Clinical features of cutaneous infantile hemangioma combined with asymptomatic infantile hepatic hemangioma and efficacy of propranolol treatment

Introduction

Infantile hepatic hemangioma (IHH) is a common liver tumor in infants and shares the same characteristics as cutaneous infantile hemangioma (IH). Propranolol is effective for symptomatic IHH. The clinical features between cutaneous IH and IHH, and treatment efficacy of IHH (smaller than 4 cm) is unclear. To evaluate the correlation of clinical features between cutaneous IH and IHH, as well as efficacy of systemic propranolol in the treatment of cutaneous IH combined with IHH.

Materials and Methods

The clinical data of infants with complicated cutaneous IH combined with IHH treated with systemic propranolol (1.5 ~ 2 mg/(kg d)) from January 2011 to October 2020 were retrospectively analyzed.

Results

Forty-five cases with IHH combined with complicated cutaneous IH were reviewed. Single cutaneous IH is more likely to be combined with focal IHH, cutaneous IH greater than 5, more likely to be combined with multiple IHH (Pearson = 0.546, p < 0.01). The mean age of focal and multiple IHH regression was 11.93 ± 14.42 months and 10.20 ± 9.15 months, respectively.

Conclusions

The number of cutaneous IH were correlated with the number of IHH. There was no difference in the age of complete remission for focal and multiple IHH.     

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。     

Oral propranolol administration is effective for infantile hemangioma in late infancy: A retrospective cohort study

The highest efficacy of oral propranolol is for infantile hemangioma (IH) in the proliferative phase. Evaluation of the effectiveness of oral propranolol is less established when it is administered in late infancy following the proliferative phase. We aimed to assess the clinical outcomes of pediatric patients managed by oral propranolol beyond the proliferative phase of IH. A retrospective cohort study in a tertiary health care referral center was conducted to track all patients with IH receiving systemic propranolol following the proliferative phase. Twenty‐eight eligible patients were managed by 2 to 3 mg/kg per day of oral propranolol for IH beyond the proliferative phase, defined at 9 months of age. The mean age at the initiation of propranolol was estimated at 11.25 (SD 2.24) months. All eligible patients experienced some degree of clinical resolution, with the average improvement rate being estimated at 77.1% (SD 16.1). Comparable results were achieved among patients who were placed on propranolol at an age older than 12 months and those managed between the age of 9 and 12 months. No serious adverse events were observed during the follow‐up duration. In conclusion, oral propranolol is a safe and effective treatment for patients with IH initiating this agent beyond the proliferative phase.     

Multiple pulmonary infantile hemangiomas responsive to oral propranolol

Intrathoracic infantile hemangiomas (IHs) are extremely rare. They may be located in the pericardium, trachea, bronchia, diaphragm, mediastinum, or the lungs and may be associated with cutaneous IHs. We present a newborn with multiple pulmonary IHs in the absence of skin lesions that showed a dramatic response to oral propranolol.     

An infant with localized vasoconstriction following topical propranolol exposure for infantile hemangioma

We describe a 3‐month‐old child with an infantile hemangioma on the forehead with a blanched macule provoked by topical treatment with propranolol. This observation demonstrates that topically applied (non‐selective) beta‐blockers may induce blanched macules at the site of application, a side effect due to peripheral vasoconstriction of blood vessels by non‐selective beta‐2 blockade. This side effect was linked due to overuse and was reversible. This case illustrates the importance of providing thorough instructions regarding topical propranolol application.     

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.     

Oral propranolol for infantile hemangiomas beyond the proliferative phase

Infantile hemangiomas grow rapidly during infancy followed by gradual involution. After involution, residual lesions sometimes remain. Despite the prognosis for eventual involution, infantile hemangiomas often cause great psychosocial morbidity that affects patients and their parents. Oral propranolol usually induces earlier involution and redness reduction in infantile hemangiomas in the proliferative phase. However, to evaluate the effectiveness of oral propranolol for infantile hemangiomas beyond the proliferative phase is difficult because of spontaneous regression. We report five Japanese patients treated with 2 mg/kg per day of oral propranolol for infantile hemangiomas beyond the proliferative phase and compared with three untreated patients. After the oral propranolol treatment for 25 weeks, all the treated patients exhibited earlier color fading than untreated patients. Four patients reached nearly complete resolution. Adverse events occurred in three patients: cold, exanthema subitum and suspected of bronchial asthma, respectively. The propranolol treatment for the patient with suspected of bronchial asthma was suspended for 4 months. Recurrence after termination of treatment was not seen. Oral propranolol (2 mg/kg per day) is a safe and effective treatment for Japanese patients with infantile hemangiomas beyond the proliferative phase.     

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.     

Consensus statement for the treatment of infantile haemangiomas with propranolol

Although most infantile haemangiomas do not require treatment due to a natural history of spontaneous involution, some require early intervention. The Australasian Vascular Anomalies Network and the Australasian Paediatric Dermatology Network have developed a consensus statement for the treatment of infantile haemangiomas with oral propranolol. Infants with haemangiomas that are life threatening, at risk of ulceration, or at risk of causing a significant functional impairment, psychological impact or physical deformity should be treated early with oral propranolol. Oral propranolol is safe and effective and in most healthy infants oral propranolol can be started in an outpatient setting.     

Metastatic neuroblastoma mimicking an infantile hemangioma

Neuroblastoma is the most common solid tumor malignancy in the first year of life. We present a rare case of a 5‐month‐old girl with an infraorbital tumor that simulated an infantile hemangioma clinically but was ultimately diagnosed as metastatic neuroblastoma.     

Clinical and radiological outcomes of infantile hemangioma treated with oral propranolol: A long‐term follow‐up study

Infantile hemangiomas (IH) undergo rapid growth during early infancy followed by gradual involution. After involution, a part of IH remain as residual lesions. Since 2008, oral propranolol has been widely used in the treatment of IH. However, long‐term outcome of IH treated with propranolol remains unknown. This study aimed to investigate the sequelae of IH treated with propranolol. In this study, propranolol was given at a dose of 2 mg/kg per day at the age of 3.8 ± 2.5 months and follow‐up visits were arranged to continue at least through the age of 4 years. Types of sequela were recorded and classified as four degrees (“none”, “minimal”, “significant” and “severe” at last visit), then subsequent therapy was evaluated with the help of magnetic resonance imaging (MRI). A total of 73 patients with complete follow up were enrolled in the study. The most common types of sequela were telangiectasia, fibrofatty tissue and erythema. Significant and severe sequelae were observed in 72.4% of treated IH; superficial IH led to more but not significantly significant and severe sequelae than mixed IH (P > 0.05). Despite propranolol treatment, surgery was still needed in 37.5% of IH at a mean age of 70.3 months, and for the main reason of surgery, fibrofatty or hemangioma residua, MRI was useful for us to choose an appropriate surgical procedure.     

Episcleral infantile hemangioma successfully treated with topical timolol

Episcleral hemangiomas are usually associated with neonatal hemangiomatosis. Recently, propranolol has been described for the treatment of this entity. We present for the first time a patient with an episcleral hemangioma without neonatal hemangiomatosis successfully treated with topical timolol.     

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。     

A further experience of propranolol for severe infantile hemangiomas of the face: an observational study

Infantile hemangiomas (IHs) are the most common proliferating embrional tumors of infancy, which are constituted by endothelial cell hyperproliferation. The authors want to report their observations of further 14 patients suffering from complicated IHs involving the facial district who were treated with propranolol. 14 patients, with ages between 3 and 12 months, completed a cycle of treatment with propanolol. The observational study aimed at focusing IHs involving the facial district. The treatment with propranolol showed good to very good results in the major part of the treated young patients. The authors want to report their experience and add more data in the confirmation of the use of β‐blockers for IH (either in efficacy or in safety profile), focusing on the efficacy of propanolol when IHs involve the face.     

口服普萘洛尔治疗婴儿血管瘤第一周不良反应研究

目的:研究口服普萘洛尔治疗婴儿血管瘤第一周发生不良反应的比率及严重程度,评估住院流程是否必须。方法:回顾性分析502例高风险婴儿血管瘤患儿口服普萘洛尔治疗第一周的临床资料,分析不良反应发生的种类、比率及相关因素。结果:502例患儿中男152例,女350例,男∶女=1∶2.3;平均年龄(3.29±2.22)个月。皮损主要分布于头颈(315例,占62.75%)、躯干(97例,占19.32%)、四肢(40例,占7.97%),多发性血管瘤(≥5个病灶)26例(5.18%),其中2例累及肝脏。合并溃疡7例(1.39%)。有早产史38例(7.57%),有低出生体重史17例(3.39%),有心脏病史47例(9.36%)。服药前发现肝功能异常21例(4.18%),TSH增高31例(6.18%)。总不良反应发生率为18.52%(93/502),其中心动过缓4.58%(23/502)、Ⅰ度房室传导阻滞0.40%(2/502),均无临床症状;胃肠道反应12.55%(63/502);食欲减退0.40%(2/502);嗜睡0.20%(1/502);手足湿冷0.40%(2/502)。比较不同性别、年龄患儿以及是否有早产史或低出生体重史、是否存在先天性心脏病史、服药前TSH是否升高、肝功能是否异常患儿在服用普萘洛尔1周后发生心动过缓和胃肠道反应的百分比,差异均无统计学意义(P值均>0.05)。结论:口服普萘洛尔治疗高风险婴儿血管瘤相对安全、不良反应发生率低,非特殊人群、无明显禁忌症的患儿可选择在门诊服药后短期监测、定期随诊调整剂量的模式,免去住院流程。     

Effects of systemic propranolol treatment on physical growth of patients with infantile hemangiomas

Propranolol has been widely used in the treatment of infantile hemangiomas since 2008. This study aimed to investigate complications of systemic propranolol therapy for infantile hemangiomas, especially its effect on infants' physical growth. In this study, propranolol was given at a dose of 2 mg/kg per day. Abnormal symptoms and growth parameters were recorded in detail during the therapy. Follow‐up visits were arranged to continue at least through the age of 2 years. A total of 76 patients with complete growth parameters were enrolled into the study. Complications of propranolol were minor, and mainly included sleeping disorders, diarrhea, decrease in fasting glucose, bronchial hyperactivity and hyperkalemia. Four (5.26%) patients' growth curve dropped off more than 20 percentiles during therapy and half of them returned to normal after withdrawal of the medications. None of them suffered from underweight, wasting or stunning when medication was stopped. Systemic propranolol was proved to be a safe treatment for problematic infantile hemangiomas and did not affect the physical growth.