Infantile hemangiomas and PHACE Syndrome

What is an infantile hemangioma?

An infantile hemangioma is a common type of birthmark. In the past, terms such as strawberry mark or strawberry birthmark were used for infantile hemangiomas. The word birthmark is a general term used to describe abnormalities of the skin. A baby can develop birthmarks either before being born or soon after birth. Birthmark is a broad term and should not be used as a specific diagnosis as there are many types of birthmarks.

Infantile hemangiomas are unlike other birthmarks, in that they grow and change greatly during the first months of life. Infantile hemangiomas are made up of endothelial cells (cells that line the inside of blood vessels), which multiply at a quicker rate than normal. Hence, it is referred to as a benign (non-cancerous) tumor. Generally, infantile hemangiomas are absent or subtle at birth and gradually appear during the first few weeks of life. Most skin hemangiomas are seen by 6 months of age. During the natural course of a hemangioma, the birthmark reaches a point of maximum growth and then begins to shrink and disappear.

Rarely, hemangiomas can develop in the internal organs of the body. For example, they can grow in the liver, airway, gastrointestinal tract, and sometimes in other organs.

Figure1: A superficial hemangioma.

What does a hemangioma look like?

Hemangiomas can occur anywhere on the skin, but most often are found on the skin of the head or neck. They may be located in the outer layers of the skin (superficial hemangioma) or under the skin in the fat (deep hemangioma). A mixed hemangioma has both superficial and deep components to it. The color of a hemangioma varies depending on whether it is superficial, deep, or mixed. Most hemangiomas are round or oval in shape, but larger lesions may follow the shape of the affected body part. The size of hemangiomas is also variable, ranging from very small (1 mm) to very large (20 cm or larger). Every hemangioma differs in how fast it grows and how long it grows before it stops.

A superficial hemangioma is a birthmark made up of blood vessel cells that is near the outer layer of the skin. It will appear bright red to purple in color, and the surface may look uneven. Often, this benign tumor is called a 'strawberry birthmark' because of its appearance.

A deep hemangioma is a birthmark made up of blood vessel cells that is located deeper in the skin or in the fat layers. A deep hemangioma can be bluish in color, or could have a normal skin color. Often, deep hemangiomas may not be seen or felt until a baby is 4-6 months old, after it has entered the proliferative (major growth) phase and becomes protuberant (bulges out from the surrounding surface).

Mixed hemangiomas are the most common type of hemangioma. These hemangiomas have both superficial and deep components.

Figure 2: A deep hemangioma.

What is the most common hemangioma seen in PHACE syndrome?

Typically, the hemangiomas that are seen in PHACE syndrome cover a large area of the skin on the head or neck (greater than 5 cm). As a result, the term segmental hemangioma has been used to describe the appearance of hemangiomas that are associated with PHACE syndrome. Segmental hemangiomas often extend over a broad area, rather than a focal point as seen with the previous examples. These segmental hemangiomas tend to be greater than 5 cm in diameter and most often span one side of the face, scalp and neck. In newborns, segmental hemangiomas can be telangiectatic (broken blood vessel-like), or flat cherry-red patches. Segmental hemangiomas of the scalp, face, or neck are present in more than 95 percent of patients with PHACE syndrome.

How is a hemangioma diagnosed and what specialist should I see?

Figure 3: A segmental hemangioma.

In most cases, the diagnosis of a hemangioma can be made by the child's primary doctor, but sometimes vascular anomalies specialists may be needed to ensure the accuracy of the diagnosis. Segmental hemangiomas can sometimes be mistaken for port-wine stains, a type of flat red birthmark, so the expertise of a pediatric dermatologist may be needed for more unusual cases.

What are some of the complications involved with hemangiomas?

Interference with function: As a hemangioma grows it can interfere with the normal functions of the region where it is located. This is most often observed around the eye (see Eye Abnormalities section). A hemangioma near the eye may obstruct the infant's vision, which may cause an irreversible loss of sight. As a result, it is important to closely monitor hemangiomas near the eyelids. Other hemangiomas that may need urgent treatment are those in the airway (see Airway Compression section), in the brain (see Intracranial Hemangiomas section), in the diaper area, and around the mouth or nose.

Ulceration: The skin over the hemangioma can break down. The skin may appear raw or shiny and might develop a scab. Ulcerations can be very painful for the child, which can lead to irritability and difficulty feeding or sleeping. They also increase the risk of infection and scarring. Hemangiomas that are located on the mouth, nose, ear, and diaper region carry a higher risk of ulceration. Ulcerations heal slowly and treatment might be recommended to speed up this process and to prevent infection and scarring.

Bleeding: The blood vessels that make up hemangiomas are not normal. When hemangiomas bleed, they tend to bleed rapidly, but only for a short period of time. The bleeding should stop with gentle, direct pressure for fifteen minutes. If bleeding returns or does not stop with pressure, the child's doctor should be promptly contacted.

How are hemangiomas treated?

In general, most infantile hemangiomas are not treated because they shrink over time and disappear completely on their own. The decision to treat a hemangioma is determined by the age of the patient and the size, location, and growth rate of the hemangioma. Hemangiomas that are located in areas that can threaten health (airway or liver) or normal development (brain, ear canal, or eye), and those hemangiomas that are potentially disfiguring (face) are treated more quickly and aggressively than hemangiomas that pose less of a risk. Children with PHACE syndrome often have large hemangiomas and are more likely to have complications that require treatment. The doctor will discuss whether treatment is needed and what treatment is best for the child. The only medication currently approved by the Federal Drug Administration (FDA) to treat infantile hemangiomas is oral propranolol. Children with PHACE are currently excluded from this FDA label as the original study performed by the pharmaceutical company excluded children with PHACE syndrome. The pros and cons of using oral propranolol or other medications in children with PHACE syndrome must be carefully considered by physicians with expertise in both treating hemangiomas and PHACE syndrome.

Treatment options include:

• Observation is used for hemangiomas that are growing slowly or not threatening function of the eye, ear, or airway. Even though most hemangiomas will not require an oral medication or surgery, we believe that all hemangiomas should be monitored closely, especially during infancy. Hemangiomas undergo the most rapid period of growth during the first months of life and should be closely monitored during this period for potential complications.
• Propranolol is a beta-blocker medication that has been used for many years to treat various health conditions. It is most often used in children to treat rhythm abnormalities or irregular/fast heart rates. Many studies have shown that it is also effective in treating complicated infantile hemangioma. This medication must be prescribed by a doctor with experience using the drug and treating infantile hemangiomas. Side effects of the medication may include a drop in blood pressure, heart rate, or body temperature. It also may cause low blood sugar if the infant does not eat regularly. By closely monitoring the patient, parents and physicians can usually minimize the chances of side effects from this treatment. Careful observation is necessary, especially in children with PHACE syndrome who may be more susceptible to blood pressure and heart rate changes as they have cardiac, aortic arch, or arterial abnormalities. This medication is given by mouth two to three times a day.
• Topical (applied directly to the skin) timolol gel is a beta-blocker medication that can be applied directly to the hemangioma two times a day. This is often used to treat small superficial hemangiomas, but is not yet approved by the FDA to treat infantile hemangioma.
• Topical corticosteroids are also effective in controlling the growth of small superficial hemangiomas, particularly on the eyelid and around the mouth.
• Surgical excision (removal) is used most frequently to reconstruct scars or to remove fibrofatty tissue (the excess skin left behind when a hemangioma resolves). Early excision is an option in selected cases. Such cases include small hemangiomas with complications that are located in areas where surgical scars will be less noticeable, when a residual abnormality is inevitable or the hemangioma threatens life or bodily function, and when drug therapy is not effective or well tolerated. The hemangiomas observed in PHACE syndrome tend to be large and involve the nose, lip, and eye; therefore, surgical excision is not possible in most cases. The pros and cons of a surgical approach must be carefully considered since the scar from surgery may be worse than leaving a hemangioma to go away on its own. Generally, re-evaluation is recommended at about age 4 to assess how much residual hemangioma is present and to consider surgery for scarring or slowly regressing (shrinking) hemangiomas.
• Laser therapy has also been used to treat hemangiomas. Because of its limited depth of penetration, the flash-lamp pulsed dye laser works well for superficial hemangiomas but has no impact on deeper or thicker hemangiomas. It is most often used to improve the telangiectasia (broken blood vessels) after regression of the hemangiomas and may be effective in treating ulcerated hemangiomas to decrease pain and encourage healing. Using the flash-lamp pulsed dye laser in babies less than 6 months of age with PHACE syndrome has been shown to have an increased risk of scarring. Continuous-wave lasers such as the argon, neodymium:yttrium-aluminum-garnet (Nd:YAG), and potassium titanyl phosphate (KTP) have also been used but require greater physician expertise and training and have a greater risk of scarring.
• Vincristine is a medication that is used to treat a variety of tumors. Recently, it has been successfully used to treat hemangiomas that threaten important functions such as vision or breathing. This medication is given as an injection into a central venous line (special type of IV line) on a weekly basis. This medication is not FDA approved to use to treat infantile hemangioma.
• Regranex gel (becaplermin) is a topical medication used once a day to heal ulcerations, but it does not slow the growth of hemangiomas. It is a fairly new medication that the FDA has approved to treat diabetic ulcers in adults. It is very expensive and may not be covered by insurance without more information from a doctor.

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