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*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 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.

Greek suffix “–oma” meaning “swelling” or “tumor” 2 major categories:

tumors (primarily hemangiomas)lf malformations

an accurate diagnosis is essential history and physical examination radiologic examination biopsy

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Vas

cula

r Tum

ors

Infantile Hemangioma› Proliferative

› RICH, NICH

Pyogenic Granuloma

Kaposiform Hemangioendotheliolma

Vas

cula

r Mal

form

atio

ns

Capillary (Port Wine)

Venous

Artieriovenous

Lymphatic

Combined Lesions› Venous-Lymphatic

› Capillary-Lymphaticovenous

Hematology/Oncology Radiology Dermatology Surgery

› Pediatric Surgery› Plastic Surgery› Otolaryngology

Basic Scientists Patient/family support staff

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Hemangiomas

exhibit cellular proliferation

grow during infancy

Vascular Malformations

dysplastic vessels

no endothelial proliferation

growth proportional to g g y

involute in childhood

never appear in an adolescent or adult

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 F>M 10% with elicited family history

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

proliferating hemangiomas› composed of foci of endothelial cells, pericytes, fibroblasts

and mast cells

mature and immature endothelial cells› express surface markers for alkaline phosphatase and factor › express surface markers for alkaline phosphatase and factor

VIII antigen

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

l li d h h g localized hemorrhage

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

1997 American Academy of Dermatology

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interference with vital structures

b l t f t possibility of permanent scarring

large facial hemangiomas

ulcerated hemangiomas

hemangiomas in a “beard distribution”

periorbital hemangiomas

lumbosacral hemangiomasg

multiple, cutaneous hemangiomas

PHACE syndrome

hypothyroidism

“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

Associated with internal hemangiomas

Most commonly in the liver

Other areas include: CNS, eye, pancreas, GI tract, lung, spleen, and the airway

Posterior fossa malformations Hemangiomas Arterial anomalies Cardiac anomalies Eye anomalies Sternal cleft or supraumbilical raphe

syndrome

20% of infants with large cervicofacialhemangiomas will have one of associated anomalies of PHACE

Pacual-Castroviejo et al Neuroradiology 16, 1978Frieden 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)deiodinase enzyme (D3)

Increased levels of D3 leading to accelerated degradation of T4/T3

Huang SA et al N Engl J Med 2000 Jul 20;343(3):185-9

Observation

Steroids Propranolol

Interferon Interferon

Chemotherapy

Laser therapy

Embolization

Surgery

Radiation

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first used in 1958 for these lesions

oral, topical or injected

t 70% response rate ~ 70%

long lived status as first line therapy

anti-angiogenic effect

decreases endothelial cell proliferation

causes endothelial cell apoptosis

› 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

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› 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

neurotoxicity in about 30% of patients› spastic diplegia (may be permanent)

› other developmental delays

other side effects: flu-like syndrome, anemia, other side effects: flu like syndrome, anemia, neutropenia

alterations in liver enzymes

mood changes

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› 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

mechanisms of action: mechanisms of action:› induces apoptosis in endothelial cells

› interferes with mitotic spindle microtubules

central access

Early:› peripheral neuropathy› constipation› jaw pain› rare hematological toxicity› 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

f l refer early

provide support

…You are NOT alone!!!!!