Personalized Approach to Chronic Antibiotic-Refractory Pouchitis: A Case Report and Review of the Literature.

Patients who undergo restorative proctocolectomy and ileoanal anastomosis can develop pouchitis as a common chronic complication. A rare subset of patients fails to respond to multiple antibiotic therapies and develop chronic antibiotic-refractory pouchitis (CARP). We present a case of a 45-year-old male with pouchitis refractory to chronic antibiotic therapy and histology demonstrating chronic inflammatory changes. Management involved mesalamine and probiotics, resulting in a positive clinical response and symptom absence on follow-up. This case highlights the intricacies of treating chronic pouchitis post ileoanal anastomosis, showcasing the efficacy of a personalized approach using mesalamine and probiotics. CARP is emerging as an entity associated with poor quality of life and increased healthcare costs. CARP fails to respond to multiple courses of antibiotic therapy. Therefore, the management of CARP is difficult and limited. Current literature on the management of CARP is scarce and mainly involves immunomodulatory therapy and probiotics. It is essential to keep this differential diagnosis in mind in patients with recurrent pouchitis episodes and start them on immunomodulator treatment and probiotics rather than repeated courses of antibiotics.

Pouchitis: Clinical Features, Diagnosis, and Treatment.

Procto-colectomy with an ileal pouch anal anastomosis is the procedure of choice for ulcerative colitis patients that require colectomy. Pouchitis is a non-specific inflammation of the ileal reservoir, and the most common, inflammatory and long-term, complication after pouch surgery for ulcerative colitis. The aetiology is still unknown, but many risk factors have been individuated. Pouchitis can be classified based on aetiology, duration, clinical course, and response to antibiotic therapy. Accurate diagnosis and classification is the key factor for an adequate management, and exclusion of secondary causes of pouchitis is pivotal. Most of the patients consistently respond to antibiotic therapy, but management of the subgroup of patients with chronic-antibiotic-resistant-pouchitis is still challenging, being this entity one of the major causes of pouch failure.

Chronic Antibiotic-Refractory Pouchitis: Management Challenges.

BACKGROUND: Pouchitis is the most common long-term complication in patients with ulcerative colitis who underwent restorative proctocolectomy with ileal pouch-anal anastomosis. The incidence of acute pouchitis is 20% after 1 year and up to 40% after 5 years. Chronic antibiotic-refractory pouchitis develops in approximately 10% of patients. AIM: To present a narrative review of published literature regarding the management of chronic antibiotic-refractory pouchitis. METHODS: Current relevant literature was summarized and critically evaluated. RESULTS: Clear definitions should be used to classify pouchitis into acute versus chronic, and responsive versus dependent versus refractory to antibiotics. Before treatment is started for chronic antibiotic-refractory pouchitis, secondary causes should be ruled out. There is a need for validated scoring systems to measure the severity of the disease. Because chronic antibiotic-refractory pouchitis is a rare condition, only small studies with often a poor study design have been performed. Treatments with antibiotics, aminosalicylates, steroids, immunomodulators and biologics have shown to be effective and safe for chronic antibiotic-refractory pouchitis. Also, treatments with AST-120, hyperbaric oxygen therapy, tacrolimus enemas, and granulocyte and monocyte apheresis suggested some efficacy. CONCLUSION: The available data are weak but suggest that therapeutic options for chronic antibiotic-refractory pouchitis are similar to the treatment strategies for inflammatory bowel diseases. However, randomized controlled trials are warranted to further identify the best treatment options in this patient population.

Greater Peripouch Fat Area on CT Image Is Associated with Chronic Pouchitis and Pouch Failure in Inflammatory Bowel Diseases Patients.

BACKGROUND: The causes of chronic antibiotic refractory pouchitis (CARP) and pouch failure in inflammatory bowel disease (IBD) patients remain unknown. Our previous small study showed peripouch fat area measured by MRI was associated with pouchitis. AIMS: To explore the relationship between peripouch fat area on CT imaging and pouch outcomes. METHODS: This is a historical cohort study. Demographic, clinical, and radiographic data of IBD patients with abdominal CT scans after pouch surgery between 2002 and 2017 were collected. Peripouch fat areas and mesenteric peripouch fat areas were measured on CT images at the middle pouch level. RESULTS: A total of 435 IBD patients were included. Patients with higher peripouch fat areas had a higher prevalence of CARP. Univariate analyses demonstrated that long duration of the pouch, high weight or body mass index, the presence of primary sclerosing cholangitis or other autoimmune disorders, and greater peripouch fat area or mesenteric peripouch fat area were risk factors for CARP. Multivariable analyses demonstrated that the presence of primary sclerosing cholangitis or autoimmuned disorders, and greater peripouch fat area (odds ratio [OR] 1.031; 95% confidence interval [CI] 1.016-1.047, P < 0.001) or mesenteric peripouch fat area were independent risk factors for CARP. Of the 435 patients, 139 (32.0%) had two or more CT scans. Multivariable Cox proportional hazard analyses showed that "peripouch fat area increase ≥ 15%" (OR 3.808, 95%CI 1.703-8.517, P = 0.001) was an independent predictor of pouch failure. CONCLUSIONS: A great peripouch fat area measured on CT image is associated with a higher prevalence of CARP, and the accumulation of peripouch fat is a risk factor for pouch failure. The assessment of peripouch fat may be used to monitor the disease course of the ileal pouch.

Effectiveness of vedolizumab treatment in two different anti-tumor necrosis factor alpha refractory pouchitis: A case report.

BACKGROUND: Refractory pouchitis is a common cause of pouch failure, which may require surgical excision of the pouch or permanent diversion. We aimed to show the effect of vedolizumab on treatment of the patient with refractory pouchitis. CASE SUMMARY: A 32-year-old male with pancolonic ulcerative colitis since the age of 25 with primary failure of infliximab and mesalamine and intolerance of azathioprine, underwent a total proctocolectomy with ileal pouch-anal anastomosis in 2012. He developed chronic diarrhea in 2014, which was watery, 30 per day and accompanied with blood and mucus affecting his quality of life. CONCLUSION: Vedolizumab is safe and effective in the management of anti-tumor necrosis factor alpha refractory pouchitis.

Difference in the frequency of pouchitis between ulcerative colitis and familial adenomatous polyposis: is the explanation in peripouch fat?

AIM: Patients with ulcerative colitis (UC) have an unexplained higher incidence of pouchitis and a greater amount of peripouch fat compared with patients with familial adenomatous polyposis (FAP). The aims of this study were to compare the peripouch fat areas between patients with UC and patients with FAP, and to explore relationship between peripouch fat and pouchitis or chronic antibiotic-refractory pouchitis (CARP). METHOD: Patients with an abdominal CT image from our prospectively maintained Pouch Database were included. Abdominal fat and peripouch fat were measured on CT images at different levels or planes. Comparisons of peripouch fat and CARP were performed before and after propensity score matching. RESULTS: A total of 277 patients with UC and 40 patients with FAP were included. Compared with patients with FAP, patients with UC were found to have a higher incidence of pouchitis (58.5% vs 15.0%, P < 0.001) and CARP (24.5% vs 2.5%, P = 0.002) and a higher total peripouch fat area (P = 0.030) and mesenteric peripouch fat area (P = 0.022) at Level-3. Univariate and multivariate analyses showed that diagnosis (UC vs FAP) and peripouch fat areas at Level-3 and Level-5 were independent risk factors for CARP. With propensity score matching, 38 pairs of patients with UC and FAP were matched successfully. After matching, patients with UC were found to have higher total peripouch fat area and higher mesenteric peripouch fat area at Level-3, and a higher incidence of pouchitis (57.9% vs 13.2%, P < 0.001) and CARP (23.7% vs 2.6%, P = 0.007). CONCLUSION: Our study demonstrates that patients with UC have more peripouch fat than those with FAP, which may explain the difference in the frequency of pouchitis and CARP between these groups of patients.

Hyperbaric oxygen therapy for chronic antibiotic-refractory ischemic pouchitis.

Hyperbaric oxygen therapy (HBOT) has been shown to be efficacious in treating various conditions, including perianal Crohn's disease. Here we present a case of a 59-year-old male with a history of ulcerative colitis, who underwent a total proctocolectomy and two-stage J-pouch construction. He later developed chronic antibiotic-refractory pouchitis with endoscopic features of ischemia. At the completion of HOBT-a total of 20 sessions of 100% oxygen at 2.5-3.0 atmospheres absolute for 60-90 minutes per session-a repeat pouchoscopy showed marked improvement of endoscopic mucosal inflammation. HBOT is known to increase tissue oxygenation, reduce tissue hypoxia, alter inflammatory pathways and promote tissue healing. This case demonstrated the therapeutic role of HBOT as well as the possible disease mechanism in chronic antibiotic-refractory pouchitis.

Role of wireless capsule endoscopy in the follow-up of inflammatory bowel disease.

The introduction of wireless capsule endoscopy in 2000 has revolutionized our ability to visualize parts of the small bowel mucosa classically unreached by the conventional endoscope, and since the recent introduction of colon capsule endoscopy, a promising alternative method has been available for the evaluation of large bowel mucosa. The advantages of wireless capsule endoscopy include its non-invasive character and its ability to visualize proximal and distal parts of the intestine, while important disadvantages include the procedure's inability of tissue sampling and significant incompletion rate. Its greatest limitation is the prohibited use in cases of known or suspected stenosis of the intestinal lumen due to high risk of retention. Wireless capsule endoscopy plays an important role in the early recognition of recurrence, on Crohn's disease patients who have undergone ileocolonic resection for the treatment of Crohn's disease complications, and in patients' management and therapeutic strategy planning, before obvious clinical and laboratory relapse. Although capsule endoscopy cannot replace traditional endoscopy, it offers valuable information on the evaluation of intestinal disease and has a significant impact on disease reclassification of patients with a previous diagnosis of ulcerative colitis or inflammatory bowel disease unclassified/indeterminate colitis. Moreover, it may serve as an effective alternative where colonoscopy is contraindicated and in cases with incomplete colonoscopy studies. The use of patency capsule maximizes safety and is advocated in cases of suspected small or large bowel stenosis.

Alicaforsen: An Emerging Therapeutic Agent for Ulcerative Colitis and Refractory Pouchitis.

Pouchitis is a relatively common complication that develops following ileal pouch-anal anastomosis in patients with complicated ulcerative colitis (UC). Both pouchitis and UC share similarities in their development, as well as in the mechanisms involving mediators of the inflammatory process. In the recent years, the discovery and investigation of biological therapies have led to advancement in the management of these disorders, and the continuation of research on this novel area holds strong implications for a future reduction in the use of invasive surgical procedures. Alicaforsen represents one of these emerging therapeutic agents, and has demonstrated promising results in both preclinical and clinical settings. This article reviews the therapeutic effects of alicaforsen for the management of UC and refractory pouchitis, with special emphasis on the mechanism of action of this therapeutic agent and the clinical studies asserting its effectiveness.

Oral beclomethasone dipropionate in chronic refractory pouchitis.

BACKGROUND: Pouchitis is the major long-term complication after ileal-pouch anal-anastomosis for ulcerative colitis. Ten to 15% of patients develop chronic pouchitis, either treatment responsive or treatment refractory. AIM: To evaluate the efficacy of oral beclomethasone dipropionate in inducing remission and improving quality of life in patients with chronic refractory pouchitis. METHODS: Ten consecutive patients with active pouchitis, not responding to 1-month antibiotic treatment, were treated with beclomethasone dipropionate 10 mg/day for 8 weeks. Clinical, endoscopic and histological evaluations were undertaken before and after treatment, according to the Pouchitis Disease Activity Index (PDAI). Remission was defined as a combination of PDAI clinical score of ≤2, endoscopic score of ≤1 and a total PDAI score of ≤4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: Eight of 10 patients (80%) achieved remission. The median total PDAI scores before and after therapy were, respectively, 12 (range 8-14) and 3 (range 2-9) (P<0.001). The median IBDQ score also significantly improved from 120 (range 77-175) to 175 (range 85-220) (p<0.001). CONCLUSION: Eight-week treatment with oral beclomethasone dipropionate appears effective in inducing remission in patients with active pouchitis refractory to antibiotic treatment.

Pouchitis: what every gastroenterologist needs to know.

Pouchitis is the most common complication among patients with ulcerative colitis who have undergone restorative proctocolectomy with ileal pouch-anal anastomosis. Pouchitis is actually a spectrum of diseases that vary in etiology, pathogenesis, phenotype, and clinical course. Although initial acute episodes typically respond to antibiotic therapy, patients can become dependent on antibiotics or develop refractory disease. Many factors contribute to the course of refractory pouchitis, such as the use of nonsteroidal anti-inflammatory drugs, infection with Clostridium difficile, pouch ischemia, or concurrent immune-mediated disorders. Identification of these secondary factors can help direct therapy.

Long term benefit of one year infliximab administration for the treatment of chronic refractory pouchitis.

BACKGROUND-AIM: The aim of this study is to identify the long term benefit of one year infliximab administration for the treatment of chronic refractory pouchitis following ileo-pouch anal anastomosis (IPAA) for ulcerative colitis (UC). METHODS: Seven patients with chronic refractory pouchitis diagnosed by clinical, endoscopic and histological criteria received infliximab 5 mg/kg at 0, 2, and 6 weeks and thereafter every 2 months for 1 year. Three patients had fistulae (1 pouch-bladder, 2 perianal) and 4 extraintestinal manifestations (2 erythema nodosum, 2 arthralgiae). All patients were refractory to antibiotics and 3 to azathioprine. Crohn's disease was excluded after re-evaluation of the history and small bowel examination with enteroclysis or capsule endoscopy. Clinical response was classified as complete, partial and no response. Fistulae closure was classified as complete, partial and no closure. The pouchitis disease activity index (PDAI) was used as an outcome measure. All patients were followed up for 3 years after discontinuation of infliximab therapy. RESULTS: After 1 year of infliximab administration 5 patients had complete clinical response, 1 partial clinical response and 1 no response, while 2 out of the 3 patients with fistulae had a complete closure. The median PDAI dropped from 11 (baseline) (range, 10-14) to 5 (range, 3-8). Extraintestinal manifestations were in complete remission too. Three years after completion of therapy, all patients with complete clinical response at one year remained in remission. CONCLUSIONS: One year infliximab administration is associated with a long term benefit in patients with chronic refractory pouchitis following IPAA for UC.

One-year infliximab administration for the treatment of chronic refractory pouchitis.

AIM: To determine the efficacy of infliximab in the treatment of chronic refractory pouchitis, following ileo-pouch anal anastomosis (IPAA) for ulcerative colitis (UC). METHODS: Seven patients (4 females, 3 males) with chronic refractory pouchitis were included in an open study. Pouchitis was diagnosed by clinical plus endoscopic and histological criteria. Three patients also had fistulae (pouch-bladder in 1 and perianal in 2). Extraintestinal manifestations were also present in 4 patients (erythema nodosum in 2, arthralgiae in 2). All patients were refractory to standard therapy. Crohn's disease was carefully excluded in all patients after re-evaluation of the history and examination of the small bowel with enteroclysis or small bowel capsule endoscopy. Patients received Infliximab 5 mg/kg at 0, 2 and 6 weeks and thereafter every 2 months for 1 year. Clinical response was classified as complete, partial, and no response. Fistulae closure was classified as complete, partial, and no closure. The pouchitis disease activity index (PDAI) was also used as an outcome measure. RESULTS: Clinically, all patients improved. After 1 year of follow-up, 5 of the 7 patients had a complete clinical response, and 2 of the 3 patients with a fistula had complete fistulae closure. At the end of the follow-up period the median PDAI dropped from 11 (baseline) (range, 10-14) to 5 (range, 3-8). Extraintestinal manifestations were in complete remission at the end of the followup period as well. CONCLUSIONS: Our results indicate that infliximab may be recommended for the treatment of chronic refractory pouchitis complicated or not by fistulae following IPAA for UC.