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

Abstract

Background Azathioprine is prescribed as a corticosteroid-sparing agent for many inflammatory conditions, including refractory atopic dermatitis (AD). There is 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 repeat measurement of thiopurine methyltransferase (TPMT) activity during treatment, and test the utility of measuring levels of the metabolites 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP). Methods Twelve children with severe, recalcitrant AD were treated with oral azathioprine and followed prospectively. Disease severity was determined by the SCORing Atopic Dermatitis Index. Baseline TPMT activity was measured and this was repeated along with 6-TGN and 6-MMP measurement at times of stable improvement, inadequate response, or change in response. Results Azathioprine therapy was associated with clinical improvement in all but one subject. There were few adverse effects. Three subjects showed a significant change in TPMT activity during treatment: two had a mild decrease and one demonstrated enzyme inducibility with an increase from the intermediate to the normal activity range. These changes, but not 6-TGN or 6-MMP levels, inversely correlated with the clinical response to therapy. Limitations Small sample size Conclusions Azathioprine can be of benefit in the treatment of recalcitrant pediatric AD. Repeat assessment of TPMT activity may be helpful for evaluation of non–response or change in response and warrants further study. In contrast, measurement of thiopurine metabolites during treatment was not clinically useful.

The European treatment of severe atopic eczema in children taskforce (TREAT) survey

“…29,30 It takes 8-12 weeks for azathioprine to reach its full therapeutic potential, which, along with adverse effects in those with low-activity thiopurine methyltransferase polymorphism, and the potential long-term risk of lymphoma, 2 may explain why the TREAT survey found azathioprine to be a less popular first-line medication. 29,30 It takes 8-12 weeks for azathioprine to reach its full therapeutic potential, which, along with adverse effects in those with low-activity thiopurine methyltransferase polymorphism, and the potential long-term risk of lymphoma, 2 may explain why the TREAT survey found azathioprine to be a less popular first-line medication.…”

Consensus‐based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II

“…AZA therapy was associated with clinical improvement in all but one patient. There were few adverse effects …”

Guidelines of care for the management of atopic dermatitis

“…It should be noted TPMT is an inducible enzyme, such that levels have been reported to change over time. 47, 48 Regular monitoring of the patient’s blood count 45, 49 and liver enzymes is also essential while taking AZA, regardless of TPMT status.…”