口服普萘洛尔治疗婴幼儿鼻部血管瘤的临床观察及随访

目的观察口服普萘洛尔治疗婴幼儿鼻部血管瘤的疗效及安全性。方法回顾性分析2011年3月—2017年3月徐州市儿童医院49例鼻部血管瘤住院患儿的临床资料,每月门诊随访并拍照,记录瘤体的变化、不良反应和复发情况,通过影像学检查和照片对口服普萘洛尔的疗效和安全性进行评价,并进行随访。口服普萘洛尔的起始剂量为0.5 mg/(kg·d),72 h内逐渐加量至1.5 mg/(kg·d)。结果 49例患儿中女32例,男17例,就诊年龄1~9个月龄,平均年龄3个月龄。治疗总疗程4~16个月龄,平均疗程6.4个月龄。最易受累的区域是鼻尖部,其次是鼻根。服药至6个月时有效率为89.4%,出现轻微不良反应患儿5例,其中以肝酶升高最多见。出现并发症8例,脂肪组织残留最常见。停药6个月后复诊无复发。结论口服普萘洛尔治疗婴幼儿鼻部高风险血管瘤安全有效,早期干预可减少鼻部变形的风险。     

普萘洛尔联合噻吗洛尔滴眼液治疗婴幼儿血管瘤

目的:评价普萘洛尔联合噻吗洛尔滴眼液治疗婴幼儿血管瘤的临床疗效和安全性。方法:血管瘤患儿130例,普萘洛尔2 mg/(kg·d),分3次口服,皮损表面外搽噻吗洛尔滴眼液适量,日4次,治疗3个月。结果:治疗8个月后随访,66例(49%)患者的瘤体缩小76%~100%,53例(42%)瘤体缩小51%~75%,10例(8%)瘤体缩小26%~50%,1例(1%)瘤体缩小25%。治疗期间无严重不良反应。结论:普萘洛尔联合噻吗洛尔滴眼液治疗婴幼儿血管瘤安全有效。     

口服普萘洛尔联合聚桂醇局部注射治疗婴幼儿血管瘤的疗效评价

目的：评价普萘洛尔联合局部注射聚桂醇治疗婴幼儿血管瘤的临床疗效。 方法：收集2014-2018年我科就诊的婴幼儿血管瘤患者，分为口服普萘洛尔组和口服普萘洛尔联合聚桂醇局部注射治疗组，随访观察12个月。结果：共治疗婴幼儿血管瘤患者43例，其中口服普萘洛尔组21例，口服普萘洛尔联合聚桂醇局部注射治疗组22例。全部患儿随访观察12个月，瘤体均有不同程度缩小、颜色变浅。口服普萘洛尔组治疗时间(148±32)天，治愈率为61.9%；联合治疗组治疗时间为(62±24)天，治愈率为95.45%，两者间差异均有统计学意义（Ps＜0.05）。43例患儿中有4例在服口服普萘洛尔1小时后出现心率减慢，经观察3 h后自行恢复正常,35例患儿血糖轻微降低，降低幅度≤0.2 mmol/L，未给予特殊处理。22例联合聚桂醇局部注射治疗患儿，7例注射局部有少量渗血。结论：口服普萘洛尔联合局部注射聚桂醇治疗婴幼儿血管瘤较单用普萘洛尔治疗疗程缩短，临床疗效更佳。     

普萘洛尔治疗婴幼儿血管瘤临床观察

目的观察普萘洛尔口服治疗婴幼儿血管瘤的临床疗效及安全性。方法选择2011年3月-2012年4月本科住院的50例婴幼儿血管瘤于心电监护下予口服普萘洛尔治疗,男18例,女32例,平均年龄4个月,治疗前完善相关实验室检查,每月复查1次,并根据体重增减情况调整用药剂量,至皮损消退后减量并停药。结果 50例患儿在用药后24h内即出现瘤体颜色变浅、质地变软或缩小。有效率为80%,其中Ⅰ级0例(差),Ⅱ级10例(中),Ⅲ级25例(好),Ⅳ级15例(优),用药时间延长,治疗效果越明显(P<0.05)。平均用药时间5个月(2～13个月),停药时间平均年龄8个月(5～27个月)。合并溃疡者,溃疡愈合时间平均9d(7～15d)。不良反应轻微,主要表现为消化道症状。结论普萘洛尔口服治疗婴幼儿血管瘤临床疗效明显,安全性好,可作为婴幼儿血管瘤的一线治疗用药。     

普萘洛尔口服治疗婴幼儿血管瘤的疗效及安全性

目的:评价口服普萘洛尔治疗婴幼儿血管瘤的疗效及安全性。方法:婴幼儿血管瘤患儿106例,口服普萘洛尔1.0~1.75 mg/kg·d,详细记录患儿血管瘤质地、大小及颜色改变,按Achauer四级分类标准进行疗效判断。结果:服药后起效时间为12~113 h,平均47 h;疗效达到Achauer标准Ⅰ级11例,Ⅱ级31例,Ⅲ级40例,Ⅳ级24例。有2例瘤体完全消退。患儿的血管瘤生长部位与治疗有效率之间无明显相关性(P>0.05)。治疗期间未见明显不良反应。结论:口服普萘洛尔治疗婴幼儿血管瘤疗效肯定,不良反应小。     

普萘洛尔治疗婴儿血管瘤的临床疗效及安全性北大核心CSCD

目的评估口服普萘洛尔治疗婴儿血管瘤的临床疗效及安全性。方法2010年7月至2011年11月北京儿童医院皮肤科病房收治血管瘤患儿90例,予口服普萘洛尔1．5～2．0mg·kg-1·d-1治疗,每月复诊记录瘤体变化,根据体重调整用药剂量,并监测服药前后患儿的血糖、心率、血压、肝肾功能、心肌酶、心电图、血管瘤局部超声等变化情况,观察疗效及安全性。结果90例患儿中82例（91．1％）口服普萘洛尔后24—48h起效。用药1～10个月的患儿88例,用药后瘤体缩小0—25％或瘤体表面颜色较前变浅7例（8．0％）,瘤体缩小26％．50％或瘤体表面颜色较前明显变浅35例（39．8％）,瘤体缩小51％～75％且瘤体表面颜色较前明显变浅23例（26．1％）,瘤体缩小大于75％或瘤体表面颜色消退23例（26．1％）。用药3～4个月疗效均优于1—2个月;用药5～6个月疗效优于3—4个月;7—8个月疗效优于5～6个月。初步观察患儿于10个月至1岁4个月间停药后瘤体未见反弹。治疗过程中可出现低血压、睡眠障碍、稀便、低血糖、肢端发凉、气道高反应、肝功能异常、心肌酶异常,大部分于用药早期出现,经随诊或对症治疗后可好转。结论普萘洛尔可抑制增生期血管瘤生长,并加速其消退,部分患儿效果显著;对消退期血管瘤初步观察亦有促进消退作用。治疗过程中不良反应程度较轻,但需严密监测,及时对症处理。     

口服普萘洛尔治疗中、高风险血管瘤159例的临床分析:3年回顾性研究

目的:探讨口服盐酸普萘洛尔治疗中、高风险婴幼儿血管瘤的疗效和可行性。方法:选取2013年3月至2016年3月期间我科门诊确诊的中、高风险血管瘤患儿,给予口服普萘洛尔治疗:首日剂量为0. 50 mg/(kg·d),分2次口服;第二天剂量增加至0. 75 mg/(kg·d),分2次口服;第三天剂量调整为1. 00 mg/(kg·d),分2～3次口服;服药1周后复诊观察患儿皮损变化情况及对药物的敏感程度,酌情加量至每日1. 50～2. 00 mg/(kg·d)维持治疗,每天分2～3次口服,连续服用6～12个月。服药期间每月复诊1次,复查血常规、血糖、血压、心电图、B超,每2～3个月复查心肌酶谱、肝肾功能、电解质等。撤药时逐渐减量,每月减量0. 50 mg/(kg·d)。患儿治疗前均完善影像学、生化检查,治疗过程中进行多普勒超声检查并观察皮损大小等,观察临床疗效及转归情况。结果:共168例中、高风险血管瘤患儿接受口服普萘洛尔治疗,其中159例完成了所有的治疗和随访,完成率为94. 64%。患者平均首诊年龄为(2. 29±0. 84)月龄,平均给药持续时间为(13. 67±4. 43)个月,平均最大给药剂量为(1. 86±0. 35) mg/(kg·d)。其中未完成治疗和随访的9例患者中,2例(1. 19%)因心脏方面的副作用停药,5例(2. 98%)治疗6个月及以上无效后行手术切除治疗,2例(1. 19%)散发型血管瘤患儿(肝脏受累)在服药4个月肝脏血管瘤完全消退后自行停药脱失。完成治疗和随访的患者中,男女患者、多发与单发血管瘤患者、节段型与散发型与局灶型、溃疡型与非溃疡型的治疗效果间比较没有明显的差异(P值均>0. 05)。结论:口服普萘洛尔对各类型的中、高风险血管瘤有明显疗效,与血管瘤分型无明显差异。     

口服普萘洛尔治疗120例婴儿血管瘤的回顾性疗效分析

目的:评价口服普萘洛尔治疗婴儿血管瘤的疗效及不良反应。方法:对120例普萘洛尔治疗至少6个月以上的婴儿血管瘤患者的临床疗效和不良反应进行评价。结果:120例患儿服药3个月有效率为59.2%,6个月有效率为96.46%,82例停药时有效率为98.78%。不良反应的发生率为21.67%。结论:口服普萘洛尔治疗婴儿血管瘤疗效好、不良反应少且轻。     

普萘洛尔治疗婴儿血管瘤复发因素分析

目的 了解口服普萘洛尔治疗婴儿血管瘤中导致复发的因素.方法 对235例口服普萘洛尔治疗且已经停用普萘洛尔6个月的血管瘤患儿复发因素进行调查,使用单因素和多因素非条件logistic回归模型进行分析.结果 235例患儿停药6个月内复发66例,复发率28.1％(66/235),其中15例属于严重复发,占复发病例的22.7％(15/66).复发的危险因素包括服药剂量为1.5 mg· kg-1·d-1(OR=3.566,95％ CI:1.306～ 9.739),首次服药时年龄＞8周(OR=5.043,95％ CI:1.248 ～ 20.376),服药疗程≤6个月(OR=17.661,95％ CI:4.899 ～ 63.665),停药时年龄＜1岁(OR=6.089,95％ CI:1.835 ～ 20.204).结论 影响普萘洛尔治疗婴儿血管瘤复发的危险因素较多,应针对这些危险因素采取措施,降低复发率.     

口服与外用普萘洛尔治疗婴幼儿草莓状血管瘤疗效比较

目的:评价口服和外用普萘洛尔治疗婴幼儿血管瘤的有效性和安全性。方法:42例血管瘤患儿随机分为A、B两组(每组21例),A组口服1.5 mg/(kg·d)普萘洛尔,B组局部外用1%普萘洛尔软膏,日3次。治疗结束后随访6个月评价疗效。结果:A组12例效果优(57.1%),B组5例效果优(23.8%),两组比较有显著性差异,(P0.05),两种方法均未出现严重的副作用。结论:口服普萘洛尔的疗效好于局部外用,但对于口服药物不能耐受的病例可选择外用普萘洛尔软膏。     

Prolonged growth of infantile hemangioma after pulsed dye laser and oral propranolol treatment

Infantile hemangiomas are the most common tumor of childhood and undergo rapid growth during early infancy followed by gradual involution. After involution, residual lesions sometimes remain. Oral propranolol usually induces earlier involution and redness reduction of infantile hemangiomas. However, the optimal treatment duration is unknown and infantile hemangiomas sometimes recur after cessation of treatment. We report three Japanese patients with recurrent infantile hemangiomas on their cheek. These patients were a 1‐month‐old female baby with a superficial infantile hemangioma, a 3‐month‐old female baby with a mixed infantile hemangioma and a 4‐month‐old male baby with a mixed infantile hemangioma. Two of them also received pulsed dye laser treatment. They did not reach complete or nearly complete resolution of infantile hemangiomas at week 25. These patients experienced regrowth of their infantile hemangioma after 20 months of age and took propranolol after the age of 24 months. There were no severe adverse effects. Propranolol may not only be therapeutic but also prophylactic. Patients with infantile hemangiomas who have taken oral propranolol should be followed up at least 6 months after cessation of treatment, especially infantile hemangiomas on the cheek, and those with partial response to propranolol may require close attention in prolonged growth.     

Topical propranolol therapy for infantile hemangiomas

The nonselective beta-adrenergic receptor antagonist propranolol is an effective therapy for infantile hemangiomas. Systemic propranolol therapy shows a rapid therapeutic effect with good drug tolerability. We report on the efficacy of local application of propranolol ointment in superficial hemangiomas of the skin. In our outpatient department, 45 children with 65 hemangiomas were treated with 1% propranolol in a hydrophilic ointment topically applied twice a day. Before start of treatment and at each visit, clinical photographs were taken. If ultrasound did not confirm occult deeper components, children were included in the study. Treatment in the proliferative phase within the first 6 months of life (including seven preterm infants) induced regression in 59% and cessation of growth in 26% of the hemangiomas. No response or proliferation of subcutaneous components was observed in 15%. Clinically, no side effects caused by the beta-receptor blocker were noticed. Treatment of two ulcerated hemangiomas of the perineal region twice using a flash lamp pulsed-dye laser and propranolol ointment in the surrounding lesion led to healing of the ulcers in 3 and 6 weeks, respectively. In six patients, topical therapy was started between the ages of 7 and 33 months. Even in these hemangiomas, improvement was obvious after 2 or 3 months. Propranolol administered topically in 1% ointment could have a beneficial effect on superficial hemangiomas of the skin. The treatment was well tolerated without side effects even in preterm infants and in children with numerous or large lesions.     

Recurrence of infantile hemangiomas treated with propranolol

Propranolol has shown to be effective in the treatment of infantile hemangiomas (IH), but several cases of recurrences have been reported so far. We describe five cases of IH recurrence after propranolol treatment was stopped in 26 patients treated with propranolol all of whom were observed for at least 9 months after treatment was discontinued. Recurrence was present in 5 of 26 cases, yielding a recurrence rate of 19%. All cases were in females. Time from withdrawal to recurrence ranged from 0 to 6 months. In four of five cases, the lesion relapsed after the age of 11 months. Four of the five cases presented partial recurrences, whereas in one case, recurrence was complete. In the majority of cases, recurrence appeared in the deep component of the IH. Early treatment withdrawal or a long proliferative phase of IH are potential causes of hemangioma recurrence, although the exact mechanism remains unclear. The vascular endothelial growth factor receptor might be involved, as well as incomplete apoptosis during treatment.     

Propranolol-resistant infantile hemangioma successfully treated with sirolimus

Infantile hemangiomas are the most common benign vascular tumors in childhood. Propranolol is the first-line treatment for infantile hemangiomas, but failures may occur. Sirolimus, an mTOR inhibitor, is a promising drug for the treatment of vascular malformations and vascular tumors. We present the case of a child with multiple infantile hemangiomasthat was successfully treated with sirolimus and propranolol after failure of combined propranolol and prednisolone treatment.     

Propranolol for infantile hemangiomas

Propranolol has been used successfully in a limited number of children with infantile hemangiomas. This multicenter retrospective study describes the efficacy and adverse effects of propranolol in infantile hemangioma. Seventy-one infants with infantile hemangiomas were treated with oral propranolol, 1 mg/kg/12 hours, for at least 12 weeks. A photograph based severity scoring assessment was performed by five observers to evaluate efficacy, utilizing a scoring system of 10 as the original infantile hemangioma before treatment and 0 as completely normal skin. The mean of the five independent measurements was used in the analysis. Propranolol was a rapid and effective treatment for infantile hemangiomas at 4 weeks (p < 0.001), at 8 weeks (p < 0.001 compared to the 4 wks value), at 12 weeks (p < 0.05 compared to the 8 wks value), and thereafter up to 32 weeks (p < 0.01 compared to the 16 wks value). The response of infantile hemangiomas to propranolol was similar regardless of sex, age at onset of treatment, type of involvement (segmental and nonsegmental), facial segments affected, special locations (eyelid, nasal tip, and parotid region), ulceration, and depth of infantile hemangiomas. Very few side effects were reported; mainly agitated sleep in 10 of 71 patients. In the series of patients in this study, oral propranolol 2 mg/kg/day was a well-tolerated and effective treatment for infantile hemangiomas. Prospective studies are needed to establish the exact role of propranolol in the treatment of infantile hemangiomas.     

Late Rebound of Infantile Hemangioma after Cessation of Oral Propranolol

Propranolol has become the first line of treatment for infantile hemangiomas (IHs), with a high response rate, but rebound growth after cessation of propranolol has been reported, primarily in the first year of life. We sought to determine the frequency and associated factors leading to late regrowth after successful treatment at an age when the proliferative phase has usually ceased. We retrospectively reviewed the clinical charts, serial photographs, and radiologic images of children with rebound IH occurring after the age of 15 months after a successful course of oral propranolol averaging 2.6 mg/kg/day (range 2–3 mg/kg/day). Thirteen (10 female, 3 male) of 212 patients (6%) treated with oral propranolol since 2008 were evaluated. The mean age at the start of treatment was 5.3 months (range 1.8–13 months), and an average of 10.3 months (range 4.5–16 months) of treatment was given. It took an average of 5.3 months (range 1–13.8 months) for a significant rebound to appear. Late rebound after successful propranolol indicates a prolonged proliferation phase of IH even after 15 months of age. This is compared with previous reports of rebound, which occurred primarily in infants younger than 1 year old. Late proliferation can occur in localized, small, mixed, and deep IH, even after several months of a positive response to propranolol. A second course of propranolol readily controlled the recurrence.     

Special management considerations for propranolol use in breastfed infants of mothers taking antihypertensives

Propranolol is approved for treatment of infantile hemangiomas (IH). IH proliferation coincides with the time when most women are breastfeeding, yet there are no reports describing the clinical effects on infants treated with propranolol while being nursed by mothers on oral antihypertensive medications. We describe two cases of breastfed infants, with mothers taking multiple antihypertensives of different drug classes, who were initiated on propranolol for IH treatment and discuss the theoretical risk of propranolol use in this setting.     

普萘洛尔和泼尼松治疗婴幼儿增生期血管瘤的临床观察

目的探讨口服普萘洛尔和泼尼松治疗婴幼儿头面部血管瘤的疗效和安全性。方法将62例头面部血管瘤患儿随机分为普萘洛尔组[1.5mg/(kg.d)]、泼尼松组(2.5mg/kg)和观察组(不做处理),比较3组患儿的血管瘤体变化情况,并检测患儿服药前、后的心率、血糖、肝肾功能和甲状腺功能。结果①治疗8周后,普萘洛尔组、泼尼松组、观察组总有效率分别为100.00%,90.48%和37.50%,普萘洛尔组和泼尼松组疗效相当(P>0.05),但均优于观察组(P均<0.01))。②普萘洛尔组在第1天服药后1h和3h心率明显低于服药前,差异均有统计学意义(P均<0.01),服药前与服药后6h心率差异无统计学意义(P>0.05);在第2天和第3天服药后1h心率均明显低于服药前,差异也均有统计学意义(P均<0.05),但服药前与服药后3h和6h心率及泼尼松组服药前与服药后1h,3h和6h心率相比,差异均无统计学意义(P均>0.05)。③普萘洛尔组和泼尼松组服药前与服药4周后肝肾功能,血糖,FT3,FT4,sTSH等检测值的差异均无统计学意义(P均>0.05)。结论普萘洛尔在治疗婴幼儿血管瘤过程中可抑制血管瘤生长,较泼尼松治疗组不良反应少,且安全性较好。     

Prospective study of the frequency of hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas

Multiple cutaneous infantile hemangiomas have been associated with hepatic hemangiomas. Screening of infants with five or more cutaneous infantile hemangiomas with abdominal ultrasound is often recommended. The aim of this study was to determine the frequency with which hepatic hemangiomas occur in infants with five or more cutaneous infantile hemangiomas compared to those with one to four cutaneous infantile hemangiomas and to characterize the clinical features of these hepatic hemangiomas. A multicenter prospective study of children with cutaneous infantile hemangiomas was conducted at pediatric dermatology clinics at Hemangioma Investigator Groups sites in the United States, Canada, and Spain between October 2005 and December 2008. Data were collected, and abdominal ultrasonography was performed on infants younger than 6 months old with five or more cutaneous infantile hemangiomas and those with one to four cutaneous infantile hemangiomas. Twenty-four (16%) of the 151 infants with five or more cutaneous infantile hemangiomas had hepatic hemangiomas identified on abdominal ultrasound, versus none of the infants with fewer than five (p = 0.003). Two of the 24 infants with hepatic hemangiomas received treatment specifically for their hepatic hemangiomas. Infants with five or more cutaneous infantile hemangiomas have a statistically significantly greater frequency of hepatic hemangiomas than those with fewer than 5. These findings support the recommendation of five or more cutaneous infantile hemangiomas as a threshold for screening infants younger than 6 months old for hepatic hemangiomas but also demonstrate that the large majority of these infants with hepatic hemangiomas do not require treatment.     

Topical Timolol for Small Hemangiomas of Infancy

Abstract: Propranolol has become the treatment of choice of large and complicated infantile hemangiomas. There is a controversy concerning the safety of systemic propranolol. Here we show that topical use of the beta‐blocker timolol can also inhibit the growth and promote regression of infantile hemangiomas. In this case series we treated 11 infantile hemangiomas in nine children including six preterm babies with the nonselective betablocker timolol. A timolol containing gel was manufactured from an ophthalmic formulation of timolol 0.5% eyedrops. This gel was applied using a standardized occlusive dressing (Finn‐Chambers) containing approximately 0.25 mg of timolol. In all infants topical timolol was associated with growth arrest, a reduction in redness and thickness within the first 2 weeks. Seven hemangiomas showed almost complete resolution, and four became much paler and thinner. No data are available on the transdermal absorption of timolol. Even supposing complete absorption of timolol from the occlusive dressing, a maximum dose of 0.25 mg of timolol would result per day and hemangioma. Regression of infantile hemangiomas treated using 0.5% timolol gel in this case series occurred earlier than spontaneous regression which is generally not observed before the age of 9–12 months. The promising results need to be verified in prospective randomized trials on topical beta blocker administration for infantile hemangiomas which should address dose, duration, and mode of application.