Use of propranolol for the treatment infantile hemangiomas in the maxillofacial region

Abstract

Propranolol has been used successfully in a limited number of children with infantile hemangiomas (IHs). This study describes the efficacy and adverse effects of propranolol in IH. Seventy-one infants with IHs were treated with oral propranolol, administered at a dose of 2 mg/kg/day, for at least 12 weeks. A photograph-based severity scoring assessment was performed by five observers to evaluate efficacy, utilizing a score of 10 as the original IHs 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 IHs at 4 weeks ( P < 0.001), at 8 weeks ( P < 0.001 compared with the value at 4 weeks), at 12 weeks ( P < 0.05 compared with the value at 8 weeks), and thereafter up to 32 weeks ( P < 0.01 compared with the value at 16 weeks). The response of IHs to propranolol was similar regardless of gender, age at the onset of treatment, type of involvement (local and extended), facial segments affected, special locations (eyelid, nasal tip, and parotid regions), ulceration, and depth of IHs. In the series of patients in this study, oral propranolol at a dosage of 2 mg/kg/day was a well-tolerated and effective treatment for IHs.

Introduction

Infantile hemangiomas (IHs) are benign tumours of endothelial cells that show a rapid proliferating phase, usually followed by variable degrees of spontaneous regression. However, problematic hemangiomas occur when they ulcerate, have massive growth, cause disfigurement, or impact normal function or cosmetic development. Common locations for problematic hemangiomas include the face, ear, orbit, and airway. These hemangiomas subsequently require early and aggressive treatment for ideal functional and cosmetic outcomes. Moreover, ulcerated IHs usually require treatment. Corticosteroids have been considered the first-line therapy for severe or complicated IHs. Other treatments, including interferon alpha, vincristine, laser therapy, topical imiquimod, and surgical excision have been reported to be effective alternatives. However, all these options have potential side effects or unknown long-term safety. Currently, no medications exist that are specifically labelled to treat IHs. Recent reports of the successful treatment of IHs in a small number of patients using the beta-blocker agent propranolol have led to considerable excitement and have prompted the large-scale use of propranolol for infants. The medical treatment of IHs in the maxillofacial region is important to cure complications and prevent disfigurement.

Materials and methods

Patients with problematic hemangiomas in the maxillofacial region were reviewed from January 2011 to August 2012. Problematic hemangiomas were defined as hemangiomas with imminent undesirable functional or cosmetic outcomes if left untreated. Alternative interventions (steroid injections, laser treatment, and surgery) would have been performed in these patients despite the availability of oral propranolol. Consent to treat with propranolol and documentation of the disease response were received from all parents whose infants and children participated in the present study.

Evaluations before and during treatment

Before treatment, all patients underwent a cardiologic examination, including clinical examination, ultrasound investigation, electrocardiogram (ECG), and blood pressure measurements. Monthly follow-up visits were scheduled for severity scoring of the IHs, physical examination (including blood pressure and heart rate measurements), and recording of adverse effects, until the end of treatment. A cerebral magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) and a cardiac ultrasound were performed in patients with segmental facial IHs before initiating therapy to rule out PHACES syndrome (Posterior fossa anomalies, Hemangiomas, Arterial lesions, Cardiac abnormalities/aortic coarctation, Eye abnormalities, Sternal abnormalities).

Dosage and duration

All patients were treated with oral propranolol; the initial dosage was 1 mg/kg/day divided three times for 1 day, and then the dosage was increased to the full dosage at 2 mg/kg/day. This dosage was maintained during the entire period of the study. A treatment period of at least 12 weeks was scheduled, however this duration could be further extended if the patient required additional time to achieve resolution of the problem that had led to the initiation of propranolol therapy. When such problems were resolved, or for IHs treated with propranolol in infancy that were expected to have completed their growth, the treatment was withdrawn.

Severity scoring system

To measure the effect of the treatment, a photograph-based visual scale was used. Front and lateral pictures of each patient were taken before treatment and at every follow-up visit. The size and colour were the main features considered for the severity score of all IHs. Measurements were obtained through photographs and ultrasound investigation pictures taken during the scheduled and other non-programmed visits. The results of the treatment of the IHs were scored from 10 to 0, with a score of 10 indicating the original size and colour of the IHs before treatment and a score of 0 indicating completely normal skin. Improvement with a value of 1–3 was considered a poor response; 4–6 indicated an estimated 50% reduction of the IHs and was considered a good response; an improvement of 7 and more was considered an excellent response.

Statistical analysis

The change in the severity score values of the IHs was evaluated using the t -test, comparing the different weeks. Statistical significance was set at a P -value of less than 0.05.

Materials and methods

Patients with problematic hemangiomas in the maxillofacial region were reviewed from January 2011 to August 2012. Problematic hemangiomas were defined as hemangiomas with imminent undesirable functional or cosmetic outcomes if left untreated. Alternative interventions (steroid injections, laser treatment, and surgery) would have been performed in these patients despite the availability of oral propranolol. Consent to treat with propranolol and documentation of the disease response were received from all parents whose infants and children participated in the present study.

Evaluations before and during treatment

Before treatment, all patients underwent a cardiologic examination, including clinical examination, ultrasound investigation, electrocardiogram (ECG), and blood pressure measurements. Monthly follow-up visits were scheduled for severity scoring of the IHs, physical examination (including blood pressure and heart rate measurements), and recording of adverse effects, until the end of treatment. A cerebral magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) and a cardiac ultrasound were performed in patients with segmental facial IHs before initiating therapy to rule out PHACES syndrome (Posterior fossa anomalies, Hemangiomas, Arterial lesions, Cardiac abnormalities/aortic coarctation, Eye abnormalities, Sternal abnormalities).

Dosage and duration

All patients were treated with oral propranolol; the initial dosage was 1 mg/kg/day divided three times for 1 day, and then the dosage was increased to the full dosage at 2 mg/kg/day. This dosage was maintained during the entire period of the study. A treatment period of at least 12 weeks was scheduled, however this duration could be further extended if the patient required additional time to achieve resolution of the problem that had led to the initiation of propranolol therapy. When such problems were resolved, or for IHs treated with propranolol in infancy that were expected to have completed their growth, the treatment was withdrawn.

Severity scoring system

To measure the effect of the treatment, a photograph-based visual scale was used. Front and lateral pictures of each patient were taken before treatment and at every follow-up visit. The size and colour were the main features considered for the severity score of all IHs. Measurements were obtained through photographs and ultrasound investigation pictures taken during the scheduled and other non-programmed visits. The results of the treatment of the IHs were scored from 10 to 0, with a score of 10 indicating the original size and colour of the IHs before treatment and a score of 0 indicating completely normal skin. Improvement with a value of 1–3 was considered a poor response; 4–6 indicated an estimated 50% reduction of the IHs and was considered a good response; an improvement of 7 and more was considered an excellent response.

Statistical analysis

The change in the severity score values of the IHs was evaluated using the t -test, comparing the different weeks. Statistical significance was set at a P -value of less than 0.05.

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Jan 24, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Use of propranolol for the treatment infantile hemangiomas in the maxillofacial region
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