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Clinical Manifestations
and Subtypes
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The most common vascular tumor is infantile hemangioma (IH), present
in approximately 4% of infants and more common in females,
Caucasians, preterm infants (particularly in those weighing < 1500
g) and infants of multiple gestations.2 A key clinical
feature is whether hemangiomas are localized (eg,
arising as a nodule or small area of skin involvement as if from a
central focus) or segmental (involving
a territory of skin) (Figs. 364-1A, B). Segmental
hemangiomas are much more likely to cause complications, often need
referral and/or treatment, and have associated extracutaneous
abnormalities.2
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IHs are characteristically either absent or present at birth
as precursor lesions such as a telangiectatic, bruiselike area or
skin pallor resembling nevus anemicus. The clinical appearance of
hemangiomas after proliferation depends on their location within
the skin. Superficial lesions appear as brightly erythematous
well-demarcated plaques, whereas deep hemangiomas
present as rubbery or soft, blue-hued subcutaneous nodules. Mixed IHs
have features of both.
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Biology and
Growth Characteristics
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Most IHs undergo a characteristic proliferative phase during
the first weeks to months of life, and growth is typically completed
by 4 to 6 months of age, except in the case of deep or large segmental IHs,
where the proliferation phase may last up to a year and, in rare
instances, even longer.3 The rate of involution
of IHs is considerably slower than the growth phase: most small
hemangiomas have involuted significantly by 2 to 3 years of age,
whereas larger, bulkier lesion may take several more years to complete
involution.
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Involution, however, does not always imply resolution without
clinical sequelae. A significant minority of IHs resolve, leaving
behind fibrofatty tissue, telangiectasias, atrophic, or stretch mark-like
residua, which if located in visable areas such as the central face
can cause permanent disfigurement.
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The pathogenesis of IHs is not well understood. More recent evidence
points to immunohistochemical and genetic similarities to placental
blood vessels, including characteristic staining for erythrocyte-type
glucose transporter protein GLUT-1.4 This can be
used as a diagnostic tool to separate IHs from other vascular anomalies.
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Pediatricians and dermatologists are aware that the vast majority
of infantile hemangiomas resolve without incident. However, prospective studies
have determined that complications occur in up to 24% of
hemangiomas in a referral population.5The most
important predictors of potential complications are size, anatomic
location, and segmental subtype. Ulceration is the most common complication
of infantile hemangiomas, occurring in approximately 15% of
cases and more commonly in areas of moisture and friction, such
as in the perioral area and in up to 50% of lesions involving
the perineum. Hemangioma size is another important predictor of
complication: those larger than 35 cm2 have a higher
rate of complications.5
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Segmental Hemangiomas
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Segmental facial hemangiomas (Fig. 364-1A)
can be associated with a group of structural malformations known
as PHACE, an acronym for posterior fossa brain
malformations, hemangiomas, arterial
anomalies, coarctation of the aorta and cardiac defects,
and eye abnormalities. When midline sternal
defects or supraumbilical abdominal raphe are present,
the condition is referred to as PHACES syndrome. This more recently
described neurocutaneous syndrome may actually be as common as Sturge-Weber
syndrome6 and has an female-to-male ratio of 8:1.
Most cases are associated with segmental hemangiomas with involvement
of either S1 or S3 segments (eFig. 364.1).
The diagnosis of PHACES is rendered in patients having a segmental
facial hemangioma and one other associated feature. A more recent
prospective study showed that structural and cerebrovascular arterial
anomalies are the most common manifestation of PHACES syndrome.7 Cardiovascular
complications such as coarctation of the aorta, aneurysms, and aortic
arch abnormalities also occur frequently in PHACES. Ocular complications (microphthalmia,
retinal vascular anomalies, etc) and ventral developmental defects
(sternal hypoplasia or pit, supraumbilical raphe) are also commonly
observed. Patients with large facial segmental hemangioma should
undergo workup to rule out PHACES syndrome, including MRI and MR
angiography of the brain, as well as ophthalmology and cardiology
assessments, including echocardiogram. Thyroid function studies should
also be performed in patients with suspected PHACE because hypothyroidism
has been reported as an association.
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Analogous to facial segmental hemangiomas, segmental hemangioma
involving the lumbosacral regions can be associated with spinal
dysraphism and genitourinary anomalies.
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Specific anatomic locations can provide clues to possible complications.
Hemangiomas located in the periorbital area can cause astigmatism
and visual axis obstruction leading to amblyopia and should be followed
closely, particularly during the growth phase (eg, the first few
months of life). Nasal tip hemangiomas can cause splaying of the
alar cartilage and are often slow to involute, causing permanent
distortion of the normal anatomy which can be difficult to surgically
correct. Large hemangiomas on the ear may cause temporary conductive
hearing loss or deformation of the cartilage. Perioral and perianal
(mucosal) hemangiomas have a high rate of ulceration,8 causing
significant pain. In addition, IH located on the lip may cause distortion
of the vermillion border or Cupid’s bow, leading to altered
anatomy and disfigurement. Hemangiomas located in the so-called
beard distribution of the mandible, chin, and upper neck have a
high risk of associated airway involvement. Infants with airway
hemangiomas often present with stridor or “noisy breathing” between
6 and 12 weeks of age; aggressive systemic treatment is warranted
in these cases. Aggressive systemic and surgical management can
help avoid the need for tracheostomy in the majority of patients.
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Infants with five or more hemangiomas or large
segmental hemangiomas have a greater risk of extracutaneous hemangiomas, particularly
involving the liver. Most often, liver hemangiomas are small and
asymptomatic and can be followed with ultrasound until stabilization
is documented. If present, Doppler examination with assessment of
flow within the hepatic vein and artery can help determine risk
of hemodynamic compromise. In rare instances, extensive intra-abdominal
hemangiomas can cause failure to thrive and high-output cardiac
failure. A rare complication is an acquired form of hypothyroidism
due to hemangioma production of type 3 iodothryonine deiodinase.9
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The major goals in management of hemangiomas are to prevent life-
or function-threatening emergencies, adequately treat ulceration,
anticipate and attempt to manage potential disfigurement, and minimize
psychosocial stress for the patient and family. Overly aggressive,
potentially scarring surgical procedures early in the proliferative
phases of hemangiomas should be avoided in tumors where the likelihood
of involution without significant cosmetic impairment is expected.
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Up to 15% of hemangiomas ulcerate,8 often
in the early proliferative stage. Ulceration occurs most frequently
on mucosal sites (lip and perineum) in segmental or large lesions.
Pain is nearly always present and should be adequately treated with
analgesia. Local wound care is important in the management of ulcerated
hemangiomas. Crust should be removed with warm compresses and, if
necessary, dilute hydrogen peroxide solution. Topical metrogel is
anecdotally effective and should be applied to ulcerated areas daily. Protective
barrier agents such as petrolatum should be used liberally, along
with nonstick dressings. Occlusion helps decrease pain and speed
healing. In severe cases, topical becalpermin gel (platelet-derived
growth factor) is useful in stimulating granulation tissue and healing.10 Pulsed
dye laser can also be used as a treatment for ulceration. For some
sites, surgical excision may be a good treatment for ulceration because
a scar will be present in any case.
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Corticosteroids are a mainstay of treatment of hemangiomas, used
topically, intralesionally, or orally. Very potent (class 1) topical
steroids are occasionally helpful for very flat hemangiomas in prominent
anatomic locations. Intralesional injections of triamcinolone may be
useful for small, well-localized hemangiomas in difficult locations,
such as the lip or nasal tip, and for treating periorbital hemangiomas.
Potential complications include skin atrophy, infection, and systemic
absorption and, for periorbital lesions, rarely, retinal artery
occlusion. Oral corticosteroids are a first-line therapy for life-
or function-threatening hemangiomas. Oral prednisolone is typically
administered in doses of 2 to 3 mg/kg/day. At
least two thirds of patients respond with shrinkage or stabilization
in size of the hemangioma. Therapy for several months is often necessary,
with a gradual taper toward the end. Potential side effects include
irritability, hypertension, immunosuppression, and growth retardation,
but treatment is usually well tolerated, with catch-up growth occurring
after cessation. High-dose corticosteroids can predispose patients
to infections such as pneumocystis pneumonia; prophylaxis with trimethoprim/sulfamethoxazole
is often given as adjunctive therapy. Gastroesophageal reflux may
also result; ranitidine or proton pump inhibitors can be helpful.
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Since 2008, more than 30 case reports have demonstrated efficacy
of propranolol in the treatment of hemangiomas. Controlled randomized trials
have not yet been performed. Propranolol is typically administered
in doses of 1 to 3 mg/kg/day divided into 2 or
3 doses. Favorable responses are often noted within days of starting
the medication. As with steroids, administration for many months
is often necessary. Potential side effects include hypoglycemia
(particularly with preoperative fasting or poor feeding), bradycardia,
hypotension, nightmares, and hypothermia. A possible concern for
propranolol use in patients with PHACE syndrome is that hypotension
or bradycardia may reduce an already compromised cerebrovascular
flow. With the introduction of propranolol, interferon alpha use will
likely decline, due to its potential neurotoxicity in young infants.
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Laser therapy, particularly the flashlamp pumped pulsed dye laser
(PDL), can be effective in treating relatively flat, superficial
hemangiomas or in “mopping up” residual telangiectasias, but
is ineffective in treating thicker and deeper lesions because of
its limited depth of penetration. The risk of scarring is higher
than in its use for port wine stains, particularly in the proliferative
phase. Other laser systems have also been used for treating hemangiomas,
including intralesional Nd-YAG and other continuous-wave laser systems.
These lasers are more operator dependent and have a higher risk
of scarring than PDL but may be appropriate in selected cases.
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Reconstructive surgical techniques are well accepted for revising
permanent scars left after hemangioma involution. Earlier surgical
excision is more controversial but is probably reasonable in hemangiomas
with a very high likelihood of leaving a baglike fibrofatty residual (eg,
pedunculated hemangiomas) or other obvious scar. If feasible, surgery
is also recommended for function-threatening hemangiomas that have
failed medical therapy. In cases where the ultimate results of involution
are less predictable, the risks of surgery must be carefully weighed
against many factors, including the rate at which involution is
occurring, the reactions of the child and parents, and local specialty
care resources. If significant uncertainty is present, it is usually
best to delay a decision until 3 to 4 years of age and reevaluate. Multidisciplinary
vascular birthmark clinics (which exist at many university medical
centers) may provide helpful consultation.