Evaluating the Safety of Oral Propranolol Therapy in Patients With PHACE Syndrome

Abstract

IMPORTANCEOral 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 PARTICIPANTSThis 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 MEASURESThe 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.

Airway Hemangiomas in PHACE Syndrome: A Multicenter Experience

“…Numerous studies have shown that large, thick hemangiomas, such as those seen in PHACE, are at overall higher risk for ulceration. 12 Propranolol is known to inhibit vasculogenesis, and ulceration occurs when the blood supply to the epidermal surface of the hemangioma is compromised. Preliminary data from the May 2020 international meeting of the Internal Society for the Study of Vascular Anomalies presented by Faith and colleagues 13 suggests that a lower dose propranolol and a slower up-titration reduce the risk of ulceration.…”

Alpha and beta adrenergic receptors modulate keratinocyte migration

“…BAR antagonists (beta blockers) are increasingly used topically to treat skin diseases. The non-specific antagonists for beta AR such as propranolol and timolol, are widely used for treating infantile hemangiomas [36][37][38][39]. Topical application of timolol is used to treat a host of dermatologic diseases [40,41], including epidermolysis bullosa [42], Kaposi sarcoma [43,44], acne and acne rosacea [45], and improving scar outcomes [46].…”

Cranio-facial-cervical and subglottic hemangioma with respiratory symptoms. A therapeutic emergency

“…Clásicamente se ha cuestionado la seguridad del propranolol en estos pacientes ya que el uso de β-bloqueantes en el contexto de la vasculopatía cerebral podría, teóricamente, aumentar el riesgo de un episodio isquémico cerebral. Sin embargo, recientemente Olsen y col publicaron un estudio multicéntrico retrospectivo con 76 pacientes con síndrome de PHACE tratados con propranolol vía oral sin encontrar diferencias significativas en la tasa de eventos adversos severos (ictus, accidentes cardiovasculares e isquémicos transitorios) respecto a aquellos que solo tenían la lesión vascular cutánea (0% vs 0,4%, respectivamente) 16 .…”