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本文引用的文献

1
Systemic treatment of pediatric atopic dermatitis with azathioprine and mycophenolate mofetil.用硫唑嘌呤和霉酚酸酯对儿童特应性皮炎进行全身治疗。
Pediatr Dermatol. 2011 Nov-Dec;28(6):689-694. doi: 10.1111/j.1525-1470.2011.01488.x. Epub 2011 Oct 4.
2
British Association of Dermatologists' guidelines for the safe and effective prescribing of azathioprine 2011.英国皮肤科医师协会2011年硫唑嘌呤安全有效处方指南。
Br J Dermatol. 2011 Oct;165(4):711-34. doi: 10.1111/j.1365-2133.2011.10575.x.
3
Common misconceptions about 5-aminosalicylates and thiopurines in inflammatory bowel disease.炎症性肠病中关于 5-氨基水杨酸和硫嘌呤的常见误区。
World J Gastroenterol. 2011 Aug 14;17(30):3467-78. doi: 10.3748/wjg.v17.i30.3467.
4
Novel thiopurine methyltransferase variant TPMT*28 results in a misdiagnosis of TPMT deficiency.新型硫嘌呤甲基转移酶变体TPMT*28导致硫嘌呤甲基转移酶缺乏的误诊。
Inflamm Bowel Dis. 2011 Jun;17(6):1441-2. doi: 10.1002/ibd.21505. Epub 2010 Oct 13.
5
Characterization of a novel sequence variant, TPMT*28, in the human thiopurine methyltransferase gene.鉴定人巯嘌呤甲基转移酶基因中的新型序列变异 TPMT*28
Pharmacogenet Genomics. 2010 Nov;20(11):700-7. doi: 10.1097/FPC.0b013e3283402ee4.
6
Thioguanine nucleotides and thiopurine methyltransferase in immunobullous diseases: optimal levels as adjunctive tools for azathioprine monitoring.免疫性大疱性疾病中的硫鸟嘌呤核苷酸和硫嘌呤甲基转移酶:作为硫唑嘌呤监测辅助工具的最佳水平
Arch Dermatol. 2009 Jun;145(6):644-52. doi: 10.1001/archdermatol.2009.81.
7
Use of pharmacogenetics, enzymatic phenotyping, and metabolite monitoring to guide treatment with azathioprine in patients with systemic lupus erythematosus.利用药物遗传学、酶表型分析和代谢物监测来指导系统性红斑狼疮患者使用硫唑嘌呤进行治疗。
J Rheumatol. 2009 Jan;36(1):89-95. doi: 10.3899/jrheum.070968.
8
Efficacy and tolerability at 3 and 6 months following use of azathioprine for recalcitrant atopic dermatitis in children and young adults.儿童和青年成人使用硫唑嘌呤治疗顽固性特应性皮炎3个月和6个月后的疗效及耐受性
J Dermatolog Treat. 2009;20(3):141-5. doi: 10.1080/09546630802512646.
9
Role of thiopurine methyltransferase activity in the safety and efficacy of azathioprine in the treatment of pemphigus vulgaris.硫嘌呤甲基转移酶活性在硫唑嘌呤治疗寻常型天疱疮的安全性和有效性中的作用。
Arch Dermatol. 2008 Sep;144(9):1143-7. doi: 10.1001/archderm.144.9.1143.
10
Monitoring of thiopurine methyltransferase activity in postsurgical patients with Crohn's disease during 1 year of treatment with azathioprine or mesalazine.对克罗恩病术后患者在接受硫唑嘌呤或美沙拉嗪治疗1年期间的硫嘌呤甲基转移酶活性进行监测。
Ther Drug Monit. 2007 Feb;29(1):1-5. doi: 10.1097/FTD.0b013e3180312b9a.

口服硫唑嘌呤治疗难治性儿童特应性皮炎:临床疗效及硫嘌呤监测。

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

机构信息

Georgetown University School of Medicine, Washington, District of Columbia, USA.

出版信息

J Am Acad Dermatol. 2013 Jan;68(1):29-35. doi: 10.1016/j.jaad.2012.07.001. Epub 2012 Aug 11.

DOI:10.1016/j.jaad.2012.07.001
PMID:22892285
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3525724/
Abstract

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.

摘要

背景

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。

目的

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。

方法

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。

结果

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。

局限性

样本量小是一个局限性。

结论

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。