Management of refractory ulcerative colitis.

A physician's approach to patients with ulcerative colitis (UC) who are refractory to standard first-line therapies must be thoughtful and systematic and include the individual's physical and emotional state as the physician examines the various dietary, medical, and surgical options currently available. It is of foremost importance to confirm that the refractory patient's symptoms are not simply due to dietary indiscretion, concomitant bowel infection (especially with Clostridium difficile), an incorrect diagnosis (eg, colitis due to infection, NSAIDs, ischemia, diverticulitis, or Crohn's disease), or even a concomitant diagnosis (eg, celiac sprue, pancreatic insufficiency, functional bowel disorder, laxative or sorbitol intake). The ability to quickly assess the status of the colonic mucosa with flexible sigmoidoscopy aids in the ability to distinguish patients with refractory inflammation from those with other diagnoses. The initiation and optimization of the long-term purine analogues azathioprine (AZA) or 6-mercaptopurine (6-MP) remain the backbone of medical therapy for patients with refractory UC. For those unresponsive to corticosteroids, quicker induction of remission may necessitate infliximab, cyclosporine, or tacrolimus. Successful induction and maintenance with AZA, 6-MP, and/or infliximab should be followed by long-term therapy with these agents. Cessation of therapy often leads to relapse. Novel therapies under investigation hold the promise of offering more options for both the induction and maintenance of remission in refractory UC patients. Discussions of surgical intervention should not be put off as a last resort but rather included in the overall treatment plan offered to the patient.