Original article
Oral azathioprine for recalcitrant pediatric atopic dermatitis: Clinical response and thiopurine monitoring

Presented in part in poster format at the Society for Pediatric Dermatology 2011 Annual Meeting, Baltimore, MD, July 7-10, 2011.
https://doi.org/10.1016/j.jaad.2012.07.001Get rights and content

Background

Azathioprine is prescribed as a corticosteroid-sparing agent for many inflammatory conditions, including refractory atopic dermatitis (AD). There are limited prospective data on its appropriate use and monitoring for children with AD.

Objectives

This study was designed to assess clinical response to azathioprine, determine the necessity for repeated measurement of thiopurine methyltransferase (TPMT) activity during treatment, and test the utility of measuring levels of the metabolites 6-thioguanine nucleotide and 6-methylmercaptopurine.

Methods

Twelve children with severe, recalcitrant AD were treated with oral azathioprine and followed prospectively. Disease severity was determined by the SCORing AD index. Baseline TPMT activity was measured and this was repeated along with 6-thioguanine nucleotide and 6-methylmercaptopurine measurement at times of stable improvement, inadequate response, or change in response.

Results

Azathioprine therapy was associated with clinical improvement in all but 1 patient. There were few adverse effects. Three patients showed a significant change in TPMT activity during treatment: 2 had a mild decrease and 1 demonstrated enzyme inducibility with an increase from the intermediate to the normal activity range. These changes, but not 6-thioguanine nucleotide or 6-methylmercaptopurine levels, inversely correlated with the clinical response to therapy.

Limitations

Small sample size is a limitation.

Conclusions

Azathioprine can be of benefit in the treatment of recalcitrant pediatric AD. Repeat assessment of TPMT activity may be helpful for evaluation of nonresponse or change in response and warrants further study. In contrast, measurement of thiopurine metabolites during treatment was not clinically useful.

Section snippets

Methods

The study was approved by the University of California, San Diego, Institutional Review Board. Patients were aged 2 to 18 years with chronic, moderate to severe AD (objective SCORing AD [SCORAD] index ≥25 and meeting Hanifin and Rajka criteria) attending the pediatric dermatology clinic and Eczema Center at Rady Children's Hospital, San Diego, CA. Patients warranting systemic treatment because of repeated failure of topical anti-inflammatory and adjunctive therapies, with significant negative

Results

Patients' baseline severity (all severe with SCORAD >40) and treatment course are presented in Table I. Age of AD onset ranged from 1 to 24 months and the median age at starting azathioprine therapy was 9.0 years. All but patient 9 had significant improvement, with a decrease in SCORAD of 27.7 ± 8.7 (mean ± SD) at the time of stable improvement just before starting taper of drug or at response plateau. No patient discontinued treatment because of adverse events. Two experienced minor

Discussion

This study provides prospective, long-term data in 12 children to support the use of azathioprine for recalcitrant AD and assessed various parameters of drug monitoring during therapy.

TPMT is the best-studied enzyme involved in thiopurine drug metabolism and illustrates the use of pharmacogenomics in clinical practice. Previously, concern for myelosuppression led to initiation of treatment at very low doses, with slow upward titration and sometimes limited effect.7 The availability of a RBC

References (19)

There are more references available in the full text version of this article.

Cited by (0)

Dr Tom is supported by a National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases research career development grant (K23AR060274).

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Arthritis and Musculoskeletal and Skin Diseases or the National Institutes of Health.

Conflicts of interest: None declared.

View full text