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Assessment of Azathioprine-Associated Lymphopenia Incidence Rates in Polish Children with Inflammatory Bowel Disease
Katarzyna Bąk-Drabik1, Anna Kaput2, Anna Jarzumbek1
1Department of Paediatrics, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland.
Insights
Lymphopenia, a side effect of azathioprine (AZA), occurred in about a quarter of pediatric patients with inflammatory bowel disease or autoimmune hepatitis. This condition was mostly transient and not linked to opportunistic infections, but warrants closer monitoring in Crohn's disease patients.
Area of Science:
- Pediatric Gastroenterology
- Immunology
- Pharmacology
Background:
- Azathioprine (AZA) and 6-mercaptopurine (6-MP) are thiopurines used for inflammatory bowel diseases (IBD) and autoimmune hepatitis (AIH).
- Adverse effects include leukopenia, primarily neutropenia and lymphopenia.
- The incidence and impact of AZA-induced lymphopenia in pediatric IBD and AIH patients are not well-characterized.
Purpose of the Study:
- To determine the incidence rate of lymphopenia in pediatric patients with Crohn's disease (CD), ulcerative colitis (CU), and AIH treated with AZA.
- To evaluate the impact of lymphopenia on opportunistic infections.
- To assess the relationship between lymphopenia, disease activity, AZA treatment, and nutritional status.
Main Methods:
- Retrospective analysis of 98 pediatric patients treated with AZA for CD, CU, or AIH.
- Assessed blood cell counts, thiopurine metabolite levels, AZA dosage, anthropometric parameters, disease activity, and infections.
Main Results:
- Lymphopenia was diagnosed in 22% of patients, severe in 2% requiring treatment discontinuation.
- Higher incidence of lymphopenia in CD (34.5%) compared to CU (3.7%) and AIH (7.7%).
- Lymphopenic patients had higher rates of mild respiratory and skin infections (32%); no opportunistic infections were reported.
Conclusions:
- Lymphopenia affected approximately 25% of pediatric patients, usually transient and not requiring AZA modification.
- Lymphopenia was significantly more frequent in CD patients, particularly those with severe disease, necessitating closer monitoring.
- AZA therapy was not significantly associated with lymphopenia occurrence.
Background And Objective:
Thiopurines (azathioprine (AZA) and 6-mercaptopurine (6-MP)), used to maintain remission in inflammatory bowel diseases (Crohn's disease (CD), ulcerative colitis (CU)) and autoimmune hepatitis (AIH), are responsible for a number of adverse effects. One is leukopenia, mainly due to neutropenia and less known lymphopenia. This study aimed to assess the incidence rate of lymphopenia in pediatric patients with CD, CU, and AIH treated with azathioprine (AZA) and to evaluate the impact of lymphopenia on the occurrence of opportunistic infections and its relationship with disease activity, treatment, and nutritional status.
Materials And Methods:
A retrospective analysis was carried out in ninety-eight (98) paediatric patients, suffering from CD, CU, or AIH and treated with AZA, in order to assay blood cell count and thiopurine metabolite levels, assess the mean AZA dose, measure the anthropometric parameters, evaluate disease activity vs. the treatment administered, and to find out concomitant infections.
Results:
Lymphopenia was diagnosed in twenty-two (22) children and evaluated as severe in two (2) cases, which were associated with treatment discontinuation. The percentage of patients with lymphopenia in the CD group (34.5%) was significantly higher vs. the CU (3.7%) and AIH (7.7%) groups. The prevalence rates of the patients with low and moderate-to-high disease activity were 13.9% and 46.1%, respectively. The patients with lymphopenia demonstrated higher prevalence rates of mild respiratory tract and skin infections (identified in 32%). No cases of opportunistic infections were reported.
Conclusions:
Lymphopenia affected approximately one-quarter of the patients observed, the condition being transient in most cases and not demanding any therapy modifications. In no case was it associated with the occurrence of any opportunistic infections. It was significantly more common in the patients with Crohn's disease and the subgroup with a more intense course of the disease, obviously suggesting a need for more frequent follow-up of the patients in those subgroups. The AZA therapy did not seem to be associated with lymphopenia occurrence in any significant way.
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