Correspondence
Propranolol for Severe Hemangiomas of Infancy
N Engl J Med 2008; 358:2649-2651June 12, 2008
- Article
To the Editor:
Despite their self-limited course, infantile capillary hemangiomas can impair vital or sensory functions or cause disfigurement. Corticosteroids are the first line of treatment for problematic infantile capillary hemangiomas1,2; other options include interferon alfa3 and vincristine.1 We have observed that propranolol can inhibit the growth of these hemangiomas. Our preliminary data from 11 children are summarized in Table 1 in the Supplementary Appendix, available with the full text of this letter at www.nejm.org.
The first child had a nasal capillary hemangioma. Despite corticosteroid treatment, the lesion was stabilized but obstructive hypertrophic myocardiopathy developed, so the patient was treated with propranolol. The day after the initiation of treatment, the hemangioma changed from intense red to purple, and it softened. The corticosteroids were tapered, but the hemangioma continued to improve. When the corticosteroids were discontinued, no regrowth of the hemangioma was noted. When the child was 14 months of age, the hemangioma was completely flat.
The second child had a plaque-like infantile capillary hemangioma involving the entire right upper limb and part of the face (Figure 1Figure 1
Photographs of Patient 2 before and after Treatment with Propranolol.). At 1 month of age, a subcutaneous component developed, and despite corticosteroid treatment, the hemangioma continued to enlarge. Magnetic resonance imaging revealed intraconal and extraconal orbital involvement, as well as an intracervical mass causing compression and tracheal and esophageal deviation (see the Supplementary Appendix). Ultrasonography showed increased cardiac output, and treatment with propranolol, at a dose of 2 mg per kilogram of body weight per day, was initiated. Seven days later, the child was able to open his eye spontaneously, and the mass near the parotid gland was considerably reduced in size. Prednisolone was discontinued at 4 months of age, without any regrowth of the hemangioma; at 9 months of age, the eye opening was satisfactory, and no major visual impairment was noted.After written informed consent had been obtained from the parents, propranolol was given to nine additional children who had severe or disfiguring infantile capillary hemangiomas (see Table 1 in the Supplementary Appendix). 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 a palpable softening of the lesion. After these initial changes, the hemangiomas continued to improve until they were nearly flat, with residual skin telangiectasias. Ultrasound examinations in five patients showed an objective regression in thickness associated with an increase in the resistive index of vascularization of the hemangioma (Table 1 in the Supplementary Appendix).
Infantile capillary hemangiomas are composed of a complex mixture of clonal endothelial cells associated with pericytes, dendritic cells, and mast cells.1 Regulators of hemangioma growth and involution are poorly understood. During the growth phase, two major proangiogenic factors are involved: basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF)1; histologic studies have shown that both endothelial and interstitial cells are actively dividing in this phase. During the involution phase, apoptosis has been shown.1 Potential explanations for the therapeutic effect of propranolol — a nonselective beta-blocker — on infantile capillary hemangiomas include vasoconstriction, which is immediately visible as a change in color, associated with a palpable softening of the hemangioma; decreased expression of VEGF and bFGF genes through the down-regulation of the RAF–mitogen-activated protein kinase pathway4 (which explains the progressive improvement of the hemangioma); and the triggering of apoptosis of capillary endothelial cells.5
Christine Léauté-Labrèze, M.D.
Eric Dumas de la Roque, M.D.
Thomas Hubiche, M.D.
Franck Boralevi, M.D., Ph.D.
Bordeaux Children's Hospital, 33 076 Bordeaux, France
christine.labreze@chu-bordeaux. fr Jean-Benoît Thambo, M.D.
Haut-Lévêque Heart Hospital, 33 600 Pessac, FranceAlain Taïeb, M.D.
Bordeaux Children's Hospital, 33 076 Bordeaux, FranceThe authors report applying for a patent for the use of beta-blockers in infantile capillary hemangiomas. No other potential conflict of interest relevant to this letter was reported.
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