The Clinical Syndrome of Pouchitis—Evaluation, Etiology, and Management
as a main agent. The fact that this condition is rare in patients who had IPAA for polyposis suggests that patients with ulcerative colitis are susceptible on an immune and/or genetic basis. A constellation of factors potentially interplay in the pathogenesis of this condition. These include stasis and bacterial overgrowth,49 oxydative stress,51 oxidation,56
dysbiosis,49,52–54
fecal hydrogen sulfite production,50 abnormal mucus,55
insufficient short-chain fatty acids to the mucosa,57
release of inflammatory mediators,58,59 expression of lymphocyte activation,61 transport,63 ischemia,40
altered immune response,60 altered tight junction,62
increased bacterial permeation,64 and, perhaps, gastric hyposecretion.66
The complex interaction between the patient, who is genetically or immunologically susceptible to ulcerative colitis, and an ileal pouch that has undergone functional adaptation to a colon-like morphology in response to fecal stasis, has been proposed as the predisposing condition for pouchitis.67
Disruption in the gut microflora of the affected
gut, malnutrition related to short-chain fatty acids in the stools, or release of oxygen-free radicals caused by transient ischemia appear to be important factors.68
One unifying hypothesis that links interaction
between epithelial metaplasia, changes in luminal bacteria, and altered mucosal immunity has been proposed. Colonic mucosa supports colonization by sulfate-reducing bacteria that produce hydrogen sulfide, causing mucosal depletion and subsequent inflammation.69
Although, in
most cases, antibiotics are effective, an immunogenetic subpopulation can develop a chronic refractory variant of pouchitis.
Classifications
Pouchitis is a diverse disease that may be classified into a variety of subtypes including: idiopathic versus secondary; remission versus active; acute less than four weeks, versus chronic more than four weeks; infrequent (fewer than three episodes per year) versus relapsing (more than three episodes per year or return of symptoms within one month of antibiotic withdrawal)70 refractory.71
versus continuous; and responsive versus
In general, patients with pouchitis respond to antibiotics and it is therefore useful to also distinguish them by their response to antibiotics. Antibiotic responsive pouchitis includes patients who respond to a two-week course of a single antibiotic and have fewer than four episodes per year. Antibiotic-dependent pouchitis includes those who have persistent symptoms requiring long-term/continuous antibiotics or probiotic therapy to keep the disease in remission or frequent episodes, more then four per year. Finally, there is antibiotic refractory pouchitis, which fails to respond to multiple antibiotics and requires other medical management.31
Treatment
Initial episodes of pouchitis are usually treated successfully with oral metronidazole 15–20mg/kg or ciprofloxacin 1,000mg/day.72 500mg bid x 14 days is usually better tolerated than metronidazole,73
Ciprofloxacin and
is also thought to lead to eradication of both C. perfringens and hemolytic Escherichia coli.74
In patients who do not respond or relapse early after single antibiotic dosing, a combination of oral metronidazole and
1. Dozois RR, Alternatives to conventional ileostomy, Chicago: Year Book Medical Publishers Inc., 1985.
2. Heppell J, Kelly KA, Phillips SF, et al., Physiologic aspects of continence after colectomy, mucosal proctectomy and endorectal
impaired butyrate excessive
epithelial altered intestinal hormones,65
ciprofloxacin is highly effective.75 as ciprofloxacin and rifaximin,76 be effective.
Other antibiotic combinations, such and ciprofloxacin and tinidazole77
may
In unremitting pouchitis, daily oral dosing with metronidazole or ciprofloxacin has been shown to reduce the median number of stools per day. However, secondary to the side effects of metronidazole, ciprofloxacin is typically used and may be effective at lower dosing 250–500mg every day (QD).78,79
Topical metronidazole (150mg/day)80 may
also be considered but may be difficult to administer secondary to altered anatomy. Recently, rifaximin has been shown in an open-label trial to be effective for maintenance therapy in antibiotic dependent pouchitis.81
Probiotics may be effective as maintenance therapy after remission has been achieved. VSL#3, which contains viable lyophilized bacteria of four strains of Lactobacillus, three Bifidobacterium species, and Streptococcus salivarius ssp Thermophillus, showed excellent rates of remission compared with placebo after nine months 85 versus 0%82
and similar results were seen by Mimura et al.83 However, recent open-labeled studies have shown much lower response rates.84,85
Anti-inflammatory agents, immunomodulators, and biologics have also been investigated for the treatment of pouchitis. Topical instillation of 5-aminosalicylic acid86
or steroids have been used with limited success
not validated by randomized controlled trials. Oral ileal release budenoside has shown some benefit in antibiotic refractory pouchitis.87 Infliximab has also been reported to be valuable in a small group of patients refractory to antibiotics and oral budenoside.88
shown to be successful in pouchitis complicated by fistulas.89,90
It has also been Other
avenues of medical therapy including AST-120 (a spherical carbon adsorbent) with the ability to adsorb small-molecular-weight toxins, inflammatory mediators, and harmful bile acids is showing promise in treating active pouchitis.91
If medical treatment fails, diversion of the
fecal stream by a loop ileostomy or pouch excision with permanent end ileostomy can give immediate and long-lasting relief of symptoms. The treatment algorithm is outlined in Figure 1.
Long-term Consequences
Long-term follow-up after IPAA is necessary because of the risk for dysplasia and cancer.29
and in patients with a history of sclerosing cholangitis.96 The publication of case reports of adenocarcinoma developing in the mid-portion of the pouch is most concerning.97
chronic atrophic pouchitis,92–94 specimen,95
A recent review of a
large series of 3,203 patients who underwent IPAA identified 11 patients with cancer. The cumulative incidence of pouch neoplasia at five, 15, and 25 years was 0.9, 1.9, and 5.1%, respectively. Dysplasia associated with pouch cancer was common. Endoscopy with biopsy failed to detect the majority of pouch dysplasia and patients may not have endoscopically visible lesions at the time of pouch cancer diagnosis. In addition, mucosectomy did not necessarily prevent cancer developing in the remaining mucosa of the anal canal.95
n ileo-anal anastomosis, Annals of Surgery, 1982;195:435–43.
3. Heppell J, Kelly KA, Pouchitis. Operative strategies in inflammatory bowel diseases, Michelassi F, Milsom JW (eds), New York: Springer, 1999:497–508.
4. de Silva HJ, Millard PR, Kettlewell M, et al., Mucosal characteristics of pelvic ilea pouches, Gut, 1991;32:61–5.
5. Fruin AB, El-Zammer O, Stucchi AF, et al., Colonic metaplasia in the ileal pouch is associated with inflammation and is not the
US GASTROENTEROLOGY & HEPATOLOGY REVIEW 25
It has been estimated to be higher in patients with presence of neoplasia in the colectomy
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