Propranolol treatment for severe infantile hemangiomas: a single-centre 3-year experience

Aim: To evaluate the effectiveness, safety and tolerability of propranolol as single‐agent treatment in patients with problematic, proliferative‐phase, infantile hemangiomas (IHs). Methods: Oral propranolol was administered at a dose of 2 mg/kg/day to 28 children. Cardiologic evaluation was performed before treatment initiation. Hemodynamic variables and blood glucose levels were monitored during the first 24 h of treatment, while the children were hospitalized. Clinical response and tolerance were assessed every month, along with photographic documentation. Macroscopic regression was considered the reduction >90% in the size of the IHs. Results: Effects on colour and growth were observed within the first month in all cases. Twenty‐four patients completed treatment after a mean duration of 7.56 months, and their hemangiomas were successfully regressed. Propranolol was administered again, with satisfactory results, in three patients (12.5%) because of hemangioma regrowth. Satisfactory response is noticeable in ongoing cases. Episodes of hypotension were noted in four patients. There were no treatment interruptions because of side effects. Conclusions: Propranolol, as first‐line treatment, yielded excellent results with very good clinical tolerance and also seems to be effective in relapses. The optimal duration of the treatment remains to be defined by long‐term observation.     

Propranolol is more effective than pulsed dye laser and cryosurgery for infantile hemangiomas

Propranolol hydrochloride is a nonselective β-blocker that is used for the treatment of hypertension, arrhythmia, and angina pectoris. In Japan, it was recently approved for the treatment of childhood arrhythmia. It has been observed to produce drastic involution of infantile hemangiomas. The aim of this prospective study was to examine propranolol’s superiority to classical therapy with pulsed dye laser and/or cryosurgery in treating proliferating infantile hemangiomas. Fifteen patients between the ages of 1 and 4 months with proliferating infantile hemangiomas received grinded propranolol tablets 2 mg/kg per day divided in three doses. Twelve patients with proliferating infantile hemangiomas receiving pulsed dye laser and/or cryosurgery were enrolled as controls. Baseline electrocardiogram, echocardiogram, and chest x-ray were performed. Monitoring of heart rate, blood pressure, and blood glucose was performed every 2 weeks. Efficacy was assessed by performing blinded volume measurements and taking photographs at every visit. Propranolol induced significantly earlier involution and redness reduction of infantile hemangiomas, compared to pulsed dye laser and cryosurgery. Adverse effects such as hypoglycemia, hypotension, or bradycardia did not occur. Conclusion: The dramatic response of infantile hemangiomas to propranolol and few side effects suggest that early treatment of infantile hemangiomas could result in decreased disfigurement. Propranolol should be considered as a first-line treatment of infantile hemangiomas.     

Propranolol therapy of infantile hemangiomas: efficacy, adverse effects, and recurrence

Objective

To evaluate the efficacy, adverse effects, and recurrence of oral propranolol for treatment of infantile hemangioma.

Methods

Participants were treated with oral propranolol three times daily, with inpatient monitoring of adverse effects. The starting dosage was 2 mg/kg per day, which had been for the remaining duration of treatment. Therapy duration was planned for 4–6 months; if there was significant relapse, the period of treatment was extended. A photograph based severity scoring assessment was performed by three observers to evaluate efficacy by visual analog scale (VAS).

Results

Sixty-one infants [median age 3.3 (1.2–8.1) months] were included in the study. The median follow-up-time was 15 (6–20) months and 53 patients completed treatment at a median age of 10.3 (8.4–18.1) months, after a duration of 8.5 (4.5–14) months. In all patients, there was significant fading of color [with a VAS of ?9 (?6 to ?9) after 6 months] and significant decrease in size of the infantile hemangiomas [with a VAS of ?8 (?3 to ?10) after 6 months]. We did not observe any life-threatening adverse effects. The therapy was interrupted due to temporary aggravation of pre-existing bronchial asthma in one child. Four cases presented partial recurrences.

Conclusions

Oral propranolol 2 mg/kg per day was a well-tolerated and effective treatment, mild adverse effects, and low recurrence for infantile hemangiomas. Propranolol should now be used as a first-line treatment in hemangiomas when intervention is required. Also, prospective studies should be needed in determining the most effective treatment dosage, optimum treatment duration, and exact mechanism of action of propranolol in future.     

Propranolol for infantile hemangiomas: a preliminary report on efficacy and safety in very low birth weight infants

Despite the relatively recent introduction of propranolol in the treatment of infantile hemangiomas, there can be little doubt of its efficacy. With regard to safety issues, there are no prior data for very low weight infants. In this study, we used propranolol in preterm and very low weight infants. We used clinical criteria to assess the response to the therapy. We noted all side effects expected from beta-adrenergic blocking drugs, and followed the patients' weight gain during propranolol treatment. Objective, clinical evidence of hemangioma regression was seen after two months in all patients. None of the patients required treatment discontinuation due to adverse side effects. During the propranolol treatment, weight gain was normal in all patients. To the best of our knowledge, this is the first report on the use of propranolol in preterm and very low weight infants, and also the first report from Turkey on the use of propranolol in infantile hemangiomas.     

Propranolol therapy for infantile hemangioma

Context

There has been widespread interest surrounding the use of beta-blockers (i.e. propranolol, timolol, nadolol, acebutolol) in the treatment of infantile hemangiomas (IH).

Objective

To review literature evaluating treatment of IH with propranolol.

Evidence Acquisition

We conducted a literature search on PubMed and investigated for case reports, case series, and controlled trials by using search terms including “hemangioma” and “propranolol.”

Results

Data suggest that beta-blockers are efficacious in cutaneous, orbital, subglottic, and hepatic hemangiomas and assist in the resolution of ulcerated hemangiomas. Improvement has also been documented in children with PHACE syndrome. Propranolol produces favorable results in children who do not respond to steroids and with no long-term adverse effects. Propranolol should be administered with caution due to rare but serious side effects including hypoglycemia, wheezing, hypotension, and bradycardia. Additionally, recurrence of lesions following the cessation of treatment has been documented.

Conclusions

Although large-scale randomized controlled trials must be conducted in order to further evaluate the safety and the possible role of propranolol in the treatment of IH, the reviewed literature suggests that propranolol carries promise as a potential replacement for corticosteroids as first-line therapy or as a part of a multimodal approach.     

Use of Propranolol for Infantile Hemangiomas

Treating infantile hemangiomas may be associated with significant morbidity. Recently, propranolol, a nonselective β-blocker, has become a reputed and successful treatment modality for infantile hemangiomas. Here, the author presents experience with oral propranolol in treatment of 14 patients with infantile hemangiomas. The drug was tolerated well and no side effects except reversible bronchospasm in 3 were observed during treatment. Eleven of the patients, younger than 1 year, showed a good response, with more than 50% reduction in the size of the hemangiomas. Although there are a limited number of patients, these results showed that oral propranolol therapy is a safe and effective choice in the treatment of infantile hemangiomas before the age of 1 year.     

Use of propranolol for infantile hemangiomas

Treating infantile hemangiomas may be associated with significant morbidity. Recently, propranolol, a nonselective β-blocker, has become a reputed and successful treatment modality for infantile hemangiomas. Here, the author presents experience with oral propranolol in treatment of 14 patients with infantile hemangiomas. The drug was tolerated well and no side effects except reversible bronchospasm in 3 were observed during treatment. Eleven of the patients, younger than 1 year, showed a good response, with more than 50% reduction in the size of the hemangiomas. Although there are a limited number of patients, these results showed that oral propranolol therapy is a safe and effective choice in the treatment of infantile hemangiomas before the age of 1 year.     

Propranolol therapy for portal hypertension in children

Administration of propranolol to 13 children with portal hypertension reduced splenic pulp pressure by greater than 50 mm H2O (P less than 0.01) in approximately 2 weeks, when the pulse rate became three fourths the initial rate. The influence was found to be greater in compensated than in decompensated portal hypertension. This observation might be interpreted to mean that the effect of propranolol in the reduction of portal venous pressure results not only from decreased intestinal blood flow secondary to decreased cardiac output but also to the stimulation of sympathetic nervous system alpha-adrenoreceptors of the portal tract. Although arterial blood pressure changes were not significant, peripheral venous pressure was reduced significantly (P less than 0.01). We conclude that propranolol has considerable usefulness in treating portal hypertension in children.     

Propranolol for infantile haemangiomas: a review

Infantile haemangiomas are the most common benign tumour of infancy. However the majority are self-resolving and only a small minority of cases require treatment, with various different medications being used in the past. Over the last few years, propranolol, a non-selective β-blocker, has become a popular and successful treatment for infantile haemangiomas. However, further research on its safety is needed if it is going to be used more frequently. This article summarises the current literature on propranolol for haemangioma treatment with emphasis on its toxicity and adverse event profile.     

Topiramate and Propranolol for Prophylaxis of Migraine

Objective

To compare efficacy and safety of topiramate (TPM) and propranolol for migraine prophylaxis in children.

Methods

In a parallel single-blinded randomized clinical trial, 5–15 y-old referred migraineurs to Pediatric Neurology Clinic of Shahid Sadoughi Medical Sciences University, Yazd, Iran from May through October 2011, were evaluated. Patients were distributed into two groups, 50 of whom were treated with 3 mg/kg/d of topiramate (TPM) and another group of 50, were treated with 1 mg/kg of propranolol for 3 mo. Primary endpoints were efficacy in reduction of monthly frequency, severity, duration and headache related disability. Secondary outcome was clinical side effects.

Results

Fifty two girls and 48 boys with mean age of 10.34?±?2.31 y were evaluated. Monthly frequency, severity and duration of headache decreased with TPM, from 13.88?±?8.4 to 4.13?±?2.26 attacks, from 6.32?±?1.93 to 2.8?±?2.12, and from 2.36?±?1.72 to 0.56?±?0.5 h, respectively. Monthly frequency, severity and duration of headache also decreased with propranolol from 16.2?±?6.74 to 8.8?±?4.55 attacks, from 6.1?±?1.54 to 4.8?±?1.6 and from 2.26?±?1.26 to 1.35?±?1.08 h, respectively. Pediatric Migraine Disability Assessment score reduced from 31.88?±?9.72 to 9.26?±?7.21 with TPM and from 33.08?±?8.98 to 23.64?±?9.88 with propranolol. Transient mild side effects were seen in 18 % of TPM and in 10 % of propranolol (P?=?0.249) groups.

Conclusions

Topiramate is more effective than propranolol for pediatric migraine prophylaxis.     

Imaging characteristics of two subtypes of congenital hemangiomas: rapidly involuting congenital hemangiomas and non-involuting congenital hemangiomas

Background: Common infantile hemangiomas (COMMON) occur in approximately 10% of infants by the age of 1 year, with a female predominance. Some hemangiomas can be fully developed at birth and are thus called congenital hemangiomas (CH). Within this population, two courses have been identified: rapidly involuting CH (RICH) and non-involuting CH (NICH). Little has been reported on the clinical prognosis and imaging features of these entities. Objective: To describe the imaging characteristics of two subtypes of CH, i.e. RICH and NICH, and to compare them with COMMON. Materials and methods: We retrospectively gathered data on 26 children presenting with CH, i.e. lesions fully developed at birth. These lesions were divided into two groups according to the clinical course: suspected RICH (n=8) and suspected NICH (n=18). We used US, CT or MRI and angiography to identify the gross anatomy and structure and the vascularization. Imaging findings were compared with the clinical course and pathology results, when available. The imaging findings in these patients were compared retrospectively with those in 26 patients with COMMON randomly chosen from the database of our multidisciplinary clinic. Results: When compared with COMMON imaging characteristics, NICH and RICH had distinctive features on US such as being heterogeneous (72% of NICH and 62.5% of RICH vs 42.3% of COMMON), visible vessels (72% of NICH and 62.5% of RICH vs 15.4% of COMMON), calcifications (17% of NICH and 37.5% of RICH vs no case of COMMON). On CT and/or MRI, we compared imaging features such as well-defined limits (67% of NICH and 60% of RICH vs 100% of COMMON), and fat stranding (29.4% of NICH and RICH vs 7.7% of COMMON). Conclusion: Distinctive imaging characteristics are observed in cases of CH with US findings of visible vessels and calcifications statistically significant.     

Successful Propranolol Treatment of a Kaposiform Hemangioendothelioma Apparently Resistant to Propranolol

A newborn with unresectable kaposiform hemangioendothelioma associated with Kasabach Merritt phenomenon, unresponsive to vincristine and prednisone, received second‐line treatment with propranolol at a dose of 2 mg/kg/day, starting at 2 months of life and continued for 13 months. There was only slight reduction in tumor mass, but measurement of propranolol levels showed extremely low plasma concentrations. The propranolol dose was progressively increased to 3.5 mg/kg/day, leading to a substantial increase in plasma levels associated with clinically relevant tumor reduction. This case highlights the importance of relating propranolol dose to its plasma concentration before considering the treatment ineffective for this vascular tumor.