Interview with Christine Léauté-Labrèze, MD

Christine Léauté-Labrèze, MD

Christine Léauté-Labrèze, MD, presented the Eugene J. Van Scott Award for Innovative Therapy of the Skin and Phillip Frost Leadership Lecture at the Sunday Plenary. She is a pediatric dermatologist at Universitaire de Bordeaux, Bordeaux, France.

Q: How did you discover that propranolol was an effective treatment for infantile hemangiomas?
A: We observed the therapeutic effect of propranolol in an infant treated with oral corticosteroids for an infantile hemangioma (IH). The child was administered propranolol at the age of 4 months for hypertrophic myocardiopathy caused by corticosteroids. Almost immediately, we observed a change in the color of the IH and saw that it had started to subside. We thought it was just a coincidence, but, three months later, we treated an infant with a highly dangerous facial IH, as it had closed off the eye completely and caused the airways to become deviated. In this infant, oral corticosteroids were ineffective after a month with high doses of treatment, and he had also started suffering from myocardial problems with tachycardia. The following day, after being administered propranolol, the IH had softened when palpated. A week later, even though we had reduced the prednisone, the child could open his eye spontaneously, and the cervical mass had considerably reduced in size. The corticoids were stopped at the age of 4 months without a relapse. At the age of 6 months, all that was left of the IH were residual telangiectasia, and we were able to stop the propranolol treatment at the age of 9 months. It was then that we actually realized that this treatment was effective.

Q: How does propranolol work in reducing hemangiomas, and are the results permanent?
A: The exact mechanism of action of propranolol on infantile hemangiomas remains unknown, mainly because the pathophysiology of hemangiomas is still unclear. We hypothesize that propranolol is able to stop the proliferation of immature endothelial cells that make up the major part of infantile hemangioma by blocking the production of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF). The treatment should be given for a minimum duration of six months to obtain a permanent result.

Q: Could you explain the treatment protocol?
A: After eliminating contraindications, mainly cardiologic abnormalities (i.e., sinus bradycardia and partial auriculoventricular block) or active bronchiolitis, oral propranolol is given at progressive dosage from 1 mg/kg/d until 2-3 mg/kg/d, under close medical supervision. To avoid severe side effects, parents should be educated on the necessity to stop propranolol in case of poor food intake — risk of hypoglycemia — and in case of wheezing. The effective propranolol dosage is maintained for six months. Relapses are possible in 10 to 15 percent of cases, and propranolol should be re-given for three or six months more, especially in infants with large or deep hemangiomas.

Q: What is the best age for the treatment of infantile hemangiomas, and are there concerns about side effects in these infants?
A: The earliest is the best. An early treatment prevents sequelae, such as permanent anatomic distortion. Propranolol is indicated before 5 months of age, and the best results are observed in infants treated before 3 months of age. In this age group, severe side effects are bradycardia, mainly in low birth weight babies; hypoglycemia, which can occur at any age in case of fasting; and bronchospasms during pulmonary infection, which are quite frequent in this age group.

Q: Do you consider this the best treatment for infantile hemangiomas, or does it need more study?
A: In 2017, propranolol is probably the best medical treatment for complicated infantile hemangiomas. Good quality clinical studies have demonstrated that propranolol is very efficient and well tolerated, compared with corticosteroids or vincristine, and fewer side effects are observed. In the close future, more data concerning long-term safety will be available. Studies are also ongoing with longer durations of treatment to avoid the problem of relapses.

Q: Are there any other options that could be better treatments for hemangiomas?
A: Other options are, of course, possible, but the best treatment is the treatment that is the most appropriate for the child and his or her family. Concerning other oral beta blockers, such as atenolol or nadolol, we have no proof of their superiority concerning efficacy, and safety data are scarce. Topical beta blockers are popular, but their use is off-label. In addition, systemic side effects have been recently reported with timolol use in low birth weight infants, and they should be applied with caution. Lasers are not recommended in the early phase of hemangiomas, but surgery is a good option when possible, especially in well-circumscribed localized hemangiomas. Ideally, the best treatment would be to prevent the occurrence of infantile hemangiomas; this is our challenge for the future.

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