Introduction
Despite recent advances in medical therapy, approximately 25% to 30% of patients with ulcerative colitis (UC) will need surgery for refractory colitis or colitis-associated neoplasia. For these patients, a total proctocolectomy with ileal pouch–anal anastomosis (IPAA) is the standard surgical option. During the past four decades, IPAA has been constantly shown to reduce the risk of UC-associated neoplasia and to improve quality of life. On the other hand, construction of an IPAA is technically demanding, with mechanical, inflammatory, and functional sequelae that can be minimized by good technique, but not completely avoided. Pouchitis and irritable pouch syndrome are the most common inflammatory and functional disorders of the pelvic pouch and will be discussed in this chapter.
Pouchitis
Pouchitis is inflammation of an ileal pouch. It can be specific (with an identifiable cause) or nonspecific. Cumulative frequencies of pouchitis after IPAA range from 23% to 46% over 10 to 11 years of follow-up. In a small clinical drug trial of prophylaxis of pouchitis with a probiotic agent, the incidence was 40% within the first 12 months after ileostomy closure.
Etiology and Pathogenesis
It is intriguing that pouchitis occurs almost exclusively in patients with underlying UC and is rarely seen in patients with a pouch who have familial adenomatous polyposis, suggesting causative factors in common with UC that may be genetic and/or systemic. In general, pouchitis results from alterations in commensal luminal microflora (dysbiosis) and subsequent abnormal mucosal immune response in genetically susceptible hosts.
Genetic Factors
Immunogenetic studies have shown that polymorphisms in genes such as those coding for interleukin-1 receptor antagonist NOD2/CARD15 or a combined carrying of TLR9-1237C and CD14-260T alleles are associated with an increased risk of chronic pouchitis.
The Microbiome
Multiple layers of evidence support the role of the microbiome in the development of pouchitis. For example, the manipulation of microflora with probiotic or antibiotic agents in patients with pouchitis is often beneficial. Although most acute episodes of pouchitis appear to be associated with dysbiosis, sometimes pathogenic bacteria, viruses, and fungi can be found in a subset of patients, especially those who present with constitutional symptoms (e.g., fever, night sweats, malaise, weight loss). Clostridium difficile is commonly present in symptomatic patients with IPAA. Other bacterial pathogens that have been implicated in flare-ups of pouchitis include Clostridium perfringens, Campylobacter species, group D streptococci (enterococci), and hemolytic strains of Escherichia coli . Case series of cytomegalovirus infection in immunocompetent patients with pelvic pouches have been reported. Opportunistic infection with fungi (such as Candida albicans ) has also been encountered in patients with chronic antibiotic-refractory pouchitis (CARP) after long-term antibiotic use.
Mucosal Immunity
Abnormalities of both innate and adaptive mucosal immunities have been implicated in the pathogenesis of pouchitis. An aberrant toll-like receptor expression pattern has been found in the inflamed ileal pouch, and a greater number of copies of human defensin-5 messenger ribonucleic acid (mRNA) have been described in the inflamed or noninflamed pouches than in the normal terminal ileum. A greater number of tissue mRNA copies of Paneth cell human defensin–5 and gut epithelium–produced β defensins were also found in both UC and familial adenomatous polyposis pouches. As in persons with IBD, mucosal adaptive immunity has been extensively studied in persons with pouchitis, with most literature from 1990s. The production of inflammatory mediators is increased, including proinflammatory cytokines, cell adhesion molecules, and vascular endothelial growth factor. Clinically, patients with antibiotic-refractory pouchitis often have other immune-mediated disorders, such as primary sclerosing cholangitis (PSC), autoimmune diseases, and autoinflammatory disorders. It appears that the B cell system may also play a role in the pathogenesis of CARP, which is typified by the presence of an excessive number of immunoglobulin (Ig)G4-expressing plasma cells in the lamina propria of pouch mucosa and/or an elevated level of serum IgG4. The latter condition is now labeled IgG4-associated pouchitis.
The pathogenesis of pouchitis is complicated. In addition to the bacterial and immunologic theories, genetic, mechanical (such as ischemia), and luminal factors (such as the use of nonsteroidal antiinflammatory drugs [NSAIDs]) contribute to the disease initiation, flare-ups, and progression.
Etiology and Pathogenesis
It is intriguing that pouchitis occurs almost exclusively in patients with underlying UC and is rarely seen in patients with a pouch who have familial adenomatous polyposis, suggesting causative factors in common with UC that may be genetic and/or systemic. In general, pouchitis results from alterations in commensal luminal microflora (dysbiosis) and subsequent abnormal mucosal immune response in genetically susceptible hosts.
Genetic Factors
Immunogenetic studies have shown that polymorphisms in genes such as those coding for interleukin-1 receptor antagonist NOD2/CARD15 or a combined carrying of TLR9-1237C and CD14-260T alleles are associated with an increased risk of chronic pouchitis.
The Microbiome
Multiple layers of evidence support the role of the microbiome in the development of pouchitis. For example, the manipulation of microflora with probiotic or antibiotic agents in patients with pouchitis is often beneficial. Although most acute episodes of pouchitis appear to be associated with dysbiosis, sometimes pathogenic bacteria, viruses, and fungi can be found in a subset of patients, especially those who present with constitutional symptoms (e.g., fever, night sweats, malaise, weight loss). Clostridium difficile is commonly present in symptomatic patients with IPAA. Other bacterial pathogens that have been implicated in flare-ups of pouchitis include Clostridium perfringens, Campylobacter species, group D streptococci (enterococci), and hemolytic strains of Escherichia coli . Case series of cytomegalovirus infection in immunocompetent patients with pelvic pouches have been reported. Opportunistic infection with fungi (such as Candida albicans ) has also been encountered in patients with chronic antibiotic-refractory pouchitis (CARP) after long-term antibiotic use.
Mucosal Immunity
Abnormalities of both innate and adaptive mucosal immunities have been implicated in the pathogenesis of pouchitis. An aberrant toll-like receptor expression pattern has been found in the inflamed ileal pouch, and a greater number of copies of human defensin-5 messenger ribonucleic acid (mRNA) have been described in the inflamed or noninflamed pouches than in the normal terminal ileum. A greater number of tissue mRNA copies of Paneth cell human defensin–5 and gut epithelium–produced β defensins were also found in both UC and familial adenomatous polyposis pouches. As in persons with IBD, mucosal adaptive immunity has been extensively studied in persons with pouchitis, with most literature from 1990s. The production of inflammatory mediators is increased, including proinflammatory cytokines, cell adhesion molecules, and vascular endothelial growth factor. Clinically, patients with antibiotic-refractory pouchitis often have other immune-mediated disorders, such as primary sclerosing cholangitis (PSC), autoimmune diseases, and autoinflammatory disorders. It appears that the B cell system may also play a role in the pathogenesis of CARP, which is typified by the presence of an excessive number of immunoglobulin (Ig)G4-expressing plasma cells in the lamina propria of pouch mucosa and/or an elevated level of serum IgG4. The latter condition is now labeled IgG4-associated pouchitis.
The pathogenesis of pouchitis is complicated. In addition to the bacterial and immunologic theories, genetic, mechanical (such as ischemia), and luminal factors (such as the use of nonsteroidal antiinflammatory drugs [NSAIDs]) contribute to the disease initiation, flare-ups, and progression.
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