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Successful Mercaptopurine Usage despite Azathioprine-Induced Pancreatitis in Paediatric Crohn's Disease
Silvia Gallego-Gutiérrez1, Víctor Manuel Navas-López2, Michal Kolorz3
1Pediatric Gastroenterology and Nutrition Unit, UGC de Pediatría, Hospital Regional Universitario de Málaga, Málaga, Spain.
Insights
Azathioprine-induced pancreatitis does not always preclude the use of mercaptopurine in pediatric Crohn's disease. Two children with Crohn's disease tolerated mercaptopurine well after experiencing pancreatitis with azathioprine.
Area of Science:
- Gastroenterology
- Pediatric Gastroenterology
- Pharmacogenomics
Background:
- Azathioprine and mercaptopurine are thiopurines used for maintaining steroid-free remission in pediatric Crohn's disease.
- Azathioprine-induced pancreatitis is a serious side effect, often considered a contraindication for subsequent thiopurine therapy.
Observation:
- Two pediatric patients with Crohn's disease developed pancreatitis after initiating azathioprine treatment.
- Both patients fully recovered after discontinuing azathioprine.
- Genetic testing for TPMT and ITPase polymorphisms revealed no relevant variants in these patients.
Findings:
- Mercaptopurine was successfully initiated in both patients following azathioprine-induced pancreatitis.
- No adverse effects were observed during mercaptopurine treatment in these cases.
- This suggests that pancreatitis from azathioprine may not be an absolute contraindication for mercaptopurine.
Implications:
- Azathioprine-induced pancreatitis should be re-evaluated as an absolute contraindication for mercaptopurine in pediatric Crohn's disease.
- Further research is needed to understand the mechanisms of thiopurine-induced adverse events.
- Personalized therapy approaches may become more feasible with a better understanding of these mechanisms.
Background:
Azathioprine [AZA] and mercaptopurine [MP] are recommended for maintenance of steroid-free remission in children with Crohn`s disease [CD]. Azathioprine-induced pancreatitis, an idiosyncratic and major side effect, has been considered as an absolute contraindication for the use of a second thiopurine in IBD patients.
Materials And Methods:
We describe two children with CD in whom MP were successfully trialled after a confirmed azathioprine-induced pancreatitis, being well tolerated in both cases.
Results:
Two boys [13 and 10 years old] started exclusive enteral nutrition after diagnosis of moderate (Pediatric Crohn's Disease Activity Index [wPCDAI] = 45) and mild [wPCDAI = 35] CD. Both developed an acute mild to moderate pancreatitis after 2 and 3 weeks, respectively, of AZA treatment but recovered fully in hospital after AZA withdrawal. They started on MP treatment without any adverse effect. They were tested for the presence of polymorphisms 238G>C, 460G>A, and 719A>G in the TPMT gene and 94C>A and 21>C in the ITPase. Both patients were wild-type for all tested polymorphisms.
Conclusions:
Azathioprine-induced acute pancreatitis should not be considered as an absolute contraindication for the use of MP. Further investigation is required to create a better understanding of the mechanism underlying the adverse events and to allow more possibilities for personalised therapy.
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