The beta-blocker propranolol appears almost 100% effective in treating severe infantile hemangiomas, according to a French case series of 32 patients.
The group, led by Dr. Véronique Sans of Children's Hospital in Bordeaux, France, found that even life-threatening hemangiomas responded dramatically to propranolol treatment, with overnight color change and lesion softening after the first dose (23 mg/kg per day).
"Symptoms such as dyspnea and hemodynamic compromise [due to the lesions] regressed within 48 hours, and spontaneous ocular opening [in children with periorbital lesions] was possible within 7 days," wrote Dr. Sans and her colleagues (DOI:10.1542/peds.2008-3458
The observations in the paper are a fairly accurate representation of propranolol's remarkable effect on these lesions, Dr. Bernard Cohen said in an interview. Last July, after Dr. Sans' colleagues made an initial public report of their experience, Dr. Cohen began using propanolol as the first-line treatment for serious infantile hemangiomas in the pediatric vascular lesions clinic at Johns Hopkins Medical Center in Baltimore.
"I haven't used steroids in any of these children since then," said Dr. Cohen, director of pediatric dermatology at the center. He and his colleagues have so far treated 41 children with propanolol and will soon publish their own experience. Although they have not had quite the 100% success rate that the French group claims, Dr. Cohen said the drug is very effective, extremely safe, and can be given without the concerns for growth and immune response that come with steroid therapy.
"I think it works better than oral steroids, but it doesn't work for everyone," he said, adding that lesions on infants responded better to the treatment than lesions on children who were older than 1 year. "If lesions are causing a lot of [functional problems], propranolol does seem to shut them down, but it did not make a dramatic difference in every one of our patients. However, it is very safeespecially compared to oral steroids."
The French team observed serendipitously that beta-blockers used for hypertension in infants positively affected the growth of hemangiomas. In 2008, following that observation, they described their index case and 10 additional cases (N. Engl. J. Med. 2008: 358:264951).
The current report comprises 32 children (mean age 4 months) with severe hemangiomas. All of the lesions imposed either life-threatening symptoms or the risk of severe disfigurement.
Treatment consisted of a course of oral propranolol at a dose of 23 mg/kg per day, initiated in an inpatient setting so that clinicians could observe the child's reaction. Blood pressure and heart rate were monitored every hour during the first 6 hours of treatment. If no adverse events occurred, the child was sent home and re-evaluated after another 10 days, with monthly evaluations afterward, Dr. Sans and her associates said.
Most of the treatments (27) were early interventions on children aged 112 months. For these children, the goal was to decrease functional risk, serious symptoms, or cosmetic complications. The other five children were 1848 months old; their treatment goal was functional risk or cosmetic risk. Thirteen of the children had received corticosteroids with no benefit.
Children who had ulcerated hemangiomas experienced complete healing within 2 months of therapy initiation. In the 11 children with ultrasound measurements, the 60-day exam showed a mean lesion thickness regression of 40%, with a lower resistivity index, indicating decreased vascular activity.
The 13 children who were taking steroids all discontinued treatment without rebound. Propranolol was discontinued in 614 months for the early-intervention cases and in 210 months for the later-intervention cases. It was restarted in two cases because of regrowth. The 12 patients with eyelid involvement experienced resolution of astigmatism and amblyopia at the end of therapy, the investigators reported.
Dr. Sans and her associates noted two adverse events. One patient had a decrease in blood pressure while sleeping, 3 hours after the first dose. Another patient discontinued propranolol after experiencing wheezing thought to be caused by allergic asthma.
The authors suggested that the optimal therapy for early intervention would be to give propranolol throughout the hemangioma's proliferative phase, usually from 4 to 12 months of age. For treatments commenced after the proliferative phase has concluded, the therapy should continue until maximum improvement is noted.
The overnight improvements of lesion softening and color change (from intense red to purple) indicated the drug's vasoconstrictive effect on the lesions' capillaries, Dr. Christine Léauté-Labrèze, also of Children's Hospital, said in the initial 2008 report.
Although Dr. Sans and her coauthors said they had no financial conflicts with regard to their paper, Dr. Léauté-Labrèze noted in the 2008 paper that she and her colleagues had applied for a patent for the use of propranolol on infantile hemangiomas. Dr. Léauté-Labrèze and her coauthorsDr. Franck Boralevi, Dr. Eric Dumas de la Roque, and Dr. Alain Taïebwho are with Children's Hospital, are also coauthors of Dr. Sans' paper.