Therapy of Distal Disease

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For mildly active distal disease, 5-ASA preparations are our first choice. If the disease is limited to the distal 15 cm, a suppository preparation of 500 mg each, given 1 to 2 times daily for 2 to 4 weeks, may control the symptoms. If the disease is more extensive but limited to the colon that is distal to the splenic flexure, an enema containing 4 g of 5-ASA, given at bedtime for 3 or 4 weeks, will be effective in 80% of patients. The patient who responds with symptomatic improvement can then be switched to oral 5-ASA at a dose of 2.4 to 2.5 g/d for long-term maintenance. Flares occurring infrequently, such as once or twice yearly, can be treated with repeat suppository or enema preparations of 5-ASA for 3- to 4-week intervals when needed. If the flares recur more frequently, a higher dose of oral 5-ASA (eg, 4.8 g/d) may be necessary for maintenance treatment. This may be reduced slowly once the patient has been in remission for several months to a lower dose (2.4 to 4.8g/d) by tapering the daily dose by 1 tablet every 2 to 4 weeks. Suppositories or enemas of 5-ASA given once or twice weekly are another option for maintenance therapy of distal disease if oral 5-ASA preparations are ineffective.

When mild distal disease is not controlled with this approach, or the disease is more severe, combined rectal 5-ASA (4 g/d enema) and oral 5-ASA (2.4 to 4.8 g/d) may prove effective. Alternatively, the addition of a hydrocortisone enema or hydrocortisone foam may be given once daily in addition to the oral 5-ASA therapy for a period of 3 to 4 weeks. If remission is not accomplished with this regimen, then prednisone 40 mg/d for 2 to 4 weeks, in addition to oral 5-ASA, maybe used. Once symptoms are controlled, pred-nisone may be reduced by decreasing the daily dose by 10 mg each week down to 20 mg/d, then reducing the daily dose by 5 mg per day each week or 2 weeks until the prednisone is stopped. Oral 5-ASA therapy (2.4 to 4.8 g/d) may be continued for long term maintenance therapy. For the patient who responds to oral prednisone but promptly worsens as the dose is reduced despite maintenance therapy with 5-ASA, then azathioprine (AZA) or 6-mercaptopurine (6-MP) can be added. We check the thiopurine methyltransferase (TPMT) red cell enzyme before starting AZA/6-MP, and if the TPMT is normal, we start with a dose of AZA 2 to 2.5 mg/kg daily or 6-MP at a dose of 1 to 1.5 mg/kg daily. A lower dose should be used in patients with a low TPMT level. There is a separate chapter on AZA use in inflammatory bowel disease (IBD) (Chapter 69, "Monitoring of Azathioprine Metabolite Levels in Inflammatory Bowel Disease"). We continue prednisone for about 2 months after starting AZA/6-MP to allow time for the drug to become effective. Occasionally, we use nicotine patches for UC, in patients who have not responded to steroids, particularly in former smokers. We start nicotine patches at an initial dose of a 7 mg/d for a week, then 14 mg/d for a week, then a 21 mg/d patch for 4 weeks as described by Sandborn and col leagues (1997). With clinical improvement, the nicotine patch dose can be reduced to the next lower dose every 2 weeks until the patches are discontinued. Once remission has been attained, prednisone can be tapered by 10 mg increments until reaching 20 mg/d and then by 5 mg/d every 1 to 2 weeks until stopped.

Unresponsive Patients

For patients who have not responded adequately to any of these measures, we recommend proctocolectomy with ileal J pouch to anal anastomosis (IAP) if the patient is under age 65 years and is in good health, or end ileostomy if the patient is obese or older. Although cyclosporine is an option, we consider the risks to outweigh the benefits compared with surgery and we share this opinion with the patient. We use infliximab for UC only within the context of an experimental trial, as it has unproved benefit for this indication.

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