CASE SUMMARY:

A 57-year-old man presents with complaints of hematemesis and chest pain. Work-up revealed pulmonary tuberculosis, and the patient was treated with INH, rifampin, ethambutol, and pyrazinamide. He then presented to the ER with hypotension after three days of intermittent left lower quadrant pain, dizziness, nausea, coffee-ground emesis, and presence of bright red blood in his stools. Physical examination revealed diffuse abdominal tenderness, especially in the left upper quadrant and left flank, but no peritoneal signs. Laboratory studies showed an elevated white blood cell count of 46,000 with 20% bandemia, metabolic acidosis (pH 7.28), and renal insufficiency (BUN/Cr=68/5.2).

DIAGNOSIS:

Antibiotic-induced pseudomembranous colitis (PMC) with a positive Clostridium difficile toxin assay and a characteristic sigmoidoscopic appearance (figure 1).

The initial KUB showed minimally thickened colonic folds in the left upper quadrant, a 2 cm staghorn calculus in the right renal pelvis, and a right ureteral stent, but no pneumoperitoneum (figure 2). To exclude perforation, a gastrografin upper GI study was performed (figure 3). For further evaluation, an emergent abdominal CT was performed without intravenous contrast, which showed diffuse colonic wall thickening, a para-esophageal hernia, and renal stones (figure 4).

Conservative intravenous antibiotic treatment failed in this patient, resulting in worsening peritonitis and sepsis. Exploratory laparotomy was performed with subtotal colectomy, ileostomy, and Hartman's procedure. The postoperative course was uneventful and the patient was discharged on postoperative day 16.

Surgical findings demonstrated an inflamed, thickened colon from cecum to rectum, with adhesions to the stomach and left kidney. Gross and histologic (figure 5) changes were characteristic of PMC. The patient's bowel was edematous and the bowel wall variably thickened. The mucosa showed numerous raised yellow-grey, friable plaques on an erythematous base. Some of these patches formed linear, confluent strips. Hematoxylin- and eosin-stained sections showed the typical findings of PMC, ranging from superficial streaming of neutrophils and mucin from the disintegrating surface epithelium to sloughing of the majority of the surface epithelium into the layered exudate with preservation of the epithelium at the base of the crypts.

The lamina propria contained lymphocytes, neutrophils, plasma cells, and abundant nuclear dust. Focal areas showed full thickness ulceration. Examination of the submucosal vessels showed rare thrombi only in the superficial vessels, near the areas of ulceration. The uninvolved mucosa was normal. There was no evidence of vasculitis, architectural distortion, mucosal fibrosis, or other changes suggestive of inflammatory bowel disease or ischemia.

DISCUSSION:

PMC, first described by Finney in 1893,1 is a well known disease entity caused by a toxin released by Clostridium difficile, a gram-positive, spore-forming anaerobic bacillus.2 The toxin causes mucosal inflammation and necrosis, with formation of yellow-colored plaques called pseudomembranes. Although PMC is most commonly associated with clindamycin, ampicillin, and the cephalosporins, virtually all antibiotics can cause PMC; there is an overall incidence of 1 to 3 cases of PMC in 100,000 outpatient courses of antibiotic therapy and 1 to 10 in every 1,000 inpatient courses.3,4 A wide range of other therapeutic agents5 also have been reported to be associated with the disorder.6 One recent case report also attributes the etiology of PMC to cytomegalovirus in immunocompromised patients.7

Clinically, virtually all patients with PMC present with diarrhea, with or without any systemic symptoms. Frequently, however, cramping, abdominal pain, fever, and leukocytosis are present. Occasionally, as in this case, acute fulminant colitis (toxic megacolon) with severe abdominal symptoms and little or no diarrhea may suggest peritonitis, and PMC may be initially overlooked.8

Treatment of PMC is often successful, with oral vancomycin or metronidazole having a 100% and 92% response rate, respectively, within 7 days.9 However, in rare cases such as the case presented here, prompt surgical intervention is critical in the patient's management.10 In a recent review of 3,300 cases of PMC, 13 patients (0.39%) required surgical intervention, with an overall mortality of 38% in this group.11 Surgical indications discussed by Lipsett et al include signs of organ failure, worsening CT scan findings on conservative therapy, or signs of peritonitis.

The correct and prompt diagnosis of PMC relies heavily on clinical suspicion and laboratory evidence of C.difficile toxins, which can be detected in 397% of patients with PMC.12 Stool culture is more sensitive but is more time consuming. Flexible sigmoidoscopic examination with biopsy also can provide definitive diagnosis of PMC. However, this procedure is expensive and carries the risk of perforation and the likelihood of precipitating toxic megacolon.

Radiographic examination, especially with CT scans, plays a very important role in raising the index of suspicion, detecting potential complications, and providing guidance in the appropriate work-up and management of PMC. In a retrospective study of 152 patients with PMC,13 18% demonstrated evidence of haustral thickening on plain films, which is highly suggestive of PMC in the appropriate clinical setting. The finding is, however, nonspecific and may represent ischemic and/or other inflammatory or infectious etiologies. In the same study, 32% of all patients demonstrated other non-specific findings which may include ascites, or colonic or small bowel ileus patterns.

In rare cases, broad transverse bands of edematous haustral folds can be seen and are thought to be fairly characteristic of PMC.14 Barium examination may demonstrate only slight irregularity or nodularity in mild cases. In severe cases, strikingly thickened haustral folds, shaggy wall contours with multiple round focal filling defects may be seen, corresponding to mucosal plaques.15 These typically range from 2 mm to 7 mm in size.

CT scanning has a higher sensitivity in detecting colonic wall abnormalities and also is better in defining the extent of disease involvement. Gaa et al reported evidence of bowel wall thickening in all 10 patients in their series, with a mean thickness of 13 mm (range 7 mm to 31 mm).16 Fishman et al reported similar findings in 88% of proven cases of PMC (n=26, mean thickness 14.7 mm, range 3 mm to 32 mm).17 The investigators also described the "accordion sign", which represents linear and parallel tracking of contrast material between thickened folds, seen in several of their patients. The specificity of this finding for PMC is not known, but it is thought to correspond to the plain film finding of broad transverse bands described above. The CT appearance of PMC is nonspecific and may demonstrate focal or diffused colonic involvement with considerable overlap of degree in wall thickness with inflammatory bowel disease.

Ultrasound detection of colonic wall thickening has also been reported in several cases.18 Downey et al19 also demonstrated the advantage of ultrasound in its ability to localize the disease processes to just the mucosal and submucosal layers in selected cases and, thus, narrowing the differential diagnoses. However, layer differentiation is not possible in more severe cases of PMC.

References

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17. Fishman BR, Kavuru M, Jones B, et al: Pseudomembranous colitis: CT evaluation of 26 cases. Radiology 180(1):57-60, 1991.

18. Oei TR, van Engelshoven JM: Pseudomembranous colitis: An ultrasound diagnosis. Eur J Radiol 15(2):154-156, 1992.

19. Downey DB, Wilson SR: Pseudomembranous colitis: Sonographic features. Radiology 180(1):61-64, 1991.