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Inflammatory bowel disease (IBD) is a spectrum of chronic, idiopathic, inflammatory intestinal conditions. IBD causes significant gastrointestinal (GI) symptoms that include diarrhea, abdominal pain, bleeding, anemia, and weight loss. IBD also is associated with a variety of extraintestinal manifestations, including arthritis, ankylosing spondylitis, sclerosing cholangitis, uveitis, iritis, pyoderma gangrenosum, and erythema nodosum.
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IBD conventionally is divided into two major subtypes: ulcerative colitis and Crohn's disease. Ulcerative colitis is characterized by confluent mucosal inflammation of the colon starting at the anal verge and extending proximally for a variable extent (e.g., proctitis, left-sided colitis, or pancolitis). Crohn's disease, by contrast, is characterized by transmural inflammation of any part of the GI tract but most commonly the area adjacent to the ileocecal valve. The inflammation in Crohn's disease is not necessarily confluent, frequently leaving "skip areas" of relatively normal mucosa. The transmural nature of the inflammation may lead to fibrosis and strictures or, alternatively, fistula formation.
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Medical therapy for IBD is problematic. Because no unique abnormality has been identified, current therapy for IBD seeks to dampen the generalized inflammatory response; however, no agent can reliably accomplish this, and the response of an individual patient to a given medicine may be limited and unpredictable. Based on this variable response, clinical trials generally employ standardized quantitative assessments of efficacy that take into account both clinical and laboratory parameters (e.g., the Crohn's Disease Activity Index). The disease also exhibits marked fluctuations in activity—even in the absence of therapy—leading to a significant "placebo effect" in therapeutic trials.
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Specific goals of pharmacotherapy in IBD include controlling acute exacerbations of the disease, maintaining remission, and treating specific complications such as fistulas. Specific drugs may be better suited for one or the other of these aims (Table 47–1). For example, glucocorticoids remain the treatment of choice for moderate to severe flares but are inappropriate for long-term use because of side effects and their inability to maintain remission. Other immunosuppressive agents, such as azathioprine, that require several weeks to achieve their therapeutic effect, have a limited role in the acute setting but are preferred for long-term management.
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