硫唑嘌呤治疗免疫相关性皮肤病专家建议

doi:10.35541/cjd.20200469

中华皮肤科杂志 ›› 2021, Vol. 54 ›› Issue (2): 116-121.doi: 10.35541/cjd.20200469

硫唑嘌呤治疗免疫相关性皮肤病专家建议

中国医师协会皮肤科医师分会自身免疫病专业委员会

中国医师协会皮肤科医师分会自身免疫病专业委员会

收稿日期:2020-05-14 修回日期:2020-08-24 发布日期:2021-01-29
通讯作者: 邓丹琪 E-mail:danqid128@sina.com

Azathioprine in the treatment of immune?related skin diseases: an expert proposal

Committee on Autoimmune Diseases, China Dermatologist Association

Committee on Autoimmune Diseases, China Dermatologist Association

Received:2020-05-14 Revised:2020-08-24 Published:2021-01-29
Contact: Deng Danqi E-mail:danqid128@sina.com

摘要/Abstract

摘要： 【摘要】硫唑嘌呤系巯嘌呤的咪唑衍生物，广泛用于自身免疫性疾病的治疗。为了规范硫唑嘌呤在皮肤科的正确应用，中国医师协会皮肤科医师分会自身免疫病专业委员会相关专家在检索和研究国内外硫唑嘌呤治疗免疫相关性疾病相关文献（主要是随机对照临床试验、专家共识或专家建议）的基础上，经反复讨论，提出硫唑嘌呤在免疫性大疱性皮肤病、皮肤血管炎、系统性红斑狼疮、皮肌炎、硬皮病等免疫性皮肤病治疗中的建议，分析硫唑嘌呤与其他药物的相互作用以及使用中的注意事项。

关键词: 硫唑嘌呤, 治疗, 自身免疫疾病, 结缔组织疾病, 天疱疮, 红斑狼疮, 系统性, 皮肌炎

Abstract: 【Abstract】 Azathioprine, an imidazole derivative of mercaptopurine, has been widely used in the treatment of autoimmune diseases. In order to standardize the application of azathioprine in dermatology, relevant experts in the Committee on Autoimmune Diseases of China Dermatologist Association searched and studied domestic and foreign literature on azathioprine for the treatment of immune-related diseases （mainly including randomized control trials, expert consensus or proposals）, and proposed a proposal after repeated discussions for azathioprine in the treatment of immune skin diseases, including immune bullous skin diseases, cutaneous vasculitis, systemic lupus erythematosus, dermatomyositis, scleroderma, etc. Interactions between azathioprine and other drugs, as well as issues needed to be considered in its application were also analyzed in this proposal.

Key words: Azathioprine, Therapy, Autoimmune diseases, Connective tissue diseases, Pemphigus, Lupus erythematosus, systemic, Dermatomyositis

中国医师协会皮肤科医师分会自身免疫病专业委员会. 硫唑嘌呤治疗免疫相关性皮肤病专家建议[J]. 中华皮肤科杂志, 2021,54(2):116-121. doi:10.35541/cjd.20200469

Committee on Autoimmune Diseases, China Dermatologist Association. Azathioprine in the treatment of immune?related skin diseases: an expert proposal[J]. Chinese Journal of Dermatology, 2021, 54(2): 116-121.doi:10.35541/cjd.20200469

参考文献 37

［1］	Wollenberg A, Szepietowski J, Taieb A, et al. Corrigendum: Consensus⁃based European guidelines for treatment of atopic eczema （atopic dermatitis） in adults and children: part I［J］. J Eur Acad Dermatol Venereol, 2019,33（7）:1436. doi: 10.1111/jdv.15719.
［2］	Paek SY, Lim HW. Chronic actinic dermatitis［J］. Dermatol Clin,2014,32（3）:355⁃361, viii⁃ix. doi: 10.1016/j.det.2014.03.007.
［3］	Verma P, Verma KK, Khanna N, et al. Effectiveness of weekly azathioprine pulse in the treatment of chronic plaque psoriasis: an open⁃label study［J］. Clin Exp Dermatol, 2016,41（7）:717⁃722. doi: 10.1111/ced.12887.
［4］	Engelmann C, Elsner P, Miguel D. Treatment of pityriasis rubra pilaris type I: a systematic review［J］. Eur J Dermatol, 2019,29（5）:524⁃537. doi: 10.1684/ejd.2019.3641.
［5］	Tal Y, Toker O, Agmon⁃Levin N, et al. Azathioprine as a therapeutic alternative for refractory chronic urticaria［J］. Int J Dermatol, 2015,54（3）:367⁃369. doi: 10.1111/ijd.12536.
［6］	Relling MV, Schwab M, Whirl⁃Carrillo M, et al. Clinical pharmacogenetics implementation consortium guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update［J］. Clin Pharmacol Ther, 2019,105（5）:1095⁃1105. doi: 10.1002/cpt.1304.
［7］	Rucci F, Cigoli MS, Marini V, et al. Combined evaluation of genotype and phenotype of thiopurine S⁃methyltransferase （TPMT） in the clinical management of patients in chronic therapy with azathioprine［J/OL］. Drug Metab Pers Ther, 2019,34（1）［2020⁃03⁃19］. http://www.metstr.com. doi: 10.1515/dmpt⁃2018⁃0037.
［8］	Wilson A, Jansen LE, Rose RV, et al. HLA⁃DQA1⁃HLA⁃DRB1 polymorphism is a major predictor of azathioprine⁃induced pancreatitis in patients with inflammatory bowel disease［J］. Aliment Pharmacol Ther, 2018,47（5）:615⁃620. doi: 10.1111/apt. 14483.
［9］	Harbour R, Miller J. A new system for grading recommendations in evidence based guidelines［J］. BMJ, 2001,323（7308）:334⁃336. doi: 10.1136/bmj.323.7308.334.
［10］	Hertl M, Jedlickova H, Karpati S, et al. Pemphigus. S2 Guideline for diagnosis and treatment⁃⁃guided by the European Dermatology Forum （EDF） in cooperation with the European Academy of Dermatology and Venereology （EADV）［J］. J Eur Acad Dermatol Venereol, 2015,29（3）:405⁃414. doi: 10.1111/jdv. 12772.
［11］	Committee for Guidelines for the Management of Pemphigus Disease, Amagai M, Tanikawa A, et al. Japanese guidelines for the management of pemphigus［J］. J Dermatol, 2014,41（6）:471⁃486. doi: 10.1111/1346⁃8138.12486.
［12］	Yanovsky RL, McLeod M, Ahmed AR. Treatment of pemphigus vulgaris: part 1 ⁃ current therapies［J］. Expert Rev Clin Immunol, 2019,15（10）:1047⁃1060. doi: 10.1080/1744666X.2020.1672535.
［13］	Sticherling M, Franke A, Aberer E, et al. An open, multicentre, randomized clinical study in patients with bullous pemphigoid comparing methylprednisolone and azathioprine with methylprednisolone and dapsone［J］. Br J Dermatol, 2017,177（5）:1299⁃1305. doi: 10.1111/bjd.15649.
［14］	Feliciani C, Joly P, Jonkman MF, et al. Management of bullous pemphigoid: the European Dermatology Forum consensus in collaboration with the European Academy of Dermatology and Venereology［J］. Br J Dermatol, 2015,172（4）:867⁃877. doi: 10. 1111/bjd.13717.
［15］	Porro AM, Hans Filho G, Santi CG. Consensus on the treatment of autoimmune bullous dermatoses: pemphigus vulgaris and pemphigus foliaceus ⁃ Brazilian Society of Dermatology［J］. An Bras Dermatol, 2019,94（2 Suppl 1）:20⁃32. doi: 10.1590/abd1806⁃ 4841.2019940206.
［16］	Yoshida A, Watanabe M, Okubo A, et al. Clinical characteristics of scleritis patients with emphasized comparison of associated systemic diseases （anti⁃neutrophil cytoplasmic antibody⁃associated vasculitis and rheumatoid arthritis）［J］. Jpn J Ophthalmol, 2019,63（5）:417⁃424. doi: 10.1007/s10384⁃019⁃00674⁃7.
［17］	中国狼疮肾炎诊断和治疗指南编写组. 中国狼疮肾炎诊断和治疗指南［J］. 中华医学杂志, 2019,99（44）:3441⁃3455. doi: 10.3760/cma.j.issn.0376⁃2491.2019.44.001.
［18］	Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association⁃European Dialysis and Transplant Association （EULAR/ERA⁃EDTA） recommendations for the management of adult and paediatric lupus nephritis［J］. Ann Rheum Dis, 2012,71（11）:1771⁃1782. doi: 10.1136/annrheumdis⁃2012⁃201940.
［19］	Parikh SV, Rovin BH. Current and emerging therapies for lupus nephritis［J］. J Am Soc Nephrol, 2016,27（10）:2929⁃2939. doi: 10.1681/ASN.2016040415.
［20］	Ordi⁃Ros J, Sáez⁃Comet L, Pérez⁃Conesa M, et al. Enteric⁃coated mycophenolate sodium versus azathioprine in patients with active systemic lupus erythematosus: a randomised clinical trial［J］. Ann Rheum Dis, 2017,76（9）:1575⁃1582. doi: 10.1136/annrheumdis⁃2016⁃210882.
［21］	Pons⁃Estel BA, Bonfa E, Soriano ER, et al. First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus （GLADEL, Grupo Latino Americano de Estudio del Lupus）⁃Pan⁃American League of Associations of Rheumatology （PANLAR）［J］. Ann Rheum Dis, 2018,77（11）:1549⁃1557. doi: 10.1136/annrheumdis⁃2018⁃213512.
［22］	Tamirou F, D′Cruz D, Sangle S, et al. Long⁃term follow⁃up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis［J］. Ann Rheum Dis, 2016,75（3）:526⁃531. doi: 10.1136/annrheumdis⁃2014⁃206897.
［23］	Dalakas MC. Inflammatory myopathies: management of steroid resistance［J］. Curr Opin Neurol, 2011,24（5）:457⁃462. doi: 10. 1097/WCO.0b013e32834a9589.
［24］	Kohsaka H, Mimori T, Kanda T, et al. Treatment consensus for management of polymyositis and dermatomyositis among rheumatologists, neurologists and dermatologists［J］. J Dermatol, 2019,46（1）:e1⁃e18. doi: 10.1111/1346⁃8138.14604.
［25］	中华医学会儿科学分会免疫学组, 《中华儿科杂志》编辑委员会, 胡坚. 幼年皮肌炎诊治建议［J］. 中华儿科杂志, 2012,50（8）:617⁃621. doi: 10.3760/cma.j.issn.0578⁃1310.2012.08.013.
［26］	Bérezné A, Ranque B, Valeyre D, et al. Therapeutic strategy combining intravenous cyclophosphamide followed by oral azathioprine to treat worsening interstitial lung disease associated with systemic sclerosis: a retrospective multicenter open⁃label study［J］. J Rheumatol, 2008,35（6）:1064⁃1072.
［27］	Iudici M, Cuomo G, Vettori S, et al. Low⁃dose pulse cyclophosphamide in interstitial lung disease associated with systemic sclerosis （SSc⁃ILD）: efficacy of maintenance immunosuppression in responders and non⁃responders［J］. Semin Arthritis Rheum, 2015, 44（4）:437⁃444. doi: 10.1016/j.semarthrit.2014.09.003.
［28］	Schram ME, Roekevisch E, Leeflang MM, et al. A randomized trial of methotrexate versus azathioprine for severe atopic eczema［J］. J Allergy Clin Immunol, 2011,128（2）:353⁃359. doi: 10. 1016/j.jaci.2011.03.024.
［29］	Sarika S, Criton S. Effectiveness of weekly azathioprine pulse in the treatment of chronic plaque psoriasis: an open⁃label study: reply to author［J］. Clin Exp Dermatol, 2017,42（7）:805⁃806. doi: 10.1111/ced.13193.
［30］	Solman L, Lloyd⁃Lavery A, Grindlay DJC, et al. What′s new in atopic eczema? An analysis of systematic reviews published in 2016. Part 1: treatment and prevention［J］. Clin Exp Dermatol, 2019,44（4）:363⁃369. doi:10.1111/ced.13885.
［31］	Paek SY, Lim HW. Chronic actinic dermatitis［J］. Dermatol Clin, 2014,32（3）:355⁃361, viii⁃ix. doi: 10.1016/j.det.2014.03.007.
［32］	Sunderkötter C, Nast A, Worm M, et al. Guidelines on dermatomyositis⁃⁃excerpt from the interdisciplinary S2k guidelines on myositis syndromes by the German Society of Neurology［J］. J Dtsch Dermatol Ges, 2016,14（3）:321⁃338. doi: 10.1111/ddg.12909.
［33］	Mathur T, Manadan AM, Thiagarajan S, et al. Corticosteroid monotherapy is usually insufficient treatment for idiopathic inflammatory myopathy［J］. Am J Ther, 2015,22（5）:350⁃354. doi: 10.1097/MJT.0b013e3182987983.
［34］	Relling MV, Gardner EE, Sandborn WJ, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther, 2011,89（3）:387⁃391. doi: 10.1038/clpt. 2010.320.
［35］	Yang J, Wang P, Qin Z, et al. NUDT15 and TPMT genetic polymorphisms are related to azathioprine intolerance in Chinese patients with rheumatic diseases［J］. Genet Test Mol Biomarkers, 2019,23（10）:751⁃757. doi: 10.1089/gtmb.2018.0313.
［36］	Kim HT, Choi R, Won HH, et al. NUDT15 genotype distributions in the Korean population［J］. Pharmacogenet Genomics, 2017,27（5）:197⁃200. doi: 10.1097/FPC.000000000 0000274.
［37］	Tanaka Y, Kato M, Hasegawa D, et al. Susceptibility to 6⁃MP toxicity conferred by a NUDT15 variant in Japanese children with acute lymphoblastic leukaemia［J］. Br J Haematol, 2015, 171（1）:109⁃115. doi: 10.1111/bjh.13518.

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硫唑嘌呤治疗免疫相关性皮肤病专家建议

Azathioprine in the treatment of immune?related skin diseases: an expert proposal

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