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Complications of pregnancy and child development after cessation of treatment with 6-mercaptopurine for inflammatory bowel disease

Zlatanic, Jusuf; Korelitz, Burton I; Rajapakse, Ramona; Kim, Peter S; Rubin, Steven D; Baiocco, Peter J; Panagopoulos, Georgia
PURPOSE: 6-Mercaptopurine (6-MP) has proven efficacy in the therapy of inflammatory bowel disease. Its teratogenicity is demonstrated in animal studies when used at very high doses, whereas human data suggest that 6-MP at maintenance doses is safe. We report the outcome of 72 pregnancies in patients with inflammatory bowel disease who were previously treated with 6-MP with three different doses of 50, 75, and 100 mg/d, for a median duration of 18 months, along with long-term follow-up of the children. METHODS: We have compared the outcome of pregnancies and development of the offspring in the following two groups: group 1, patients with inflammatory bowel disease who conceived 6 months to 22 years after stopping 6-MP (median 72 months); and group 2, patients with inflammatory bowel disease who never received 6-MP prior to conception. All pregnancies were evaluated in terms of outcome: live full-term birth, premature delivery, stillbirth, spontaneous abortion, ectopic pregnancy, and therapeutic dilatation and curettage. Data on children were obtained regarding birth weight, congenital anomalies, and development. RESULTS: Group 1 included 72 pregnancies carried by 29 women. There were 51 live births (4 premature), 16 spontaneous abortions, 1 stillbirth, 2 therapeutic abortions due to abnormal amniocentesis, and 2 ectopic pregnancies. The total incidence of fetal loss was 29.2%. In group 2, 75 women had 140 pregnancies resulting in 120 live births (8 premature), 18 spontaneous abortions, and 2 stillbirths. There were no cases of ectopic pregnancies or abnormal amniocentesis. The total incidence of fetal loss was 14.3%. There was no increase in the incidence of developmental defects when the mothers had been treated with 6-MP prior to pregnancy. CONCLUSIONS: The incidence of fetal loss is higher in women with inflammatory bowel disease who had been previously treated with 6-MP compared with those who had not. Whether this was related to the older age at conception in 6-MP group, longer duration of disease, initially more severe disease, or use of 6-MP we cannot tell
PMID: 12642735
ISSN: 0192-0790
CID: 65348

6MP for fathers with IBD at the time of conception: the value of a large clinical experience over unrelated controls [Letter]

Korelitz BI; Rajapakse RO; Zlatanic J; Baiocco PJ; Gleim GW
PMID: 11007251
ISSN: 0002-9270
CID: 65355

Outcome of pregnancies when fathers are treated with 6-mercaptopurine for inflammatory bowel disease [see comments] [Comment]

Rajapakse RO; Korelitz BI; Zlatanic J; Baiocco PJ; Gleim GW
OBJECTIVE: The outcomes of pregnancies after maternal use of 6-mercaptopurine (6-MP) for inflammatory bowel disease (IBD) during pregnancy have been reported, but data are lacking for outcomes when the fathers use this drug. METHODS: Subjects were male patients with IBD seen at one center between 1970 and 1997. Patients and their wives were interviewed. Group 1 comprised pregnancies fathered by men who were taking 6-MP. This group was further subdivided into those conceived within 3 months of 6-MP use and those conceived at least 3 months after 6-MP was stopped. Group 2 comprised pregnancies fathered by men with IBD, similar in characteristics to group 1, who had not taken 6-MP before fertilization. Information was collected regarding the fathers, the mothers, and the pregnancies, as well as the health of the children, in a historical cohort study. RESULTS: There were 50 pregnancies in group 1 (13 in 1A and 37 in 1B) and 90 pregnancies in group 2. Four of the 13 pregnancies in group 1A were associated with complications. There were two spontaneous abortions, and two congenital anomalies including a missing thumb in one and acrania with multiple digital and limb abnormalities in the other. Risk of complications was significantly increased when compared with group 1B (p < 0.013) and group 2 (p < 0.002). CONCLUSION: The incidence of pregnancy-related complications was significantly increased when the fathers used 6-MP within 3 months of conception
PMID: 10710057
ISSN: 0002-9270
CID: 11810

Optimum duration of treatment with 6-mercaptopurine for Crohn's disease

Kim PS; Zlatanic J; Korelitz BI; Gleim GW
OBJECTIVE: 6-Mercaptopurine (6MP) and azathioprine are immunomodulators used in the treatment of refractory Crohn's disease. Studies have confirmed their efficacy and value in maintenance of remission, but it is our purpose to determine how long 6MP/azathioprine should be continued once remission has been accomplished. METHODS: Careful follow-up was accomplished in patients with Crohn's disease seen at one medical center who were treated with 6MP for > or = 6 months, who achieved remission within 1 yr of initiation of therapy, and who were in prolonged clinical remission (> or = 6 months without steroids). The time-to-relapse was calculated in those who continued treatment, in those who stopped treatment for reasons other than a relapse, and in the whole sample, taking into account that they could be treated with the drug, or could not, as a function of time. The influence of concomitant variables on the time-to-relapse rate was evaluated. RESULTS: A total of 120 patients met the inclusion criteria. The cumulative probabilities of relapse at 1, 2, 3, and 5 yr for those who continued to take 6MP and for those who stopped the therapy for reasons other than a relapse are as follows: Patients maintained on 6MP (n = 84): 1 yr, 29%; 2 yr, 45%; 3 yr, 55%; 5 yr, 61%. Patients who terminated 6MP (n = 36): 1 yr, 36%; 2 yr, 71%; 3 yr, 85%; 5 yr, 85%. Sex, distribution of disease, duration of disease, time to remission on 6MP, and concomitant 5-ASA use did not influence the relapse rates. Younger age was associated with a higher rate of relapse in patients who were maintained on 6MP. A higher daily dose of 6MP was associated with a higher relapse rate. CONCLUSIONS: Discontinuation of 6MP, while Crohn's disease is in remission, leads to higher relapse rates and continuation of 6MP reduces the likelihood of relapse. Therefore, we favor the indefinite use of 6MP once remission has been achieved
PMID: 10566725
ISSN: 0002-9270
CID: 56483

Allergic reactions to 6-mercaptopurine during treatment of inflammatory bowel disease

Korelitz BI; Zlatanic J; Goel F; Fuller S
Hypersensitivity reactions to 6-mercaptopurine (6-MP) or azathioprine occur during the treatment of inflammatory bowel disease (IBD), raising significant diagnostic and therapeutic challenges. Charts of 591 patient with IBD treated with 6-MP in a single center were retrospectively reviewed. All allergic reactions were recorded along with results of rechallenge, desensitization, and subsequent course of IBD. Sixteen (2.7%) allergic reactions to 6-MP were noted, with fever being the most common (14 cases). Nine of these were rechallenged with 6-MP with recurrence of the same symptoms. Azathioprine was tried in six patients and in five the same symptoms recurred. Four patients underwent successful desensitization to either 6-MP or azathioprine; all four plus another patient who tolerated direct switch to azathioprine entered long-term remission. Among the remaining 11, 5 required surgery, 2 are well on methotrexate, and 4 have chronic symptoms while being treated with other medications. If an allergic reaction to 6-MP occurs during the treatment of IBD, direct switching to azathioprine is probably not justified. Instead, desensitization to either 6-MP or azathioprine should be attempted. Patients who can tolerate these medications after previous allergic reactions have improved outcomes compared with patients who resort to other forms of treatment
PMID: 10372932
ISSN: 0192-0790
CID: 12001

Large sessile colonic adenomas: use of argon plasma coagulator to supplement piecemeal snare polypectomy

Zlatanic, J; Waye, J D; Kim, P S; Baiocco, P J; Gleim, G W
BACKGROUND: Residual adenoma is frequently found at the site of endoscopically resected large sessile adenomas on follow-up examination. We evaluated the efficacy of a thermal energy source, the argon plasma coagulator, to destroy visible residual adenoma after piecemeal resection of sessile polyps. METHODS: Seventy-seven piecemeal polypectomies with or without the use of argon plasma coagulator were analyzed retrospectively. All polyps were sessile, 20 mm or greater in size. The results from three groups of patients were compared. The study group was composed of patients who had visible residual adenoma after piecemeal polypectomy and had the base of the polypectomy site treated with the argon plasma coagulator. The first comparison group consisted of patients who underwent standard piecemeal polypectomy in whom the colonoscopist thought that all adenomatous tissue was removed and no further treatment was necessary. The second comparison group included patients in whom visible residual adenoma was left at the base after piecemeal resection of large adenomas. Follow-up colonoscopy was performed approximately 6 months after the initial procedure to check for recurrent/residual adenomatous tissue. RESULTS: The argon plasma coagulator was used after 30 piecemeal polypectomies in an attempt to eradicate visible residual adenomatous tissue; at follow-up, 50% of these cases had complete eradication of adenoma. The group in whom all visible tumor was removed by piecemeal polypectomy alone had an adenoma eradication rate of 54% on follow-up colonoscopy. In the patients in whom visible residual adenoma was left at the site the recurrence rate was 100% on the follow-up examination. Bleeding necessitating endoscopic therapy occurred once (3.3%) in the argon plasma coagulator group; there were four (12.5%) bleeding episodes and one (3.1%) confined retroperitoneal perforation in the complete piecemeal polypectomy group and no complications in the group in which polypectomy was incomplete. CONCLUSIONS: Argon plasma coagulator ablation of residual adenomatous tissue at the polypectomy base is safe and useful. It helps to complete the eradication of large sessile polyps when there is visible evidence of residual polyp.
PMID: 10343218
ISSN: 0016-5107
CID: 491682

Outcome of pregnancies when fathers are treated with 6-mercaptopurine for inflammatory bowel disease [Meeting Abstract]

Rajapakse, RO; Korelitz, BI; Zlatanic, J; Baiocco, PJ; Gleim, GM
ISSN: 0016-5085
CID: 53472

Inflammatory bowel disease and immune thrombocytopenic purpura: is there a correlation? [Case Report]

Zlatanic J; Korelitz BI; Wisch N; Kim P; Ammirati M; Schwarz S; Gruenstein S; Lipsey L
Different hematologic abnormalities are often encountered in patients with inflammatory bowel disease. Among them anemia, leukocytosis, and thrombocytosis are commonly seen. Leukopenia and thrombocytopenia are observed mostly as a side effect of therapy, particularly with use of immunosuppressive drugs. Immune thrombocytopenic purpura is rarely reported in association with inflammatory bowel disease. We present two cases with combination of these entities along with a literature review and treatment options. Immune thrombocytopenic purpura in these patients presented as an extraintestinal manifestation of inflammatory bowel disease mediated by a disturbance of the immune system
PMID: 9399771
ISSN: 0002-9270
CID: 12207

Significance of WBC differential when leukopenia is induced by 6-MP for IBD [Letter]

Korelitz BI; Zlatanic J; Smith MJ; Lipe RJ; Baiocco PJ; Gleim GW
PMID: 9352894
ISSN: 0016-5085
CID: 65364

The differential white blood count when leukopenia is induced by 6MP in the treatment of inflammatory bowel disease (IBD) [Meeting Abstract]

Korelitz, BI; Smith, MJ; Lipe, RJ; Zlatanic, J; Gleim, GM
ISSN: 0016-5085
CID: 688582