Close attention required for infantile hemangiomas

Caption: Focal IH in 3-month-old female before and after 8 months' treatment with oral propranolol

One evolving and under-researched area of dermatology includes infantile hemangiomas (IH), according to Dawn Marie Davis, M.D., associate professor, Departments of Dermatology and Pediatrics, and section head, Pediatric Dermatology, at the Mayo Clinic in Rochester, Minn.

Dawn Marie Davis, M.D.The first publication regarding oral propranolol for IH¹ came about when physicians used it to treat cardiac abnormalities in patients with IH, according to Dr. Davis. “The hemangiomas shrunk right before their eyes," she says.

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"These patients probably had posterior fossa malformation, hemangioma, arterial, cardiac and eye abnormalities (PHACES) syndrome,” Dr. Davis explains. She sees two to three patients monthly with PHACES and estimates that 5% or fewer of infantile hemangiomas present high risk of functional or other (often delayed) complications.

"There may be posterior brain anomalies, heart anomalies or eye and ear anomalies. Infants are too young to developmentally manifest symptoms, and they can't articulate them. So children can be up to a couple years old before they are otherwise detected," she says.

NEXT: Detecting complications

Caption: Focal IH in 3-month-old female before and after 8 months' treatment with oral propranolol

Detecting complications

To detect complications early, her patients with suspected PHACES undergo imaging of the head and heart, plus eye exams. For children with large IH in the pelvic girdle, which can mark a syndrome known as PELVIS, SACRAL or LUMBAR, Dr. Davis advises to "Get imaging of the abdomen and pelvis, and do a very thorough cutaneous exam because many of the signs are present on the skin." These include skin tags, lipomyelomeningocele, imperforate anus and anomalous external genitalia.

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Treating troublesome IH early can help avoid or minimize complications, she says.

The most comprehensive, current guidelines come from a 2013 consensus statement.² Per these guidelines, “We usually prescribe approximately 2 mg/kg per day, divided into three doses, as our ideal dose" of propranolol, she notes. But, in practice, "That ranges from 1 mg/kg to 3 mg/kg per day, divided three times daily."

To avoid potentially dangerous blood-pressure troughs, she says, patients must take propranolol with food or feedings. Additionally, parents must monitor their child's oral intake for changes, such as a diminished appetite or vomiting with illness.

"We don't want children to take propranolol, then vomit it right back up. We also don't want parents to think the child has vomited the propranolol, but they haven't, and give them more." These somewhat complex requirements demand that physicians and parents cultivate strong relationships and effective communication, Dr. Davis adds.

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Also, dermatologists must warn parents that IH can recur once treatment stops. Fortunately, she says, “We know that the earlier you start propranolol, and the longer a child stays on propranolol, the less likely the child is to have rebound," which usually responds to a second medication course.

NEXT: More research required

Caption: Focal IH in 3-month-old female before and after 8 months' treatment with oral propranolol

More research required

With systemic propranolol, "We've all learned by trial and error. And because it's such a newly discovered drug for this purpose, that people have investigated in many different ways, we still have much to learn about propranolol regimens," Dr. Davis says.

Propranolol works best on growing IH, but it has been shown to shrink some stable IH, she notes. Ultimately, "We'd like to know if there is a better dosing schedule and target dose. We also need more information regarding side effects," she says.

Studies report hypotension, hypoglycemia (which can occur if a patient takes propranolol on an empty stomach) and bronchospasm (in patients with a history of reactive airways), "But we don't know how common they are," she says.

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As the number of children being hospitalized to initiate treatment of IH with propranolol is decreasing, "We need to better define hospital admission criteria," she says. And with several antihypertensive beta blockers similar to propranolol available, "Perhaps we need to perform research on them – other drugs in the same class may work better. Or maybe we'll find that propranolol is the best, and we just happened to hit it the first time."

For ulcerating hemangiomas, options include pulsed dye laser and topical becaplermin (platelet-derived growth factor). Better yet, she says, is preventing potentially problematic small, flat IH from ulcerating by applying topical timolol twice daily for up to several months.

"I like to prescribe the gel, because it's easier to control and doesn't run like the solution," she says.

Disclosures: Dr. Davis reports no relevant financial interests.

References

1. Léauté-labrèze C, Dumas de la roque E, Hubiche T, Boralevi F, Thambo JB, Taïeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008;358(24):2649-51.

2. Drolet BA, Frommelt PC, Chamlin SL, et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics. 2013;131(1):128-40.