Increased Crypt Apoptosis Is a Feature of Autoimmune-Associated Chronic Antibiotic Refractory Pouchitis

Abstract

Restorative proctocolectomy with IPAA is the surgical treatment of choice in patients with ulcerative colitis who require colectomy. Pouchitis is the most common long-term complication in patients with IPAA. While immune-mediated disorders frequently coexist with IBD, they appear to be associated with an increased risk for chronic antibiotic-refractory pouchitis. This study aimed to evaluate histologic features of autoimmune-associated chronic antibiotic-refractory pouchitis in comparison with controls and to assess their possible diagnostic utility. Clinical definition for autoimmune-associated chronic pouchitis included 1) chronic antibiotic-refractory pouchitis with response only to corticosteroids, immunomodulators, or biologics; 2) positive serum autoantibodies, including antinuclear antibody, rheumatoid factor, and antimicrosomal antibody; and 3) concurrent immune-mediated disorders. Various histologic features of pouch biopsy specimens were evaluated. The investigation was conducted at a tertiary referral center. From our Pouchitis Registry, all eligible patients with autoimmune-associated pouchitis (n = 17) were included. The control groups included 16 patients with nonautoimmune-associated chronic antibiotic-refractory pouchitis, 39 with antibiotic-responsive pouchitis, and 19 patients with normal pouches. Various histologic features of pouch biopsy specimens were evaluated. In comparison with the control groups, the autoimmune-associated pouchitis group showed a significant increase in deep crypt apoptosis (p < 0.001). It also showed more pyloric gland metaplasia in comparison with antibiotic-responsive pouchitis and normal pouches. With the use of apoptosis score which we developed as a diagnostic marker for autoimmune-associated chronic antibiotic-refractory pouchitis, we constructed a receiver operating curve and obtained an area-under-curve value of 0.89 (95% CI: 0.79, 0.99). Increased deep crypt apoptosis is a distinctive histologic feature of autoimmune-associated chronic antibiotic-refractory pouchitis, and this feature may aid in the diagnosis and differential diagnosis in pouchitis.