Oral propranolol shown safe in PHACE



This story appears courtesy of MDedge News



LAHAINA, HAWAII – Reassuring evidence of the safety of oral propranolol for treatment of complicated infantile hemangiomas in patients with PHACE syndrome comes from a recent multicenter study.
Dr. Moise L. Levy, professor of dermatology and pediatrics at Dell Medical School, Austin, Tex., and physician-in-chief at Dell Children's Medical Center

Oral propranolol is now well-ensconced as first-line therapy for complicated infantile hemangiomas in otherwise healthy children. However, the beta-blocker’s use in PHACE (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects, and Eye abnormalities) syndrome has been controversial, with concerns raised by some that it might raise the risk for arterial ischemic stroke. Not so, Moise L. Levy, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“I’m not suggesting you use propranolol with reckless abandon in this population, but this stroke concern is something that should be put to bed based on this study,” advised Dr. Levy, professor of dermatology and pediatrics at Dell Medical School in Austin, Tex., and physician-in-chief at Dell Children’s Medical Center.

PHACE syndrome is characterized by large, thick, plaque-like hemangiomas greater than 5 cm in size, most commonly on the face, although they can be located elsewhere.

“There was concern that if you found severely altered cerebrovascular arterial flow and you put a kid on a beta-blocker you might be causing some harm. But what I will tell you is that in this recently published paper this was not in fact an issue,” he said.

Dr. Levy was not an investigator in the multicenter retrospective study, which included 76 patients with PHACE syndrome treated for infantile hemangioma with oral propranolol at 0.3 mg/kg per dose or more at 11 academic tertiary care pediatric dermatology clinics. Treatment started at a median age of 56 days.

There were no strokes, TIAs, cardiovascular events, or other significant problems associated with treatment. Twenty-nine children experienced mild adverse events: minor gastrointestinal or respiratory symptoms, and sleep disturbances were threefold more frequent than reported with placebo in another study. The investigators noted that the safety experience in their PHACE syndrome population compared favorably with that in 726 infants without PHACE syndrome who received oral propranolol for hemangiomas, where the incidence of serious adverse events on treatment was 0.4% (JAMA Dermatol. 2019 Dec 11. doi: 10.1001/jamadermatol.2019.3839).

‘Hemangiomas – but we were taught that they go away’

Dr. Levy gave a shout-out to the American Academy of Pediatrics for publishing interdisciplinary expert consensus-based practice guidelines for the management of infantile hemangiomas, which he praised as “quite well done” (Pediatrics. 2019 Jan;143[1]. pii: e20183475. doi: 10.1542/peds.2018-3475).

Following release of the guidelines last year, he and other pediatric vascular anomalies experts saw an uptick in referrals from general pediatricians, which has since tapered off.

“It’s probably like for all of us: We read an article, it’s fresh on the mind, then you forget about the article and what you’ve read. So we need a little reinforcement from a learning perspective. This is a great article,” he said.

The guidelines debunk as myth the classic teaching that infantile hemangiomas go away. Explicit information is provided about the high-risk anatomic sites warranting consideration for early referral, including the periocular, lumbosacral, and perineal areas, the lip, and lower face.

“The major point is early identification of those lesions requiring evaluation and intervention. Hemangiomas generally speaking are at their ultimate size by 3-5 months of age. The bottom line is if you think something needs to be done, please send that patient, or act upon that patient, sooner rather than later. I can’t tell you how many cases of hemangiomas I’ve seen when the kid is 18 months of age, 3 years of age, 5 years, with a large area of redundant skin, scarring, or something of that sort, and it would have been really nice to have seen them earlier and acted upon them then,” the pediatric dermatologist said.

The guidelines recommend intervention or referral by 1 month of age, ideally. Guidance is provided about the use of oral propranolol as first-line therapy.

“Propranolol is something that has been a real game changer for us,” he noted. “Many people continue to be worried about side effects in using this, particularly in the young childhood population, but this paper shows pretty clearly that hypotension or bradycardia is not a real concern. I never hospitalize these patients for propranolol therapy except in high-risk populations: very preemie, any history of breathing problems. We check the blood pressure and heart rate at baseline, again at 7-10 days, and at every visit. We’ve never found any significant drop in blood pressure.”

Dr. Levy reported financial relationships with half a dozen pharmaceutical companies, none relevant to his presentation.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

By Bruce Jancin
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