Infantile Hemangioma: Natural History

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 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
  20083582649-2651
•  
•  

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 2009124e423-e431
4
Mechanisms of Action

• - ß2-adrenergic receptors are present on
  endothelial cells of infantile hemangiomas. (1)
•  
• ß-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 ß-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A.T., F. Majurier, PhD, unpublished data 2.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.
200512 (2)409 420
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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.

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Demonstrative Case Patient shortly after birth,
Jan 2009.
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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.