The adverse effect profile of oral azathioprine in pediatric atopic dermatitis, and recommendations for monitoring

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Abstract

Background

Azathioprine is efficacious in the treatment of severe childhood atopic dermatitis; however, robust data on adverse effects in this population are lacking.

Objective

We sought to assess adverse effects of azathioprine treatment in a pediatric atopic dermatitis cohort, and make recommendations for monitoring based on these data.

Methods

Blood test results for all 82 children prescribed oral azathioprine for atopic dermatitis in our department between 2010 and 2012 were collated prospectively, and clinical notes were reviewed retrospectively.

Results

Mean age at commencing azathioprine was 8.3 years (SEM 0.4). Mean maximum doses were 2.4 mg/kg (SEM 0.1) and 1.5 mg/kg (SEM 0.1) for normal and reduced serum thiopurine-S-methyltransferase levels, respectively. Adverse effects on blood indices occurred in 34 of 82 patients (41%), with pronounced effects in 18 of 82 (22%) after a median time of 0.4 years. Two patients stopped therapy as a result of abnormal blood indices. Clinical adverse effects occurred in 16 of 82 (20%), two resulting in cessation of therapy. Incidence of adverse effects was unaffected by age, sex, thiopurine-S-methyltransferase level, and drug dose on multivariate regression.

Limitations

Comparison with other studies is limited by varying definitions of adverse effects.

Conclusion

Oral azathioprine was associated with few pronounced adverse effects for the duration of use and dosage in this cohort. Recommendations for monitoring are made.

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Most cited references 17

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Azathioprine in dermatology: the past, the present, and the future.

R Swerlick, Dhyanesh Patel, Calvin McCall (2006)

For several decades, dermatologists have utilized azathioprine to treat numerous debilitating skin diseases. This synthetic purine analog is derived from 6-mercaptopurine. It is thought to act by disrupting nucleic acid synthesis and has recently been found to interfere with T-cell activation. The most recognized uses of azathioprine in dermatology are for immunobullous diseases, generalized eczematous disorders, and photodermatoses. In this comprehensive review, the authors present recent advancements in the understanding of azathioprine and address aspects not covered in prior reviews. They (1) summarize the history of azathioprine; (2) discuss metabolism, integrating information from recent publications; (3) review the mechanism of action with attention paid to the activities of azathioprine not mediated by its 6-mercaptopurine metabolites and review new data about inhibition by azathioprine of the CD28 signal transduction pathway; (4) thoroughly examine thiopurine s-methyltransferase genetics, its clinical relevance, and interethnic variations; (5) review prior uses of azathioprine in the field of dermatology and grade the level of evidence; (6) discuss the use of azathioprine in pregnancy and pediatrics; review (7) key drug interactions and (8) adverse effects; (9) suggest a dosing and monitoring approach different from prior recommendations; and (10) explore the future of azathioprine, focusing on laboratory considerations and therapeutic application.

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Eczema severity in preadolescent children and its relation to sex, filaggrin mutations, asthma, rhinitis, aggravating factors and topical treatment: a report from the BAMSE birth cohort.

C. Söderhäll, C F Wahlgren, I Kull … (2013)

Filaggrin (FLG) mutations are major genetic determinants for eczema, but their role in eczema severity needs further investigation. Children with eczema are at higher risk of having asthma and rhinitis but it is not known if this risk is associated with the severity of eczema. To investigate eczema severity in relation to sex, FLG mutations, asthma, rhinitis and topical treatment among preadolescent children in a population-based cohort. Parental questionnaires were used to obtain data on symptoms of eczema, asthma, and rhinitis among 3301 preadolescent children. Eczema severity was evaluated based on sleep disturbance, extent of disease and total time with eczema the previous year. Genotyping was performed in 1854 individuals for three common FLG mutations (R501X, R2447X and 2282del4). Results Eczema was more prevalent among girls (14·5%) than boys (9·4%). FLG mutations were detected in 13·1% of children with mild eczema and 12·5% with moderate-to-severe eczema. Of children with moderate-to-severe eczema, 45·1% had rhinitis and 22·0% had asthma compared with 32·7% and 13·8% of children with mild eczema, respectively. Children with moderate-to-severe eczema used moisturizers and topical glucocorticoids more frequently than children with mild eczema. Boys used moisturizers less frequently than girls. More preadolescent girls than boys had eczema. FLG mutations did not influence eczema severity in our population-based cohort. Prevalence of rhinitis and asthma was associated with eczema severity, with the highest prevalence among boys with moderate-to-severe eczema. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

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Thiopurine S-methyltransferase pharmacogenetics: insights, challenges and future directions.

Bifang Li-Wang, Richard Weinshilboum (2006)

The thiopurine S-methyltransferase (TPMT) genetic polymorphism is one of the most 'mature' examples in pharmacogenetics. That is true because of its importance clinically for the individualization of thiopurine drug therapy and also because TPMT has provided novel insights into molecular mechanisms responsible for the functional effects of common genetic polymorphisms. This review will summarize the development of our understanding of the role of inheritance in the regulation of TPMT as well as the clinical implications of that genetic regulation. It will also summarize recent studies in which TPMT pharmacogenetics has enhanced our understanding of molecular mechanisms by which common polymorphisms influence or alter function. TPMT pharmacogenetics highlights the potential clinical importance of the translation of pharmacogenetics from bench to bedside, the potential for basic pharmacogenetic research to provide insight into mechanisms by which genetic polymorphisms can alter function, and the challenges associated with the achievement of both of those goals.

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Author and article information

Contributors

Veronica A. Kinsler

Journal

Journal ID (nlm-ta): J Am Acad Dermatol

Journal ID (iso-abbrev): J. Am. Acad. Dermatol

Title: Journal of the American Academy of Dermatology

Publisher: Mosby

ISSN (Print): 0190-9622

ISSN (Electronic): 1097-6787

Publication date PMC-release: 1 January 2015

Publication date (Print): January 2015

Volume: 72

Issue: 1

Pages: 108-114

Affiliations

[a ]Pediatric Dermatology Department, Great Ormond Street Hospital for Children National Health Service (NHS) Foundation Trust, London, United Kingdom

[b ]Department of Medicine, St George's Hospital, London, United Kingdom

[c ]Department of Dermatology, Royal Free Hospital, London, United Kingdom

[d ]Genetics and Genomic Medicine, University College London (UCL) Institute of Child Health, London, United Kingdom

Author notes

[∗ ]Reprint requests: Veronica A. Kinsler, MD, PhD, Pediatric Dermatology Department, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London WC1N 3JH. v.kinsler@ 123456ucl.ac.uk

Article

Publisher ID: S0190-9622(14)01905-7

DOI: 10.1016/j.jaad.2014.08.048

PMC ID: 4274333

PubMed ID: 25440430

SO-VID: fe64be66-6a6d-49f5-9427-b7c701323951

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

The adverse effect profile of oral azathioprine in pediatric atopic dermatitis, and recommendations for monitoring

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Abstract

Background

Objective

Methods

Results

Limitations

Conclusion

Related collections

Pediatric Pulse: Advancing Neonatal and Child Health

Most cited references 17

Azathioprine in dermatology: the past, the present, and the future.

Eczema severity in preadolescent children and its relation to sex, filaggrin mutations, asthma, rhinitis, aggravating factors and topical treatment: a report from the BAMSE birth cohort.

Thiopurine S-methyltransferase pharmacogenetics: insights, challenges and future directions.

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