infantile hemangioma, also known as birthmarks, is a disease of the pediatrics. most birthmarks fade away by the 12th year of life. however, others necessitate treatment and care.

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https://create.kahoot.it/create#/new/survey/done

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Done by: Farah el Soheil
Instructor: Dr. Zeina Shrayteh

4. Lebanese International University
School of Pharmacy
Pharmacy Practice Experience III & IV
Spring 2019
Management of Infantile Hemangiomas
Clinical Practice Guideline
April 25,2019

5. Introduction
Etiology
Epidemiology
Risk stratification
Intervention
Available
therapies
When to seek
medical help
Future
highlights
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A type of birthmarks formed by collection of extra blood vessels in
the skin
Most common tumor of infancy (5% of infants) : Benign vascular
neoplasms
Marked by early proliferation followed by spontaneous involution
More common in:
• Girls
• Twins
• Preterm infants or with low birth weight
• White
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*Bright red bump or patch
*Size ranges from 0.5-5 cm
*Well circumscribed and focal
*Superficial IH evolves from small red
patches to bright red bumps
*Deeper IH tends to be purple to blue

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Cutaneous
Head & neck (60%)
Trunk (25%)
Extremities (15%)
Extra-cutaneous
Liver
GI
Larynx
CNS
Pancreas
Gallbladder
Etc
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Most rapid
growth occurs
from birth till
4 weeks
Complete
growth by 4-6
months of age
Proliferation
slows by 6-12
months
Complete
involution by
5-7 years
Ideal
intervention
by 1 month of
age
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11. *
Facial
(Scarring &
disfigurement)
Airway
Periorbital
(Functional
impairment)
Ulcerative (lip,
neck, diaper
area,armpit)
Intracranial/
aortic arch
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Leading hypothesis
Circulating
endothelial
progenitor cells
migrate to
locations in which
conditions are
favorable for
growth
• Hypoxia
• Developmental field
disturbance
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Fairly straightforward
appearance, pattern of
growth
Skin biopsy: stain positive
for GLUT1
Other possible biomarkers
• VEGF, urinary MMPs
Further evaluation through
doppler or MRI
If multiple hemangioma and
younger than 6 months,
ultrasound the liver

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Life threatening complications
Functional impairment or ulceration
Structural anomalies
PHACE syndrome
LUMBAR syndrome
Permanent disfigurement
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Airway
(subglottis)
Mistaken as
reactive
airway disease
Barky cough &
biphasic
stridor
Associated
with
segmental
lower face IH
Liver IHs
Focal/multifo
cal/diffuse
Associated with
high output CHF
and
hypothyroidism
In patients
with 5 or more
cutaneous IHs
Ulcerated IH
Severe
bleeding is
rare
Severe
coarctation of
the aorta
Associated
with PHACE /
LUMBAR
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Feeding
Lips and
mouth
Strabismus
Mechanical
ptosis
Astigmatism
Amblyopia
• IH size >1cm
• Upper eyelid
involvement
• Associated ptosis
• Eyelid margin
changes
• Medial location
Visual
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Blurred vision
(pressure) or
closed eyelid

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Associated with significant pain, bleeding, and
secondary infection & scarring
Types of IHs at higher risk of ulceration
Superficial and
mixed types,
segmental His
Those involving
the scalp, neck,
and perioral,
perineal,
perianal
Intertriginous
sites caused by
maceration and
friction
protuberant IHs
can ulcerate as
a result of
trauma
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Cerebrovascular anomalies (90% of patients with PHACE)
Cardiac anomalies (67%)
Structural brain anomalies (52%)
The
hallmark of
PHACE
syndrome
Large (>5 cm in diameter) segmental IH
Involves the face, scalp, and/or neck, rarely located on the torso and
upper extremity instead
Risk if a large IH of the head or neck is 30%
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LUMBAR
syndrome
“lower half of the body” equivalent of PHACE syndrome
segmental, involving the lumbosacral or perineal skin and often
extending onto 1 leg
Minimally proliferative morphologically, with telangiectatic vascular
stains predominating over bulkier superficial hemangiomas
Rarely, undergrowth or overgrowth of an affected limb may be
present
Regional correlation between cutaneous IH and site of anomaly
Myelopathy, particularly spinal dysraphism, is the most common
extracutaneous anomaly
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Age of child
(Anticipated
IH growth)
Health
considerations
(Prematurity)
Anatomic site
& size
Actual or
potential
complications
Parental
preferences
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24. Systemic
Treatment
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Previously Systemic
or intra-lesional
corticosteroids
Now
propranolol
Superior to paracetamol
and ibuprofen in
ulcerated IH
Superior to oral
captopril
Safer than systemic
corticosteroids
Priming with oral
prednisolone at weeks
2,4,8 showed better
reduction of IH size
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Propranolol is DOC
Non-selective b
blocker
Vasoconstriction
Angiogenesis inhibition
Induction of apoptosis,
Inhibition of NO & RAS
system
Starting dose : 0.6
mg/kg bid
Gradual increase
over 2 weeks to 1.7
mg/kg bid
Inpatient if younger
than 8 weeks
Dose : 2-3 mg/kg/day
Except in
•PHACE syndrome
•Increased risk of stroke
•Adverse effects(Sleep
disturbance)
TID dosing: to avoid
changes in BP
With or after feeding:
to avoid hypoglycemia
For at least 6 months
• Until 12 months of
age to decrease the
risk of rebound
growth
Risk factors for
rebound: deep
morphology and
female gender
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Hypoglycemia:
sweating,TC,
tremor,
lethargy, poor
feeding, apnea
Sleep
disturbance
Bronchial
irritation
Clinically
symptomatic
bradycardia
and
hypotension
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ECG screening only in:
• If baseline HR below normal for age
• Family history of congenital heart conditions or arrythmia
• History of arrythmia or one is auscultated during exam
In office monitoring of HR and BP:
• 2 hours post first dose of propranolol
• On increasing dose for 5 weeks of gest age or older
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If PO propranolol is contraindicated (asthma, COPD, PHACE),
poorly tolerated or ineffective
The optimal dosing remains unclear
2 to 5 mg/kg per day
Optimal dosing : 2 to 3
mg/kg/day for 4 to 12
weeks followed by a
gradual taper and
completion of therapy
by 9 to 12 months of
age
Shorter treatment
durations (1–6 weeks)
may be considered with
multiple intermittent
courses as needed
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Cushingoid
appearance
Infection,
Mood
changes
Growth
retardation
Hypertension
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For IHs that are relatively
small and well localized
Treat focal, bulky IHs during
proliferation or in critical
locations (eg, the lip)
Not for large lesions
• Larger volume of steroids
necessary
• Difficulty of obtaining even
distribution throughout the
tumor
• Potential for local complications
in lesions that are mostly flat or
superficial
Triamcinolone alone or in
conjunction with
betamethasone, with
injections given on average
every 4 to 6
Repeat injections are often
administered (1 to 7 in total)
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Transient
Cushingoid
features &
Failure to thrive
Local skin
complications
• Fat and dermal
atrophy
• Pigmentary
changes
Adrenal
suppression
when large
doses (eg, >4
mg/kg)
Central retinal
artery embolization
after injection into
IHs of the upper
eyelid due to high
injection pressures
or volumes
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Topical timolol maleate
• 0.5% gel-forming
solution
Used in the treatment of
pediatric glaucoma as a
first-line
Shows efficacy with
minimal adverse effects
The greatest
improvement is in color
With a longer duration of
treatment, improvement
in size, extent & volume
Best responses were
observed in thinner
superficial IHs ( <1 mm
thick)
Early topical timolol
treatment inhibit IH
growth ( time of initiation
< 6 months)
Rarely requires
subsequent systemic BB
treatment
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Caution when
using timolol
(more than 1
drop BID or when
treating preterm
or young infants)
Local irritation
(nearly half of
the adverse
events))
No
cardiovascular
events were
reported
No adverse
events that
necessitate
drug
discontinuation
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Surgical interventions are not performed in infancy
• Anesthetic risks are of greater concern
• The tumor is highly vascular
• higher risk of blood loss
• iatrogenic injury
• inferior outcome
Deferring surgery until the child is 3 to 5 years of age
• The lesion may resolve on their own
• The tumor is smaller than it was during infancy thus easier task
• The IH primarily is adipose tissue instead of blood vessels thus
safer operation
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36. IHs that ulcerate, obstruct or
deform vital structures (such
as the airway or orbit)
IH that involve aesthetically
sensitive areas
Lesions that are refractory to
pharmacotherapy
Well localized Lesions
Involuted IHs that have left
residues
Thinned skin, scar, fibrofatty
tissue, telangiectasias
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PDL is effective and safe in
removing residual macular
erythema and superficial
telangiectasias in involuting
or involuted IHs
Erbium-yttrium-aluminum-
garnet ameliorates textural
changes in small case series
It’s controversial whether or
not to use PDL in infancy due
to increased risk of side
effects
PDL penetrates only into the
superficial dermis so deeper
elements of the IH (that
increase the risk of residual
skin changes) are not affected
Every 2-4 wks until complete
healing
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Skin atrophy Bleeding
Scarring &
ulceration
Purpura &
pigmentation
changes
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Rapid growth
Ulceration
BleedingPain
All findings that
indicate that a
lesion is no
longer low risk
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For
superficial
IHs (red to
milky-white
or gray)
lesions
gradually
flatten
and shrink
from the
center
outward
Proceeds more slowly
than growth, starts by 5
months & is completed
by 4 years of age
Residual changes, such
as telangiectasias,
redundant skin, or a
scar may be left 43

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Ensure that Hemangioma Severity
Score can accurately be interpreted
by primary care physicians
Find scores that capture the vast
majority of high-risk IHs requiring
specialty care without overreferring
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How safe is
topical
timolol as a
treatment
during early
infancy?
Is outpatient
in-office
cardiovascul
ar
monitoring
for
propranolol
truly needed
in healthy
infants 5
weeks or
older?
What is the
role of the
pediatrician
in managing
infants
placed on β-
blocker
therapies
(both topical
and
systemic) ?
How
accurate are
primary care
physicians in
identifying
high-risk IHs.
?
Are pediatric
trainees
receiving
adequate
training in
risk
stratification
and
management
of IHs?
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*
* Retrieved from
https://www.aan.com/guidelines/home/getguidelinecontent/900
* Infantile Hemangioma. (2018, January 30). Retrieved from
https://www.yalemedicine.org/conditions/infantile-hemangioma/
* Infantile Hemangioma: Practice Essentials, Background,
Pathophysiology. (2019, February 6). Retrieved from
https://emedicine.medscape.com/article/1083849-overview
* UpToDate. (n.d.). Retrieved from
https://www.uptodate.com/contents/infantile-hemangiomas-
management
* Vascular Birthmark Institute New York | Hemangiomas, Vascular
Malformations. (n.d.). Retrieved from https://www.vbiny.org/