OBJECTIVE: Infantile hemangiomas (IHs) are the most-common soft-tissue tumors of infancy. We report the use of propranolol to control the growth phase of IHs.
METHODS: Propranolol was given to 32 children (21 girls; mean age at onset of treatment: 4.2 months) after clinical and ultrasound evaluations. After electrocardiographic and echocardiographic evaluations, propranolol was administered with a starting dose of 2 to 3 mg/kg per day, given in 2 or 3 divided doses. Blood pressure and heart rate were monitored during the first 6 hours of treatment. In the absence of side effects, treatment was continued at home and the child was reevaluated after 10 days of treatment and then every month. Ultrasound measurements were performed after 60 days of treatment.
RESULTS: Immediate effects on color and growth were noted in all cases and were especially dramatic in cases of dyspnea, hemodynamic compromise, or palpebral occlusion. In ulcerated IHs, complete healing occurred in <2 months. Objective clinical and ultrasound evidence of longer-term regression was seen in 2 months. Systemic corticosteroid treatment could be stopped within a few weeks. Treatment was administered for a mean total duration of 6.1 months. Relapses were mild and responded to retreatment. Side effects were limited and mild. One patient discontinued treatment because of wheezing.
CONCLUSION: Propranolol administered orally at 2 to 3 mg/kg per day has a consistent, rapid, therapeutic effect, leading to considerable shortening of the natural course of IHs, with good clinical tolerance.
Comments
Systemic vs. Topical �-blocker for the Treatment of Superficial Infantile Hemangioma
Hemangioma of infancy is the most common benign tumor of childhood, occurring with an incidence of >2% of infants,(1) in general, and 10% of Caucasian children,(2) in particular. Infantile hemangioma of the eyelid can lead to sight-threatening amblyopia.(3,4) If not treated promptly, the condition can lead to irreversible blindness.(3,4) Although benign, severe infantile hemangioma can be life-threatening. However, even if the hemangioma is not life- or sight-threatening, it is usually cosmetically or psychologically traumatizing to the child and parents.
Corticosteroids (intralesional injection and oral) are considered first-line therapies for the treatment of hemangioma.(5–7) Alternative options include interferon alpha, laser,(8) embolization, surgical resection, (1,9,10) immumodulators, and, most recently, propranolol.(11,12) Systemic adverse effects are associated with all of the currently available treatments. (3-7, 9, 10, 13-15)
Recently, systemic propranolol was used successfully to treat advanced infantile hemangioma.(11,12) This modality represents a substantial contribution in the treatment infantile hemangioma. We read with great interest the report of Sans et al.(12) Thirty-two children with infantile hemangioma were treated in their study with oral propranolol resulting in a rapid and dramatic reduction in color and growth of hemangioma in all cases. Propranolol was administered for a mean duration of 6.1 months. During treatment, children were evaluated after 10 days of treatment and then monitored monthly. These reports provide the ground work to suggest that propranolol represents an alternative and effective option for the treatment infantile hemangioma. While these results are promising, however, systemic propranolol, as suggested in these articles, has the potential to cause severe systemic adverse effects, including bronchospasm, hypoglycemia, hypotension, severe bradycardia, heart block, and congestive heart failure.(12, 16) A close monitoring may be required during the course of propranolol treatment.(12)
Guo et al.(17) first reported the benefit of topical timolol solution (a ß-blocker) for treating a large eyelid capillary infantile hemangioma in a 4-month-old infant. With this treatment, the authors showed substantial improvement after a few weeks of topically applied timolol (0.5% solution) onto the surface of the tumor. Further, we studied and found a consistent reduction of superficial periocular capillary hemangiomas in more children following topical application of 0.5% timolol solution. Moreover, no local or systemic side effects occurred in any patient (manuscript pending publication).
Topical application of timolol for hemangioma may reduce local or systemic side effects and the need for the close medical monitoring necessary when using propranolol. While we cannot advise that all infants with hemangiomas be treated with topical timolol, we do suggest that topical timolol can be used at least as an alternative or adjunctive therapy for localized superficial cutaneous hemangiomas. Further studies on the utility of topical β-blockers for the treatment of infantile hemangiomas are in progress at our institutions.
References
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Conflict of Interest:
None declared