When Should Chronic Pouchitis Be Treated as Crohn’s Disease?
Maya Kayal, MD and Benjamin L. Cohen MD, MAS
Approximately 30% of ulcerative colitis patients will require surgery during their disease course (1). The preferred and most common surgery is the staged total proctocolectomy with ileal pouch-anal anastomosis (IPAA). Despite the benefits of intestinal continuity and improved quality of life, IPAA is associated with multiple complications, the most common of which is pouchitis. Characterized by inflammation of the pouch reservoir, pouchitis has a wide range of clinical manifestations that include urgency, increased frequency, hematochezia and abdominal or pelvic pain. The prevalence of pouchitis increases with time, with cumulative incidence rates of 25% at 1 year, 35% at 3 years and 45% at 5 years (2).
Antibiotics are the mainstay of treatment for acute pouchitis and have been shown to induce remission at rates of approximately 80% after a single course (3). After initial successful treatment, however, approximately 60% of patients will develop at least one recurrence and up to 20% of patients will develop chronic pouchitis. Defined as clinical symptoms that last longer than four weeks, chronic pouchitis is categorized as antibiotic dependent or antibiotic refractory. Patients with chronic antibiotic dependent pouchitis respond well to antibiotics, but experience greater than three relapses per year when antibiotics are withdrawn. In contrast, patients with chronic antibiotic refractory pouchitis have persistent symptoms and objective inflammation on pouchoscopy despite multiple antibiotic courses (4).
It is difficult to distinguish between chronic antibiotic refractory pouchitis and Crohn’s disease of the pouch, particularly because standardized diagnostic criteria for Crohn’s disease of the pouch are lacking. A recent systematic review and meta-analysis of available studies reported a standardized incidence rate of 10.3% (95% confidence interval, 6.1%-15.4%) for development of Crohn’s disease of the pouch (5). Crohn’s disease of the pouch describes a clinical phenotype characterized by inflammation of the pouch or afferent limb resistant to antibiotics, stricturing of the pouch body, afferent limb or proximal small bowel, and/or fistulizing disease involving the perineum or small bowel (6). Timing of these features is critical in differentiating Crohn’s disease from post-operative complications, with incidence of strictures or fistulas more than one year after IPAA highly suggestive of Crohn’s disease (5). Of note, stricture of the pouch-anal anastomosis is not generally considered to be Crohn’s disease of the pouch. Endoscopic features consistent with Crohn’s disease include mucosal ulcerations of the afferent limb, distinct inflammation patterns in the pouch body and afferent limb, areas of nodularity, inflammatory pseudopolyps, or the presence of fistulous tracts (6). Granulomas noted on mucosal biopsy are specific for Crohn’s disease, however only present in approximately 10% of cases (7). One study has also suggested that pyloric gland metaplasia present in pouch biopsies may be associated with Crohn’s disease of the pouch (8).
The treatment of chronic antibiotic refractory pouchitis and Crohn’s disease of the pouch is similar and consists of steroids and biologics such as infliximab, vedolizumab and ustekinumab (9-13). Despite this, it is important to make the distinction between the two disorders and confirm the diagnosis of Crohn’s disease. A meta-analysis of available studies has demonstrated that anti-TNF agents have a higher and faster rate of efficacy in patients with Crohn’s disease of the pouch than those with chronic refractory pouchitis (14). Additionally, patients with Crohn’s disease of the pouch are at significant risk for pouch failure with reported frequencies up to 45% (15). Once the diagnosis is confirmed, appropriate treatment for Crohn’s disease should be instituted early in order to decrease the risk of pouch excision.