Georgetown University School of Medicine, Washington, District of Columbia, USA.
J Am Acad Dermatol. 2013 Jan;68(1):29-35. doi: 10.1016/j.jaad.2012.07.001. Epub 2012 Aug 11.
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.
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.
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.
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.
Small sample size is a limitation.
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.
巯嘌呤用于治疗多种炎症性疾病,包括难治性特应性皮炎(AD),可作为皮质类固醇的辅助药物。目前有关其在 AD 儿童中合理应用和监测的前瞻性数据有限。
本研究旨在评估巯嘌呤治疗 AD 的临床反应,确定治疗期间重复测量硫嘌呤甲基转移酶(TPMT)活性的必要性,并检验测量代谢产物 6-硫鸟嘌呤核苷酸和 6-甲基巯基嘌呤水平的效用。
12 例严重、难治性 AD 患儿接受口服巯嘌呤治疗,并进行前瞻性随访。疾病严重程度采用 SCORing AD 指数进行评估。在治疗稳定改善、疗效不佳或反应改变时,测定 TPMT 活性的基线值,并重复测定 TPMT 活性,同时测定 6-硫鸟嘌呤核苷酸和 6-甲基巯基嘌呤水平。
除 1 例患者外,其余患者接受巯嘌呤治疗后均有临床改善。不良反应少见。3 例患者在治疗期间 TPMT 活性发生显著变化:2 例轻度下降,1 例表现为酶诱导作用,活性从中等水平升高至正常范围。这些变化(而非 6-硫鸟嘌呤核苷酸或 6-甲基巯基嘌呤水平)与治疗的临床反应呈负相关。
样本量小是一个局限性。
巯嘌呤可用于治疗难治性儿科 AD。重复评估 TPMT 活性可能有助于评估无反应或反应改变,值得进一步研究。相比之下,治疗期间测定硫嘌呤代谢产物无临床意义。