[开放获取]    环磷酰胺治疗自身免疫性皮肤病中国专家共识

doi:10.35541/cjd.20210039

Abstract

Abstract: 【Abstract】 Cyclophosphamide is a broad-spectrum antineoplastic drug, and is also used as an immunosuppressant for the treatment of a variety of autoimmune skin diseases, such as systemic lupus erythematosus, dermatomyositis, scleroderma, pemphigus and pemphigoid. This consensus summarizes the mechanism of action, indications, usage and dosage of cyclophosphamide, adverse reactions and cautions during the treatment of immune skin diseases with it, as well as its application in special populations. It is hoped that this consensus will provide a reference for physicians in dermatology and relevant specialities in rational application of cyclophosphamide in the treatment of immune-related skin diseases.

Key words: Cyclophosphamide, Therapy, Lupus erythematosus, systemic, Dermatomyositis, Scleroderma, systemic, Autoimmune skin diseases, Expert consensus

Autoimmune Disease Group, China Dermatologist Association. Chinese expert consensus on cyclophosphamide for the treatment of autoimmune dermatoses[J]. Chinese Journal of Dermatology, 2021, 54(9): 765-770.doi:10.35541/cjd.20210039

References ［36］

［1］	Madondo MT, Quinn M, Plebanski M. Low dose cyclophospha⁃mide: mechanisms of T cell modulation［J］. Cancer Treat Rev, 2016,42:3⁃9. doi: 10.1016/j.ctrv.2015.11.005.
［2］	Christine Lutsiak ME, Semnani RT, Pascalis RD, et al. Inhibition of CD4+25+ T regulatory cell function implicated in enhanced immune response by low⁃dose cyclophosphamide［J］. Blood,2005,105（7）:2862⁃2868. doi: 10.1182/blood⁃2004⁃06⁃2410.
［3］	Viaud S, Flament C, Zoubir M, et al. Cyclophosphamide induces differentiation of Th17 cells in cancer patients［J］. Cancer Res,2011,71（3）:661⁃665. doi: 10.1158/0008⁃5472.CAN⁃10⁃1259.
［4］	Yue Y, Song ZL, Li JH, et al. Posttransplant cyclophosphamide for HLA⁃haploidentical transplantation in patients with mucopolysaccharidosis［J］. J pediatr Hematol Oncol, 2018,40（6）:e350⁃e354. doi: 10.1097/MPH.0000000000001157.
［5］	Liu HY, Yan YL, Zhang FL, et al. The immuno⁃enhancement effects of tubiechong （eupolyphaga sinensis） lyophilized powder in cyclophosphamide⁃induced immunosuppressed mice［J］. Immunol Invest, 2019,48（8）:844⁃859. doi: 10.1080/08820139. 2019.1588291.
［6］	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.
［7］	Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus［J］. Ann Rheum Dis, 2019,78（6）:736⁃745. doi: 10.1136/annrheumdis⁃2019⁃215089.
［8］	中华医学会风湿病学分会. 多发性肌炎和皮肌炎诊断及治疗指南［J］. 中华风湿病学杂志, 2010,14（12）:828⁃831. doi: 10.3760/cma.j.issn.1007⁃7480.2010.12.008.
［9］	Yang SH, Chang C, Lian ZX. Polymyositis and dermatomyositis ⁃ challenges in diagnosis and management［J］. J Transl Autoimmun, 2019,2:100018. doi: 10.1016/j.jtauto.2019.100018.
［10］	吴炜, 邓丹琪. 多发性肌炎/皮肌炎治疗研究进展［J］. 中国皮肤性病学杂志, 2020,34（3）:338⁃342. doi: 10.13735/j.cjdv.1001⁃7089.2019.03.034
［11］	Kowal⁃Bielecka O, Fransen J, Avouac J, et al. Update of EULAR recommendations for the treatment of systemic sclerosis［J］. Ann Rheum Dis, 2017,76（8）:1327⁃1339. doi: 10.1136/annrheumdis⁃2016⁃209909.
［12］	Kersten BE, den Broeder N, van den Hoogen F, et al. Treatment with cyclophosphamide i.v. pulse therapy is an option for effective treatment of skin fibrosis in patients with early systemic sclerosis［J］. Rheumatology （Oxford）, 2020,59（7）:1550⁃1555. doi: 10.1093/rheumatology/kez487.
［13］	鲁静浩, 李明. 系统性硬皮病相关间质性肺病的药物治疗进展［J］. 复旦学报（医学版）, 2018,45（5）:740⁃743,747. doi: 10.3969/j.issn.1672⁃8467.2018.05.023.
［14］	Murrell DF, Peña S, Joly P, et al. Diagnosis and management of pemphigus: recommendations of an international panel of experts［J］. J Am Acad Dermatol, 2020,82（3）:575⁃585. doi: 10.1016/j.jaad.2018.02.021.
［15］	Amagai M, Tanikawa A, Shimizu T, et al. Japanese guidelines for the management of pemphigus［J］. J Dermatol, 2014,41（6）:471⁃486. doi: 10.1111/1346⁃8138.12486.
［16］	中国医疗保健国际交流促进会皮肤科分会. 寻常型天疱疮诊断和治疗专家建议（2020）［J］. 中华皮肤科杂志, 2020,53（1）:1⁃7. doi: 10.35541/cjd.20190703.
［17］	中国医师协会皮肤科医师分会自身免疫性疾病亚专业委员. 大疱性类天疱疮诊断和治疗的专家建议［J］. 中华皮肤科杂志, 2016,49（6）:384⁃387. doi: 10.3760/cma.j.issn.0412⁃4030. 2016.06.003.
［18］	陈喜雪, 丁治云, 王明悦, 等. 米诺环素和烟酰胺联合小剂量糖皮质激素治疗62例大疱性类天疱疮［J］. 临床皮肤科杂志, 2015,44（12）:816⁃818.
［19］	中华医学会风湿病学分会. 白塞病诊断和治疗指南［J］. 中华风湿病学杂志, 2011,15（5）:345⁃347. doi: 10.3760/cma.j.issn. 1007⁃7480.2011.05.015.
［20］	Hatemi G, Christensen R, Bang D, et al. 2018 update of the EULAR recommendations for the management of Behçet′s syndrome［J］. Ann Rheum Dis, 2018,77（6）:808⁃818. doi: 10. 1136/annrheumdis⁃2018⁃213225.
［21］	Abdelfattah⁃Hassan A, Shalaby SI, Khater SI, et al. Panax ginseng is superior to vitamin E as a hepatoprotector against cyclophosphamide⁃induced liver damage［J］. Complement Ther Med, 2019,46:95⁃102. doi: 10.1016/j.ctim.2019.08.005.
［22］	Zee RS, Mbanefo EC, Le LH, et al. IPSE, a parasite⁃derived host immunomodulatory protein, is a potential therapeutic for hemorrhagic cystitis［J］. Am J Physiol Renal Physiol, 2019,316（6）:F1133⁃F1140. doi: 10.1152/ajprenal.00468.2018.
［23］	Ponticelli C, Escoli R, Moroni G. Does cyclophosphamide still play a role in glomerular diseases?［J］. Autoimmun Rev, 2018,17（10）:1022⁃1027. doi: 10.1016/j.autrev.2018.04.007.
［24］	Iqubal A, Iqubal MK, Sharma S, et al. Molecular mechanism involved in cyclophosphamide⁃induced cardiotoxicity: old drug with a new vision［J］. Life Sci, 2019,218:112⁃131. doi: 10.1016/j.lfs.2018.12.018.
［25］	Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis［J］. N Engl J Med, 2005,353（21）:2219⁃2228. doi: 10.1056/NEJMoa043731.
［26］	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.
［27］	Schultz B, Hook K. Bullous diseases in children: a review of clinical features and treatment options［J］. Paediatr Drugs, 2019,21（5）:345⁃356. doi: 10.1007/s40272⁃019⁃00349⁃3.
［28］	Demir S, Sag E, Kaya Akca U, et al. The challenge of treating pulmonary vasculitis in Behçet disease: two pediatric cases［J］. Pediatrics, 2019,144（2）:e20190162. doi: 10.1542/peds.2019⁃0162.
［29］	Ujiie H, Iwata H, Yamagami J, et al. Japanese guidelines for the management of pemphigoid （including epidermolysis bullosa acquisita）［J］. J Dermatol, 2019,46（12）:1102⁃1135. doi: 10. 1111/1346⁃8138.15111.
［30］	Medhat BM, Behiry ME, Sobhy N, et al. Late⁃onset systemic lupus erythematosus: characteristics and outcome in comparison to juvenile⁃ and adult⁃onset patients⁃a multicenter retrospective cohort［J］. Clin Rheumatol, 2020,39（2）:435⁃442. doi: 10.1007/s10067⁃019⁃04776⁃y.
［31］	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.
［32］	房强, 陈伯权. 环磷酰胺对乙脑灭活疫苗和减毒活疫苗免疫效果的比较［J］. 中国医学科学院学报, 1989,（05）:317⁃321.
［33］	Hashmi K, Khan B, Ahmed P, et al. Allogeneic stem cell transplantation in chronic myeloid leukaemia⁃⁃2 1/2 year experience［J］. J Pak Med Assoc, 2005,55（11）:478⁃482.
［34］	Yang L, Yan C, Zhang F, et al. Effects of ketoconazole on cyclophosphamide metabolism: evaluation of CYP3A4 inhibition effect using the in vitro and in vivo models［J］. Exp Anim, 2018,67（1）:71⁃82. doi: 10.1538/expanim.17⁃0048.
［35］	Chang TK, Yu L, Maurel P, et al. Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: response to cytochrome P⁃450 inducers and autoinduction by oxazaphosphorines［J］. Cancer Res, 1997,57（10）:1946⁃1954.
［36］	Holford NH. Clinical pharmacokinetics and pharmacodynamics of warfarin. Understanding the dose⁃effect relationship［J］. Clin Pharmacokinet, 1986,11（6）:483⁃504. doi: 10.2165/00003088⁃198611060⁃00005.

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Chinese expert consensus on cyclophosphamide for the treatment of autoimmune dermatoses

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