Guidelines for Specialty Referral for Infants with Vascular Birthmarks “Babies With Birthmarks”

Proposed by the Vascular Birthmarks Foundation – May 2007 – www.birthmark.org

Mission Statement: Babies With Birthmarks is an international educational effort directed toward primary pediatric health care providers, to provide them with guidelines to identify and appropriately refer infants with vascular birthmarks for appropriate evaluation and treatment as needed.

Key Players: Infants with a vascular birthmark; primary care medical professionals who examine infants, medical specialists with expertise in vascular birthmarks and the associated problems; medical insurance companies, government officials, advocacy groups, and families affected by a vascular birthmark

Vision: These guidelines are proposed based on information provided below. Once approved, they will be translated and distributed to medical professionals all over the world to assist them in timely and appropriate specialty referral for infants with vascular birthmarks, as needed.

Statement in Support: Every year, 40,000 children are born in the US with a vascular birthmark that requires the opinion of a medical specialist. Despite the frequency of the problem, the diagnosis, classification and treatment of vascular birthmarks has not been uniformly included in primary care residency training curriculums. As a result, many primary care physicians do not learn about the critical importance of early identification, assessment, and treatment for many of these infants. Recently, specialists from a variety of fields have recognized a significant unmet medical need in the diagnosis and treatment of vascular birthmarks, and have organized multi-disciplinary treatment centers. To date, there are less than one dozen such treatment centers in the United States and few outside of the United States. Lacking access to informed care, many infants with hemangiomas miss the window of opportunity for more effective and less costly early intervention. Other infants with vascular birthmarks and malformations are inappropriately diagnosed due to the outdated information regarding diagnosis and are therefore inappropriately identified with the incorrect lesion. Most vascular lesions are labeled as a hemangioma and left to resolve on their own when in fact that may be a malformation which may require intervention to prevent expansion of the non-involuting lesion. The goal of Babies With Birthmarks is to provide guidelines that can be used by all primary care providers who care for infants with a vascular birthmark.

Recommendations for routine well-baby care in the US include examination at 4 weeks of age. Babies With Birthmarks suggests that the 4-week check up is the optimal time to detect a vascular birthmark that may require intervention. The following guidelines were designed to help determine appropriate referral to a vascular birthmark specialist or team.

Lesions of the Head and Neck Area (85% occur in this region). Imaging is often required to accurately assess these cases:

• All flat red/pink stains present at birth and still present at the four-week check up should be examined by a vascular birthmark specialist if the stain is in the V-1 dermatome to rule-out Sturge-Weber Syndrome. A pediatric eye specialist should also examine the infant to rule-out glaucoma. An MRI should also be done to rule out minigeal involvement.
• All birthmark (flat or raised) in the V-3 dermatome, should be examined by a vascular birthmark specialist and an pediatric ENT to rule out airway, palate, gum involvement. If stridor is present at 4 weeks, this is an indication of possibly airway involvement.
• All birthmarks (flat or raised) at the base of skull should be examined by a vascular birthmark specialist and a neurologist to rule-out nerve involvement, especially large, rapidly growing lesions.
• All birthmarks (flat or raised) in the orbit area should be examined by a pediatric eye specialist first to rule out vision impairment and then a vascular birthmark specialist to assess possible syndromes.
• All birthmarks, especially rapidly proliferating lesions, of the nasal tip should be referred to a vascular birthmark specialist and possibly an ENT to prevent cartilage erosion from the lesion.
• All birthmarks that are a wide distribution of the head and neck area and are very rapidly proliferating should be sent immediately to a vascular birthmark specialist to rule out a life-threatening syndrome called Kassabach-Merritt. A pediatric hematologist should also be consulted to conduct blood work to determine if platelets and fibrinogen levels are compromised.
• All birthmarks of the head and neck area that bleed or are ulcerating should be referred to a vascular birthmark specialist and/or a pediatric ENT.

Lesions of the Extremities and Trunkal area (imaging is often required to assess these cases):

• When an infant presents at birth with a vascular stain on the extremities and/or trunk area, the infant should be referred to a vascular birthmark specialist and possibly a pediatric orthopedic specialist to assess for Klippel-Trenaunay Syndrome.
• Infants presents with a rapidly proliferation large focal lesion of the body should be referred to a vascular birthmark treatment specialist and possibly a pediatric hematologist to rule out Kassabach-Merrit Syndrome.
• Infants presenting with base of spine rapidly proliferating lesions should be referred to a neurologist and a vascular birthmark specialist to rule out neurologic involvement.
• Infants presenting with deformities of the body with a vascular stain should be seen by a vascular birthmark specialist and possibly a pediatric orthopedic surgeon.
• Infants presenting with a vascular birthmark that is bleeding or ulcerating should be seen by a vascular birthmark specialist and pediatric dermatologist or other specialist.
• Infants presenting with a stain or raised lesion in the diaper area (perienal lesions) should be seen by a vascular birthmark specialist and a pediatric dermatologist or other laser specialist.

Lesions that are internal (always require imaging to confirm):

• Infants presenting with distending abdomen and enlarged liver should be examined for possibly hemangiomas of the liver.
• Infants presenting with airway stridor should be examined for the presence of a vascular lesions.
• Infants presenting with seizure who have a cranial stain should be examined for brain involvement.
• Infants presenting with blood in the stool who have large vascular stains of the body and extremities should be examined for internal involvement.
• Infants presenting with 3 or more hemangiomas should undergo ultrasound to rule out internal lesions.

Always refer an infant to a specialist when:

• At the four week check-up the lesion has rapidly proliferated.
• At the four week check-up, the lesion continues to grow and other milestones are negatively affected.
• At the four week check-up if the lesion is bleeding or ulcerating.
• At the four-week check-up if the lesion has spontaneously appeared.
• At the four-week check up if the lesions shrinks and swells intermittently.
• At the four-week check up if the lesion has darkened or spread.
• At the four-week check up if the child is experiencing breathing problems.
• Three or more lesions are noted at check up.

Diagnosis/Classification/Treatment of Vascular Birthmarks:

AAD Summer 1999 James F. Nigro, MD New York, New York July 31, 1999
Diagnosis and Management of Hemangiomas and Vascular Malformations in Childhood

I. Nomenclature of hemangiomas and vascular malformations

a. The major obstacle to the understanding and management of vascular birthmarks

b. Mulliken and Glowacki demonstrated that there are only two major types of vascular birthmarks based on differences in the following categories:
-Clinical
-Histologic
-Hematological
-Radiological
-Skeletal

c. Histologic features are the most important differences
-Hemangiomas have plump endothelia, increased mast cells, and multilaminated basement membranes
-Malformations have flat endothelia, normal mast cell numbers, and a thin basement membrane

d. Modern Nomenclature
-Hemangiomas are superficial, deep, or combined and may be proliferating or involuting
-Vascular malformations may be capillary, venous, arterial, lymphatic, or a combination of these

II. Hemangiomas

a. Introduction
-True benign neoplasm’s
– Comprised of capillaries and venules in superficial and/or deep dermis
-Present during first few weeks of life
-Rapid proliferation and slow involution
-Most resolve completely without major complications

b. Incidence
-Female: male 3:1
-More common in Caucasians than in African Americans
-May be present in 10-20% of premature infants
-Solitary in 80% of patients

c. Location
-Based on percentage of body surface area, they are more common on the face
-By strict numbers, about 30% occur on the face or scalp

d. Precursor Lesions
-Appear prior to the actual proliferation of the hemangioma
-Pale patches
-Telangiectasia
-Macular erythema
-Bluish discoloration
-May be confused with port wine stain or nevus anemicus

e. Proliferative Phase
-Superficial lesions: red, raised, firm, well-demarcated
-Deep lesions; bluish, soft, slowly enlarging
-Wide variation in size -Growth phase: 3-12 months

f. Involution Phase
-Color change from bright to dull red
-Central greying
-Gradual softening
-Eventual resolution *50% by 5 years, 70% by 7 years, 90% by 9 years

g. Alarming Hemangiomas
-Vital/Important structures: eye, larynx, distal extremities
-Cosmetically sensitive regions: nose, lip, ear -Very large trunal resolution

h. Minor Complications
-Bleeding rare in these low flow lesions
-Infection: rare
-Ulceration: rapidly growing lesions and in the diaper area
-Residua: Telangiectasia, atrophy, hypopigmentation

i. Diffuse Neonatal Hemangiomatosis
-Multiple, small, cutaneous lesions
-Dome shaped, uniform in size
-May be associated with visceral lesions
· Liver, GI, CNS
· May be asymptomatic
· High-output cardiac failure, hemorrhage, obstructive jaundice, coagulopathy
-Involution of cutaneous and visceral lesions by age 2 years
-Ultrasound or MRI studies are indicated
-Treat symptomatic patients

j. Kasabach-Merritt Syndrome -hemangioendotheliama or tufted angioma
-extremely is usually involved
-coagulopathy associated with platelet trapping within lesions
-high mortality rate in untreated cases
-treatment
· Surgical excision
· Interferon
· Systemic corticosteroids

k. Associated Syndromes
-less common than with vascular malformations
-PHACE(S) syndrome
· Posterior fossa CNS malformations (Dandy Walker)
· Hemangioma
· arterial anomalies
· cardiac anomalies
· eye anomalies and (sternal defects)
-lumbosacral lesions
· spinal anomalies
· genitourinary anomalies

I. Therapy

-observation
· photography
· regular follow-up visits
· reserve right to initiate therapy at a later date

-systemic corticosteriods
· 2-3 mg/kg/day for 4-6 week and then slowly taper
· younger infants may require a longer or second course
· immunizations: hold until off steroids for 1 month
· side effects: increased appetite, change in sleep patterns, fussiness

-intralesional corticosteroids
· 3-5 mg/kg/dose
· systemic absorption is significant
· potential adverse side effects
· soft tissue atrophy
· eyelid necrosis
· perforation of the globe
· retinal artery occlusion

-topical corticosteroids
· high potency
· may be effective in small superficial hemangiomas

-interferon alpha
· antiangiogenic activity
· 3 million units/meter sq/day subcutaneous
· treatment is required for several months
· excellent results in severe or life threatening hemangiomas unresponsive to corticosteroids
· adverse effects
· fever
· neutropenia
· spastic diplegia
· motor delay

-laser
· tunable yellow dye (flash lamp pumped pulse dye)
· very thin or precursor hemangiomas
· ulcerations
· residual telangiectasia
· Nd: YAG
· Bulky facial lesions
· Increased risk of scarring
· Experimental

-surgical excision
· protuberant lesions
· consider surgical consultation when parents are very anxious
· avoid if hemangioma is diffuse -duoderm
· excellent pain control in ulcerated perineal lesions

-cryosurgery
· risk of scarring
· good results are possible with experienced hands

III. Capillary Malformations (Port Wine Stains)

a. Introduction
-vascular malformations limited to dermal blood vessels
-present at birth
-permanent
-associated with other vascular malformations and congenital syndromes

b. Incidence
-0.3% of neonates
-equal sex and racial predilection
-50% of facial PWS restricited to one trigeminal sensory region -remainder involve more than one, cross midline, or are bilateral

c. Appearance
-pink, well-circumscribed patches
-growth is commensurate with growth of the child
-darken and thicken with age

d. Sturge-Weber syndrome -facial port wine stain
· V1 trigeminal sensory region must be involved
-CNS
· Seizures
· Mental retardation
· Railroad track calcifications or cortex
-opthalmologic
· Ipsilateral choroidal angiomatosis
· Glaucoma (can be seen with V2 lesions involving eyelid)

e. Treatment

-tunable dye laser
· Treatment of choice
· Multiple treatments required (average 6.4)
· Very good to excellent results in most patients
· Few side effects

-Anesthesia
· General: infants and children with large lesions
· Topical: older patients with large or small lesions
· None: most adults with small lesions

-psychological evaluation

-neurologic and opthalmologic exam

-other lasers, tattooing, excision, radiation are not indicated

IV. Venous Malformations

a. clinical features
-bluish patch or mass with indistinct borders
-present at birth but may not be evident
-compressible
-phleboliths, thrombosis, hemorrage
-frequently confused with deep hemangiomas

b. treatment
-none
-surgical excision
· Image prior to surgery to determine extent of lesion -sclerotherapy
-elastic stockings

V. Arteriovenous Malformations

a. clinical features
-high flow-may involve bone, muscle, viscera
-often undiagnosed until adulthood
-discoloration or pulsatile mass may be noted

b. treatment -surgical excision -embolization

VI. Lymphatic Malformations

a. localized or diffuse
b. may slowly enlarge over time
c. may be confused with deep hemangiomas
d. superficial lesions may respond to laser therapy
e. incomplete surgical excision can lead to massive overgrowth
f. support garments

VI. Syndromes Associated with Vascular Malformations

a. Klippel-Trenaunay
-definition: soft tissue hypertrophy and bony overgrowth of extremity with PWS
-clinical features
· Usually single lower extremity
· Overgrowth not present at birth
· Significant limb length discrepancy
· Prominent hypertrophy of foot and toes
· No CNS or visceral anomalies
-treatment
· Premature epiphyseal closure of longer leg
· Surgical debulking is usually not feasible

b. Maffucci’s syndrome venous malformations -enchondromes -distal extremities

c. Blue Rubber Bleb Nevus syndrome -venous malformations of skin and GI tract -compressible, painful lesions -GI hemorrage is common cause of death

d. Gorham’s syndrome -venous and lymphatic malformations involving skin and skeleton -osteolytic bone disease

e. Proteus syndrome: PWS, partial gigantism, macrocephaly, epidermal nevi

f. Wyburn-Mason syndrome: retinal and CNS AVM, facial PWS

g. Riley-Smith syndrome: cutaneous venous malformation, macrocephaly

h. Cobb syndrome: venous malformations of spinal cord, truncal PWS

i. Bannayan-Zonana syndrome: subcutaneous/ visceral venous malformation, lipomas, macrocephaly