口服普萘洛尔治疗婴儿血管瘤的近期和远期安全性

doi:10.3760/cma.j.issn.0412-4030.2019.08.019

摘要/Abstract

摘要： 【摘要】婴儿血管瘤是婴儿期最常见的肿瘤，其发病率可达4% ~ 5%。血管瘤可分为高、中、低三个风险等级。目前对于高危血管瘤患者采取口服药治疗，系统治疗的一线药物为普萘洛尔（β受体阻滞剂）。应用普萘洛尔治疗血管瘤至今已有10年时间，因其有效率高及安全性好成为系统治疗的首选药物，但其远期不良反应仍需进一步研究评估。

关键词: 血管瘤, 普萘洛尔, 婴儿, 远期安全性, 近期安全性

Abstract: 【Abstract】 Infantile hemangioma is the most common tumor in infancy, with an incidence of 4% - 5%. According to the risk level, hemangioma is divided into 3 levels: high risk, medium risk and low risk. At present, the first-line treatment of high-risk hemangioma is oral propranolol （β-receptor blockers）. It has been 10 years since infantile hemangioma was treated with propranolol for the first time, and propranolol has been the drug of first-choice in systematic treatment due to its high efficacy and good safety, but its long-term adverse effect needs further evaluation.

Key words: Hemangioma, Propranolol, Infant, Long?term safety, Short?term safety

于鲁李丽马琳. 口服普萘洛尔治疗婴儿血管瘤的近期和远期安全性[J]. 中华皮肤科杂志, 2019, 52(8): 586-589.

Yu Lu, Li Li, Ma Lin. Short- and long-term safety of oral propranolol in the treatment of infantile hemangioma[J]. Chinese Journal of Dermatology, 2019, 52(8): 586-589.

参考文献 41

［1］	Kilcline C, Frieden IJ. Infantile hemangiomas: how common are they? A systematic review of the medical literature［J］. Pediatr Dermatol, 2008,25（2）:168⁃173. doi: 10.1111/j.1525⁃1470.2008. 00626.x.
［2］	Léauté⁃Labrèze C, Hoeger P, Mazereeuw⁃Hautier J, et al. A randomized, controlled trial of oral propranolol in infantile hemangioma［J］. N Engl J Med, 2015,372（8）:735⁃746. doi: 10.1056/NEJMoa1404710.
［3］	杨舟, 李丽, 徐子刚, 等. 普萘洛尔治疗婴儿血管瘤的临床疗效及安全性［J］. 中华皮肤科杂志, 2012,45（7）:466⁃469. doi: 10.3760/cma.j.issn.0412⁃4030.2012.07.003.
［4］	Shehata N, Powell J, Dubois J, et al. Late rebound of infantile hemangioma after cessation of oral propranolol［J］. Pediatr Dermatol, 2013,30（5）:587⁃591. doi: 10.1111/pde.12190.
［5］	Chu DH, Castelo⁃Soccio L, Wan J, et al. Retrospective analysis of beta⁃blocker instituted for treatment of hemangiomas （RABBIT study）［J］. Clin Pediatr （Phila）, 2014,53（11）:1084⁃1090. doi: 10.1177/0009922814535660.
［6］	Chang L, Gu Y, Yu Z, et al. When to stop propranolol for infantile hemangioma［J］. Sci Rep, 2017,7:43292. doi: 10.1038/srep43292.
［7］	马琳. 儿童皮肤病学［M］. 北京：人民卫生出版社, 2014:143⁃164.
［8］	Csoma ZR, Dalmády S, Ábrahám R, et al. Infantile haemangioma: clinical and demographic characteristics, experiences in the treatment［J］. Orv Hetil, 2017,158（39）:1535⁃1544. doi: 10.1556/ 650.2017.30838.
［9］	Xue L, Sun C, Xu DP, et al. Clinical outcomes of infants with periorbital hemangiomas treated with oral propranolol［J］. J Oral Maxillofac Surg, 2016,74（11）:2193⁃2199. doi: 10.1016/j.joms. 2016.04.021.
［10］	Léaute⁃Labrèze C, Boccara O, Degrugillier⁃Chopinet C, et al. Safety of oral propranolol for the treatment of infantile hemangioma: a systematic review［J］. Pediatrics, 2016,138（4）. pii: e20160353. doi: 10.1542/peds.2016⁃0353.
［11］	Stringari G, Barbato G, Zanzucchi M, et al. Propranolol treatment for infantile hemangioma: a case series of sixty⁃two patients［J］. Pediatr Med Chir, 2016,38（2）:113. doi: 10.4081/pmc.2016.113.
［12］	Techasatian L, Komwilaisak P, Panombualert S, et al. Propranolol was effective in treating cutaneous infantile haemangiomas in Thai children［J］. Acta Paediatr, 2016,105（6）:e257⁃e262. doi: 10.1111/apa.13378.
［13］	Furuta S, Sato H, Tsuji S, et al. Effective treatment for infantile hemangioma with long⁃pulsed dye laser with oral propranolol medication: a preliminary report［J］. Pediatr Surg Int, 2016,32（9）:857⁃862. doi: 10.1007/s00383⁃016⁃3942⁃x.
［14］	杨宝峰, 陈建国. 药理学［M］. 第3版. 北京: 人民卫生出版社, 2015:103⁃111.
［15］	Petrovic J, Trifunovic B, Vukomanovic G, et al. Oral propranolol for infantile hemangiomas: a prospective study on the role of 48⁃hour Holter monitoring in additional safety assessment［J］. J Dermatolog Treat, 2017,28（6）:554⁃558. doi: 10.1080/09546634. 2016.1277177.
［16］	Salice P, Giovanni BM, Giavarini A, et al. Cardiovascular profile of propranolol after multiple dosing in infantile hemangioma［J］. Pharmacology, 2017,99（1⁃2）:75⁃78. doi: 10.1159/000450755.
［17］	易兰芬, 文红霞, 黄穗, 等. 婴幼儿血管瘤患者口服小剂量普萘洛尔前后动态心电图的比较［J］. 中国当代儿科杂志, 2016,18（4）:345⁃349. doi: 10.7499/j.issn.1008⁃8830.2016.04.013.
［18］	de Graaf M, JMPJ B, Raphaël MF, et al. Adverse effects of propranolol when used in the treatment of hemangiomas: a case series of 28 infants［J］. J Am Acad Dermatol, 2011,65（2）:320⁃327. doi: 10.1016/j.jaad.2010.06.048.
［19］	Puttgen KB, Summerer B, Schneider J, et al. Cardiovascular and blood glucose parameters in infants during propranolol initiation for treatment of symptomatic infantile hemangiomas［J］. Ann Otol Rhinol Laryngol, 2013,122（9）:550⁃554. doi: 10.1177/00034 8941312200903.
［20］	Mei⁃Zahav M, Blau H, Hoshen M, et al. Propranolol treatment for infantile hemangioma does not increase risk of childhood wheezing［J］. Pediatr Pulmonol, 2017,52（8）:1071⁃1075. doi: 10. 1002/ppul.23683.
［21］	van Veen MR, van Hasselt PM, de Sain⁃van der Velden MG, et al. Metabolic profiles in children during fasting［J］. Pediatrics, 2011,127（4）:e1021⁃e1027. doi: 10.1542/peds.2010⁃1706.
［22］	Yang TB, McMahon P, De Léon DD, et al. Use of propranolol for treating hemangiomas in infants with previously diagnosed hypoglycemic conditions［J］. Pediatr Dermatol, 2016,33（6）:e381⁃e384. doi: 10.1111/pde.12975.
［23］	Cavalli R, Buffon RB, de Souza M, et al. Tumor lysis syndrome after propranolol therapy in ulcerative infantile hemangioma: rare complication or incidental finding?［J］. Dermatology, 2012,224（2）:106⁃109. doi: 10.1159/000337553.
［24］	Pavlakovic H, Kietz S, Lauerer P, et al. Hyperkalemia complicating propranolol treatment of an infantile hemangioma［J］. Pediatrics, 2010,126（6）:e1589⁃e1593. doi: 10.1542/peds. 2010⁃0077.
［25］	Wang C, Wang Q, Xiang B, et al. Effects of propranolol on neurodevelopmental outcomes in patients with infantile hemangioma: a case⁃control study［J］. Biomed Res Int, 2018,2018:5821369. doi: 10.1155/2018/5821369.
［26］	刘卫平. 探讨口服普萘洛尔治疗婴幼儿血管瘤对生长发育的影响［J］. 中国医疗美容, 2016,6（11）:54⁃56. doi: 10.3969/j.issn.2095⁃0721.2016.11.026.
［27］	Phillips RJ, Penington AJ, Bekhor PS, et al. Use of propranolol for treatment of infantile haemangiomas in an outpatient setting［J］. J Paediatr Child Health, 2012,48（10）:902⁃906. doi: 10. 1111/j.1440⁃1754.2012.02521.x.
［28］	Fernando SJ, Leitenberger S, Majerus M, et al. Use of intravenous propranolol for control of a large cervicofacial hemangioma in a critically ill neonate［J］. Int J Pediatr Otorhinolaryngol, 2016,84:52⁃54. doi: 10.1016/j.ijporl.2016.02.005.
［29］	Kado M, Shimizu A, Matsumura T, et al. Successful treatment of infantile hemangiomas with propranolol in low⁃birth⁃weight infants［J］. J Craniofac Surg, 2017,28（3）:789⁃793. doi: 10.1097/SCS.0000000000003542.
［30］	Vergine G, Marsciani A, Pedini A, et al. Efficacy of propranolol treatment in thyroid dysfunction associated with severe infantile hepatic hemangioma［J］. Horm Res Paediatr, 2012,78（4）:256⁃260. doi: 10.1159/000337253.
［31］	桂永浩, 薛辛东. 儿科学［M］. 3版. 北京：人民卫生出版社, 2015:364⁃365.
［32］	González⁃Llorente N, Del OI, Muñoz⁃Ollero N, et al. Study of cognitive function in children treated with propranolol for infantile hemangioma［J］. Pediatr Dermatol, 2017,34（5）:554⁃558. doi: 10.1111/pde.13229.
［33］	Gonski K, Wargon O. Retrospective follow up of gross motor development in children using propranolol for treatment of infantile haemangioma at Sydney Children′s Hospital［J］. Australas J Dermatol, 2014,55（3）:209⁃211. doi: 10.1111/ajd. 12156.
［34］	Moyakine AV, Hermans DJ, Fuijkschot J, et al. Propranolol treatment of infantile hemangiomas does not negatively affect psychomotor development［J］. J Am Acad Dermatol, 2015,73（2）:341⁃342. doi: 10.1016/j.jaad.2015.04.053.
［35］	董建勇, 李凯, 岳琳琳, 等. 口服普萘洛尔对血管瘤患儿体格发育的近期影响［J］. 中国口腔颌面外科杂志, 2016,14（6）:510⁃513.
［36］	吴凡. 普萘洛尔治疗婴幼儿血管瘤的临床疗效和对神经系统发育影响的评估［D］. 济南: 山东大学, 2016.
［37］	Moyakine AV, Kerstjens JM, Spillekom⁃van KS, et al. Propranolol treatment of infantile hemangioma （IH） is not associated with developmental risk or growth impairment at age 4 years［J］. J Am Acad Dermatol, 2016,75（1）:59⁃63.e1. doi: 10.1016/j.jaad. 2016.02.1218.
［38］	Hu L, Zhou B, Huang H, et al. Effects of systemic propranolol treatment on physical growth of patients with infantile hemangiomas［J］. J Dermatol, 2016,43（10）:1160⁃1166. doi: 10. 1111/1346⁃8138.13324.
［39］	Steenen SA, van Wijk AJ, van der Heijden GJ, et al. Propranolol for the treatment of anxiety disorders: Systematic review and meta⁃analysis［J］. J Psychopharmacol, 2016,30（2）:128⁃139. doi: 10.1177/0269881115612236.
［40］	Moyakine AV, Spillekom⁃van KS, van der Vleuten CJM. Propranolol treatment of infantile hemangioma is not associated with psychological problems at 7 years of age［J］. J Am Acad Dermatol, 2017,77（1）:105⁃108. doi: 10.1016/j.jaad.2017.01.025.
［41］	Castaneda S, Melendez⁃Lopez S, Garcia E, et al. The role of the pharmacist in the treatment of patients with infantile hemangioma using propranolol［J］. Adv Ther, 2016,33（10）:1831⁃1839. doi: 10.1007/s12325⁃016⁃0391⁃9.

[1]	林杨杨宫泽琨赵丽李钦峰. 与卡介苗接种相关的婴儿瘰疬性苔藓七例[J]. 中华皮肤科杂志, 2019, 52(8): 533-536.
[2]	肖媛媛徐子刚徐哲向欣刘盈马琳杨舟. 长春新碱联合糖皮质激素治疗11例婴儿期Kasabach-Merritt综合征[J]. 中华皮肤科杂志, 2018, 51(8): 601-603.
[3]	耿清伟王敏宋秀祖. 皮肤上皮样血管瘤22例临床病理分析[J]. 中华皮肤科杂志, 2018, 51(6): 459-462.
[4]	叶雯霞金宛宛全和和薛细貌童艺高宇. 595 nm染料激光联合外用0.5%马来酸噻吗洛尔溶液治疗浅表型婴儿血管瘤的疗效评价[J]. 中华皮肤科杂志, 2018, 51(12): 888-892.
[5]	申春平王榴慧王华汤建萍彭晓霞冯国双李云珠马琳. 除湿止痒软膏治疗轻度婴儿期特应性皮炎的有效性及安全性多中心临床研究[J]. 中华皮肤科杂志, 2017, 50(4): 279-282.
[6]	郭艳萍刘姿薇张颖徐锐姜海燕. 婴儿皮肤及内脏血管瘤一例[J]. 中华皮肤科杂志, 2015, 48(4): 284-284.
[7]	杨正生李力王亚斐杨会君. 姜黄素对豚鼠银屑病样动物模型的药效评价及对增殖细胞核抗原表达的影响[J]. 中华皮肤科杂志, 2015, 48(3): 175-178.
[8]	徐教生徐子刚周春菊韩晓峰肖媛媛徐哲张立新马琳. 婴儿纤维性错构瘤12例临床病理分析[J]. 中华皮肤科杂志, 2015, 48(11): 807-809.
[9]	何文飞王城张红梅谢贤镛. 幼儿全身泛发纤维瘤病一例[J]. 中华皮肤科杂志, 2014, 47(8): 603-604.
[10]	王松挺乔建军. 米其林轮胎婴儿综合征一例[J]. 中华皮肤科杂志, 2014, 47(10): 757-757.
[11]	张西克李小静郭晓辉张秀娟李志锋. 新生儿暂时性萎缩性回状红斑一例[J]. 中华皮肤科杂志, 2013, 46(6): 445-445.
[12]	廖恒利林新瑜. 婴儿巨大尖锐湿疣一例[J]. 中华皮肤科杂志, 2013, 46(5): 323-323.
[13]	房思宁李放娟姚勇丰杜晓红黄小芳. 新生儿色素失禁症一例[J]. 中华皮肤科杂志, 2013, 46(4): 294-294.
[14]	郭坤李静周明耿松梅. 多发性丛状血管瘤一例[J]. 中华皮肤科杂志, 2013, 46(2): 142-142.
[15]	郭昊刘新媛李一雷郑松李久宏. 疣状血管瘤一例[J]. 中华皮肤科杂志, 2012, 45(9): 682-682.