GOTHENBURG, SWEDEN - Oral propranolol proved superior to oral prednisone for treatment of complicated infantile hemangiomas in a retrospective, blinded, matched-pairs comparative study.
"We believe that propranolol should be a first-line therapy for problematic infantile hemangiomas. It brought a more rapid and impressive degree of improvement. And although there were no serious adverse events in either treatment group, the overall safety profile of propranolol was superior," Dr. Janie Bertrand said at the annual congress of the European Academy of Dermatology and Venereology.
She added a caveat, however: This was a small retrospective study. Definitive conclusions regarding propranolol’s place in the treatment of problematic infantile hemangiomas must await the outcome of a large ongoing, international, prospective, randomized clinical trial, said Dr. Bertrand, a dermatology resident at the University of Montreal.
In the interim, the blinded, matched-pairs study moves the field beyond the realm of anecdotal experience. The study involved 12 pairs of infants treated for complicated infantile hemangiomas on the eyelid, cheek, forehead, nose, parotid gland, and/or lip at an academic pediatric tertiary medical center. The infant pairs were matched for age, as well as the location, size, and type of hemangioma. Twelve infants were treated with a mean propranolol dose of 2.7 mg/kg per day starting at a mean age of 3.6 months. The other 12 received oral prednisone at a mean dose of 2.8 mg/kg per day starting at age 3.2 months.
Two blinded evaluators assessed the degree of clinical improvement based on medical photographs taken 1, 2, and 6 months after the start of treatment. They also rated the degree of improvement at 6 months using a 100-mm visual analog scale.
After 1 month, 4 of 12 children on propranolol were rated as showing moderate improvement, meaning a 25%-50% improvement over baseline, while the other 8 showed good improvement, with a 50%-75% gain. In contrast, just one child in the prednisone group showed moderate improvement, seven showed a slight improvement of less than 25%, three were unchanged from baseline, and one was worse.
Results were also significantly better in the propranolol group at 2 and 6 months. After 6 months on propranolol all patients showed good to excellent improvement, whereas the prednisone group showed slight to moderate improvement.
Using the visual analog scale, the evaluators rated the propranolol group as showing a mean 78.7% improvement, compared with baseline, while the prednisone group had a mean 44.8% improvement, Dr. Bertrand said.
The mean treatment duration was 12.7 months in the prednisone arm and 10.6 months with propranolol.
Adverse events in the propranolol group consisted of sleep disturbance in six patients, transient asymptomatic hypotension in one, and vomiting in one. Two patients in the prednisone group experienced oral thrush, one had hypertension, one had growth failure, two displayed irritability, and one developed insomnia.
Clinical improvement was apparent after just a few days on propranolol, probably because of the beta-blocker’s vasoconstrictive effect. Likely mechanisms of clinical benefit include stimulation of apoptosis, downregulation of angiogenic factors, and reduction of skin levels of inflammation-promoting matrix metalloproteinase-9, according to Dr. Bertrand.
Until the results of the ongoing international, randomized trial are in, a baseline cardiac evaluation should be considered mandatory when oral propranolol is being considered for treatment of an infantile hemangioma. The drug should be used with caution in patients at risk for hypoglycemia, as well in those with bronchospastic disease or PHACE syndrome with cerebrovascular anomalies. A prospective study of topical beta-blocker therapy as a means of reducing the risk of systemic side effects is warranted, she added.
Dr. Bertrand declared having no relevant financial interests. The study was conducted with university funding.