Infantile Hemangioma: Natural History
& Treatment
- Involution phase: 50% of infantile hemangiomas show
complete involution by age 5 years & 70% by age 7 years.
- Medical care of clinically significant hemangiomas has been
limited to a few medications: corticosteroids, interferon alfa,
vincristine, & imiquimod.
- Beta-blockers, most specifically Propranolol, have recently
been serendipitously been shown to induce involution of
infantile hemangiomas.
Discovery of Propranolol as a treatment for
infantile hemangiomas.
Initial case report:
-A 9 wk old baby with a rapidly growing segmental facial
hemangioma & ocular complications s/p 4 wk course of
corticosteroids.
- The baby developed high output cardiac failure &
propranolol was started.
- 7 days later, the hemangioma was significantly smaller.
At 9 months of age, visual function was restored.
Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo J-B, Taïeb A. Propranolol for severe hemangiomas
of infancy. N Engl J Med 2008;358:2649-2651
Follow-up Case Series:
Patients with a life-threatening laryngeal
hemangiomas.
- N = 32 patients
- Mean age = 4 months
- 1 patient dropped out because of respiratory side-effects from
propranolol.
- Immediate effects on color and growth were noted in all patients
& were especially dramatic in cases of dyspnea, hemodynamic
compromise or palpebral occlusion.
Sans, V. et al. Pediatrics 2009;124:e423-e431
Mechanisms of Action
- β2-adrenergic receptors are present on endothelial cells of
infantile hemangiomas. (1)
-β-Adrenergic receptor stimulation activates signal transduction
pathways of angiogenic factors such as VEGF or bFGF.
- Blockade of angiogenic factors thought to cause
vasoconstriction of vessels within hemangiomas.
- A study of the use of β-blockers for treatment of cardiac
hypertrophy revealed that carvedilol reversed levels of both
protein and mRNA for VEGF to baseline values. (2)
1. M. Cario-André, PhD, C.L-L., L.J. Nissen, PhD, A.T., F. Majurier, PhD, unpublished data
2. Shyu KG, Liou JY, Wang BW, Fang WJ, Chang H. Carvedilol prevents cardiac hypertrophy and
overexpression of hypoxia-inducible factor-1 and vascular endothelial growth factor in pressureoverloaded rat heart. J Biomed Sci. 2005;12 (2):409 –420
Is Propranolol the 1st line treatment for
infantile hemangiomas?
-Not yet! It is currently only used in severe cases & several
questions need to be addressed before it can be more widely
used.
- What is the optimal dosing, dose escalation, & length
of therapy? May recur if stopped to early.
- What are the risks in patient subsets that may have
different vascular characteristics-such as in PHACES
syndrome [posterior fossa, hemangioma, arterial, cardiac,
& sternal abnormality]?
- There is an ongoing RCT comparing Propranolol to placebo
that should provide answers to some of these questions.
Demonstrative Case: Patient shortly after birth, Jan 2009.
Demonstrative Case: Patient 6 Weeks after Propanolol, March 2009.
Significant involution with fibrofatty replacement has already occurred.
Demonstrative Case: Patient 9 months after Propanolol, October
2009.
The lesion has involuted, clinically resolved and there is minimal
stranding of the retro-ocular fat and thickening of eyelids.