Download Misuse of the nomenclature continues to exist Delay of

*There are no relevant financial relationships to disclose
*I will be discussing off-label use of medications
Misuse of the nomenclature continues to exist
 Delay of recognizing complications and a need for
intervention compromises patient care
 The standard of care is shifting to new medical
interventions
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Upon completion of this educational activity, you will be
able to:
1) Review the nomenclature and correct misnomers in the
definition of hemangiomas and vascular
malformations.
2) Review the characteristics of a hemangioma that may
indicate further evaluation and/or intervention is
necessary.
3) Review the current trends in management of
proliferative capillary hemangiomas.
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Greek suffix “–oma” meaning “swelling” or “tumor”
2 major categories:
 tumors (primarily hemangiomas)
 malformations
lf
an accurate diagnosis is essential
 history and physical examination
 radiologic examination
 biopsy
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Infantile Hemangioma
Vascular Tumors
› Proliferative
› RICH, NICH
Pyogenic Granuloma
 Kaposiform Hemangioendotheliolma
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Capillary (Port Wine)
Venous
 Artieriovenous
 Lymphatic
 Combined Lesions
Vascular Malformations
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› Venous-Lymphatic
› Capillary-Lymphaticovenous
Hematology/Oncology
Radiology
 Dermatology
 Surgery
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› Pediatric Surgery
› Plastic Surgery
› Otolaryngology
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Basic Scientists
Patient/family support staff
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Hemangiomas
 exhibit cellular
proliferation
 g
grow duringg infancyy
 involute in childhood
 never appear in an
adolescent or adult

Vascular Malformations
 dysplastic vessels
 no endothelial proliferation
 growth proportional to
patient’s growth
 never regress
most common tumor of childhood
 Prevalence 3-10% in Caucasian infants
 less in Asian, very low in African descent
 limited epidemiologic data
 as high as 30% incidence in LBW premature infants
 F>M
 10% with elicited family history
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60% in the H & N region
characteristic time cycle
› appear typically within first 2-4 weeks of life
› begin involution between 12-18 months of life
› nearly 90% resolved by 9 years of age
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proliferating hemangiomas
› composed of foci of endothelial cells, pericytes, fibroblasts
and mast cells
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mature and immature endothelial cells
› express surface markers for alkaline phosphatase and factor
VIII antigen
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mast cells
› may produce angiogenic factor or secrete dysfunctional
angiogenic inhibitors
› numerous angiogenic factors have been identified and
cloned
 bFGF (basic fibroblast growth factor)
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disfigurement
 ulceration
 infection
 localized
l li d hemorrhage
h
h g
 compression of vital structures
 high output cardiac failure
 Kassabach-Merritt Phenomenon (KMP)
 psychological stress

size
location
 presence of complications
 age of the patient
 rate of growth at the time of evaluation
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1997 American Academy of Dermatology
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interference with vital structures
possibility
b l t off permanentt scarring
large facial hemangiomas
ulcerated hemangiomas
hemangiomas in a “beard distribution”
periorbital hemangiomas
 lumbosacral hemangiomas
g
 multiple, cutaneous hemangiomas
 PHACE syndrome
 hypothyroidism
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“Beard” distribution
Orlow, et al J Peds 1997
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Neurological and/or
genitourinary defects
 Tethered cords Albright et al

Pediatrics 83:977-980,1989
Renal anomalies
 Bony sacral anomalies
 Leptomeningocele
 Imperforate anus
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Associated with internal
hemangiomas
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Most commonly in the liver
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Other areas include: CNS, eye,
pancreas, GI tract, lung, spleen, and
the airway
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Posterior fossa malformations
Hemangiomas
Arterial anomalies
Cardiac anomalies
Eye anomalies
Sternal cleft or supraumbilical raphe
syndrome
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20% of infants with large cervicofacial
hemangiomas will have one of associated
anomalies of PHACE
Pacual-Castroviejo et al Neuroradiology 16, 1978
Frieden et al Arch Dermatol 132:307 311,1996
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http://www.radinfonet.com
Large liver hemangioma associated with
hypothyroidism
 Functionally active T4/T3 are degraded by type 3
deiodinase enzyme (D3)
 Increased levels of D3 leading to accelerated
degradation of T4/T3
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Huang SA et al N Engl J Med 2000 Jul
20;343(3):185-9
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Observation
Steroids
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Propranolol
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Interferon
Chemotherapy
Laser therapy
Embolization
Surgery
Radiation
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 first used in 1958 for these lesions
 oral, topical or injected
 response rate
t ~ 70%
 long lived status as first line therapy
 anti-angiogenic effect
 decreases endothelial cell proliferation
 causes endothelial cell apoptosis
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Cushingoid facies
personality changes
gastric irritation
weight gain
diminished gain of height and weight
immunosuppression
non-systemic fungal infections
(all complications usually resolve with discontinuation of therapy)
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hypertension
suppression of hypothalamic-pituitary adrenal
function
 hyperglycemia
 myositis
 osteoporosis
 cataracts
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close monitoring of height and weight
BP checks
urine checks
stool checks
physical exam every 1-2 weeks until on a stable dose
NO live immunizations
MD visit if temp > 38.5
Caution if varicella exposure (Call MD immediately)
initial dose of 2-3 mg/kg/day
given QD in the am
 most common preparations
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› Prelone 15 mg/5cc
› Pediapred 1mg/1cc
(always give with Ranitidine)
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first described for use in hemangiomas in 1989
mechanism of action: anti-angiogenic agent, down
regulates bFGF
 response in about 60% of patients
 alpha-2a or alpha-2b
 subcutaneous injection
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neurotoxicity in about 30% of patients
› spastic diplegia (may be permanent)
› other developmental delays
other side effects: flu
flu-like
like syndrome, anemia,
neutropenia
 alterations in liver enzymes
 mood changes
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neurological exam weekly
› if neurological changes occur—consider discontinuing
drug
baseline CBC and LFTs, then every other week
 thyroid function
 physician experience
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Non selective -blocker
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Inhibits B1 and B2 adrenergic receptors
Pure antagonist without partial agonistic effects
Lipophilic properties
Membrane stabilizing characteristics
Eff
Effect
› 2 days decrease in color
› Long term use needed
› Effective for older patients with hemangiomas
Early: Vasoconstriction, decreased release of nitric
oxide
 Intermediate: Blocking of pro-angiogenic signals
 Long term: Induction of apoptosis
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
chemotherapy agent
› used in the treatment of many malignant and non-
malignant disorders
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mechanisms of action:
› induces apoptosis in endothelial cells
› interferes with mitotic spindle microtubules
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central access
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Early:
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peripheral neuropathy
constipation
jaw pain
rare hematological toxicity
*very limited long term effects
(usually tolerated well)
An appreciation of the complexities of categorizing
vascular anomalies
 Clinical recognition of “at risk” capillary
hemangiomas
 Basic understanding of the use of medical
interventions in the treatment of Proliferative
Capillary Hemangiomsa
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look carefully
know when to investigate further
 refer
f early
l
 provide support
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…You are NOT alone!!!!!
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