15-35: Inflammatory Bowel Disease

The term “inflammatory bowel disease” includes ulcerative colitis and Crohn disease. The diagnosis and management of each will be reviewed in the sections below. In the United States, there are approximately 1.6 million people with IBD with adjusted annual incidences of 12.2 cases/100,000 person-years for ulcerative colitis and 10.7 cases/100,000 person-years for Crohn disease. These diseases can occur at any age but most commonly begin in adolescents and adults under age 40 years. The natural history of both varies from mild, often intermittent disease symptoms to severe disease characterized by elevated inflammatory markers and mucosal ulcerations that may lead to intestinal complications (bleeding, strictures, fistulas, surgery), nutritional deficiencies, and impaired quality of life. Both diseases may be associated with several extraintestinal manifestations, including oral ulcers, oligoarticular or polyarticular nondeforming peripheral arthritis, spondylitis or sacroiliitis, episcleritis or uveitis, erythema nodosum, pyoderma gangrenosum, hepatitis and sclerosing cholangitis, and thromboembolic events.

PHARMACOLOGIC THERAPY

Although ulcerative colitis and Crohn disease appear to be distinct entities, several pharmacologic agents are used to treat both. Despite extensive research, there are still no specific therapies for these diseases. The mainstays of therapy are 5-aminosalicylic acid derivatives, corticosteroids, immunomodulating drugs (such as mercaptopurine or azathioprine and methotrexate) and other small-molecule agents, and biologic therapies.

A. 5-Aminosalicylic Acid (5-ASA)

5-ASA is a topically active agent that has a variety of anti-inflammatory effects. It is used in the active treatment of ulcerative colitis and Crohn disease and during disease inactivity to maintain remission. It is readily absorbed from the small intestine but demonstrates minimal colonic absorption. Several oral and topical compounds have been designed to target delivery of 5-ASA to the colon or distal small intestine. Commonly used formulations of 5-ASA are sulfasalazine, mesalamine, and azo compounds.

1. Oral formulations

Mesalamine compounds are oral 5-ASA formulations that are either coated in various pH-sensitive resins (Asacol, Apriso, and Lialda) that release 5-ASA throughout the colon or packaged in timed-release capsules (Pentasa) that release 5-ASA in the small intestine and colon. Side effects of these compounds are uncommon but include nausea, rash, diarrhea, pancreatitis, and acute interstitial nephritis. Sulfasalazine and balsalazide are two oral formulations that contain 5-ASA linked by an azo bond to another agent (sulfapyridine or an inert peptide, respectively) in order to prevent small intestine absorption. Following cleavage of the azo bond by colonic bacteria, 5-ASA is released in the colon. The sulfapyridine group is absorbed and may cause side effects in 15–30% of patients, including nausea, oligospermia, leukopenia, agranulocytosis, impaired folate metabolism, and hypersensitivity (fever, rash, hemolytic anemia, pneumonitis). Because of its side effects, sulfasalazine is used less frequently than balsalazide and other 5-ASA agents. It should ...