Autoinflammatory Disorder-Associated Pouchitis

Abstract

Introduction: The autoinflammatory diseases (AInD) have features of systemic inflammation that commonly manifest as fever, rash, arthritis, or serositis of multiple organ systems. The role of autoinflammation in the pathogenesis of pouchitis and its contribution to chronic antibiotic-refractory pouchitis (CARP) are unknown. We describe a 52-year-old woman with UC who underwent proctocolectomy and a 2-stage J pouch surgery at the age of 40 for the treatment of toxic megacolon. The surgery was complicated by anastomotic leak and pelvic abscess that was surgically drained. After surgery, she had symptoms and pouch endoscopy findings consistent with pouchitis that were persistent for years, despite a combination of oral ciprofloxacin 500 mg twice a day and rifaximin 200 mg every day, consistent with CARP. She developed recurrent abscesses in the perianal region on the fourchette of the vagina and was diagnosed with ano-vaginal fistula treated with seton placement. Four years after the pouch surgery, the patient presented with fever, left-sided chest heaviness, and abdominal pain. An echocardiogram showed a moderate pericardial effusion without tamponade, for which she was treated with indomethacin and colchicine. She also had intermittent episodes of fever and arthralgia involving the shoulder, low back, and lower extremities. Genetic testing for nucleotide-binding oligomerization domain-containing protein 2/caspase recruitment domain-containing protein 15 (NOD2/CARD15) revealed 2 mutations: 3020insC and IVS8+158 (Figure 1). She was started on 6-mercaptopurine and celecoxib for the treatment of an AInD, with resolution of the symptoms of fever and arthralgia. This case introduces the concept of “pouchitis with AInD features.” An autoinflammatory etiology should be suspected, and appropriate genetic testing pursued in patients with chronic pouchitis and a spectrum of systemic manifestations that include periodic fevers, arthritis, rash, and serositis. Anti-inflammatory and/or immunosuppressive medications, including colchicine, would be treatment considerations.Figure 1: Structure of the NOD2/CARD15 gene and location of mutations detected in this case (bold). The IVS8+158 variant is rare in Crohn’s disease but characteristic of NOD2-associated autoinflammatory disorder (NAID).