Management of Pouchitis

Management of Pouchitis Paolo Gionchetti, Claudia Morselli, Fernando Rizzello, Rosy Tambasco, Gilberto Poggioli, Silvio Laureti, Federica Ugolini, Filippo Pierangeli, Massimo Campieri Introduction Risk Factors Total proctocolectomy with ileal pouch-anal anasto- The risk of developing pouchitis is much higher in mosis (IPAA) proposed for the first time by Parks in patients with pre-operative extra-intestinal manifes- 1978 [1], represents nowadays the surgical treatment tations [8] and primary sclerosing cholangitis [9]. of choice for the management of patients with famil- More controversial is the predictive role of anti-neu- ial adenomatous polyposis (FAP) and ulcerative coli- trophil cytoplasmic antibody with a perinuclear pat- tis (UC) [2, 3]. This procedure allows the removal of tern (p-ANCA) [10-15] and of the pre-operative the whole diseased colorectal mucosal and has the extent of UC [16-17]. Similarly to UC, smoking may great advantage of preserving the anal sphincter be protective against the development of pouchitis function. Most patients undergoing IPAA for severe (Table 1) [18]. The surgical technique (different type colitis or for chronic continuous disease will achieve of reservoir) does not influence the frequency of pou- excellent functional results and physical well-being. chitis [19-20]. In a prospective evaluation of health related quality of life (HRLQ) after IPAA, a significant improvement of HRQL has been shown, assessed with both generic Etiology and disease-specific measures, with many patients experiencing improvements as early as 1 month post- The etiology is still unknown and is likely to be mul- operatively [4]. However pouchitis, a non-specific tifactorial; a variety of hypotheses have been suggest- (idiopathic) inflammation of the ileal reservoir, is the ed, including bacterial overgrowth due to faecal sta- most common long-term complication after pouch sis, mucosal ischemia of the pouch, missed diagnosis surgery for UC [5]. of Crohn’s disease, recurrence of UC and a novel form of IBD. Most likely pouchitis is the results of the interaction of a genetical and immunological suscep- Epidemiology, Risks Factors and Etiology tibility and an ileal mucosa that has adapted from its absorptive function to a new role of that of a reser- Frequency voir with a colon-like morphology in response to faecal stasis [21]. The true incidence is still difficult to determine, depending on the diagnostic criteria used to define the syndrome, the accuracy of the evaluation and, particularly, on the duration of the follow-up. Reported incidence rates vary between 10 and 59%; Table 1. Pouchitis: predictive factors most patients experience their first episode of acute Positive Association pouchitis within 12 months after surgery, but some Extra-intestinal manifestations may suffer their first attack some years later [6]. Primary sclerosing cholangitis Recently, Simchuk et al. performed a retrospective Antineutrophil cytoplasmic antibody with a perinuclear review of patients who underwent IPAA with a mean staining pattern (p-ANCA) follow-up of 3 years: the incidence of pouchitis was Extent of preoperative UC 59%, but it increased with the duration of follow-up Negative Association [7]. Smoking 302 P. Gionchetti, C. Morselli, F. Rizzello, R. Tambasco, G. Poggioli, S. Laureti, F. Ugolini, F. Pierangeli, M. Campieri Diagnosis ical symptoms, endoscopic appearance and histologic findings, represents an objective and reproducible 26 The diagnosis of pouchitis should be based on clini- scoring system for pouchitis [ ]. Active pouchitis is Ն7 cal, endoscopic and histologic criteria; the key point defined by a total PDAI score and remission is 7 is that endoscopic and histopathologic evaluation is defined as a score < . Once diagnosis is made, pouch- required to make the diagnosis of pouchitis. itis can be further classified. The disease activity can be defined as remission, mild-moderate (increased stool frequency, urgency, infrequent incontinence) or Clinical Diagnosis severe (dehydration, frequent incontinence). Pouchi- tis can also be defined on the basis of the duration of Յ4 4 The most frequent symptoms which characterise this disease: acute ( weeks) or chronic (> weeks). syndrome include increased stool frequency and flu- Another way to classify this syndrome considers the idity, rectal bleeding, abdominal cramping, urgency, following patterns: infrequent (a single or two acute malaise and tenesmus, and in most severe cases, episodes), relapsing (more than three acute episodes) incontinence and fever [21]. Patients with pouchitis in about two thirds of cases, continuous or chronic may also have extra-intestinal manifestations such as disease (a treatment responsive form requiring a arthritis, ankylosing spondylitis, pyoderma gan- maintenance therapy or a treatment-resistant form). 15 grenosum, erythema nodosum and uveitis [8]. These About % of patients have a chronic disease and extra-intestinal manifestations may develop for the some of them require surgical excision or exclusion of first time with pouchitis, but frequently patients have the pouch because of impairment of reservoir function previously experienced these extra-intestinal mani- and poor quality of life. festations before surgery. The PDAI, nowadays, is the most frequently used scoring system in clinical studies to determine pouchitis disease activity. The validity of PDAI and the Endoscopic Findings necessity of its application in epidemiological, patho- physiological or clinical studies, as well as in clinical A clinical diagnosis should be confirmed by practice in order to make a correct diagnosis of pou- 27 endoscopy and histology. With endoscopy the chitis, have been shown by Shen et al. [ ] in a study mucosa of the neo-terminal ileum above the pouch evaluating the correlation between symptoms, should be normal. Inflammation of the pouch endoscopy and histologic findings in patients with mucosa, with mucosal erythema, edema, friability, IPAA for UC. They found that symptoms alone do petechiae, granularity, loss of vascular pattern, not reliably diagnose pouchitis, whereas an evalua- mucosal haemorrhages, contact bleeding, mucus tion including symptoms, endoscopy and histology is 25 exudates, erosions and small superficial mucosal the best way to make the diagnosis. In fact, % of ulcerations can be present with varying degrees of patients with a high symptom score did not, in any of 36 severity [22-23]. Inflammation may be uniform or the cases, reach the PDAI diagnostic criteria and % more severe to the distal part of the pouch. of patients with minimal symptoms achieved a PDAI score ജ7 because of significant endoscopic and histologic inflammation [27]. Histologic Findings Differential Diagnosis Histologic examination shows acute inflammatory cell infiltrate with crypt abscesses and ulcerations on a background of chronic inflammatory changes with Before treatment is started, it is important to exclude villous atrophy and crypt hyperplasia [24-25]. other less frequent causes of pouch dysfunction or pouch inflammation, and this is particularly neces- sary in the case of a refractory patient. An anasto- Disease Activity Score and Classification motic stricture, with consequent outlet obstruction and faecal stasis, is a common complication of IPAA; Because of the great variability in the results of reports this increases stool frequency, makes the defecation on the incidence of pouchitis and in the assessment of painful with an incomplete evacuation predisposing therapy due to the lack of standardised diagnostic cri- to pouchitis. Diagnosis could be made by evacuation teria, Sandborn and colleagues developed a pouchitis pouchography, while the stricture can usually be disease activity index (PDAI). This 18-point index, cal- dilated with a finger or a rubber dilator. culated via three separate 6-point scales based on clin- Infectious etiology, caused by intestinal pathogens such as Shigella, Escherichia coli, Salmonella, Clostridi- Management of Pouchitis 303 um difficile, should be ruled out by microbiology ana- pathogenesis of acute pouchitis has led clinicians to lysis and pouch biopsy. Multiple cases of treat patients with antibiotics, which have become cytomegalovirus infection have been reported showing the mainstay of treatment, in absence of controlled the need for using monoclonal immunofluorescent trials. Usually metronidazole represents the most staining for CMV for the examination of pouch biopsies common first therapeutic approach, and most when treatment with antibiotics has proven unsuccess- patients with acute pouchitis respond quickly to ful. In these patients the CMV infection must be exclud- administration of 1–1.5 g/day [33-34]. A double- ed before starting immune modifier therapy [28-29]. blind, randomised, placebo-controlled, crossover Cuffitis is the inflammation of the retained rectal trial was carried out in 1993 by Madden et al. [22] to mucosa (columnar cuff) above the anal transitional assess the efficacy of 400 mg three times a day of zone (ATZ) after stapled anastomosis between the metronidazole per os in 13 patients (11 completed pouch and the top of the anal canal; this kind of both arms of the study) with chronic, unremitting inflammation, usually mild and not related to inflam- pouchitis, defined by the presence of recurrent or mation of the pouch, can cause anal discomfort, peri- persistent symptoms with almost six bowel move- anal irritation and pouch dysfunction. Clinically sig- ments a day and typical endoscopic

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