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6-mercaptopurine (6-MP) and azathioprine (AZA) are used to treat inflammatory bowel disease (IBD). Side effects include infection, leukopenia, hepatitis, and pancreatitis. The level of thiopurine methyltransferase (TPMT), which metabolizes 6-MP to 6-methylmercaptopurine, may reflect the risk of side effects. We sought to evaluate the relationship between the side effects of these medications and the TPMT level of pediatric patients with IBD. The medical records of our patients who were diagnosed with IBD and who received 6-MP or AZA were reviewed for measured TPMT levels. All red blood cell (RBC) TPMT levels were determined at the Mayo Medical Laboratories, Rochester, MN. The occurrence of leukopenia, elevated aminotransferases, and pancreatitis was evaluated. Twenty-two patients, mean age 13.7 years, received 6-MP or AZA and had TPMT levels measured. The TPMT levels ranged 10.7-27.5 U/mL RBC with a mean of 17.2 +/- 3.2 U/mL RBC. Two children had levels below the accepted norm of 13.8 U/mL RBC. One of these patients (50%) developed both elevation of aminotransferases and leukopenia. Of all, 20 children had normal levels, 3 (15.0%) exhibited side effects: hepatitis (n = 2) and leukopenia (n = 1). We conclude that side effects of 6-MP or AZA occur despite normal TPMT levels.

Background: The effectiveness of 6-mercaptopurine combined with azathioprine in treating severe ulcerative colitis has been shown in several adult studies. Reported pediatric experiences are rare. The purpose of this study was to investigate the safety and the potential efficacy of 6-mercaptopurine and azathioprine in the treatment of active ulcerative colitis in a pediatric population., Methods: The medical records of patients with active ulcerative colitis who were under observation at The Children's Hospital of Philadelphia and its satellite clinics from January 1984 through December 1997 were retrospectively reviewed. Patients were included who had received a diagnosis of ulcerative colitis, who met no criteria for Crohn's colitis, and who had received treatment with 6-mercaptopurine and azathioprine. They were then analyzed for the development of side effects, the indication to use 6-mercaptopurine and azathioprine, and the ability to discontinue corticosteroid use in those patients taking 5-acetylsalicylic acid products who were corticosteroid-dependent or whose disease was refractory to treatment. Excluded from the corticosteroid analyses were patients who underwent surgery for their disease and patients treated with 5-acetylsalicylic acid only. Statistical analysis was performed by the Kaplan-Meier survival curve and paired Student's t-test., Results: In a review of 200 medical records of patients with active ulcerative colitis, 20 patients met the criteria. The patients' average age at the initiation of treatment with 6-mercaptopurine and azathioprine was 13.8 years. Sixteen patients (80%) were corticosteroid dependent and 3 (15%) had ulcerative colitis refractory to corticosteroid treatment. One patient had severe colitis treated with 5-acetylsalicylic acid only. Discontinuation of corticosteroid was accomplished in 12 (75%) of 16 patients. The median time to discontinuation of corticosteroid after initiation of 6-mercaptopurine and azathioprine therapy was 8.4 months. Eight patients (67%), observed from 3 months to 65 months, have continued without corticosteroid therapy. Side effects included pancreatitis and shingles that resulted in discontinuation of 5-acetylsalicylic acid, leukopenia corrected by withholding 6-mercaptopurine, and self-resolved hepatitis., Conclusions: The data support the safety of 6-mercaptopurine and azathioprine use in the treatment of pediatric patients with ulcerative colitis; side effects were minimal and reversible. Eighteen (90%) of 20 patients tolerated the therapy well. The results also show that 12 (75%) of 16 pediatric patients with ulcerative colitis will benefit from the use of 6-mercaptopurine and azathioprine after initial discontinuation of corticosteroid therapy. Although 6-mercaptopurine and azathioprine may not prevent further relapses, medical management of these flares may be less intense and may not require long-term corticosteroid use. Prospective clinical trials in pediatric patients are necessary to delineate further the role of 6-mercaptopurine and azathioprine in pediatric ulcerative colitis.

Background: Recurrence of Crohn's disease after surgery is a common occurrence, pointing to the need for a strategy to prevent recurrent disease. We report the postoperative course of 10 patients who required intestinal resections for complications related to Crohn's disease., Methods: All patients had a Pediatric Crohn's Disease Activity Index score of 10 or greater. Among these patients, 5 began treatment with 6-mercaptopurine in the perioperative period. All 10 had received various combinations of prednisone and salicylate compounds. Patients who were given 6-mercaptopurine did not discontinue the medication until 2 years after the surgery., Results: To date, none of the five patients who were placed on 6-mercaptopurine have had recurrence of their Crohn's disease (mean disease-free period 32.6 +/- 18.4 months). Among those five patients not receiving 6-mercaptopurine there have been three relapses (mean time to relapse 3.7 +/- 1.2 months). Log-rank sum analyses of Kaplan-Meier survival curves show benefit to patients receiving 6-mercaptopurine in preventing relapses after intestinal resection (p < 0.05)., Conclusions: Although the underlying pathophysiologic reasons leading to the high relapse rate after intestinal surgery in Crohn's disease are unknown, we conclude that treatment with 6-mercaptopurine in the perioperative period may be warranted to help prevent the recurrence of Crohn's disease after surgery.