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).
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
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.
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
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
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
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
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