To the Editor: Despite their self-limited course, infantilecapillary hemangiomas can impair vital or sensory functionsor cause disfigurement. Corticosteroids are the first line oftreatment for problematic infantile capillary hemangiomas1,2;other options include interferon alfa3 and vincristine.1 Wehave observed that propranolol can inhibit the growth of thesehemangiomas. Our preliminary data from 11 children are summarizedin Table 1 in the Supplementary Appendix, available with thefull text of this letter at www.nejm.org.
The first child had a nasal capillary hemangioma. Despite corticosteroidtreatment, the lesion was stabilized but obstructive hypertrophicmyocardiopathy developed, so the patient was treated with propranolol.The day after the initiation of treatment, the hemangioma changedfrom intense red to purple, and it softened. The corticosteroidswere tapered, but the hemangioma continued to improve. Whenthe corticosteroids were discontinued, no regrowth of the hemangiomawas noted. When the child was 14 months of age, the hemangiomawas completely flat.
The second child had a plaque-like infantile capillary hemangiomainvolving the entire right upper limb and part of the face (Figure 1).At 1 month of age, a subcutaneous component developed, and despitecorticosteroid treatment, the hemangioma continued to enlarge.Magnetic resonance imaging revealed intraconal and extraconalorbital involvement, as well as an intracervical mass causingcompression and tracheal and esophageal deviation (see the Supplementary Appendix).Ultrasonography showed increased cardiac output, and treatmentwith propranolol, at a dose of 2 mg per kilogram of body weightper day, was initiated. Seven days later, the child was ableto open his eye spontaneously, and the mass near the parotidgland was considerably reduced in size. Prednisolone was discontinuedat 4 months of age, without any regrowth of the hemangioma;at 9 months of age, the eye opening was satisfactory, and nomajor visual impairment was noted.
Figure 1. Photographs of Patient 2 before and after Treatment with Propranolol.
Panel A shows the patient at 9 weeks of age, before treatment with propranolol, after 4 weeks of receiving systemic corticosteroids (at a dose of 3 mg per kilogram of body weight per day for 2 weeks and at a dose of 5 mg per kilogram per day for 2 weeks). Panel B shows the patient at 10 weeks of age, 7 days after the initiation of propranolol treatment at a dose of 2 mg per kilogram per day while prednisolone treatment was tapered to 3 mg per kilogram per day. Spontaneous opening of the eye was possible because of a reduction in the size of the subcutaneous component of the hemangioma. Panel C shows the patient at 6 months of age, while he was still receiving 2 mg of propranolol per kilogram per day. Systemic corticosteroids had been discontinued at 2 months of age. No subcutaneous component of the hemangioma was noted, and the cutaneous component had considerably faded. The child had no visual impairment. Panel D shows the child at 9 months of age. The hemangioma had continued to improve, and the propranolol treatment was discontinued.
After written informed consent had been obtained from the parents,propranolol was given to nine additional children who had severeor disfiguring infantile capillary hemangiomas (see Table 1in the Supplementary Appendix). In all patients, 24 hours afterthe initiation of treatment, we observed a change in the hemangiomafrom intense red to purple; this change was associated witha palpable softening of the lesion. After these initial changes,the hemangiomas continued to improve until they were nearlyflat, with residual skin telangiectasias. Ultrasound examinationsin five patients showed an objective regression in thicknessassociated with an increase in the resistive index of vascularizationof the hemangioma (Table 1 in the Supplementary Appendix).
Infantile capillary hemangiomas are composed of a complex mixtureof clonal endothelial cells associated with pericytes, dendriticcells, and mast cells.1 Regulators of hemangioma growth andinvolution are poorly understood. During the growth phase, twomajor proangiogenic factors are involved: basic fibroblast growthfactor (bFGF) and vascular endothelial growth factor (VEGF)1;histologic studies have shown that both endothelial and interstitialcells are actively dividing in this phase. During the involutionphase, apoptosis has been shown.1 Potential explanations forthe therapeutic effect of propranolol — a nonselectivebeta-blocker — on infantile capillary hemangiomas includevasoconstriction, which is immediately visible as a change incolor, associated with a palpable softening of the hemangioma;decreased expression of VEGF and bFGF genes through the down-regulationof the RAF–mitogen-activated protein kinase pathway4 (whichexplains the progressive improvement of the hemangioma); andthe triggering of apoptosis of capillary endothelial cells.5
Christine Léauté-Labrèze, M.D. Eric Dumasde la Roque, M.D. Thomas Hubiche, M.D. Franck Boralevi, M.D.,Ph.D. Bordeaux Children's Hospital 33 076 Bordeaux, France christine.labreze{at}chu-bordeaux.fr
Jean-Benoît Thambo, M.D. Haut-Lévêque HeartHospital 33 600 Pessac, France
Alain Taïeb, M.D. Bordeaux Children's Hospital 33 076 Bordeaux, France
The authors report applying for a patent for the use of beta-blockersin infantile capillary hemangiomas. No other potential conflictof interest relevant to this letter was reported.
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