First published online July 20, 2009
British Journal of Radiology (2009) 82, 890-895
© 2009 British Institute of Radiology
doi: 10.1259/bjr/57970083
A description of CT features of Clostridium difficile infection of the small bowel in four patients and a review of literature
B WEE, FRCR
1
J A D POELS, FRCR
1
I J MCCAFFERTY, FRCR
1
P TANIERE, FRCPath
2 and
J OLLIFF, FRCR
1
Departments of 1 Radiology 2 Pathology, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Birmingham B15 2TH, UK
Correspondence: B Wee, Department of Radiology, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Birmingham B15 2TH, UK. E-mail: b_wee{at}hotmail.com
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Abstract
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Clostridium difficile associated disease is an increasingly common cause of morbidity and mortality. Pseudomembranous colitis following hospital-administered antibiotic treatment is the most common symptomatic manifestation. Small bowel enteritis caused by C. difficile, however, is rarely described. Here, we present a series of four patients with hospital-acquired small bowel enteritis caused by C. difficile, discuss its CT and histopathological features, and review the current literature.
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Introduction
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Clostridium difficile infection of the small bowel is a rare entity that is now increasingly being recognised as a potential life-threatening condition. Although C. difficile infection of the large bowel is well recognised and has a significant morbidity and mortality rate for the at-risk patient, only 21 cases [1–15] of C. difficile of the small bowel have been reported in the literature. With C. difficile rates increasing, it is plausible that small bowel enteritis is more prevalent than previously suspected. Increased reporting of this condition will alert clinicians of its potential presence and increase the index of suspicion. Early recognition of this disease is paramount; this has significant therapeutic implications because early reports of this condition demonstrate a high mortality rate.
We present a series of four patients diagnosed with C. difficile enteritis, all of whom had positive C. difficile toxin (CDT) and correlative histopathological examinations. One underwent open biopsy of the small bowel and three had small bowel resections. We review the imaging features with particular emphasis on CT imaging.
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Methods and materials
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The diagnosis of C. difficile enteritis was made on histopathological examination of the affected bowel with concomitant positive CDTs. The clinical notes were also reviewed retrospectively for clinical correlation.
All four patients were identified by the histopathologist, as they had features of pseudomembranous mucosal enteritis on small bowel histopathological examination. The pathological specimens, which were all surgically obtained, ranged from a transmural ileal biopsy measuring 15 mm in length to several segments of small bowel 2–7 cm in length. The surgical specimens were obtained following laparotomy for suspected post-operative obstruction in Case 1, colectomy for colitis in Cases 2 and 3, and laparotomy for suspected small bowel ischaemia in Case 4.
The antecedent illness requiring hospital admission for each patient was also recorded (Table 1
). Retrospective review of the antibiotic history confirms use of several types of antibiotics with differing lengths of treatment prior to the suspicion of disease onset.
CDTs A and B were demonstrated by enzyme-linked immunosorbent assay (ELISA) in stool samples (C. difficile Tox A/B II kit; Techlab, Blacksburg, VA). These patients also underwent abdominal CT (Lightspeed plus; General Electric, Milwaukee, WI) with oral and intravenous contrast performed during their illness, allowing retrospective review of the images. The mean time difference between the CT images and histological sampling was 3.75 days (range, 1–7 days).
Two experienced radiologists reviewed the CT images and consensus was reached. Scans were examined for evidence of mucosal wall thickening (defined as >3 mm), ascites (small, moderate, large), mesenteric or retroperitoneal fatty stranding, luminal distension (>2.5 cm) and mural gas.
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Results
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The average age of the four patients involved was 49 years (range, 33–76 years). All four patients had received antibiotics before becoming symptomatic with enteritis. Three patients had undergone gastrointestinal surgery. One patient was immunocompromised with HIV. Only one patient had small bowel disease only, with no features of colitis. The others had mucosal thickening affecting the caecum. One of the four patients in this series died (Table 1
).
The histological changes observed in the small bowel were comparable to those usually seen in large bowel lesions. The villous mucosa showed extensive ulceration with deposits of mucin, fibrin and polymorphs on the surface. There were occasional fibrin thrombi in the subepithelial lamina propria, patchy epithelial lysis in the glands and focal gland rupture with volcanic-like eruption of mucin into the lumen. The lamina propria contained a mild mixed inflammatory cell infiltrate that included lymphocytes and polymorph neutrophils (Figure 1).
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Figure 1. Crypt eruption (yellow stars) and pseudomembranes (black arrows) are typical histological findings in small bowel pseudomembranous colitis.
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When assessed by CT, all patients had mesenteric or retroperitoneal fatty stranding. Three patients had ascites of varying degrees. Distension of the small bowel containing gas or fluid was present in three patients. There were varying amounts of small bowel mural thickening, with the terminal ileum being most affected. Two patients had gross caecal and small bowel thickening; one had moderate thickening of the caecum and terminal ileum; and one had only subtle small bowel thickening. One patient had gas within the wall of the small bowel and intrahepatic portal venous gas (Table 2; Figures 2–5).
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Figure 2. Thickened caecum (white arrow) and terminal ileum (red arrow) with grossly dilated small bowel loops.
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Figure 3. (a,b) Grossly thickened ileal loops in the pelvis and terminal ileum (red arrows) with intraluminal contrast.
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Figure 4. Dilated fluid-filled large and small bowel loops. The terminal ileum (red arrow) and caecum (white arrow) are clearly abnormal.
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Discussion
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C. difficile involving the small bowel is a rare but increasingly recognised entity. It is a gram-positive organism that does not invade mucosa; instead, it produces clinical signs and symptoms from exotoxins A and B. These toxins bind and enter intestinal cells, causing mucosal cell shedding. The development of shallow ulcers follows, from which serum proteins, mucus and inflammatory cells flow outward, forming pseudomembranes. Of the 21 cases reported so far (Table 3), a total of 9 deaths were recorded [2, 5–7, 9, 12–15]. Our series of 4 cases had 1 death recorded, resulting in an overall mortality figure of 40% (10 of 25 patients).
The pathophysiology of C. difficile enteritis is poorly understood. There appears to be several predisposing factors resulting in increased susceptibility to this infection, i.e. prior antibiotic therapy, altered intestinal anatomies, inflammatory bowel disease and immunosuppression.
The organism has been shown to be present in jejunal aspirates, suggesting that the small bowel may act as a reservoir [16]. The suggested pathogenesis includes (i) changes in the small bowel flora after colectomy, resulting in "colonisation" of the small bowel, (ii) removal of the mechanical action of the ileocaecal valve, which inhibits C. difficile colonisation of the terminal ileum and (iii) phenotypic changes of the small intestine epithelium following gastrointestinal surgery [3, 7, 13, 15].
The relationship between pseudomembranous colitis and antibiotic therapy has long been established, and it appears from a review of the literature that this relationship also exists for C. difficile enteritis. 19 of the 21 previous cases have reported antibiotic use prior to the onset of illness. All four cases in this series also had a history of antibiotic use. LaMont and Trnka [4] and Mann et al [3] reported the two exceptions to the literature. LaMont and Trnka [4] reported the case of a 23-year-old woman with a history of partial colectomy for Crohn's ileocolitis. No antibiotic was prescribed before the onset of illness, although the patient was on a maintenance dose of 15 mg prednisolone for mild residual Crohn's disease. Mann et al [4] reported a case occurring in a 35-year-old woman with an ileal pouch–anal anastomosis for ulcerative colitis. Again, no antibiotic was prescribed prior to the onset of illness, although there was a history of recurrent pouchitis requiring courses of prednisolone, metronidazole, codeine phosphate and loperamide.
Another significant risk factor is the presence of surgically altered intestinal anatomies. The two cases described by LaMont and Trnka [4] and Mann et al [3], in which antibiotics were not used, share similarities in that both patients had altered gastrointestinal anatomies preceding the onset of disease. Most cases in the reported literature have either a pre-existing history of gastrointestinal surgery either pre-dating the onset of illness (9 cases) or acutely following treatment of the antecedent illness, e.g colorectal cancer or inflammatory bowel disease (10 cases).
Immunosuppresion as a risk factor has been raised in a study by Lundeen et al [1], in which five of the six cases were on prednisone. Our series contained one case where the patient was immunosuppressed with HIV. Indeed, its role is supported by the fact that several previous reports [4, 9] show prior immunosuppresion with prednisolone for inflammatory bowel disease. As mentioned previously, the case described by LaMmont and Trnka [4] occurred in a patient on a maintenance dose of 15 mg prednisolone for Crohn's disease without any previous history of antibiotic use. It seems, therefore, that immunosuppresion may be a risk factor for the development of this illness.
The radiological features and description of this condition are scanty. Unsurprisingly, the previous reports focus on the clinical presentation, predisposing factors and sequelae. Furthermore, several cases were reported before the routine use of abdominal CT. A review of previous reports provides some description of the imaging findings on CT. The largest case series of six patients [1] provided only a cursory description of dilated loops of small bowel on CT. Kim et al [2] described free fluid within the pelvis, although the bowel loops were noted to be normal. Conversely, Tjandra et al [12] demonstrated dilated small bowel loops with no free abdominal fluid. Jacobs et al [11], Hayetian et al [15] and Kralovich et al [13] described cases with dilated thick-walled small bowel. The cases reported by Kuntz et al [9] and Tjandra et al [12] demonstrated intramural gas within the small bowel. Table 4 provides a summary of CT findings from the previous case reports.
The CT findings in our series reveal that ascites, mesenteric fatty stranding and small bowel distension feature prominently. All cases had mesenteric fatty stranding and three cases had ascites. Fluid-filled distended small bowel was identified in three of the four cases. Intramural gas was demonstrated in a single patient who subsequently died. As in the case described by Kuntz et al [9], this suggests that this is a poor prognostic sign.
Mural thickening involving the small bowel varies in length and severity, ranging from a very short segment in the mid-ileum to several loops of the mid and terminal ileum. It does not appear as florid as that of pseudomembranous colitis. Mural thickening was also seen in the large bowel, primarily in the caecum, although its appearances are not as exuberant as those in pseudomembranous colitis. It is likely that the presence of caecal thickening is an early sign heralding the onset of pseudomembranous colitis, demonstrating the close relationship between this disease and C. difficile enteritis. We suggest that, in a certain subgroup of patients with appropriate risk factors, the radiographical and clinical features of early pseudomembranous colitis should prompt suspicion of concurrent C. difficile enteritis.
The presence of ascites points towards a more acute cause of inflammation and has been advocated as a sign of differentiation between pseudomembranous colitis and Crohn's disease, although it only occurs, on average, in 35% of cases [17]. Similarly, we propose that the presence of ascites with distended fluid-filled small bowel should alert the radiologist to the presence of C. difficile enteritis. As with pseudomembranous colitis, the disease is primarily mucosal and, although mesenteric or retroperitoneal stranding was common, it was minor. This may help to differentiate from other forms of enteritis which involve the entire wall thickness, such as Crohn's disease. Mural and vascular enhancement helps to distinguish the disease from ischaemia. However, in the absence of intravenous contrast, ischaemia cannot be excluded from a list of differential diagnoses.
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Conclusions
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It is likely that the occurrence of C. difficile enteritis is more prevalent than previously suspected and is probably under-diagnosed. Although the radiological features are non-specific, in the right context and with appropriate risk factors, C. difficile enteritis should be suspected if the described findings are present.
Received for publication December 8, 2008.
Revision received April 15, 2009.
Accepted for publication May 1, 2009.
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References
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Abstract
Introduction
