toxin B (cytotoxin). One theory explains the variable severity of clinical disease through differential production rates of one toxin or the other by selected bacterial isolates. Most experts, however, believe that these variations are due to host factors.
The toxins bind to the mucosa, attack the membranes and the microfilaments of the mucosal cells, and subsequently result in cytoplasmic contraction, hemorrhage, inflammation, cellular necrosis, and protein loss. They also interfere with mucosal protein synthesis, stimulate granulocyte chemotaxis, and increase capillary permeability, intestinal myoelectric responses, and peristalsis. Intestinal tissue invasion by C difficile has been reported in fatal cases of pseudomembranous colitis in pediatric patients with hematologic malignancy.
Etiology
Pseudomembranous colitis usually is associated with antibiotic use, which may alter the balance of normal gut flora and allow overgrowth of certain organisms. [4] Clindamycin, lincomycin, ampicillin, and cephalosporin have been implicated in most of the reported cases, but any antimicrobial agent (including antifungal, antiviral, and metronidazole) could incite the disease, regardless of the amount administered or the route of administration.
C difficile, a gram-positive, spore-forming, anaerobic bacillus, is isolated in almost all of these cases. Rare cases have been related to Staphylococcus aureus, Salmonella species, Clostridium perfringens, Yersinia species, Shigella species, Campylobacter species, cytomegalovirus, Entamoeba histolytica, and Listeria species.
Conditions other than antimicrobial administration could predispose to C difficile pseudomembranous colitis. Such conditions include bowel ischemia, recent bowel surgery, uremia, dietary change, change in bowel motility, malnutrition, chemotherapy, shock, and Hirschsprung disease.
Epidemiology
The incidence of antibiotic-associated diarrhea ranges from 5% to 39%, depending on the antibiotic type. Pseudomembranous colitis complicates 10% of cases of antibiotic-associated diarrhea. C difficile is found in the stool of 15-25% of asymptomatic, antibiotic-treated, hospitalized adults. Similar numbers were found in debilitated patients and in patients who received one dose of prophylactic antibiotics before surgical procedure.
C difficile is an unusual component of healthy bowel flora. It is found in 3-5% of healthy adults; however, as many as 50% of infants and children harbor the bacteria and its toxins. Pseudomembranous colitis is a surprisingly rare disease in infants and young children—a population recognized as frequent asymptomatic colonizers. The low incidence of colitis in the pediatric population is attributed to the strength of the immune system. Antibodies to C difficile frequently are detected in infected young patients.
About 25% of human C difficile isolates are nontoxigenic. C difficile colitis is the fourth most common nosocomial disease reported to the Centers for Disease Control and Prevention. C difficile is one of the most frequently isolated enteric pathogens, second only to Campylobacter jejuni. [5]
High-risk populations [6] include elderly people, patients in the intensive care unit (ICU), people with uremia, people with burns, people undergoing abdominal surgery, women undergoing cesarean delivery, and patients with cancer. One suggestion is that these patients do not have greater susceptibility to the disease but are at heightened risk of nosocomial infection. C difficile can be transmitted nosocomially, via the hands of personnel or by contaminated objects. It can survive in spore form for as long as 5 months on hospital floors.
Prognosis
The overall mortality for pseudomembranous colitis is 2%. The mortality in untreated elderly or debilitated patients is 10-20%. Even with surgical intervention, mortality and morbidity in patients with toxic megacolon remain high (35% and 66%, respectively). [7]
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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).
