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Pouchitis in Children: Therapeutic Options.

Pouchitis is an unfortunate common complication of the ileal pouch-anal anastomosis procedure, an otherwise very attractive surgical option in patients with ulcerative colitis (UC). The fact that the same pouch in familial polyposis is hardly complicated by pouchitis suggests that the basic inflammatory process in UC might participate in the pathophysiology. We review the clinical features of pouchitis, the diagnostic approach, and the many therapeutic considerations, including more recent data on prebiotics and probiotics.

Journal Article↗

Evaluation of the inflammatory infiltrate in pouchitis with 111In-labeled granulocytes.

BACKGROUND: The aim of this study was to elucidate the inflammatory infiltrate in pouchitis and define the changes following metronidazole therapy. METHODS: Twenty-seven patients underwent functional grading, sigmoidoscopic and histological scoring, 111In-labeled granulocyte scanning, and 4-day fecal collections for 111In-labeled granulocyte excretion. Six of the patients with pouchitis underwent repeat studies after 1-month treatment with metronidazole, 400 mg three times daily. RESULTS: The grade of macroscopic inflammation in the pouch mucosa (sigmoidoscopic score) correlated well with the acute histological score (P < 0.0001), chronic histological score (P < 0.001), 4-hour 111In scan (P < 0.001), 24-hour 111In scan (P < 0.001), and with 4-day fecal 111In excretion (P < 0.001). After metronidazole therapy there was decreased inflammatory grade sigmoidoscopically and histologically on the 4- and 24-hour scans and decreased 4-day fecal 111In granulocyte excretion. CONCLUSIONS: This study confirms that the inflammatory infiltrate in pouchitis is acute or chronic, is characterized by neutrophils, is usually localized to pouch mucosa, and is always decreased after metronidazole therapy.

Acute Disease↗

Comparison of the Moskowitz criteria and the pouchitis disease activity index (PDAI) for diagnosis of ileoanal pouch inflammation.

OBJECTIVE: To prospectively compare two indices for diagnosis of pouchitis: Moskowitz criteria and pouchitis disease activity index (PDAI). PATIENTS AND METHODS: Fifty-six consecutive patients with an ileoanal pouch for ulcerative colitis were recruited. A clinical questionnaire was composed and the Oresland functional score calculated. Pouchoscopy and biopsy were performed after cleansing of the pouch. RESULTS: Seven patients had pouchitis according to both Moskowitz and PDAI ('positive' group). Five patients had PDAI > or = 7, but did not fulfil the Moskowitz criteria ('negative' group). The pouchoscopy and Oresland functional scores were similar between the two groups. The biopsy neutrophilia and ulceration were more prominent in the 'positive' group (chi2=5.18, P < 0.05), whereas urgency (chi2=8.4, P < 0.001), evacuation difficulties (chi2=5.18, P < 0.05) and history of bleeding per pouch (chi2=4.18, P < 0.05) were more pronounced in the 'negative' group. CONCLUSION: Moskowitz criteria may be broadly in agreement with the PDAI; these, however, cannot be regarded as interchangeable.

Journal Article↗

Refractory pouchitis: does it reflect underlying Crohn's disease?

Typical 'pouchitis' is a well recognised complication of ileal pouches in ulcerative colitis. Infrequently, a refractory pouchitis (RP) presents with certain clinical, endoscopic, and pathological features resembling Crohn's disease and is often ascribed to misdiagnosis of the initial colitis. To test that hypothesis and to identify risk factors for RP, this study reviewed cases of presumed ulcerative colitis with ileal pouches constructed at The Mount Sinai Hospital between 1973 and 1986. Twenty four cases with RP (16 Kock pouches and eight pelvic pouches) and 21 controls were compared for eight clinical variables. The original colectomy slides from 15 RP and 18 control cases were reviewed blindly, classified into five histological categories (corresponding to definite ulcerative colitis, definite Crohn's disease, and three indeterminate groups), and scored for 23 histological features. There were no significant clinical differences between RP and control cases except for more frequent extraintestinal manifestations (38% v 5%) and male preponderance (79% v 43%) in RP. There were also no significant differences between the distributions of RP cases and controls among the five histological categories or in the 23 histological features studied. Refractory pouchitis therefore does not seem to reflect underlying Crohn's disease, but may be linked to immunological mechanisms that are manifested clinically as extraintestinal complications.

Adult↗

Cyclosporin A retention enemas in refractory distal ulcerative colitis and 'pouchitis'.

The aim of this study was to evaluate the use of cyclosporin enemas in patients with distal ulcerative colitis and 'pouchitis' resistant to all conventional medical therapy. In an trial 12 patients with distal ulcerative colitis unresponsive to treatment with topical and oral corticosteroids, 5-aminosalicylic acid, and oral immunosuppressive therapy together with 1 patient with 'pouchitis' unresponsive to repeated courses of antibiotics, topical corticosteroids, and oral mesalazine received 250 mg cyclosporin administered daily as a retention enema. Changes in symptoms and the sigmoidoscopic/histologic appearances of the rectal mucosa were assessed at monthly intervals. Seven of 12 patients with ulcerative colitis improved. There was a strong correlation between clinical and histologic improvement (p < 0.005). Four of 12 patients showed no response. Three of these required colectomy, two of whom had more extensive disease than had previously been documented. The patient with pouchitis showed improvement in symptoms and 'pouchoscopy' appearance but not in histologic score. Cyclosporin blood concentrations were very low and side effects negligible. Cyclosporin A retention enemas are safe and may be useful in the treatment of severe refractory distal ulcerative colitis. A controlled trial would now seem warranted.

Adult↗

Pouchitis (pouch ileitis).

Construction of a continent ileostomy or ileo-anal reservoir after (procto)colectomy has provided many patients suffering from inflammatory bowel disease-in particular ulcerative colitis or polyposis coli--with a major improvement in their social wellbeing. However, complications are rather frequent and pouchitis is one of the most important chronic ones, to be defined as the combination of bothersome clinical symptoms (abdominal pain, bloating, increased faecal output, sometimes fever) with evident endoscopic abnormalities of the reservoir ileal mucosa (oedema, reddened mucosa, minor flat up to large irregular ulcerations). The contribution of pouch biopsies is limited, because chronic inflammation is always demonstrable and evidence of acute inflammation is only rarely present. Although backwash ileitis does not promote the occurrence of pouchitis, the immunological mechanism might be highly comparable. Cultures of faecal content for specific pathogens is necessary; bacterial anaerobic or aerobic overgrowth appears to be of no major significance in the development of pouchitis. Nevertheless, a short-term course with metronidazole is nearly always effective, although recurrences are far from rare. In this situation a course of corticosteroid enemas or even maintenance therapy (2-3 wk) should be advised. Experience with mesalazine compounds is limited and should be expanded.

Anastomosis, Surgical↗

Dysbiosis and pouchitis.

BACKGROUND AND METHODS: The exact aetiology of pouchitis is unknown, but an association with dysbiosis has been suggested. This is a retrospective review of 17 studies published between 1985 and 2005, identified by a search of the Medline, Pubmed and Embase databases. RESULTS: The methodology of the studies varied widely. Many were performed at a time when the distinction between a healthy and an inflamed pouch was vague; misclassification of patients makes the analysis of data difficult and conclusions uncertain. CONCLUSION: The evidence that dysbiosis is a cause of pouchitis is poor. Nevertheless, available data allow the construction of an algorithm to aid management and suggest a structured approach for future research.

Algorithms↗

Pouchitis: risk factors, etiology, and treatment.

A Medline literature review of pouchitis has been conducted, and relevant information from this search and the authors' own experience has been used to produce an overview on pouchitis at the current time. Particular attention is given to etiology, pathophysiology, and clinical management.

Antidiarrheals↗

Arthritis accompanying ileal pouchitis or undifferentiated HLA B27-related spondyloarthropathy?

The case of an HLA B27(+) patient who developed inflammatory arthritis accompanying ileal pouchitis, following total proctocolectomy for familial adenomatous polyposis is presented for the first time in the literature. Based on its clinical presentation and serology, it can be classified either as arthritis accompanying ileal pouchitis, or as an undifferentiated spondyloarthropathy.

Adult↗

Cancer risk assessment in long-standing pouchitis. DNA aberrations are rare in transformed neoplastic pelvic pouch mucosa.

BACKGROUND: In a small subgroup of patients with ulcerative colitis (UC) undergoing proctocolectomy and restorative ileal pouch-anal anastomosis (IPAA), a colonic-like pouch mucosa with severe and persistent villous atrophy (type C pattern) develops. Neoplastic transformation of the mucosa in the neorectum may occur in these patients. We hypothesized that genetic alterations associated with colorectal carcinoma (CRC) could be an early finding in this transformational process and thus potentially useful as clinical monitors in carcinoma risk assessment. METHODS: In six patients with long-standing severe pouchitis and a type C-pattern mucosa, biopsies were obtained from five different locations of the pouches. DNA was PCR-amplified and analyzed by automated fragment analysis for loss of heterozygosity (LOH) at chromosome 5q14-22, 17p12-13, and 18q12-22. Point mutations of the K-ras and adenomatous polyposis coli (APC) genes were studied by sequencing. RESULTS: The patients had varying degrees of dysplasia and one displayed DNA aneuploidy. Loss of heterozygosity at 5q15-22 was detected in three of five biopsies in one patient. This particular patient had no signs of dysplasia or DNA aneuploidy and a normal exon 15 sequence of the APC gene. No alterations of either the K-ras or the APC genes or LOH of 5q, 17p, or 18q were seen in any of the other patients. CONCLUSION: Dysplasia, aneuploidy, and LOH in 5q may all reflect different parts of an atrophic mucosa-dysplasia-carcinoma sequence, in line with current concepts of carcinogenesis for CRC in long-standing pouchitis. Further studies of histological and molecular events in IPAA patients with severe atrophy are warranted.

Adult↗

Pouch and pouchitis.

Pouchitis is an inflammation of unknown origin occurring in the ileal pouch after IPAA. It is considered by many to be a form of ulcerative colitis that recurs in the pouch and rarely, if ever, occurs in patients with FAP. Most patients respond to a short course of antibiotics. When remission cannot be maintained or the disease is nonresponsive to prolonged treatment with antibiotics, anti-inflammatory agents or steroids may be useful. A variety of alternative drugs have been tried with mixed success and should be considered as experimental. Rarely, when pouchitis is refractory to medical management, excision of the pouch may be required.

Humans↗

Stricture and pouchitis after ileal pouch-anal anastomosis.

Ileal pouch-anal anastomosis is a surgical procedure used for the treatment of people with chronic ulcerative colitis and familial adenomatous polyposis. The surgery is intended to preserve anal sphincter function, but it carries a risk for certain complications, including pouchitis and anastomotic stricture. The purpose of this article is to review the clinical manifestations, causes, and treatment of anastomotic stricture and pouchitis after ileal pouch-anal anastomosis.

Anastomosis, Surgical↗

Risk of dysplasia in long-term ileal pouches and pouches with chronic pouchitis.

BACKGROUND & AIMS: Recent reports have suggested the mucosa of an ileal reservoir could be at risk of neoplasia. Risk factors may include the age of the pouch, chronic pouchitis, and previous colonic neoplasia. This study examined a group of such patients to determine the risk of dysplasia. METHODS: From a cohort of 1221 patients with ileal pouches, 171 patients with possible risk factors were selected. Successful contact was made with 138 patients who were invited for endoscopy and multiple biopsies. Biopsy specimens were stained with H&E and p53, scored for inflammatory changes including villous atrophy, and analyzed by flow cytometry. RESULTS: One hundred six patients took part and fell into 1 or more of the following clinical categories: chronic pouchitis (n = 34), pelvic pouch for > or =12 years (n = 42); Kock pouch for > or =14 years (n = 29), and neoplasia in colectomy specimen (n = 11). Thirty-three patients had severe villous atrophy. One patient of 106 (95% confidence interval, 0.9% +/- 1.6%) with a long-standing pouch had low-grade dysplasia that was multifocal. DNA analysis by flow cytometry showed aneuploidy in this patient and 2 others. CONCLUSIONS: These data suggest that the development of dysplasia in ileal pouches performed for ulcerative colitis is probably a rare event within 15-20 years of pouch surgery.

Adult↗

Preoperative terminal ileal and colonic resection histopathology predicts risk of pouchitis in patients after ileoanal pull-through procedure.

OBJECTIVE: This study seeks to compare the histopathology of preoperative terminal ileal and colonic resection specimens with pouch biopsies after the ileoanal pull-through (IAPT) procedure. SUMMARY BACKGROUND DATA: Pouchitis is the most frequent complication of transanal continent reservoirs in patients after IAPT. METHODS: The authors conducted 751 consecutive pouch biopsies on 73 patients with inflammatory bowel disease or familial adenomatous polyposis who underwent IAPT by a single surgeon over a 10-year period. In this preliminary report, a pathologist, in blinded fashion, has graded 468 of the IAPT pouch biopsies and 67 of the patients' preoperative terminal ileal and colonic resection histopathology to date. Colonic histopathology was graded by the extent and severity of disease, terminal ileal and pouch histopathology by active inflammation, chronic inflammation, lymphocyte aggregates, intraepithelial lymphocytes, eosinophils, and villous blunting. RESULTS: Extent of colonic disease (gross and microscopic) was a significant predictor of active inflammation in subsequent IAPT pouch biopsy specimens. Also, the gross extent of colonic disease exhibited a significant linear association with pouch inflammation. However, the severity of colonic disease was not significantly predictive of active inflammation in subsequent IAPT pouch biopsies. Terminal ileal active and chronic inflammation were significant predictors of subsequent IAPT pouch inflammation. Although lymphocyte aggregates and intraepithelial lymphocytes were not predictive, terminal ileum eosinophils and villous blunting were significant predictors of active inflammation in subsequent IAPT pouch biopsy specimens. CONCLUSIONS: Preoperative terminal ileal and colonic histopathology predicts active inflammation of pouches after IAPT. Patients who are preoperatively assessed to have extensive disease of the colon, ileal disease ("backwash ileitis"), or both appear to be at greater risk for the development of pouchitis after IAPT.

Adenomatous Polyposis Coli↗

Pouchitis-associated iritis (uveitis) following total proctocolectomy and ileal pouch-to-anal anastomosis in ulcerative colitis.

A 26-year-old woman with ulcerative colitis treated with a proctocolectomy and ileal pouch-to-anal anastomosis developed an erosive and ulcerative pouchitis. Although no ophthalmological manifestations were present before the staged surgical procedures, iritis developed after appearance of the pouchitis. Both conditions subsequently resolved with oral corticosteroids and metronidazole.

Adrenal Cortex Hormones↗

[Pouchitis after ileo-anal anastomosis with a reservoir in hemorrhagic rectocolitis].

DEFINITION AND FREQUENCY: An ileoanal anastomosis with creation of an ideal pouch is proposed as the treatment for familial adenomatous polyposis and ulcerative hemorrhagic rectocolitis. The ideal pouch may become inflammatory in 10 to 30% of the cases. The diagnosis of pouchitis is based on a clinical, endoscopid and histological criteria. PATHOGENIC HYPOTHESES: Pouchitis is a late complication, mainly after ileoanal anastomosis for ulcerative rectocolitis. The pathogenic mechanism is a subject of debate. Fecal stasis, bacterial pollution, mucine secretion and the underlying inflammatory disease could be involved. TREATMENT: Antibiotics active against anaerobic bacteria, such as metronidazole, are generally given. In case of failure, common antiinflammatory agents used in inflammatory bowel disease are indicated.

Anal Canal↗

Results of pouch surgery after ileo-anal anastomosis: the implications of pouchitis.

The ileal pouch-anal operation is the procedure of choice for those suitable patients requiring surgery for chronic ulcerative colitis or familial adenomatous polyposis. The functional results are generally good but pouchitis remains a significant and poorly understood complication. This review encompasses factors relating to pouchitis, e.g., bacteriological, functional and histological changes, with emphasis on its biology and treatment, and the long-term implications.

Anal Canal↗

Perinuclear anti-neutrophil cytoplasmic antibody and refractory pouchitis. A case-control study.

Refractory pouchitis (RP) is a debilitating complication of ileal pouch reservoirs that affects approximately 2.5% of patients. Although the cause of RP is unknown, it is frequently hypothesized that it reflects underlying Crohn's disease. Since perinuclear anti-neutrophil cytoplasmic antibody (pANCA) is found in approximately 70% of ulcerative colitis patients but only rarely in Crohn's disease patients, it may help distinguish Crohn's disease from ulcerative colitis. Therefore, to test whether RP reflects "missed" Crohn's disease, we determined the ANCA status of 26 patients with RP. The pANCA was positive in 42% of cases [50% of Kock pouch cases and 33% of ileoanal pull-through (IAPT) cases] and 57% of matched control subjects without pouchitis (N = 42, P = NS). Moreover, 3/6 (50%) of IAPT RP subjects whose signs and symptoms most suggested Crohn's disease tested positive for pANCA. When compared to controls, IAPT cases exhibited significantly more preoperative extraintestinal manifestations (EIMs) of inflammatory bowel disease (P < 0.05). The presence of preoperative EIMs was 100% predictive of postoperative EIMs (P < 0.05). Review of pouch biopsies from cases of RP revealed no pathognomonic histologic features of Crohn's disease. These data confirm our previous suggestion that RP does not reflect underlying Crohn's disease but may be associated with the EIMs of inflammatory bowel disease.

Adult↗