Propranolol found to rapidly shrink severe hemangiomas

Skin & Allergy News,  Sept, 2008  by Sharon Worcester

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DESTIN, FLA. -- Propranolol appears to have impressive beneficial effects on severe hemangiomas of infancy, according to a letter in the New England Journal of Medicine.

"Keep your eyes out for more information on this interesting work," Dr. Bari Cunningham said at a meeting sponsored by the Alabama Dermatology Society.

According to the letter written by Dr. Christine Leaute-Labreze of Bordeaux (France) Children's Hospital and her colleagues, two infants with severe complicated hemangiomas who were treated with corticosteroids for the hemangiomas also were treated with propranolol--a nonselective [beta]-blocker--for other medical indications. Both experienced rapid improvements in the problematic hemangiomas (N. Engl. J. Med. 2008;358:2649-51).

The first child had a nasal capillary hemangioma that stabilized on corticosteroids. The child was treated with propranolol when obstructive hypertrophic myocardiopathy developed. Within 1 day of propranolol administration, the hemangioma changed in color from intense red to purple and the lesion softened. The improvements continued even after corticosteroids were discontinued; no regrowth was noted. The hemangioma was flat when the child was 14 months of age, the physicians noted.

The second child had a plaque-like capillary hemangioma of the entire right upper arm and part of the face that occluded the right eye. The hemangioma continued to enlarge when the child was 1 month old after a subcutaneous component developed. MRI revealed intraconal and extraconal orbital involvement and an intracervical mass causing compression and tracheal and esophageal deviation.

Propranolol at 2 mg/kg per day was initiated because of increased cardiac output, and 7 days later the child was able to open his eye; the mass near the parotid gland had reduced considerably. No regrowth was noted after prednisolone treatment was discontinued at 4 months. When the child was 9 months old, the hemangioma was dramatically reduced. He had no visual impairment.

The findings prompted a pilot study in which nine additional infants with severe hemangiomas were treated with propranolol only.

"In all patients, 24 hours after the initiation of treatment, we observed a change in the hemangioma from intense red to purple; this change was associated with palpable softening of the lesion," the researchers wrote.

Improvements continued until the lesions were nearly flat, and ultrasound in five infants demonstrated regression in thickness and a resulting increase in the resistive index of hemangioma vascularization.

The investigators offered three hypotheses for the effects of propranolol: vasoconstriction (and thus the quick change in color and hardness of the lesions); decreased expression of vascular endothelial growth factor and basic fibroblast growth factor (major proangiogerlic factors involved with hemangioma growth) occurring via down-regulation of the RAF / mitogen-activated protein kinase pathway, which would explain the progressive improvement seen; and the triggering of apoptosis of capillary endothelial cells.

It is apparent why the findings in the first two infants piqued the interest of these investigators, Dr. Cunningham said. She added that she would need more information--particularly whether the effects of the propranolol in the nine infants in the pilot study were as dramatic as those in the first two infants (the correspondence only included photos of the first two) and about the effects on all of the infants' blood pressure--before she would consider using propranolol for the treatment of severe hemangiomas of infancy.

BY SHARON WORCESTER

Southeast Bureau

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