eMedicine Specialties > Radiology > Gastrointestinal

Colitis, Pseudomembranous

Author: Vinay K Gheyi, MD, MBBS, Radiologist, Christiana Care Health System
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
Contributor Information and Disclosures

Updated: Mar 15, 2010

Introduction

Background

Pseudomembranous 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 See the images of pseudomembranous colitis below.

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.

Recent studies

Valiquette et al, in a study of abdominal CT in patients with the BI/NAP1/027 hypervirulent strain of C difficile, found that CT could provide prognostic information additional to what could be obtained by clinical and laboratory parameters. They also found that patients who underwent CT were younger, had higher peak white blood cell counts and serum creatinine levels, and were more likely to experience fever than those who did not undergo CT. However, there were no differences in CT findings before and after emergence of BI/NAP1/027. The authors noted that pleural effusion, colonic wall thickness greater than 15 mm, a peak white blood cell count of 30 x 10⁹ cells or greater/L, an albumin level less than 20 g/L, and immunosuppression were independently associated with complicated C difficile infection.⁴

Ben-Horin et al investigated the effects of combination therapy with antibiotics and immunomodulators in patients with inflammatory bowel disease (IBD) and C difficile infection. They found that patients on combination therapy fared worse than those treated with antibiotics alone. For example, ulcerative colitis, abdominal tenderness, or severe bloody diarrhea was more common in patients who received the combination therapy. In addition, multivariate analysis revealed that only the combination therapy tended to be independently associated with the primary outcome of death or colectomy within 3 months of admission, in-hospital megacolon, bowel perforation, hemodynamic shock, or respiratory failure. The authors noted that treatment with 2 or 3 immunomodulators was correlated with the primary outcome, independent of disease severity at presentation.⁵

According to a study by Zilberberg et al, elderly patients (65 y or greater) represent approximately 50% of ICU patients with C difficile -associated disease and have a higher 30-day mortality than younger patients. Elderly patients were 68% more likely to experience 30-day mortality than the younger group. The authors suggested the use of a simple prediction rule incorporating determinants of 30-day mortality may help optimize treatment decisions in such cases.⁶

Pathophysiology

PMC is a descriptive term for colitides associated with pseudomembrane formation on the colonic mucosa. 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.⁷ Key steps in the pathogenesis of C difficile — mediated diarrhea and colitis include the following:

1. Disruption of colonic flora by an antibiotic or antineoplastic agent with antibacterial activity
2. Colonization with C difficile
3. Elaboration of toxin A and toxin B, both of which mediate cytoskeletal derangement in target cells
4. Mucosal injury and inflammation³

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.

Frequency

United States

Antibiotic 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/Morbidity

Mortality rates of PMC in various series vary from 1.1-3.5%.⁷ 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.⁷ 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

Age

Definite 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

Presentation

Infection 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.⁷ 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 Examination

It 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 Techniques

Of 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

Differential Diagnoses

Appendicitis
Colitis, Ischemic
Colon, Diverticulitis
Crohn Disease
Typhlitis
Ulcerative Colitis

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