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Importance: Oral propranolol is widely considered to be first-line therapy for complicated infantile hemangioma, but its use in patients with PHACE (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, eye anomalies) syndrome has been debated owing to concerns that the cardiovascular effects of the drug may increase the risk for arterial ischemic stroke., Objective: To assess the incidence of adverse events among patients with PHACE syndrome receiving oral propranolol for infantile hemangioma., Design, Setting, and Participants: This multicenter retrospective cohort study assessed the incidence of adverse events among 76 patients with PHACE syndrome receiving oral propranolol for infantile hemangioma at 11 tertiary care, academic pediatric dermatology practices. Medical records from January 1, 2010, through April 25, 2017, were reviewed., Exposures: Patients received oral propranolol, 0.3 mg/kg/dose or more., Main Outcomes and Measures: The main outcome was the rate and severity of adverse events occurring throughout the course of treatment with oral propranolol, as documented in the medical records. Adverse events were graded from 1 to 5 using a scale derived from the Common Terminology Criteria for Adverse Events and were considered to be serious if they were grade 3 or higher., Results: A total of 76 patients (59 girls and 17 boys; median age at propranolol initiation, 56 days [range, 0-396 days]) met the inclusion criteria. There were no reports of serious adverse events (ie, stroke, transient ischemic attack, or cardiovascular events) during treatment with oral propranolol. A total of 46 nonserious adverse events were reported among 29 patients (38.2%); the most commonly reported nonserious adverse events were sleep disturbances and minor gastrointestinal tract and respiratory tract symptoms. In a comparison with 726 infants who received oral propranolol for hemangioma but did not meet criteria for PHACE syndrome, there was no significant difference in the rate of serious adverse events experienced during treatment (0 of 76 patients with PHACE syndrome and 3 of 726 patients without PHACE syndrome [0.4%])., Conclusions and Relevance: This study found that oral propranolol was used to treat infantile hemangioma in 76 patients with PHACE syndrome and that no serious adverse events were experienced. These data provide support for the safety of oral propranolol in this patient population.

Screening electrocardiography (ECG) before initiation of propranolol for treatment of infantile hemangiomas (IH) is controversial. A retrospective chart review was conducted to assess the utility of pretreatment ECG in infants with IH starting propranolol. Although nearly half of the ECGs were abnormal, no contraindications to treatment were identified from screening ECG, and no association was found between any of the reported side effects and abnormal ECG. These results support previously published data, and in a larger cohort, providing further confirmation that pretreatment ECG is not necessary in most infants with IH., (© 2018 Wiley Periodicals, Inc.)

Background: Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited., Methods: We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs., Results: Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol., Conclusions: This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by Pierre Fabre Dermatologie; ClinicalTrials.gov number, NCT01056341.).

The objective of this retrospective study of patients evaluated between July 2008 and October 2011 in seven pediatric dermatology centers was to combine collective clinical experience using oral propranolol therapy in 32 infants with PHACE syndrome (Posterior fossa [brain malformations present at birth], Hemangioma [usually covering a large area of the skin of the head or neck >5 cm]; Arterial lesions [abnormalities of the blood vessels in the neck or head]; Cardiac abnormalities or aortic coarctation [abnormalities of the heart or blood vessels that are attached to the heart]; Eye abnormalities) with cervical or intracranial arterial anomalies. Patients were given an average daily dose of oral propranolol of 1.8 mg/kg divided two or three times per day for an average duration of 12.3 months. The main outcome measure was adverse neurologic events. Seven (22%) patients were categorized as being at higher risk for stroke, defined on magnetic resonance imaging as severe, long-segment narrowing or nonvisualization of major cerebral or cervical vessels without anatomic evidence of collateral circulation, often in the presence of concomitant cardiovascular comorbidities. Only one patient developed a change in neurologic status during propranolol treatment: mild right hemiparesis that remained static and improved while propranolol was continued. An additional three patients had worsening hemangioma ulceration or tissue necrosis during therapy. This is the largest report thus far of patients with PHACE syndrome treated with propranolol. Although no catastrophic neurologic events occurred, serious complications, particularly severe ulcerations, were seen in a minority of patients, and given the sample size, we cannot exclude the possibility that propranolol could augment the risk of stroke in this population. We propose radiologic criteria that may prove useful in defining PHACE patients as being at high or standard risk for stroke. We continue to advise caution in using systemic beta-blockers, particularly for children with vascular anomalies at higher risk for stroke. Use of the lowest possible dosage, slow dosage titration, three times per day dosing to minimize abrupt changes in blood pressure, and close follow-up, including neurologic consultation as needed, are recommended., (© 2012 Wiley Periodicals, Inc.)

Infantile hemangiomas (IH) are benign tumors of endothelial-like cells. Occurring in 4.5% of children, they are the most common tumor of childhood. The great majority of patients with IH will not need treatment, but 10% require systemic treatment. Many treatments have been described for the treatment of IH, but the Food and Drug Administration has not approved any. Over the last decade, numerous reports of successful treatment of IH with propranolol have been published. Despite its widespread use, little is known regarding the proper dosing, safety monitoring, and during of treatment or long-term outcomes for propranolol treatment of IH. Given its potential side effects, detailed education regarding proper administration of the medication as well as warning signs to watch for is necessary for parents and caretakers. Herein, we provide a parental handout that practitioners can individually tailor for use in their clinics when educating parents and caretakers about the use of propranolol for IH. Updates will also need to be made as more is learned regarding the optimal dosing and safety monitoring when using propranolol for this indication., (© 2013 Wiley Periodicals, Inc.)

Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in nature and anticipate that they will be revised as more data are made available.

Propranolol is a non-selective beta-adrenergic antagonist successfully used in a case of kaposiform hemangioendothelioma (KHE) associated with Kasabach-Merritt phenomenon (KMP). We report 11 patients treated with propranolol for KHE and the related variant tufted angioma (TA), six of whom also had KMP. The varied responses to treatment, with only 36% responding in our series, demonstrate the need for further study of this medication before routine use for these indications., (Copyright © 2012 Wiley Periodicals, Inc.)

Pharmacological therapies for infantile hemangiomas were considered effective only during the proliferative phases. Recently reported beneficial effects of propranolol may extend beyond the proliferative phase of infantile hemangiomas. The purpose of the study was to assess the effect of oral propranolol therapy for infantile hemangiomas beyond the proliferative phase of these lesions. Members of the Society for Pediatric Dermatology were invited to participate in a multicenter retrospective study. Only children with infantile hemangiomas with documented cessation of lesions' growth or those older than 12 months of age were eligible for the study. Clinical and demographic information and digital photographs before, at the start, and following the treatment were collected. Scaled panels of photographs were distributed among preselected experienced pediatric dermatologists. Visual analog scale was used to assess photographs for each case. Paired t-test was used for statistical analyses. Data on 49 eligible patients from eight pediatric dermatology centers was collected. Seven cases were excluded because of insufficient photographic documentation. The age of the patients at the start of propranolol therapy ranged 7 to 120 months (mean 28 mos, median 22 mos). The duration of propranolol therapy ranged 1 to 8 months (mean 3.6 mos). The mean visual analog scale score before the treatment was 6.8 ± 2.15, and mean reduction in the visual analog scale score at the assessment was 2.6 ± 1.74 (p < 0.001). The rate of visual analog scale reduction was 0.4 per month before the start of the therapy, while this rate was accelerated to 0.9 per months following the therapy (p < 0.001). No significant side effects were reported. We conclude that propranolol is effective in infantile hemangiomas, including post-proliferative phase, and should be considered as the first-line therapy in that setting., (© 2011 Wiley Periodicals, Inc.)

Hepatic infantile hemangiomas may be associated with morbidity and mortality, and traditional therapies may be associated with significant side effects. Since propranolol has been recently used successfully to treat cutaneous infantile hemangiomas, we decided to use it in three patients who presented with hepatic and skin hemangiomatosis. Three patients with skin and hepatic infantile hemangiomas, two of whom had evidence of cardiovascular compromise and one of whom had extensive liver involvement and hypothyroidism, were treated with oral propranolol. Regression of both skin and hepatic hemangiomas was noted in all patients, as was resolution of the cardiac symptoms and decreased thyroid requirement in two patients each. Propranolol was well tolerated without any adverse effects. Propranolol should be considered as a potential first-line therapy in patients with symptomatic hepatic hemangiomatosis., (© 2011 Wiley Periodicals, Inc.)

Background: Propranolol hydrochloride has been prescribed for decades in the pediatric population for a variety of disorders, but its effectiveness in the treatment of infantile hemangiomas (IHs) was only recently discovered. Since then, the use of propranolol for IHs has exploded because it is viewed as a safer alternative to traditional therapy., Observations: We report the cases of 3 patients who developed symptomatic hypoglycemia during treatment with propranolol for their IHs and review the literature to identify other reports of propranolol-associated hypoglycemia in children to highlight this rare adverse effect., Conclusions: Although propranolol has a long history of safe and effective use in infants and children, understanding and recognition of deleterious adverse effects is critical for physicians and caregivers. This is especially important when new medical indications evolve as physicians who may not be as familiar with propranolol and its adverse effects begin to recommend it as therapy.

Background/Objectives: Infantile hemangiomas (IHs) are common benign vascular tumors of infancy. IHs tend to grow in the first few months of life and then gradually involute over years, often leaving fibrofatty residua or textural changes in their place. Classically, these lesions are painless throughout their entire natural history; however, we now report on seven patients with involuted IH with intermittent but persistent sensory symptoms. Methods: This is a multicenter case series in which members of the Birthmarks Focused Study Group of the Pediatric Dermatology Research Alliance (PeDRA) and the Hemangioma Investigator Group contributed patients with IH and dysesthesias from their clinical practices. Charts were then reviewed to document clinical details. Results: Seven patients were included, presenting at an average age of 14.6 years (range 3‐48 years) for complaints related to discomfort in the region of involuted IH. The majority (6/7) reported pain or tenderness to the area. One patient reported pruritus. All patients reported intermittent symptoms. The length of symptoms ranged between 4 months and 5 years. Treatment was attempted in 5/7 patients. Ice, oral propranolol, topical capsaicin, and intralesional triamcinolone partially improved symptoms. Conclusions: Persistent cutaneous dysesthesias were present in seven patients, in most cases many years after completion of involution. Further research is needed to fully elucidate the pathophysiology and optimal treatments for this IH complication. [ABSTRACT FROM AUTHOR]

The author discusses infantile hemangioma (IH), defined as the most common tumor of childhood, and details the needed therapy to prevent IH from having major or life-threatening consequences. He references the article "Rebound growth of infantile hemangiomas after propranolol therapy" by S. D. Shah and colleagues which appeared within the issue, in which they report about their findings of a study assessing the incidence of rebound growth, IH characteristics, and treatment factors.

The article offers a summary of the guidance presented in the clinical report "Diagnosis and Management of Infantile Hemangioma (IH)" published in the online version of the journal "Pediatrics" in 2015. Topics covered include congenital hemangiomas, pyogenic granuloma or lobular capillary hemangioma, the epidemiology of IH, its pathogenesis and histopathology, its clinical presentation, and its complications. Also discussed are the management of ulcerated IH and medical therapy for IH.