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Infantile Hemangioma: Natural History & Treatment

Infantile Hemangioma: Natural History & Treatment. - Involution phase: 50% of infantile hemangiomas show complete involution by age 5 years & 70% by age 7 years.

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Infantile Hemangioma: Natural History & Treatment

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  1. 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.

  2. 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 functionwas 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

  3. 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

  4. 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 M. Cario-André, PhD, C.L-L., L.J. Nissen, PhD, A.T., F. Majurier, PhD, unpublished data 2.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 pressure-overloaded rat heart. J Biomed Sci. 2005;12 (2):409 –420

  5. 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.

  6. Demonstrative Case: Patient shortly after birth, Jan 2009.

  7. Demonstrative Case: Patient 6 Weeks after Propanolol, March 2009. Significant involution with fibrofatty replacement has already occurred.

  8. 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.

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