Pouch Disease Activity Index Research Articles

Clinical utility of C-reactive protein in patients with ileal pouch anal anastomosis†

Inflammatory and noninflammatory complications of ileal pouch-anal anastomosis (IPAA) are common after restorative proctocolectomy for ulcerative colitis (UC). The clinical utility of C-reactive protein (CRP) in ileal pouch disorders has not been investigated. All IPAA patients with underlying UC who had serum CRP tested within 2 weeks of pouch endoscopy were included. The correlation between the level of serum CRP and the Pouch Disease Activity Index (PDAI) scores were evaluated. Diagnostic accuracy of CRP in assessing disease activity by PDAI endoscopy subscores was evaluated. There were 83 patients (with a total 88 CRP tests), including normal pouches (n = 7), active pouchitis (n = 6), chronic pouchitis (n = 18), Crohn's disease of the pouch (n = 23), cuffitis (n = 13), irritable pouch syndrome (n = 10), and surgery-associated complications (n = 11). Levels of CRP did not differ significantly among healthy and diseased pouch groups. CRP levels significantly correlated with the PDAI endoscopy subscores in the pouch body (P = 0.006) and afferent limb (P = 0.03). A CRP level of greater than 0.7 mg/dL for CRP using the receiver operating characteristics curve obtained the best sensitivity of 69.7% and specificity of 63.6% to detect active pouch inflammation. Serum CRP levels correlated with endoscopic inflammation in the pouch and afferent limb. Elevated CRP levels might be useful to monitor the degree of inflammatory activity in pouch noninvasively. However, the CRP level as a snapshot had a limited role in distinction between healthy and diseased pouch conditions diagnosed based on longitudinal clinical and endoscopic evaluation.

Bacterial community diversity in cultures derived from healthy and inflamed ileal pouches after restorative proctocolectomy

Pouchitis is believed to occur as a reaction to dysbiosis. In this study we assessed differences between mucosal bacterial communities cultured from noninflamed and inflamed ileal pouches. Thirty-two ileal pouch patients, 22 with ulcerative colitis (UC) and 10 with familial adenomatous polyposis (FAP), underwent symptomatic, endoscopic, and histological assessment. The Objective Pouchitis Score (OPS) and the Pouch Disease Activity Index (PDAI) were used to diagnose pouchitis. Seven UC patients had pouchitis (UC+), 15 had a noninflamed pouch (UC-), 9 had a noninflamed pouch (FAP-), and 1 FAP patient had pouchitis (FAP+). Biopsies taken from the ileal mucosa of the pouch were cultured under aerobic and anaerobic conditions. Following standardized DNA extraction a polymerase chain reaction (PCR) was performed to generate 16S rRNA gene products. A "fingerprint" of the bacterial community within each sample was created using terminal-restriction fragment length polymorphism (T-RFLP) profiling. Species richness and evenness were determined using T-RF band lengths and relative band intensities. From the 64 DNA samples, 834 bands were detected, of which 179 represented different species (operational taxonomic units [OTUs]). The average species richness for the FAP-, FAP+, UC-, and UC+ groups was 26, 35, 23.9, and 29.6 per patient, with the average species diversity within the groups of 10.6, 29, 8.3, and 11.4, respectively. Similar trends were observed when the anaerobic and aerobic-derived bacterial groups were analyzed separately. No significant differences were found between the bacterial cultures derived from any of the clinical groups or between pouchitis and nonpouchitis patients.

Faecal M2-pyruvate kinase: a novel, noninvasive marker of ileal pouch inflammation

Dimeric M2-pyruvate kinase (dM2-PK) is overexpressed in tumour cells with rapid cell turnover. Its concentrations correlate well with the staging and metastatic capability of the tumour cells. We investigated the use of faecal dM2-PK as a noninvasive marker of pouch inflammation (pouchitis) in patients having undergone restorative proctocolectomy. Stool samples were obtained from 46 patients with ulcerative colitis (UC) and eight with familial adenomatous polyposis. Pouchitis was defined using the objective pouchitis score (OPS) and the pouch disease activity index. Faecal dM2-PK was measured using a quantitative sandwich-type enzyme immunoassay (ScheBo Biotech UK) and the results compared with reciprocal faecal calprotectin concentrations. Using the OPS, 6 of the 46 patients with UC had pouchitis and prepouch ileitis, 13 had UC pouchitis alone, and 27 had a non-inflamed UC pouch. One patient with familial adenomatous polyposis had pouchitis and prepouch ileitis and 7 had an non inflamed pouch. Respective median dM2-PK values (U/ml) for these five groups were 49.5 (4.5-110), 12 (1-192.3), 2.2 (0.1-95.2), 19.5 and 1 (0.1-3). Statistically significant differences were noted between inflamed and non inflamed pouches (P<0.0001). dM2-PK correlated significantly with the OPS, pouch disease activity index, endoscopic appearances, acute histological and neutrophil scores (<0.0001). The receiver operating characteristic analysis demonstrated a sensitivity and specificity of 80 and 70.6%, respectively. dM2-PK and faecal calprotectin concentrations correlated closely (r=0.87, P<0.0001). This study demonstrates that faecal dM2-PK is a sensitive marker of pouch inflammation and that its concentration directly correlates with the objective markers of pouchitis severity.

S1118 Pregnancy, Disease Activity and IBD Medication: This Two-Edged Sword from a Patient Perspective

Background: Ileal pouch anal anastomosis (IPAA) is the surgical treatment of choice for ulcerative colitis (UC) patients. The procedure is safe and effective but is also associated with long term complications such as pouch inflammation (pouchitis) reported in up to 60% of patients. The reasons for pouch inflammation are vague and prediction of pouchitis is still impossible. Normal pouch status is usually defined clinically and there is lack of longitudinal studies investigating the processes occurring in a “normal” pouch. Aim: To evaluate the clinical, laboratory, endoscopic and histologic characteristics of normal pouches longitudinally. Methods: UC Patients undergoing IPAA were prospectively followed up at a pouch clinic. Clinical, laboratory, endoscopic and histologic evaluation was performed at least yearly. Normal pouch status was defined at first visit as no previous episodes of pouchitis and pouch disease activity index (based on clinical, endoscopic and histologic scores, maximum 6 points each)<7 for the first two years of follow up without antibiotic or anti inflammatory treatment. Patients were used as their own controls, thus only patients with≥2 follow up visits were included. Results: Out of 167 pouch patients 25 (15%, 12 males, average age 47.4 ±14.6 years) were recruited to the “normal pouch” cohort. Time since surgery was 8±6.3 (range 3-14). Average number of bowel movements: 6.2±2/day. Fifteen (66%) patients had an elevated ESR or CRP and the average ESR and CRP were 36±21.4 and 6.5±7.8, respectively. Fourteen patients (56%) had an endoscopic score ≥2 and 8 (32%)≥3; Ten patients (40%) had a histologic score≥2 in at least one endoscopy. Moreover, in 9 patients (36%) endoscopic or histologic scores increased over a 5 year follow up. Four patients (16%) developed an episode of pouchitis within 5 years of follow up. Interestingly, in a control group of familial adenomatous polyposis pouch patients, increased inflammatory indices, endoscopic or histologic scores were not observed, and no episodes of pouchitis were reported. Conclusions: An ileal pouch in UC patients is an inflammatory condition per se. Subclinical inflammation exists in the majority of clinically “normal pouch” patients and tends to increase over time. Overt pouchitis developed at a rate of 16%/ five years. The lack of correlation between clinical, endoscopic and histologic scores necessitates their combined use for patient follow up. Anti inflammatory therapeutic interventions may be advised.

P178 - A pilot study of elemental diet for chronic pouchitis

P178 - A pilot study of elemental diet for chronic pouchitis

P151 - How variable is the Mayo score between observers and might this affect trial recruitment or outcome?

P151 - How variable is the Mayo score between observers and might this affect trial recruitment or outcome?

Fecal Coliform Testing to Identify Effective Antibiotic Therapies for Patients With Antibiotic-Resistant Pouchitis

Empiric antibiotic therapy (eg, a combination of ciprofloxacin and metronidazole) is effective in treating the majority of patients with inflammation of the ileal reservoir (pouchitis). Unfortunately, up to 20% of patients develop refractory or rapidly relapsing disease. We developed a fecal sensitivity analysis to determine which antibiotics are most likely to be effective in patients who do not respond to empiric antibiotic therapy or have relapsed after long-term therapy. Fecal samples from 15 patients with active pouchitis (pouch disease activity index [PDAI], > or =7) who failed standard antibiotic treatment were inoculated onto Iso-sensitest agar. Antibiotic testing discs were added, incubated, and sensitivity patterns were recorded. Patients then were treated with antibiotics based on predicted sensitivity; PDAI scores were assessed 4 weeks later. Thirteen patients enrolled in the study had failed to enter remission after treatment with ciprofloxacin and metronidazole and 2 patients had relapsed after maintenance treatment with ciprofloxacin. Antibiotic coliform sensitivity testing showed ciprofloxacin resistance in all samples, co-amoxiclav resistance in 4 samples, trimethoprim resistance in 11 samples, and cefixime resistance in 8 samples. All 15 patients were treated with an antibiotic to which their fecal coliforms were sensitive; 12 (80%) achieved clinical remission (PDAI score, 0). Fecal coliform sensitivity analysis can identify effective antibiotic therapies for patients with antibiotic-resistant pouchitis. This targeted antibiotic approach is recommended in all patients who fail to respond to empiric antibiotic treatment or relapse after long-term antibiotic therapy.

Faecal calprotectin: a noninvasive diagnostic tool and marker of severity in pouchitis

In pouchitis, the mucosa is infiltrated by activated polymorphonuclear neutrophils capable of producing calprotectin, a stable antimicrobial myelomonocytic protein. The aim is to assess the ability of faecal calprotectin to differentiate between inflamed and noninflamed ileal pouches, and to correlate this with inflammation severity using the newly developed Objective Pouchitis Score. Fifty-four stool samples were collected from patients who had undergone restorative proctocolectomy; 46 from patients with ulcerative colitis and eight from those with familial adenomatous polyposis coli. Faecal calprotectin concentrations were determined by quantitative enzyme-linked immunosorbant assay. Of the ulcerative colitis patients, six were diagnosed with pouchitis and pre-pouch ileitis (median faecal calprotectin: 865 microg/g, with a range of 95-2350 microg/g); 13 had pouchitis alone (145, 33-3350 microg/g) and 27 were uninflamed (56, 4-705 microg/g). Of the familial adenomatous polyposis patients, one had pouchitis and pre-pouch ileitis (305 microg/g), and seven had noninflamed pouches (9, 6-26 microg/g). Stool samples obtained from pouchitis patients had significantly higher calprotectin concentrations compared with those obtained from uninflamed pouches (Mann-Whitney: P<0.0001). Faecal calprotectin concentrations correlated closely with the Objective Pouchitis Score, the Pouch Disease Activity Index and endoscopic and histological inflammatory scores (Spearman rank test: P values <0.0001). Using a faecal calprotectin threshold of >or=92.5 microg/g to define a positive result, Receiver Operating Characteristic analysis demonstrated a sensitivity of 90% and a specificity of 76.5%. Faecal calprotectin measurement is a useful noninvasive tool in the diagnosis of acutely inflamed ileal pouches and correlates well with the severity of pouchitis.

The Assessment of a Rapid Noninvasive Immunochromatographic Assay Test for Fecal Lactoferrin in Patients with Suspected Inflammation of the Ileal Pouch

Pouchitis is a common complication after ileal pouch-anal anastomosis. Diagnosis is based on the Pouch Disease Activity Index, which comprises clinical symptoms, endoscopic appearance, and histologic confirmation. A Pouch Disease Activity Index > or = 7 confirms pouchitis. Fecal lactoferrin is a marker of intestinal inflammation, which can aid in the diagnosis of pouchitis. The IBD EZ VUE test is a simple, rapid, noninvasive test for fecal lactoferrin. Our goal was to study the sensitivity and specificity of this test in the diagnosis of pouchitis. Consecutive patients with pouch dysfunction were recruited from October 2005 to July 2006. A fecal sample was collected before calculation of the Pouch Disease Activity Index. An IBD EZ VUE test was performed on each fecal sample and the results correlated with the diagnosis of pouchitis to calculate sensitivity and specificity of the IBD EZ VUE test. There were 32 patients (21 healthy and 11 inflamed pouches). The IBD EZ VUE test was positive in 14 patients. It had a sensitivity of 100 percent and a specificity of 86 percent in diagnosing pouchitis. The positive predictive value was 76 percent. There were three false-positive results. The IBD EZ VUE test is a sensitive method that may remove the need for invasive pouch investigations and lead to greater confidence when antibiotic therapy is commenced. Further investigations may be reserved for those patients who have a positive lactoferrin test and fail to respond to antibiotic treatment.

Medium-term results of oral tacrolimus treatment in refractory inflammatory bowel disease

This study aimed to evaluate the efficacy of oral tacrolimus in patients with inflammatory bowel disease (IBD) refractory to conventional therapy, including azathioprine, 6-mercaptopurine, and infliximab. Retrospective review of all patients with IBD treated with oral tacrolimus was undertaken. Tacrolimus was administered t an initial dose of 0.05 mg/kg twice daily, aiming for serum trough levels of 5-10 ng/mL. We evaluated clinical response, a retrospective estimated Crohn's disease activity index (CDAI) for Crohn's disease (CD), modified Truelove-Witts index for ulcerative colitis (UC), and modified pouch disease activity index (mPDAI) for pouchitis. Patients had been monitored clinically for benefit and side effects and by whole blood tacrolimus level approximately every 4 weeks for the duration of treatment. Clinical remission was defined as an estimated CDAI <150 (CD), an inactive disease score on the Truelove-Witts index (UC), and mPDAI <5 (pouchitis). Twelve patients with CD, six with UC, and one with pouchitis, all resistant to previous therapies, were treated for a median of 5 months. After 4 weeks 10 CD (83%), four UC (67%) patients, and one pouchitis patient had a clinical response. There was a median reduction of the estimated CDAI of 108 points (range 35-203; P = 0.002) and stool frequency of three per day at week 4. Remission was achieved in 42% (5/12) of CD and 50% (3/6) of UC patients at the end of follow-up. Side effects included temporary elevated creatinine (n = 1), tremor (n = 3), arthralgia (n = 1), insomnia (n = 1), and malaise (n = 1). Four patients discontinued treatment due to side effects. CONCLUSION-: Oral tacrolimus is well tolerated and effective in patients with refractory IBD in the short- to medium-term. Further controlled, long-term evaluation is warranted.

Mental Disorder and Psychologic Distress in Patients With Ulcerative Colitis After Ileal Pouch-Anal Anastomosis

The aim of this study was to determine if ileal pouch-anal anastomosis in patients with ulcerative colitis is a psychologic burden for patients, the frequency of mental disorders, the amount of psychologic distress, and their possible disease-related determinants. These factors were studied in patients with ulcerative colitis after ileal pouch anal anastomosis and were compared with ulcerative colitis patients without ileal pouch-anal anastomosis and the general German population. A total of 37 patients with ulcerative colitis after ileal pouch-anal anastomosis (age 46.8 +/- 11.8 years; 35 percent female) and 62 patients with ulcerative colitis without ileal pouch-anal anastomosis (age 44.4 +/- 13.9 years; 37 percent female) completed the following questionnaires: medical and sociodemographic questionnaire of the German Competence Network "Inflammatory Bowel Diseases" and the German version of the Hospital Anxiety and Depression Scale. Disease activity was measured in patients with ileal pouch-anal anastomosis by the Pouch Disease Activity Index and in patients without ileal pouch-anal anastomosis by the German Inflammatory Bowel Disease Activity Index. Psychologic distress was assessed by the subscale scores of the Hospital Anxiety and Depression Scale. A probable mental disorder was identified if a patient scored 11 or higher in at least one subscale of the Hospital Anxiety and Depression Scale. The frequency of a probable psychiatric disorder in patients with ileal pouch-anal anastomosis (16 percent) and without ileal pouch-anal anastomosis (23 percent) did not differ from that in the general German population (17 percent). Ulcerative colitis patients with or without ileal pouch-anal anastomosis did not differ in the amount of psychologic distress. Ileal pouch-anal anastomosis patients had higher levels of anxiety than the general population (P < 0.01). Regression models of disease-related factors predicting mental disorder and psychologic distress showed no significant results. Ileal pouch-anal anastomosis neither increases nor decreases the frequency of mental disorders or the amount of psychologic distress in ulcerative colitis patients.

The diagnosis and treatment of pouchitis in inflammatory bowel disease.

The ileal pouch anal anastomosis (IPAA) procedure has become the preferred surgical option for most patients with ulcerative colitis who require surgical removal of the colorectum. The vast majority of patients with this new anatomy will either not develop pouchitis or develop a few discrete episodes of acute pouchitis. However approximately one fourth of patients will develop recurrent pouchitis, with 5% being categorized as chronic pouchitis requiring maintenance therapy or, on rare occasion, pouch excision. Factors that are associated with an increased risk of pouchitis include primary sclerosing cholangitis, extraintestinal manifestations, and nonsmokers. Controversy surrounds other risk factors such as extent of colitis, backwash ileitis, preoperative pANCA levels, and carrying a specific allele for IL-1 receptor antagonist. The etiology of pouchitis is unknown, but theories range from genetic susceptibility, bacterial overgrowth, ischemia, and fecal stasis, to a recurrence of ulcerative colitis in the pouch, a missed diagnosis of Crohn's disease, or possibly a novel third form of inflammatory bowel disease. Some patients with symptoms of pouchitis will not have inflammation of the pouch, but rather, irritable pouch syndrome. Thus, endoscopic investigation with biopsy is important for declaring whether a patient has pouchitis. Indeed, the more commonly used scores, such as the pouch disease activity index, incorporate both endoscopic and histologic criteria. Not surprisingly, treatment options for patients with pouchitis resemble that of regular inflammatory bowel disease, although there have only been a few controlled trials. Antibiotics are the mainstay of therapy, with metronidazole and ciprofloxacin demonstrating benefit in controlled trials. Probiotics are effective for maintaining remission of pouchitis. Mesalamine, corticosteroids, and immunomodulators have been used with some success. Occasionally, patients with well-documented ulcerative colitis as the indication for IPAA will develop what appears to be Crohn's disease of the pouch, on the basis of granulomatous inflammation, pre-pouch ileitis, or fistulae. The treatment is similar to Crohn's disease, including the use of infliximab. Dysplasia within the pouch mucosa itself is quite rare. Reports of dysplasia occurring in patients with IPAA are usually due to neoplastic change within the residual cuff of rectal or transition zone mucosa just below the pouch, rather than in the ileal mucosa of the pouch. With further elucidation of the genetic basis for inflammatory bowel disease, we should be able to more accurately classify patients with ulcerative colitis and Crohn's disease genotypically. Hopefully, this will also bring more clarity to the heterogeneous population of patients with pouchitis and allow for more focused therapeutic strategies.

Effect of enteral inulin on the pouch disease activity index and on epithelial gene expression within the ileoanal pouch: A randomized, placebo-controlled crossover study

Effect of enteral inulin on the pouch disease activity index and on epithelial gene expression within the ileoanal pouch: A randomized, placebo-controlled crossover study