Malignant neoplasms subsequent to treatment of inflammatory bowel disease with 6-mercaptopurine.

OBJECTIVE: Most complications of 6-mercaptopurine (6MP) used in the treatment of inflammatory bowel disease (IBD) occur early, whereas neoplasms occur late in the course. Concern persists that the risk is increased when 6MP is used. We report our experience with malignant tumors developing over 27 yr of treating IBD patients with 6MP. METHODS: A total of 591 patients with IBD treated with 6MP between 1969 and 1997 were followed or traced until present to identify all malignant tumors and blood dyscrasias that had developed to determine the type, distribution, and duration of the IBD, the dose and duration of 6MP therapy, the concurrent versus previous use of 6MP, the incidence and probable relationship of 6MP to specific neoplasms, and whether the 6MP had been effective in treatment. RESULTS: A total of 550 patients (93%) fulfilled the criteria for follow-up; these included 380 with Crohn's disease (CD) and 170 with ulcerative colitis (UC). Twenty-five patients had developed neoplasms (16 of 380 CD and nine of 170 UC) (p = 0.66). In half of the cases, the goal of therapy had been achieved with 6MP. In 10 patients, the neoplasm was diagnosed while the patients were taking 6MP (40%) and in 15, many years after the 6MP had been terminated (60%). The incidence of neoplasms (25 of 550) was 2.7/1000 patient-years of follow-up. The most common neoplasms were found in the bowel (eight of 550, 1.6%; five CD, and three UC), and breast (three, 0.5%; two CD, and one UC). Non-Hodgkins lymphomas occurred in two patients with CD; one was cerebral and the other abdominal. One patient with CD developed leukemia. The duration of 6MP therapy ranged from 5 months to 22 yr, with a mean of 5 yr. The dose of 6MP ranged from a quarter of a tablet/day (12.5 mg) to 100 mg/day, with the majority in a range from 50 to 75 mg/day. CONCLUSION: In no instance could a neoplasm be attributed to the use of 6MP. The incidence of colon cancer is not greater than that with long standing colitis. Suspicion of a relationship between 6MP and leukemia/lymphoma persists, but the incidence is low. This must be weighed against the improved quality of life due to 6MP for patients with IBD.

Shingles during the course of treatment with 6-mercaptopurine for inflammatory bowel disease.

OBJECTIVE: Our aim was to study the frequency, severity, and outcome of patients with Crohn's disease and ulcerative colitis treated with 6-mercaptopurine (6MP) who developed shingles during treatment, and to recommend management. While varicella can be severe in young people immunocompromised by steroids, the incidence of herpes zoster in older people with inflammatory bowel disease (IBD) and whether its severity is influenced by 6MP and azathioprine are unknown. METHODS: Data were collected from our IBD Center on 550 patients with IBD to identify those who developed shingles while on 6MP, its severity, the dose and duration of 6MP, and the management of the 6MP. RESULTS: Twelve of 550 patients with IBD treated with 6MP developed shingles. In two with herpes zoster ophthalmicus the pain was prolonged, and one patient developed encephalitis which was brief and uncomplicated; in nine patients the course was benign. Acyclovir should be the treatment of choice even though it was available in only three cases. CONCLUSIONS: Shingles occurs more often in IBD patients treated with 6MP than in those who are not, but the course is usually benign and there has been no mortality. The 6MP should be stopped temporarily until severity is established but if the underlying disease warrants further treatment the 6MP should be restarted.