At the AGA Spring Postgraduate Courses, Dr. Maria Abreu from the University of Miami began the session with updates on clinical aspects of inflammatory bowel disease. It has become increasingly apparent that Crohn's disease, in particular, is most often a chronic, progressive, transmural disease with a high lifetime risk for complications (e.g. strictures and fistulae) that often lead to the need for surgical resections. Furthermore, once initiated on corticosteroid therapy, a large proportion of individuals become steroid-dependent and are at risk for the multitude of steroid-related complications.
With the advent of more effective therapies, such as combination treatment with anti-tumor necrosis factor (anti-TNF) biologic therapy and immunosuppressives, it is important to risk stratify patients from the point of diagnosis or referral for the factors associated with progressive or complicated disease. Those factors include extensive disease presenting at a young age, deep mucosal ulcerations, fistulizing disease, high serologic titers of antibodies targeting intestinal microflora (pANCA, ASCA, etc), cigarette smoking, and the early need for corticosteroids). These are individuals for whom a heightened awareness of health maintenance issues (now incorporated into AGA quality guidelines) should be implemented, such asupdated vaccinations, ppd and chest x-rays prior to anti-TNF therapy, smoking cessation, dual x-ray absorptiometry scans, and early attempts at steroid-sparing.
Dr. Stephen B. Hanauer
Dr. Corey Siegel from the Dartmouth-Hitchcock Inflammatory Bowel Disease Center then segued into the (safety) and risks of immunosuppressive and biologic therapies for IBD, both alone and in combination. Dr. Siegel emphasized the underlying risks of progressive Crohn's disease and how "undertreatment" of the disease is substantial. He advised reviewing the much less common complications within the context of the chronic diseases and in terms that patients can comprehend; such as using absolute risks rather than risk ratios and utilization of tools such as a 10,000-patient diagram to demonstrate the rarity of many complications. Nevertheless, it is important to recognize that, aside from risks of intracellular pathogens, combination therapy is not associated with an increased risk of serious infections and that corticosteroids are associated with the biggest risk of infections. Viral infections such as Herpes zoster, non-melanotic skin cancer, Epstein-Barr virus-related and hepatosplenic T cell lymphomas are increased in patients receiving immunosuppressives. However, the absolute risk of those lymphomas is very small, approximately 6 in 10,000 in patients on combination therapy. Finally, Dr. Siegel described the serologic assay for the JC virus as being an important tool to determine and minimize the risk of developing progressive multifocal leukoencephalopathy for patients receiving, or about to receive natalizumab (Tysabri).
Dr. David Rubin from the University of Chicago then reviewed the prophylaxis against and the management of post-operative recurrence of Crohn's disease by discussing risk stratification based on factors associated with early disease recurrence in the setting of Crohn's disease and pouchitis in ulcerative colitis. Important factors related to the early recurrence of Crohn's disease include cigarette smoking, rapidly progressive or complicated disease, and extensive ileocolonic disease. Risks for pouchitis after ileo-anal anastomoses for ulcerative colitis include extraintestinal manifestations, smoking, and primary sclerosing cholangitis. Dr. Rubin emphasized the need to achieve mucosal healing and shared lessons he has learned related to the early endoscopic appearance of the pre-anastomotic ileum after an ileal resection. At present it appears that prophylaxis with combination immunosuppressives and antibiotics are effective for patients with a moderate risk of recurrence, whereas introduction or re-treatment with biologic therapies are looking to be the most effective prophylactic or therapeutic approach for patients with a high risk of clinical recurrence. While the probiotic VSL#3 has evidence for preventing pouchitis when administered at the time of re-anastomosis of the pouch to intestinal contiguity, optimal approaches at preventing pouchitis remain to be determined.
Dr. Darrell Pardi from the Mayo Clinic, Rochester, Minn., then provided an update on the overlapping spectrum of microscopic and collagenous colitis that seems to have peeked in incidence over the past decade, particularly in middle aged women. Risk factors include numerous medications but NSAIDs, in particular, as well as the presence of other autoimmune disorders, including celiac disease (particularly in patients with steatorrhea or weight loss). The most effective therapy has been budesonide, although some patients do become "budesonide-dependent." Dr. Pardi also favors bismuth therapy, but he says that the best evidence is in favor of budesonide for both short- and long-term use.
Finally, Dr. William Chey from the University of Michigan, Ann Arbor, ended the session by discussing some overlapping features between IBD and IBS, mucosal inflammation and related nerve-gut interactions, and the potential role of the intestinal microflora in initiating and perpetuating IBS symptoms. It is becoming apparent that the microbiota in IBS patients differs from that in healthy patients, and these differences may lead to novel diagnostic tests and treatments for IBS. He reviewed the spectrum of external factors affecting the gut microflora, including therapeutic foods (prebiotics), probiotics, and antibiotics. Recently, the non-absorbed antibiotic, rifaximin, has been demonstrated to have therapeutic potential in subgroups of IBS patients.
