Pouchitis after ileal pouch‐anal anastomosis in ulcerative colitis: Diagnosis,management, risk factors,and incidence

Restorative proctocolectomy with ileal pouch‐anal anastomosis has been the surgical treatment of choice for patients with ulcerative colitis who require surgery. Quality of life after this procedure is satisfactory in most cases; however, pouchitis is a troublesome condition involving inflammation of the ileal pouch. When a patient presents with symptoms of pouchitis, such as increased bowel movements, mucous and/or bloody exudates, abdominal cramps, and fever, endoscopy is essential for a precise diagnosis. The proximal ileum and rectal cuff, as well as the ileal pouch, should be endoscopically observed. The reported incidence of pouchitis ranges from 14% to 59%, and antibiotic therapy is the primary treatment for acute pouchitis. Chronic pouchitis includes antibiotic‐dependent and refractory pouchitis. Intensive therapy including antitumor necrosis factor antibodies and steroids may be necessary for antibiotic‐refractory pouchitis, and pouch failure may occur despite such intensive treatment. Reported risk factors for the development of pouchitis include presence of extraintestinal manifestations, primary sclerosing cholangitis, non‐smoking, and postoperative non‐steroidal anti‐inflammatory drug usage. In the present review, we focus on the diagnosis, endoscopic features, management, incidence, and risk factors of pouchitis in patients with ulcerative colitis who underwent ileal pouch‐anal anastomosis.     

Suppurative granulomatous inflammation in the ileo-anal pouch

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is commonly performed for medically refractory ulcerative colitis (UC), however with multiple possible complications, most notably pouchitis, cuffitis, Crohn's disease of the pouch and irritable pouch syndrome. We present a unique case of suppurative granulomatous inflammation in the ileal pouch mucosa, most likely infective in nature, that is unrelated to recognised causes of such pathology, especially yersiniosis.     

Clostridium Difficile-Associated Pouchitis

Pouchitis is the most common long-term sequela of ileal pouch-anal anastomosis (IPAA) following total proctocolectomy. No single pathogen is identified as being solely responsible for the pathogenesis of the disease. Here we describe a case of Clostridium difficile-associated pouchitis that was successfully treated with ciprofloxacin and tinidazole. Diagnosis and management of a patient with medically refractory pouchitis associated with Clostridium difficile infection is described. A 63-year-old male with underlying ulcerative colitis and IPAA presented with increased stool frequency and seepage for 2 months, which partially responded to oral metronidazole. While on the antibiotic therapy, pouch endoscopy was performed and showed severe pouchitis. Assays for Clostridium difficile toxins in stool specimens were positive. He was treated with a 4-week course of ciprofloxacin 500 mg BID and tinidazole 500 mg TID. His symptoms resolved within several days from the initiation of therapy. A repeat pouch endoscopy at week 5 showed a complete resolution of mucosal inflammation of the pouch, while tests for Clostridium difficile toxins became negative. Clostridium difficile-associated pouchitis is rare. However, Clostridium difficile infection should be excluded in patients with chronic refractory pouchitis.     

Misdiagnosis of specific cytomegalovirus infection of the ileoanal pouch as refractory idiopathic chronic pouchitis

PURPOSE: Chronic nonspecific reservoir ileitis (pouchitis) occurs in 5 to 10 percent of patients who undergo ileal pouch-anal anastomosis for ulcerative colitis. Specific infection of the ileal pouch-anal anastomosis with cytomegalovirus has not been reported. AIM: We report two patients with specific cytomegalovirus infection of the ileal pouchanal anastomosis, initially misdiagnosed as idiopathic chronic pouchitis. CASE SERIES: Patient 1 had ileal pouchanal anastomosis for ulcerative colitis. Three years later she had diarrhea, fever, pelvic pain, and pouch inflammation at endoscopy consistent with pouchitis. She had no response to medical therapy. Repeat endoscopy showed persistent inflammation and biopsies showed cytomegalovirus. She had symptomatic improvement after treatment with intravenous ganciclovir, 10 mg/kg/day for ten days (stopped for rash). Repeat pouch biopsies were negative for cytomegalovirus. Patient 2 had ileal pouch-anal anastomosis for ulcerative colitis. Nine years later she had resection of obstructing stricture at previous loop ileostomy site. She underwent reoperation with ileostomy and pouch defunctionalization for peritonitis. Four weeks later she had fever and bloody discharge from the diverted pouch. Pouch endoscopy with biopsy showed inflammation consistent with pouchitis. She had no response to medical therapy. Re-examination of pouch biopsies with a specific monoclonal immunofluorescent stain showed cytomegalovirus. She had symptomatic improvement after treatment with intravenous ganciclovir, 10 mg/kg/day for 21 days. Repeat pouch biopsies were negative for cytomegalovirus. CONCLUSIONS: Specific cytomegalovirus infection of the ileal pouch-anal anastomosis may be misdiagnosed as idiopathic refractory chronic pouchitis. Cytomegalovirus must be excluded before immune modifier therapy or pouch excision in these patients.     

A Concise Critical Analysis of Serologic Testing for the Diagnosis of Lyme Disease

Pouchitis is an inflammatory complication after restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA). IPAA is the surgical treatment of choice in patients with ulcerative colitis (UC) who require colectomy. Initial episodes of acute pouchitis generally respond to antibiotics but significant numbers of cases eventually become dependent on or refractory to antibiotics. Management of chronic antibiotic refractory pouchitis is challenging and can ultimately lead to pouch failure. The etiopathogenesis is unknown though recent studies have implicated bacterial dysbiosis of the pouch microbiota, NOD2 polymorphism, and Clostridium difficile infection in the development of severe pouchitis. Early identification of risk factors can help in tailoring therapy and reducing cases of chronic pouchitis.     

Adenocarcinoma in the ileal pouch: late risk of cancer after restorative proctocolectomy

Restorative proctocolectomy and ileal pouch-anal anastomosis is the surgical treatment of choice for patients with ulcerative colitis. As a long-term complication of this procedure, chronic pouchitis impairs the outcome in a number of patients. Aneuploidia and dysplasia have been observed after long-lasting inflammation of ileal mucosa. The question arises whether chronic inflammation of ileal mucosa predisposes to malignant transformation similar to the situation in the chronically inflamed colon. Cancer of the ileal mucosa has been reported in patients with Brooke's ileostomy and in patients with Kock pouch but not as yet in those with an ileoanal pouch. We report a patient with carcinoma in an ileoanal pouch originating from terminal ileal mucosa who had been suffering from pancolitis with long-term backwash ileitis before, and from chronic pouchitis after, restorative proctocolectomy. This case demonstrates the importance of regular follow-up with pouchoscopy and random biopsies in all patients with long-standing inflammation of the ileal mucosa.     

Secondary pouchitis in a post-operative patient with ulcerative colitis, successfully treated by salvage surgery

We report a case of secondary pouchitis, defined as a mucosal inflammatory lesion in the ileal reservoir provoked by pouch-related complication following total colectomy and pouch anal anastomosis, which was successfully treated by salvage surgery- A 20-year-old woman with ulcerative colitis developed acute severe bloody diarrhea following proctocolectomy, ileal pouch-anal anastomosis and diverting ileostomy. She was diagnosed as having a secondary pouchitis mainly caused by a peripouch abscess and partly concerned with the abnormal pouch formation. The remnant rectum and ileal pouch were excised and ileal pouch-anal anastomosis and diverting ileostomy were constructed. The postoperative course was uneventful with no sign of pouchitis. Salvage surgery may be indicated to treat secondary pouchitis when caused by surgery-related complications.     

Mucosal changes in ileal pouches after restorative proctocolectomy for ulcerative and crohn's colitis

PURPOSE: Inflammation and dysplasia may affect the ileal pouch after restorative proctocolectomy and ileal pouchanal anastomosis. The aim of this prospective study was to evaluate the morphologic changes and the risk of dysplasia within the pouch after ileal pouch-anal anastomosis. METHODS: Thirty-seven patients with ileal pouch-anal anastomosis underwent endoscopies and biopsies of the pouch: 21 patients were affected by ulcerative colitis and 16 by Crohn's colitis. The mucosal biopsy specimens were studied to investigate the degree of acute and chronic inflammation and the occurrence of dysplasia. A score system was calculated for each patient and correlated with the histologic diagnosis of ulcerative colitis or Crohn's colitis. RESULTS: After a median follow-up of 85 (range, 7–198) months, the inflammation histologic score evaluated was 3.8 (95 percent confidence interval, 2.4–5.1) and 3.5 (95 percent confidence interval, 2.6–4.3), respectively, in patients with Crohn's colitis and ulcerative colitis (mean and 95 percent confidence interval;P=0.74, not significant), and no patient developed mucosal dysplasia. Fifteen patients (40.5 percent) developed clinical pouchitis that occurred in Crohn's colitis (9/16 patients or 56 percent) and in ulcerative colitis (6/21 patients or 28 percent;P not significant). The score was 4.1 (95 percent confidence interval, 3.2–5) in patients with pouchitis and 3.2 (95 percent confidence interval, 2.1–4.3) in patients without clinical pouchitis (P=0.012) and was 4.1 (95 percent confidence interval, 2.6–5.5) and 4 (95 percent confidence interval, 2.9–5.3), respectively, in pouchitis patients with Crohn's colitis and ulcerative colitis. CONCLUSION: No difference in the inflammation histologic score was observed in ileal pouches after restorative proctocolectomy for ulcerative and Crohn's colitis. In our series, which includes those patients with longer follow-up (>5 years) or with chronic unremitting pouchitis, no case of dysplasia was found. The occurrence of pouchitis was higher in the case of ileal pouch-anal anastomosis for Crohn's disease than for ulcerative colitis, but no difference in the severity of the histologic score was noted.Presented at the XVIIth Biennial Congress of the International Society of University Colon and Rectal Surgeons, Malmö, Sweden, June 7 to 11, 1998.     

Clinical approach to diseases of ileal pouch-anal anastomosis

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for ulcerative colitis (UC) patients with medically refractory disease or dysplasia. IPAA significantly improves quality of life in UC patients who require surgery. However, certain inflammatory and noninflammatory diseases can develop after the surgery, including pouchitis, Crohn's disease of the pouch, cuffitis, and irritable pouch syndrome. The etiology and pathogenesis of these disease conditions of IPAA are largely unknown. Accurate diagnosis and classification are important for appropriate management. Endoscopic evaluation is the most important tool for the diagnosis and differential diagnosis.     

Indeterminate colitis: the real story

PURPOSE: Up to one in five patients undergoing surgery for ulcerative colitis will have ambiguous histology, with features of both ulcerative colitis and Crohn's disease, and are categorized as having indeterminate colitis. We hypothesized that functional outcomes in indeterminate colitis patients undergoing ileal pouch-anal anastomosis are comparable with those of ulcerative colitis patients undergoing ileal pouch-anal anastomosis. METHODS: Physician-conducted interviews of 120 consecutive ileal pouch-anal anastomosis patients with a preoperative diagnosis of ulcerative colitis were reviewed, with a mean follow-up of 54 months. All colectomy specimens were reviewed by a single pathologist. Any changes in histologic diagnosis from ulcerative colitis to indeterminate colitis or Crohn's disease, frequency of postoperative complications, pouch function, and long-term postoperative medication usage were recorded. RESULTS: Although postoperative fistulas were more common in indeterminate colitis than ulcerative colitis (26 vs. 10 percent; P = 0.02, chi-squared), no indeterminate colitis patient required a permanent ileostomy as compared with six ulcerative colitis patients. Long-term functional results were similar. Overall, two-thirds of patients developed pouchitis. Ulcerative colitis and Crohn's disease patients were more likely to have had >3 episodes of pouchitis (58 and 72 percent) compared with indeterminate colitis patients (29 percent; P = 0.006, chi-squared). A greater number of Crohn's disease patients required maintenance oral antibiotic therapy (64 percent) to achieve satisfactory functional results compared with both indeterminate colitis and ulcerative colitis patients (20 and 28 percent; P = 0.014, chi-squared). CONCLUSIONS: Although ileal pouch-anal anastomosis patients with indeterminate colitis have more postoperative fistulas, long-term function is equal to that of ulcerative colitis patients and better than Crohn's disease patients. Ileal pouch-anal anastomosis should be offered to patients with indeterminate colitis and those with severe colitis in whom clear differentiation between indeterminate colitis and ulcerative colitis cannot be made.     

Pouchitis

While restorative proctocolectomy with ileal pouch-anal anastomosis has significantly improved the quality of life in patients with underlying ulcerative colitis who require surgery, complications can occur. Pouchitis as the most common long-term complication represents a spectrum of disease processes ranging from acute, antibiotic- responsive type to chronic antibiotic-refractory entity. Accurate diagnosis using a combined assessment of symptoms, endoscopy and histology and the stratification of clinical phenotypes is important for treatment and prognosis the disease. The majority of patients respond favorably to antibiotic therapy. However, management of chronic antibiotic-refractory pouchitis remains a challenge.     

Pouchitis and pre-pouch ileitis developed after restorative proctocolectomy for ulcerative colitis： A case report

We report a case of pouchitis and pre-pouch ileitis, and inflammation in the neo-terminal ileum proximal to the pouch, developed after restorative proctocolectomy for ulcerative colitis. A 35-year old female presented with fever and abdominal pain five weeks after ileostomy closure following proctocolectomy. ComputEd tomography showed collection of feces in the pouch and proximal ileum. A drainage tube was placed in the pouch perianally, and purulent feces were discharged. With antibiotic treatment, her symptoms disappeared, but two weeks later, she repeatedly developed fever and abdominal pain along with anal bleeding. Pouchscopy showed mucosal inflammation in both the pouch and the pre-pouch ileum. The mucosal cytokine production was elevated in the pouch and pre-pouch ileum. With antibiotic and corticosteroid therapy, her symptoms were improved along with improvement of endoscopic inflammation and decrease of mucosal cytokine production. The fecal stasis with bacterial overgrowth is the major pathogenesis of pouchitis and pre-pouch ileitis in our case.     

Is Ileal pouch-anal anastomosis really the procedure of choice for patients with ulcerative colitis?

PURPOSE: Ileal pouch-anal anastomosis is widely claimed to have replaced total proctocolectomy with ileostomy as the “procedure of choice” for ulcerative colitis, largely on the basis of a perceived improved quality of life. There exists relatively little support for this assertion in the literature. Our aim was to determine if educated patients choosing total proctocolectomy with ileostomy have a similar quality of life as with ileal pouch-anal anastomosis. METHODS: All patients with ulcerative colitis referred to a single surgeon and deemed an appropriate surgical candidate were educated and then offered ileal pouch-anal anastomosis or total proctocolectomy with ileostomy. Age, gender, and complications (including pouchitis) were recorded prospectively, and all patients were questioned regarding functional outcome and level of satisfaction. They were then asked to complete a slightly modified Inflammatory Bowel Disease Questionnaire, which was analyzed by categoric and overall scores. RESULTS: Sixty-seven patients underwent elective surgery for ulcerative colitis during the study period. Fifty-five patients chose ileal pouch-anal anastomosis, and 12 had total proctocolectomy with ileostomy. The groups were similar except for younger age and longer follow-up in the ileal pouch-anal anastomosis group. Patients undergoing ileal pouch-anal anastomosis had significantly more short-term or long-term complications (49vs. 8 percent), with pouchitis being the most frequent complication. There was no difference in level of satisfaction between the two groups, and no patient in either group wishes they had undergone the other procedure. There was no difference in the overall or any categoric Inflammatory Bowel Disease Questionnaire score. CONCLUSION: Patient satisfaction with both procedures was similarly high. Patients who undergo ileal pouch-anal anastomosis can expect a high level of satisfaction, with a good quality of life. However, educated patients choosing an ileostomy can achieve the same quality of life, without the higher complication rate associated with a pelvic pouch.     

Possible role of human cytomegalovirus in pouchitis after proctocolectomy with ileal pouch-anal anastomosis in patients with ulcerative colitis

AIMTo detect the presence of human cytomegalovirus(HCMV)proteins and genes on the ileal pouch of patients with ulcerative colitis who have undergone proctocolectomy with ileal pouch-anal anastomosis(IPAA).METHODSImmunohistochemistry,polymerase chain reaction(PCR)and PCR sequencing methods were utilized to test the presence of HCMV in pouch specimens taken from 34 patients in 86 endoscopies.RESULTSHCMV genes and proteins were detected in samples from 12(35.2%)patients.The rate of detection was significant in the endoscopies from patients diagnosed with pouchitis(5 of 12,41.6%),according to the Japanese classification of pouchitis,in comparison to patients with normal pouch(7 of 62,11.2%;P = 0.021).In all patients with pouchitis in which the HCMV was detected,it was the first episode of pouchitis.The virus was not detected in previous biopsies taken in normal endoscopies of these patients.During the followup,HCMV was detected in one patient with recurrent pouchitis and in 3 patients whose pouchitis episodes improved but whose positive endoscopic findings persisted.CONCLUSIONHCMV can take part in the inflammatory process of the pouch in some patients with ulcerative colitis who have undergone proctocolectomy with IPAA.     

Pouchitis: A spectrum of diseases

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for ulcerative colitis and familial adenomatous polyposis patients who require surgery. Pouchitis is the most common longterm complication after IPAA. Patients with pouchitis represent a heterogeneous group in terms of pathogenesis, clinical presentation, disease course, and prognosis, suggesting a wide range of disease mechanisms. Before the diagnosis of pouchitis is made, other inflammatory and non-inflammatory disease conditions, such as Crohn’s disease, cuffitis, and irritable pouch syndrome, should be ruled out. Pouch endoscopy is the most important tool for diagnosis and differential diagnosis. Accurate diagnosis and classification are essential for appropriate management. Although the majority of patients with pouchitis respond to antibiotic therapy, a subset of these patients cannot achieve remission by means of antibiotics and thus require anti-inflammatory or immunosuppressive treatment.     

Diagnosis and Management of Pouchitis and Ileoanal Pouch Dysfunction

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the surgical treatment of choice for patients with medically refractory ulcerative colitis (UC) or UC with dysplasia and for the majority of patients with familial adenomatous polyposis. However, UC patients with IPAA are susceptible to inflammatory and noninflammatory sequelae, such as pouchitis, Crohn’s disease of the pouch, cuffitis, and irritable pouch syndrome, in addition to common surgery-associated complications, which adversely affect the surgical outcome and compromise health-related quality of life. Pouchitis is the most frequent long-term complication of IPAA in patients with UC, with a cumulative prevalence of up to 50%. Pouchitis may be classified based on the etiology into idiopathic and secondary types, and the management is often different. Pouchoscopy is the most important tool for the diagnosis and differential diagnosis in patients with pouch dysfunction. Antibiotic therapy is the mainstay of treatment for active pouchitis. Some patients may develop dependency on antibiotics, requiring long-term maintenance therapy. Although management of antibiotic-dependent or antibiotic-refractory pouchitis has been challenging, secondary etiology for pouchitis should be evaluated and modified, if possible.     

Diagnosis and treatment of ileal pouch diseases in patients with underlying ulcerative colitis

Opinion statement Ileal pouch-anal anastomosis (IPAA) after total proctocolectomy is the surgical treatment of choice for ulcerative colitis (UC) patients with medically refractory disease or dysplasia. IPAA significantly improves quality of life in UC patients who require surgery. However, certain inflammatory and noninflammatory diseases can develop after the surgery, including pouchitis, Crohn’s disease (CD) of the pouch, cuffitis, and irritable pouch syndrome. The cause and pathogenesis of these disease conditions of IPAA are largely unknown. Accurate diagnosis and classification are important for appropriate management.     

Synchronous cytomegalovirus and Clostridium difficile infection of the pouch: a trigger for chronic pouchitis?

Pouchitis occurs in up to one half of patients after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Cytomegalovirus (CMV) and Clostridium difficile are among the commonest secondary identifiable etiologies. A 17-year-old male with ulcerative colitis underwent IPAA due to refractory disease. Nine months later he experienced bloody diarrhea and fever. Laboratory testing and endoscopy confirmed pouch inflammation. Testing for C. difficile toxins A and B was positive. Histology revealed affluent inclusion bodies and immunohistochemistry detected reactivity against CMV protein. Treatment with metronidazole and vancomycin offered partial improvement, whereas the addition of gancyclovir led to a successful recovery. One month after completion of treatment symptoms recurred. Repeat testing precluded an identifiable infectious cause and the diagnosis of idiopathic chronic pouchitis was established. The patient is currently on maintenance treatment with the probiotic compound VSL#3.     

Modified pouchitis disease activity index: a simplified approach to the diagnosis of pouchitis

PURPOSE: Pouchitis is the most common complication of ileal pouch-anal anastomosis for ulcerative colitis. Our previous study suggested that symptoms alone are not reliable for the diagnosis of pouchitis. The most commonly used diagnostic instrument is the 18-point pouchitis disease activity index consisting of three principal component scores: symptom, endoscopy, and histology. Despite its popularity, the pouchitis disease activity index has mainly been a research tool because of costs of endoscopy (especially with histology), complexity in calculation, and time delay in determining histology scores. It is not known whether pouch endoscopy without biopsy can reliably diagnose pouchitis in symptomatic patients. The aim of the present study was to determine whether omitting histologic evaluation from the pouchitis disease activity index significantly affects the sensitivity and specificity of diagnostic criteria for pouchitis. METHODS: Ulcerative colitis patients with an ileal pouch-anal anastomosis and symptoms suggestive of pouchitis were evaluated. Patients with chronic refractory pouchitis and Crohns disease were excluded. Patients with pouchitis disease activity index scores of seven or more were diagnosed as having pouchitis. Different diagnostic criteria were compared on the basis of the pouchitis disease activity index component scores. Nonparametric receiver-operating-characteristic curves were used to measure proposed pouchitis scores diagnostic accuracy compared with diagnosis from the pouchitis disease activity index. The receiver-operating-characteristic area under the curve measured how much these diagnostic strategies differed from each other. RESULTS: Fifty-eight consecutive symptomatic patients were enrolled; 32 (55 percent) patients were diagnosed with pouchitis. With the use of the pouchitis disease activity index as a criterion standard, the use of only symptom and endoscopy scores (modified pouchitis disease activity index) produced an area under the curve of 0.995. Establishing a cut-point of five or more for diseased patients resulted in a sensitivity equal to 97 percent and specificity equal to 100 percent. CONCLUSIONS: Diagnosis based on the modified pouchitis disease activity index offers similar sensitivity and specificity when compared with the pouchitis disease activity index for patients with acute or acute relapsing pouchitis. Omission of endoscopic biopsy and histology from the standard pouchitis disease activity index would simplify pouchitis diagnostic criteria, reduce the cost of diagnosis, and avoid delay associated with determining histology score, while providing equivalent sensitivity and specificity.