Pathogenesis of and unifying hypothesis for idiopathic pouchitis.
Ileal pouch-anal anastomosis is the procedure of choice in the surgical management of refractory ulcerative colitis. Pouchitis affects up to 60% of patients following ileal pouch-anal anastomosis for ulcerative colitis. It overlaps significantly with ulcerative colitis such that improvements in our understanding of one will impact considerably on the other. The symptoms are distressing and impinge significantly on patients' quality of life. Despite 30 years of scientific and clinical investigation, the pathogenesis of pouchitis is unknown; however, recent advances in molecular and cell biology make a synergistic hypothesis possible. This hypothesis links interaction between epithelial metaplasia, changes in luminal bacteria (in particular sulfate-reducing bacteria), and altered mucosal immunity. Specifically, colonic metaplasia supports colonization by sulfate-reducing bacteria that produce hydrogen sulfide. This causes mucosal depletion and subsequent inflammation. Although in most cases antibiotics lead to bacterial clearance and symptom resolution, immunogenetic subpopulations can develop a chronic refractory variant of pouchitis. The aims of this paper are to discuss proposed pathogenic mechanisms and to describe a novel mechanism that combines many hypotheses and explains several aspects of pouchitis. The implications for the management of both pouchitis and ulcerative colitis are discussed.
Coffey
J Calvin
JC
School of Medicine and Medical Sciences University College Dublin, St Vincent's University Hospital, Dublin, Ireland. calvincoffey@hotmail.com
Rowan
Fiachra
F
Burke
John
J
Dochery
Neil G
NG
Dochery
Neil
N
Kirwan
William O
WO
O'Connell
P Ronan
PR
D001003:Anal Canal / Q000382:microbiology / Q000473:pathology / Q000601:surgery; D000714:Anastomosis, Surgical / Q000379:methods; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001419:Bacteria / Q000254:growth & development*; D003093:Colitis, Ulcerative / Q000601:surgery; D039021:Colonic Pouches / Q000382:microbiology / Q000473:pathology; D003937:Diagnosis, Differential; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology*; D008679:Metaplasia / Q000473:pathology; D011183:Postoperative Complications; D019449:Pouchitis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology
D000900:Anti-Bacterial Agents