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113
Pedro Moreira
Propranolol in the treatment of an extensive facial and orbital
infantile hemangioma
Figure 5. 24-months-old boy, after treatment.
Figure 6. T2-weighted FSE craniofacial-orbital MRI images, after
treatment.
Figure 7. Gadolinium-enhanced T1-weighted craniofacial-orbital
MRI images, after treatment.
DISCUSSION
Since 2008 when for the first time it was reported the efficacy
of propranolol in inhibiting the growth and controlling the prolife-
rative phase of problematic hemangiomas (2), some reports have
been published that included hemangiomas with orbital involve-
ment (6-9), but to the authors knowledge none was described as
having the characteristics and extension of this portuguese case.
Such cases with deep orbital involvement may not be mana-
geable with local therapies like i
ntralesional corticosteroids injec-
tion, laser therapy or surgical intervention, given the potential risk
of injury to the ocular globe, the extra-ocular muscles and the op-
tic nerve. Systemic pharmacologic treatment with corticosteroids or
chemotherapeutic agents may be associatedwith significant adverse
events, with increased likelihood considering the duration of treatment.
The therapeutic effect of propranolol on hemangiomas,
which are composed of a complex mixture of clonal endothelial
cells (associated with intersticial cells as pericytes, dendritic cells
and mast cells), is thought to be related with three different me-
chanisms: vascoconstriction, inhibition of angiogenesis and induc-
tion of apoptosis.
Epinephrine can cause both vasoconstriction and vasodilata-
tion by activating both the α1 and β2 receptors, respectively. Pro-
pranolol has a β-blocker effect, without the α-antagonistic effect,
and so inhibits the epinephrine mediated vasodilation, resulting in
the vasoconstriction of endothelial cells. A clinical improvement is
immediately visible as a change in color associated with a palpable
softening of the hemangioma.
During the growth phase of hemangiomas, two major proan-
giogenic factors are involved and have their expression increased:
basic fibroblast growth factor (bFGF) and vascular endothelial
growth factor (VEGF). Still in this phase, histological studies have
shown that both endothelial and interstitial cells are actively di-
viding. Some studies demonstrated that β-blockers can decrease
the expression of bFGF and VEGF genes, which leads to the in-
hibition of angiogenesis, and thus might explain the progressive
improvement of the hemangioma.
Apoptosis is a feature of the involution phase of hemangio-
mas. It is regulated by various pathways, with the probable invol-
vement of the β1 adrenergic receptor. It has been hypothesized
that the blockage of this β1 adrenoreceptor by propranolol, tri-
ggers apoptosis of capillary endothelial cells at an increased rate.
This molecular mechanism might also explain the progressive im-
provement of the hemangioma.
Hypoglicemia, bradycardia, hypotension and bronchoes-
pasm are well known potential side effects of propranolol, a non
selective beta-blocker. They all can be adequately managed, fulfi-
lling an initial pediatric assessment before initiation of therapy and
monitoring such parameters throughout therapy with frequent
pediatric follow-up visits (
2-5)
.
In current literature, the duration of treatment with pro-
pranolol ranges widely, between 3 and 18 months, and supports
discontinuation of therapy through gradual tapering at the end of
the course over a 2-week period, to minimize the risk of a hypera-
drenergic withdrawal response (5-10). In our patient, therapy was
continued until complete resolution, treatment for 19 months,
and propranolol was tapered through a 2-months period, given
the registered fact of failure to obtain progressive regression at 13
months of treatment, during an attempt to lower the propranolol dose.
The successful outcome with no side effects in this patient,
avoiding severe visual impairment during the critical period of vi-
sual development, supports the effectiveness of oral propranolol
treatment for problematic hemangiomas, and possibly as a first
line treatment in these cases.
REFERENCES
1. Haggstrom AN, Drolet BA, Baselga E, et al. Prospective Study of
Infantile Hemangiomas: Clinical Characteristics Predicting Complications
and Treatment. Pediatrics. 2006;118:882-7.
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