You are in: eMedicine Specialties > Radiology > GASTROINTESTINAL Colitis, PseudomembranousArticle Last Updated: Sep 19, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 8
  Author: Vinay K Gheyi, MD, MBBS, Chief of Radiology, Department of Radiology, McGuire VA Medical Center, Richmond, Virginia Coauthor(s): John S Wills, MD, Associate Professor of Radiology, Thomas Jefferson University; Chair, Department of Radiology, Pennsylvania Hospital; Raul N Uppot, MD, Instructor in Radiology, Harvard Medical School;, Assistant Radiologist, Department of Radiology, Section of Abdominal Imaging and Interventional Radiology, Massachusetts General Hospital Editors: John L Haddad, MD, Clinical Associate Professor, Department of Radiology, Weill Medical College of Cornell University; Director of Body MRI, Department of Radiology, Methodist Hospital in Houston; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Spencer B Gay, MD, Professor of Radiology, Director of Body Computed Tomography, Department of Radiology, University of Virginia Health Sciences Center; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Eugene C Lin, MD, Consulting Staff, Department of Radiology, Virginia Mason Medical Center Author and Editor Disclosure Synonyms and related keywords: clostridium difficile disease, PMC INTRODUCTIONSection 2 of 8
  BackgroundPseudomembranous colitis (PMC) is a descriptive term for colitides defined by the presence of pseudomembranes on the colonic or small intestinal mucosa.1 Although small intestine can be involved in PMC, most cases encountered in the modern era involve only the colon. Clostridium difficile infection is responsible for virtually all cases of PMC and for as many as 20% of cases of antibiotic-induced diarrhea without colitis.2 The etiology of antibiotic-associated diarrhea and colitis not caused by C difficile is poorly understood, and a variety of other organisms have been implicated as causative agents, including Staphylococcus aureus, Candida species, Clostridium perfringens, and salmonellosis.3 Pseudomembranous lesions in the intestinal tract, originally reported in 1893, were thought to be caused by S aureus on the basis of its recovery in the stool samples of affected patients. With time, S enterocolitis (involving both small intestine and colon) became an accepted entity. Widespread antibiotic use made PMC a common problem, and it became apparent that the disease primarily involved the colon and only rarely involved the small intestine. In 1977, C difficile was recognized as the pathogen responsible for the development of PMC. PathophysiologyPMC is a descriptive term for colitides associated with pseudomembrane formation on the colonic mucosa (see Images 1-2). Pseudomembrane production is not always related to antibiotic administration; it may also may result from mucosal ischemia. However, the most common cause of PMC is C difficile overgrowth secondary to antibiotic therapy. Other causative factors for PMC are abdominal surgery, colonic obstruction, uremia, and prolonged hypotension causing hypoperfusion of the bowel. PMC also has been described with lymphoma, leukemias, and advanced HIV infection.4 Key steps in the pathogenesis of C difficile—mediated diarrhea and colitis include the following:
Although clindamycin and lincomycin classically have been linked to PMC, virtually all antibiotics can cause PMC. Cephalosporins and ampicillin may be the most common antibiotics associated with PMC on the basis of their widespread use.1 Most cases of PMC are associated with oral rather than parenteral administration of antibiotics.1 PMC can begin within days after initiation of antibiotic therapy or can occur up to 6 weeks after discontinuation. The basic mechanism in pathogenesis of PMC is overgrowth of C difficile and toxin production by the organism that causes a wide spectrum of illnesses ranging from mild diarrhea to life-threatening PMC. The anaerobes that are normally present in the colon control colonization by C difficile; therefore, antibiotics that are most active against anaerobic organisms are more commonly associated with PMC. Toxin-mediated direct endothelial damage is the accepted theory for pathogenesis of PMC. Production of at least 2 types of toxins by the C difficile organism is required for clinical expression. Toxin A is an enterotoxin, while toxin B is a cytotoxin. FrequencyUnited StatesAntibiotic use is commonly associated with diarrhea without colitis. Overall rates of antibiotic-associated diarrhea in hospitals range from 3.2-29%. As many as 25% of patients develop self-limiting diarrhea following ampicillin or clindamycin administration. Of hospitalized patients, 15% of those receiving beta-lactam antibiotics and approximately 10-25% receiving clindamycin develop diarrhea. Few of these patients actually develop PMC. C difficile is responsible for development of antibiotic-associated diarrhea in 20-30% of patients and in more than 90% of patients who develop antibiotic-associated PMC.3 Mortality/MorbidityMortality rates of PMC in various series vary from 1.1-3.5%.4 PMC causes significant morbidity because of its variable and nonspecific clinical manifestations at presentation, potentially difficult endoscopic diagnosis, and delayed results of stool assays. Approximately 5% of patients may present with features suggestive of acute abdomen or sepsis with resultant unwarranted laparotomy.4 Overall morbidity and economic burden of antibiotic-associated diarrhea are difficult to quantify; however, various studies have demonstrated significantly higher death rates and increased hospital costs.3 AgeDefinite age-related susceptibility is observed with C difficile, with adults being more susceptible than children. Neonates can harbor the organism and its toxin without apparent consequence. In addition, older children, despite frequent antibiotic use, rarely develop PMC. The exact cause of such age-related susceptibility is not clear. It may be secondary to lack of mature enterocytic membrane receptor for the toxin, preventing binding of the toxin to the bowel wall and subsequent production of PMC.1 Clinical DetailsInfection with toxigenic C difficile causes a spectrum of diseases ranging from the asymptomatic carrier state, particularly in neonates, to a fulminant relapsing and occasionally fatal colitis.3 The typical clinical presentation is diarrhea, abdominal pain, fever, leukocytosis, and an often-overlooked history of recent/concurrent use of antibiotics. Hospital inpatients may be asymptomatic or may only have mild-to-moderate symptoms.4 In severe cases, life-threatening colitis may develop, progressing to toxic megacolon and subsequent perforation. In rare cases, extraintestinal manifestations occur, including bacteremia, osteomyelitis, and splenic abscess. Other clinical manifestations that have been described are reactive arthritis and tenosynovitis. As with other reactive arthritides following enteric infections, many patients are positive for human leukocyte antigen (HLA)-B27.3 Nonspecific symptomatology of PMC mimics features of acute abdomen, especially sepsis or intra-abdominal infection and abscess. Most of these patients undergo ultrasound or CT examination without clinical suspicion of PMC.1 Thus, it is important for radiologists to recognize the radiologic features of PMC, since the radiologist is often the first physician to suggest the diagnosis. Preferred ExaminationIt is important to note that even though the diagnosis of PMC may be suggested by imaging, it is not the method of choice for establishing the diagnosis. This is done by stool assays for C difficile toxins or colonoscopy. Limitations of TechniquesOf patients with PMC, 90% or more demonstrate either C difficile or its toxins in stool samples.3 A variety of enzyme-linked immunosorbent assay (ELISA) tests that detect toxin A or B are available. When strict diagnostic criteria that include clinical diarrhea, positive cytotoxin assay, and positive culture are used, a sensitivity of 63-94% and specificity of 75-100% can be achieved.3 Flexible sigmoidoscopy alone without the use of colonoscopy may not detect up to 10% of cases of PMC. When PMC is not accompanied by pseudomembrane formation, endoscopic findings are relatively nonspecific, but a biopsy may reveal changes typical of PMC.3 Colonoscopy characteristically demonstrates 2- to 10-mm adherent yellow plaques; however, colonoscopy may be negative or nonspecific in 25-70% of patients.1 DIFFERENTIALSSection 3 of 8
Appendicitis Colitis, Ischemic Colon, Diverticulitis Crohn Disease Typhlitis Ulcerative Colitis RADIOGRAPHSection 4 of 8
FindingsPlain films of the abdomen are notoriously insensitive for diagnosis of PMC. The findings may range from normal to nonspecific, but as plain films are often the first studies to be ordered, it is important to be aware of these findings. Classic findings consist of the following:
Barium enema Contrast enemas should be avoided in patients with possible PMC because of potential risk for perforation. Barium enemas are rarely indicated, especially with the advent of cross-sectional imaging. Barium enema findings may vary, depending on the severity of the disease. In the milder forms, nodular filling defects involving the mucosa may be observed that coalesce as the disease progresses, giving an irregular appearance to the bowel wall (see Image 4). The serrated outline of the colon does not result from mucosal ulceration but, rather, is a consequence of trapped barium between the plaquelike membranes. Degree of ConfidencePlain radiographic abnormalities may be observed in only 32% of cases of PMC.5 False Positives/NegativesPlain film findings may suggest a diagnosis of PMC but usually are insensitive. Even if the radiographs demonstrate abnormalities, they tend to underestimate the extent and severity of the disease.4 CT SCANSection 5 of 8
FindingsWith increased use of CT as a primary imaging modality in the evaluation of patients with diffuse abdominal pain or fever, it is critical for radiologists to recognize CT features of PMC.1 CT findings, although not specific, may be highly suggestive of PMC, and CT is excellent for evaluation of the extent of PMC (Ros, 1996).1
Degree of ConfidenceThe sensitivity of detection of PMC on CT is approximately 85%. Specificity of CT is low (approximately 48%), since other types of colitis can cause a similar appearance.6 ULTRASOUNDSection 6 of 8
FindingsUltrasound is not commonly used for evaluation of possible PMC; however, it may be helpful in evaluation of postoperative patients in surgical intensive care units who are on antibiotics and develop nonspecific abdominal symptoms.1 Thickened colon may be discovered incidentally during ultrasound examination of the abdomen. Ultrasound findings rely on wall thickening of the colon, as well as the target sign, demonstrated by hyperechoic mucosa in the background of hypoechoic edematous submucosa. Ascites may be an associated finding and has been observed in as many as 77% of cases.7 MULTIMEDIASection 7 of 8
REFERENCESSection 8 of 8
Colitis, Pseudomembranous excerpt Article Last Updated: Sep 19, 2007 | |||||||||||||||||||||||||||||||||||||||||||||||||
