Diagnosing and treating pediatric hemangiomas

By Beth Ann Drolet, MD

What are hemangiomas and what is the pathogenesis?

Infantile hemangiomas are the most common tumors of childhood, occurring in 1 percent of infants. Most hemangiomas are found in the skin, but rarely, they may occur in the liver, spleen, gastrointestinal tract, airway, thorax and central nervous system. While most are benign in their behavior, they often cause extreme parental distress, and complications may lead to considerable morbidity and permanent disfigurement depending on their location and size. Hemangiomas are vascular tumors that are characterized by a rapid growth phase followed by a spontaneous involution phase. The pathogenesis of these vascular tumors is just now being elucidated. There are cellular and immunohistochemical similarities between infantile hemangiomas and the chronic villus cells of the placenta.

Which infants are at risk to develop hemangiomas?

A large study recently completed by a multi-institutional collaborative group of pediatric dermatologists identified several risk factors for the development of hemangiomas. Hemangiomas are more common in Caucasians, females and premature infants. This study demonstrated a 25 percent increased risk with every 500 gm less of birth weight. Although not previously considered to be inherited, the study found that 34 percent of infants had a family history of a vascular anomaly. This data has led to new studies to evaluate this and other possible genetic links to this disease.

Pediatric hemangioma case presentation A 2-month-old Caucasian male presented to dermatology for a rapidly enlarging mass over the left eye. The infant was the product of a twin gestation and was born prematurely at 35 weeks. Shortly after birth, the parents noted multiple red cutaneous patch on the left upper eyelid and trunk. These were rapidly progressive, particularly the lesion over the left eye. The parents brought the patches to the attention of their primary care physician, both at the initial newborn infant visit as well as at the 1-month-old well-child check. (See Figure 1.) The patches were diagnosed as hemangiomas. The parents were subsequently reassured these lesions were benign and did not require treatment. By the time of the 2-month-old visit, the left upper eyelid swelling was causing significant obstruction of the visual field, and the patient was able to open his eye only 10 to15 percent when compared to his right eye. On physical examination there was a 2.7 cm x 2.0 cm, soft, warm mass on the left upper eyelid with 70 to 80 percent occlusion of the left eye. (See Figure 2.) There were four, red, elevated plagues measuring 5 mm to 6 cm distributed on the right wrist, left eye, right abdomen, right buttock, chin and right upper arm. There was no hepatospleenomegaly or cardiac murmurs. Due to the visual obstruction of the left eye and the impending amyblopia, the patient was started on oral corticosteroids for treatment.

Figure 1. Figure 2.

What is the natural history of infantile hemangiomas and are there risk factors for rapid growth?

Infantile hemangiomas are classically considered "birthmarks," but unlike most birthmarks, they are uniquely dynamic. This dynamic clinical behavior can be explained at the cellular level. In contrast to other vascular lesions, which are the result of errors in vascular development, hemangiomas are true vascular tumors. The cells of infantile hemangiomas are mitotically active, and this explains the biologic behavior. At birth hemangiomas are either absent or barely evident, but they proliferate in the first few weeks to months of life. Eventually the mitotic activity slows and proliferations stops. The tumor undergoes spontaneous involution over several months to years. Recent evidence suggests most hemangiomas will reach their maximum size by 5 months of age, however, there is great individual variability in the rate and duration of proliferation. Some infants will have minimal or no growth of their tumor, while others will experience proliferation at an alarming rate.

What are common complications of hemangiomas?

Even though most hemangiomas will resolve spontaneously, there is a significant potential for complications. A recent prospective study demonstrated that 24 percent of infants with hemangiomas will have complications related to their tumor. This may be an underestimation as this study did not account for permanent disfigurement. Size, location and subtype of hemangiomas are all risk factors for poor outcome. The larger the hemangioma, the higher the risk for complications. Location also plays a crucial role in the impact of hemangiomas. Small, slowly proliferating lesions still may be problematic or even life threatening if they compromise a vital structure. (See Table 1.) Perhaps the single most important risk factor for poor outcome is hemangioma subtype. Hemangiomas appear to occur in two different patterns – focal and segmental. A segmental hemangioma is defined as a lesion that arises multifocal from what appears to be an embryologic "segment." (See Figure 3a.) In contrast, focal hemangiomas are lesions that arise from a solitary "focus." (See Figure 3b.) Segmental hemangiomas have been found to have an 11 times increased risk of complications and need for treatment. Furthermore, they are much more likely to be associated with systemic malformations.

Table 1 - High risk location
Location	Complication
Eyelids	Functional impariment: amblyopia
Ear	Functional impairment
"Beard" region	Functional impairment: subglottic airway obstruction
Forehead	Disfigurement
Upper lip	Disfigurement, ulceration
Lower lip	Disfigurement, ulceration
Nasal tip	Disfigurement
Anogenital region	Ulceration
Neck	Ulceration
Large segmental facial	PHACES association

Figure 3a.

Figure 3b.

Potential complications of hemangiomas can be divided into three categories:

Ulceration: Ulceration, the most frequent complication, can be excruciatingly painful and carries the risk of infection, hemorrhage and scarring. Ulceration results from necrosis and typically occurs in deep, rapidly enlarging hemangiomas, but occasionally may even be present at birth. Infants with ulcerated hemangiomas often are irritable, feed poorly and are unable to sleep. Pain may precede the ulceration and probably is the result of ischemia and necrosis within the hemangioma. Hemorrhage, although rare and usually inconsequential, can be very alarming to parents. In most cases blood loss is minimal and can be controlled with direct pressure. Hemangiomas of the anogenital region are particularly at risk for ulceration and infection, and these infants will have severe pain on urination or defecation. Superinfection may lead to cellulitis, osteomyelitis, septicemia, and in some cases, has been lethal.

Functional impairment: Periorbital hemangiomas pose considerable risk to vision and should be carefully monitored. Amblyopia may result from obstruction of the visual axis, however, the most common complication, astigmatism, is caused by insidious compression of the globe or extension of the tumor into the retrobulbar space. All patients with periocular hemangiomas should be evaluated by an ophthalmologist. Hemangiomas involving the ear may obstruct the external auditory canal resulting in otitis or a decrease in auditory conduction, which ultimately may cause speech delay.

Permanent disfigurement: Accurate prediction of which hemangiomas are likely to cause permanent damage is a formidable task, and the choice of appropriate treatment (if any) depends on several factors. These include the location and rate of growth of the hemangioma, depth within the skin, age of the patient and presence or threat of complications. Hemangiomas with prominent dermal components, particularly those involving the lips, nose, ears and forehead, are at greatest risk for scarring. In these locations, large or rapidly growing lesions will leave residual fibrofatty tissue, even after the hemangioma has involuted. In some instances the fibrofatty tissue is relatively easy to surgically remove (nasal tip), whereas in others the surgical scar may be quite conspicuous (upper lip). Hemangiomas complicated by deep ulceration frequently will leave residual scarring of the epidermis.

When do I have to worry about an airway hemangioma?

Airway hemangiomas may be life threatening given their potential for proliferation with subsequent obstruction. Subglottic hemangiomas are manifest by hoarseness and stridor. Progression to respiratory failure may be rapid, often occurring at 6 to 12 weeks old. Approximately 50 percent of these infants will have associated cutaneous hemangiomas, thus "noisy breathing" in an infant with a cutaneous hemangioma warrants direct visualization of the airway. Infants with cutaneous hemangiomas involving the chin, lips, mandibular region and neck (beard region) are at greatest risk for airway involvement. Close clinical observation of asymptomatic, young infants with extensive facial hemangiomas in the "beard" distribution is indicated as 60 percent of these patients will develop symptomatic airway hemangiomas.

When should a workup be completed to rule out visceral hemangiomas?

Multiple cutaneous (diffuse hemangiomatosis) and large facial hemangiomas may be associated with visceral hemangiomas. Infants with numerous cutaneous hemangiomas should be observed carefully for signs and symptoms of visceral lesions, which may present with organomegaly or high-output cardiac failure. A screening abdominal ultrasound should be considered when there are more than five cutaneous lesions.

When are hemangiomas associated with congenital malformations?

Large hemangiomas of the segmental subtype more often are associated with congenital abnormalities. PHACES association (consisting of Posterior fossa malformations, Hemangiomas, Arterial anomalies, Coarctation of the aorta and cardiac anomalies, Eye anomalies and Sternal cleft), described only 10 years ago, is a relatively common disorder seen in 20 percent of infants with large segmental facial hemangiomas. Infants with large facial hemangiomas should be referred to a pediatric dermatologist given the high risk of complications, need for treatment and associated malformations. Spinal dysraphic conditions have been described in infants with hemangiomas overlying the lumbosacral spine. Radiological imaging is indicated in infants with true hemangiomas over the lumbosacral region.

When should hemangiomas be treated?

The management of hemangiomas continues to be an area of considerable controversy. Given the wide spectrum of disease, unpredictable biologic behavior and natural tendency for involution, the greatest challenge in caring for infants with hemangiomas is determining which infants need an aggressive treatment regimen or are at highest risk for complications.

Subsequent to use of  X-irradiation in the 1940s and 1950s, many experts decried the used of aggressive therapy for these self-limiting tumors, and studies indeed demonstrated that the results of radiation or excisional surgery were worse than in those left untreated. Nevertheless, the development of newer therapeutic options and the prospect of newly developed inhibitors of angiogenesis have led many authors to question the wisdom of a uniformly hands-off approach. The decision to treat should be tailored to each specific hemangioma, taking into account the patient's age, location of the hemangioma, size of the hemangioma, rate of growth of the hemangioma and potential for complications. (See Table 2.)

Table 2 - Therapeutic considerations

Is the hemangioma going to cause a life-threatening complication (airway, high-output cardiac failure)?

Is the hemangioma going to cause permanent functional impairment (eyelids, ear canal, nose, lips)?

Is the hemangioma ulcerated or at high risk for ulceration (diaper region, upper back, neck, cartliage of the ear, nose and lip)?

What is the age of the infant?

Is the hemangioma proliferating rapidly or for a long period?

Is there high risk of permanent disfigurement?

Can the residual disfigurement easily be repaired with acceptable scarring?

Is there a prolonged or abortive involutional phase?

 

How are hemangiomas treated?

When treatment is indicated, the standard of care is oral corticosteroids. In 1968, Esterly et al first described the beneficial effects of oral steroids for infants with large hemangiomas. Several case series and retrospective papers have confirmed the antiproliferative effect of oral corticosteroids, however, there never has been a prospective double-blinded trial to demonstrate response rate in infants with hemangiomas. Other treatment options include intralesional corticosteroids, topical corticosteroids and laser therapy. 

What do parents worry about?

The effect of a hemangioma, particularly a facial hemangioma, on the parents of an affected infant should not be underestimated. Studies have demonstrated that parental reactions of disbelief, fear and mourning were common and similar in intensity to parental reactions to permanent congenital malformations. It is important to educate and prepare parents regarding what to expect. Active emotional support of parents can be very important. There are few disease processes that are so visible both to the parent and the public. Imagine watching the rapid growth of a tumor on your infant's face, while the doctors tell you "Not to worry, it is going to go away." Parents have reported being barraged with comments by strangers including accusations of child abuse. Family members frequently encourage parents to "have that taken care of." Realize that many parents will have seen pictures of massive hemangiomas on TV or the Internet. Reassure the parents that even though hemangiomas proliferate and grow, they usually do not expand beyond the margins of the original lesion. Hemangiomas mark out their territory by 4 to 6 weeks of life. "Growth" means thickening or swelling of the hemangioma. Showing parents photographs of hemangiomas before and after spontaneous involution can be reassuring. It is important to frequently address parents' questions regarding their concerns of cosmetic outcomes, bleeding and complications.

Beth Ann Drolet, MD, is medical director of both Dermatology and Birthmarks and Vascular Anomalies and a pediatric dermatologist at Children's Hospital of Wisconsin. She also is an associate professor of Dermatology at the Medical College of Wisconsin.

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