History
Infantile hemangiomas exhibit a characteristic evolution, with early rapid growth (proliferation) followed by slow involution. [1] The earliest sign of a superficial infantile hemangioma is blanching of the involved skin. This may be followed by fine telangiectasias and then a red or crimson macule. Rarely, a shallow ulceration may be the first sign of an incipient infantile hemangioma.
Rapid growth during the neonatal period (birth to 4 wk) is the historical hallmark of infantile hemangiomas. This rate is characteristically beyond the growth rate of the infant, thereby differentiating this neoplasm from vascular malformations that grow commensurate with the infant. As proliferation ensues, the infantile hemangioma becomes elevated and may be dome shaped, lobulated, plaquelike, tumoral, or any combination of these morphologies. [3, 4] The proliferation phase occurs during the first year, with the most growth occurring during the first 4-6 months of life. Proliferation slows considerably between the middle and end of the first year of life; however, most hemangiomas have completed this phase by age 4 months. During this time, the hemangioma may remain quiescent or may begin to involute. [43]
The involutional phase of an infantile hemangioma may be rapid or prolonged. No specific characteristics appear to influence the rate or completeness of involution of infantile hemangiomas. The exception is a separate type of hemangioma referred to as a rapidly involuting congenital hemangioma (RICH), which proliferates in utero and is fully developed at birth. [44] RICHs tend to completely involute during the second year of life. Congenital hemangiomas are not considered to be a variant of the infantile hemangioma.
Fifty percent of infantile hemangiomas complete involution by age 5 years and 70% by age 7 years; the remainder may take an additional 3-5 years to complete the process. [2] Of lesions that have involuted by age 6 years, 38% have residual evidence with scar formation, telangiectasia, or redundant or anetodermic skin. Infantile hemangiomas that take longer to involute have a higher incidence of permanent cutaneous residua. Eighty percent of infantile hemangiomas that complete involution after age 6 years may exhibit cutaneous residua. [45]
Physical Examination
Eighty percent of infantile hemangiomas are focal and solitary. Sixty percent of cutaneous hemangiomas occur on the head and neck, 25% on the trunk, and 15% on the extremities (see image below). Hemangiomas also can occur in extracutaneous sites, including the liver, gastrointestinal tract, larynx, CNS, pancreas, gall bladder, thymus, spleen, lymph nodes, lung, urinary bladder, and adrenal glands.
This proliferating superficial infantile hemangioma on the trunk required no therapy.
Features of early proliferating superficial infantile hemangiomas (birth to age 6 wk) include blanching of the involved skin, followed by fine telangiectasias, and then a red or crimson macule or papule that often is surrounded by a faint halo of vascular blanching. Occasionally, an infantile hemangioma is heralded by a shallow ulceration, especially lip and buttock lesions (see image below). [31]
Exquisitely painful ulcerated mixed hemangioma (superficial and deep) of the left deltoid in a 6-month-old female infant. This lesion was treated successfully with pulsed dye laser.
As infantile hemangiomas proliferate (birth to age 12 mo), depending on their size and depth, their morphology and texture may be dome shaped, bosselated, plaquelike, tumoral, or any combination of these morphologies.
If the infantile hemangioma is located in the subcutaneous tissue, the overlying skin may be completely normal. Color varies with the depth from the surface and can be bright red or crimson (superficial dermis), purple, blue, or flesh colored with predominant involvement of the deeper tissues. Telangiectases and large superficial veins radiating from the infantile hemangioma often are associated. The consistency is firm, rubbery, and tense and expands with increased intravascular pressure (eg, with crying when on the head and neck). Tenderness to palpation is a variable generally uncommon feature of infantile hemangiomas.
Most infantile hemangiomas reach a maximum size of 0.5-5 cm, but they can range from the size of a pinhead to greater than 20 cm in diameter. Most infantile hemangiomas remain well circumscribed and focal. A minority may be segmental in nature, covering a larger portion of the cutaneous surface. This variant has more superficial than deep involvement, as is seen with extensive facial lesions (see image below).
This superficial and deep infantile hemangioma resulted in astigmatism of the left eye, requiring spectacles to correct the refractive error and to prevent amblyopia. Further growth of this hemangioma necessitated a course of oral prednisolone. The hemangioma shrunk rapidly, and the patient's astigmatism decreased such that the spectacles were unnecessary 1 month after beginning steroids.
Another variant is the infantile hemangioma with minimal or arrested growth (IH-MAG). These have been previously referred to as abortive, reticular, or telangiectatic infantile hemangiomas. By definition these IHs have a proliferative component equaling less than 25% of their total surface area. They are mostly flat and may simply present with an erythematous blush of the affected skin.
As its prior name suggests, an abortive or reticular infantile hemangioma often has telangiectasia coursing through it. This variant may be confused with a capillary malformation; however, the growth characteristics and presence of visible telangiectases assist in differentiation. This variant has been seen in association with underlying vascular and other extracutaneous congenital anomalies (PHACE and PELVIS syndromes and with underlying vascular anomalies on an extremity) as well as demonstrating a predilection for the lower body, in contradistinction to classic IHs. [46, 47]
During involution, which may begin as early as a few months from birth or as late as 2-3 years, the infantile hemangioma resolves centrifugally from the center of the lesion. This is less notable with deeper lesions. The superficial lesions become less red, taking on a duskier maroon-to-purple color, and finally regaining normal flesh tones (often referred to as "graying"). With involution, the infantile hemangiomas become softer and more compressible with decreased tenderness, and they exhibit less expansion during increased intravascular pressure (eg, crying).
During the late involution phase (quiescent residual lesions), the skin may return to normal with no evidence of a previous pathologic process. Approximately 50-60% of all hemangiomas resolve incompletely, leaving permanent changes in the skin. These changes include telangiectases, superficial dilated veins, stippled scarring, anetoderma or epidermal atrophy (particularly with superficial lesions), hypopigmentation, and/or redundant skin with fibrofatty residua (especially with subcutaneous lesions). [45]
Complications
No demographic, prenatal, and perinatal factors have been shown to be associated with higher rates of complications. [34]
Ulceration
Ulceration occurs in 10-15% of infantile hemangiomas, especially combined superficial and deep lesions. The cause of ulceration is not clear but may be a result of outstripped blood supply to the overlying skin or secondary to the action of certain cytokines.
Ulceration usually occurs in tense, rapidly proliferating hemangiomas and occurs more commonly in the anogenital region, lip, and chest, although any site may develop an ulcer. The ulcerations are extremely painful and result in scar formation upon healing, which may take months. A white discoloration seen early in the course (usually within the first 3 months of life), mimicking that seen in early involution, may herald an impending ulceration, particularly in segmental infantile hemangiomas. [48]
Secondary infection can occur, but cellulitis, abscess, and bacteremia are rare.
While intermittent bleeding is common, serious hemorrhage appears to be rare. Life-threatening arterial hemorrhage has been reported in at least 7 infants, mostly complicating segmental hemangiomas of the head and neck. Closer observation and imaging studies to assess underlying vasculature may be helpful in very high-risk cases. [49]
Treatment for ulcerated hemangiomas includes bio-occlusive dressings (especially hydrocolloid dressings), topical anesthetics like lidocaine jelly 2% for associated pain, pulsed-dye laser (PDL) surgery, topical timolol (warning: monitor for systemic absorption), oral propranolol, becaplermin gel (human recombinant platelet-derived growth factor), [50] external compression therapy (for limb lesions), and, occasionally, topical or oral antibiotics. [51] PDL surgery has been reported to be effective for ulcerated superficial hemangiomas and often decreases pain, even before the ulcer has reepithelialized. [52]
Airway obstruction
Airway obstruction is a rare complication of hemangiomas; upper lip lesions very seldom obstruct both nasal passages. This can be a problem for young infants who are obligate nose breathers. Cervical parapharyngeal or palatal hemangiomas can cause acute or subacute obstruction.
Insidious signs and symptoms, such as sleep apnea, cor pulmonale, or even failure to thrive, can be associated with hemangiomas in the upper aerodigestive tract. Laryngeal (often referred to as subglottic) hemangiomas present early (6-8 wk) with symptoms of inspiratory or biphasic stridor, especially with feeding or crying. Cough, cyanosis, or hoarseness may be associated findings. The diagnosis is confirmed by direct laryngoscopy, MRI, soft tissue anteroposterior neck radiographs, or esophagography.
Prompt consultation with a pediatric otolaryngologist should be sought for all suspected cases. Treatment includes systemic beta-blockers like propranolol, corticosteroids, or interferon alfa, as well as excisional or laser surgery. Tracheostomy is sometimes necessary until the airway becomes patent.
Upper airway hemangiomas appear to be associated more commonly with superficial cutaneous hemangiomas involving the mandibular branch of the trigeminal nerve (beard area hemangiomas). [53] They can occur without cutaneous involvement.
Visual obstruction
Visual obstruction should be considered whenever a hemangioma involves the eyelids or periorbital tissues.
Hemangiomas can lead to visual deprivation amblyopia by 3 separate mechanisms: physical obstruction of the visual axis, astigmatism from direct pressure on the anterior segment from eyelid involvement (upper eyelid is more common than lower eyelid), and unilateral myopia. Strabismus can result either secondary to amblyopia or from paralysis of the extraocular muscles infiltrated by an orbital hemangioma.
A pediatric ophthalmologist should evaluate all children with periorbital hemangiomas using refraction with retinoscopy, with upper eyelid lesions requiring the most frequent observation. A thorough discussion of periocular hemangiomas is beyond the scope of this chapter; however, a review by Ceisler and colleagues describes the appropriate evaluation and potential treatments. [54]
Also see Capillary Hemangioma.
Other complications
Diffuse neonatal hemangiomatosis is a potentially life-threatening condition characterized by numerous cutaneous hemangiomas accompanied by visceral hemangiomas. When more than five cutaneous hemangiomas are present, the risk of visceral lesions rises. The liver and gastrointestinal tract are affected most often, although any organ can be involved. Congestive heart failure is a cause of early mortality because of increased vascular volume. Evaluation should include an imaging study of the liver (eg, ultrasonography, MRI) and stool guaiac tests to rule out intestinal bleeding from gut hemangiomas if there is clinical concern. Oral propranolol is effective for hastening regression of hepatic hemangiomas. Systemic corticosteroids, interferon alfa, and conventional surgery are alternative treatments if propranolol is ineffective or contraindicated.
Kasabach-Merritt phenomenon (KMP) is marked by platelet sequestration and severe thrombocytopenia associated with a rapidly proliferating vascular neoplasm. This can be accompanied by a potentially fatal, generalized bleeding disorder. KMP is heralded by rapid enlargement, edema of the surrounding tissues, and accompanying purpura. [55] Most cases of KMP are associated with kaposiform hemangioendothelioma or tufted angioma and not infantile hemangiomas, as previously believed. [35] The early reports of KMP were described in lesions in which a clinical, not histological, diagnosis was made. Vincristine and radiotherapy have been effective in several cases of KMP caused by kaposiform hemangioendotheliomas and tufted angiomas.
Patients with PHACE syndrome present with hemangiomas and one or more extracutaneous congenital anomalies. Reports have also described intracranial invasion of associated infantile hemangiomas. [56] PHACE syndrome is an acronym denoting posterior fossa abnormalities (characteristically Dandy-Walker malformation and other forms of brain hypoplasia), hemangiomas (cervicofacial, segmental/>5 cm in diameter), arterial anomalies (especially carotid, cerebral, and vertebral), cardiac anomalies (especially coarctation of the aorta), eye abnormalities, and, rarely, midline ventral abnormalities (sternal clefting or supraumbilical raphe). See Mortality/Morbidity.
Segmental infantile hemangiomas involving the perineal area may be associated with other underlying congenital anomalies as delineated in the PELVIS or SACRAL syndromes. [39] The acronymic PELVIS syndrome describes the association of a perineal hemangioma with any of the following: external genital malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, or skin tag. SACRAL syndrome is spinal dysraphism with anogenital, cutaneous, renal, and urologic anomalies, associated with an angioma of lumbosacral localization.
An isolated midline lumbosacral hemangioma may be a cutaneous marker for underlying occult spinal dysraphism, the most common being an intraspinal lipoma with resultant tethered cord. Spinal imaging should be performed in these cases. Symptoms may not occur for several years and which infants require corrective surgery has been debated, because as many as 10% of the population have asymptomatic tethering of the spinal cord. The decision should be left to a neurosurgeon with experience with this condition.
Rarely, infantile hemangiomas have been implicated in cases of consumptive hypothyroidism. [57] This was initially reported with hepatic hemangiomas; however, this has also been reported with bulky cutaneous infantile hemangiomas. [58] This phenomenon appears be secondary to high activity of the type 3 iodothyronine deiodinase enzyme in hemangioma tissue, which is responsible for degradation of T4 to reverse T3 (rT3). One case reported also demonstrated increased production of a thyrotropinlike hormone from a hepatic hemangioma. [59] Thyroid function tests should be ordered in the appropriate clinical setting.
Psychosocial problems associated with disfiguring facial hemangiomas can be significant. [41] During infancy and early childhood, parents often have reactions of loss and grief. Parental feelings of disbelief, panic, or fear often are associated with the rapid growth of these lesions. The variability in the natural course, in regard to timing and completeness of resolution, adds to parental anxiety. Parental stress is heightened by strangers who stare, startle, or raise questions about causality, such as trauma (especially implied or suspected child abuse), infection, or cancer. Psychosocial stigmatization can be problematic for both parents and patients with disfiguring facial hemangiomas. Lesions that result in significant facial or obvious disfigurement should be addressed before the child starts school.
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Histopathology of a proliferating infantile hemangioma with plump endothelial cells in the dermis.
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This proliferating superficial infantile hemangioma on the trunk required no therapy.
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Exquisitely painful ulcerated mixed hemangioma (superficial and deep) of the left deltoid in a 6-month-old female infant. This lesion was treated successfully with pulsed dye laser.
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This superficial and deep infantile hemangioma resulted in astigmatism of the left eye, requiring spectacles to correct the refractive error and to prevent amblyopia. Further growth of this hemangioma necessitated a course of oral prednisolone. The hemangioma shrunk rapidly, and the patient's astigmatism decreased such that the spectacles were unnecessary 1 month after beginning steroids.
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Segmental infantile hemangioma in a female infant with PHACE syndrome involving the posterior neck and right forehead associated with an absent right vertebral artery and a laryngeal hemangioma.
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Segmental infantile hemangioma with minimal or arrested growth of the bilateral buttocks and posterior thigh in this male infant with PELVIS syndrome (complicated by cutaneous ulceration, hypospadias, anal stenosis, intraspinal lipoma with tethered cord). The white material is a barrier diaper cream.
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Superficial proliferating infantile hemangioma on the lower extremity
