A BSTRACT C V

Marc S. Itskowitz, MD, and Paul J. Lebovitz, MD
A
BSTRACT
Almost all cases of pseudomembranous colitis reported during the
past 3 decades have been associated with antimicrobial use. We report a case of
nonantibiotic-associated pseudomembranous colitis and review similar cases in the
literature that suggest the need for increased clinical awareness of this condition.
A 77-year-old white female presented with a history of watery diarrhea,
abdominal cramping, and a 30-lb weight loss during the past 6 weeks. She
denied recent antibiotic use, which was confirmed by contacting her pharmacist.
Colonoscopy revealed severe focal ulceration of the colonic mucosa and adherent yellow plaques in the rectum and sigmoid colon, pathologic features consistent with pseudomembranous colitis. The result of a stool cytotoxin assay was
positive for Clostridium difficile. The patient was treated with oral vancomycin and
exhibited rapid improvement. In a review of the literature, we found 9 well-documented cases of nonantibiotic-associated pseudomembranous colitis in patients
without predisposing factors. Most of those patients were elderly women who presented with diarrhea and abdominal pain. The diagnosis of pseudomembranous
colitis was confirmed by colonoscopy, by the identification of C difficile in stool
culture, or by cytotoxicity assay. Treatment usually was initiated with oral vancomycin and dosages differed. In the 9 cases reviewed, the mortality rate was
11% and the rate of relapse, 33%.
CLINICAL VIGNETTE
Nonantibiotic-Associated Pseudomembranous Colitis:
A Case Report and Review of the Literature
(Adv Stud Med. 2003;3(10):571-574)
seudomembranous
colitis
(PMC) was first described in
1893, when a patient who had
severe diarrhea was found at
autopsy to have “diphtheritic
colitis.”1 PMC was attributed to mucosal
ischemia or viral infection until 1977, when
a toxin that produced cytopathic changes in
tissue culture cells was identified in stool
specimens from affected patients.2 Within a
year of that report, Clostridium difficile, a
spore-forming, gram-positive anaerobic
P
bacillus, had been identified as the source of
the cytotoxin.3 Almost all cases of PMC
reported during the past 3 decades have
been associated with antimicrobial use. We
report a case of nonantibiotic-associated
PMC and review similar cases in the literature that suggest the need for increased clinical awareness of this condition.
CASE REPORT
A 77-year-old white female presented
with a 6-week history of watery diarrhea,
Dr Itskowitz is Assistant Professor of Medicine, Drexel University College of Medicine; Associate Program
Director, Internal Medicine Residency Program, Allegheny General Hospital, Pittsburgh, Pennsylvania.
Dr Lebovitz is Assistant Professor of Medicine, Drexel University College of Medicine; Director, Division of
Gastroenterology, Allegheny General Hospital, Pittsburgh, Pennsylvania.
Drs Itskowitz and Lebovitz have reported they have no financial or advisory relationships with corporate organizations related to this activity.
Off-Label Product Discussion: The authors of this article do not include information on off-label use of products.
Correspondence to: Marc Itskowitz, MD, Department of Internal Medicine, Allegheny General Hospital, 490
East North Avenue, Ste 103, Pittsburgh, PA 15212.
Advanced Studies in Medicine
571
CLINICAL VIGNETTE
abdominal cramping, and a 30-lb weight loss. Her
medical history included a myocardial infarction
4 years prior to admission and a 10-year history of
osteoarthritis, for which she had recently begun
treatment with diclofenac 50 mg twice daily. The
patient’s other medications included diltiazem
120 mg once daily and transdermal nitroglycerin
0.4 mg/hour for 12 hours daily. She denied recent
antibiotic use, which was confirmed by contacting
her pharmacist. Physical examination revealed an
elderly white female with orthostatic hypotension,
decreased skin turgor, and dry mucous membranes.
Her abdomen was mildly distended with left lower
quadrant tenderness. Rectal examination revealed
no masses and the presence of loose dark stools
that were negative for fecal occult blood.
Colonoscopy revealed severe focal ulceration of
the colonic mucosa with adherent yellow plaques
in the rectum and sigmoid colon, pathologic features consistent with PMC (Figure). The stool
cytotoxin assay was positive for C difficile.
Treatment with oral vancomycin produced rapid
improvement.
LITERATURE
In a review of the literature from 1966 to
1999, we found 9 well-documented cases of
nonantibiotic-associated PMC in patients without
predisposing factors (Table). Most patients were
elderly (mean age, 69 years). There was a striking
predominance of females (89%) among the cases
reported. The most common clinical features
Figure. Severe Focal Ulceration of Colonic Mucosa With Adherent
Pseudomembranous Exudative Yellow Plaques
572
reported included diarrhea (in all patients),
abdominal pain (3 patients), weight loss
(2 patients), and anorexia (1 patient). The mean
duration of symptoms prior to diagnosis was
26 days. The diagnosis of PMC was confirmed by
colonoscopy in 7 of the patients and by the results
of both stool culture and cytotoxicity assay for
C difficile in 6 patients. Treatment was most commonly initiated with oral vancomycin at varying
doses. In the 9 cases reviewed, 1 patient died and
3 patients relapsed.
DISCUSSION
Earlier teaching about the pathogenesis of
PMC centered on the overgrowth of C difficile
caused by antibiotic suppression of the normal
bowel microflora, which appears to be the major
risk factor for the development of PMC. However,
the mechanism of disease is probably more complex, because many of the antibiotics that cause
PMC are active against C difficile and other bowel
microflora, and because diarrhea does not develop
in many patients who become colonized with
C difficile. Although C difficile can be detected in
the stool of only 2% to 3% of healthy adults in the
United States, retrieval of C difficile from stool
occurs in 20% of asymptomatic adults who have
recently been treated with antibiotics.4 PMC was
reported before the antibiotic era; Finney’s original
description of the disease preceded the advent of
antimicrobial therapy by more than 40 years.1
Thus, factors other than antimicrobial therapy
must account for the disturbance in bowel
microflora and the enhanced toxin production, both of which predispose patients to
PMC. The role of other medications in
this disease is not known. PMC has been
reported during gold therapy and during
treatment with diclofenac, an anti-inflammatory agent that inhibits cyclooxygenase
and reduces intracellular concentrations
of free arachidonate in leukocytes. 5
Gentric and Pennec reported a case of
diclofenac-induced PMC in 1992.6 That
article presents the second reported case
of PMC associated with diclofenac use.
The complex interaction among the
normal microflora of the intestine, antibiotics and other drugs that affect the microbial environment, and procedures that alter
motility may contribute to the proliferation of pathogens.7 In the absence of
antimicrobial treatment, PMC may occur
after surgery and in patients with chronic,
debilitating illnesses. Other risk factors for
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PSEUDOMEMBRANOUS COLITIS
PMC include spinal fracture, intestinal obstruction, carcinoma, leukemia, chemotherapy for cancer, severe burns, uremia, intestinal obstruction,
and heavy-metal poisoning.8 PMC is also a recognized complication of Hirschsprung’s disease
unrelated to antibiotic use.9 It has been suggested
that bowel ischemia may cause nonantibiotic-asso-
ciated PMC.10 Antibiotic-associated susceptibility
to C difficile appears to increase with age, and
mesenteric ischemia occurs at a higher rate in elderly patients with diffuse vascular disease.11 Elderly
patients with mesenteric ischemia may be at higher
risk for the overgrowth of C difficile and for PMC.
Additional studies are needed to address the quan-
Table. Nonantibiotic-Associated Pseudomembranous Colitis: Features, Diagnosis,Treatment, and Outcome
Patient
Age (y),
Gender
Clinical Features
Stool Culture
Positive for
C difficile
Stool Culture
Positive for
C difficile
Toxin
Endoscopy
Treatment
Outcome
80, F10
Diarrhea for 8 d,
weight loss of 6 lb
No
No
Yes
Vancomycin
500 mg po qd
Improvement
92, F11
Diarrhea for 2 wk
Yes
Yes
No
Vancomycin 250 mg
po tid for 3 d
Improvement
78, F11
Diarrhea for 1 d
Yes
Yes
No
Vancomycin 250 mg
po tid for 3 d
Improvement
74, F11
Abdominal pain,
diarrhea for 5 d
Yes
Yes
Yes
Vancomycin
250 mg po tid
for 10 d
Initial improvement;
disease recurred,
and patient underwent
urgent colectomy
69, F12
Diarrhea for 3 mo
No
No
Yes
Metronidazole 1.5 g
qd for 7 d
Improvement
57, F13
Anorexia,
abdominal pain,
diarrhea for 2 mo;
weight loss of 10 lb
Yes
Yes
Yes
Vancomycin
500 mg po
q 6 h for 1 wk
Initial improvement;
patient required
second course of vancomycin for recurrent
disease, was readmitted
with a colonic perforation, and died after
surgery
22, M14
Abdominal pain,
diarrhea for 4 wk
Yes
No
Yes
Vancomycin
250 mg po q 8 h
Rapid improvement
67, F15
Diarrhea for 3 d
No
Yes
Yes
Vancomycin 1 g po
bid for 10 d
Partial improvement
82, F 16
Diarrhea, weakness,
confusion
Yes
Yes
Yes
Vancomycin
500 mg po qid
Initial improvement but
disease recurred 2 wk
later; no response to
metronidazole 750 mg
po tid for 8 d, after
which patient improved
with vancomycin 500 mg
po qid and was discharged with treatment
of vancomycin 125 mg
po bid for prophylaxis
F = female; qd = daily; po = by mouth; M = male; bid = twice daily; qid = 4 times daily; tid = 3 times daily.
Advanced Studies in Medicine
573
CLINICAL VIGNETTE
titative or qualitative changes that occur in the
bowel microflora in patients with sustained
hypoxemia and bowel ischemia.
CONCLUSION
PMC caused by C difficile may occur without
prior antibiotic therapy, surgery, or overt systemic
illness. The occurrence of nonantibiotic-associated
PMC underscores the importance of obtaining a
stool cytotoxicity assay for C difficile and of considering sigmoidoscopy in the evaluation of patients
with acute and persistent diarrhea. Patients who
have an acute diarrheal illness associated with fecal
leukocytes often have been exposed to an infectious
agent or have underlying inflammatory bowel disease. When more common causes of acute enteritis
and colitis have been ruled out, PMC should be
considered in patients who develop persistent diarrhea, even those without a history of antibiotic use.
This case report and review of the literature demonstrate that PMC may occur in patients who have no
underlying illness and have not received recent
antibiotic therapy.
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