For Beth Drolet, MD, a pediatric dermatologist in Wisconsin, the tremendous impact oral propranolol has had on the treatment of severe infantile hemangioma is written on the faces of children diagnosed with the condition in recent years.
“You can tell which drugs the kids were on by their age,” said Dr. Drolet, professor of dermatology and pediatrics at the Medical College of Wisconsin, Milwaukee. “If they were born before 2008, before we used this medication, those kids have had multiple surgeries and are still not looking that good. But we rarely see that in the kids born after.”
Because of this landmark treatment, “thousands of kids won’t have to grow up disfigured,” she said in an interview. But for individual dermatologists, even those who routinely work with children, treatment with oral propranolol poses unique challenges. In many cases, they refer appropriate patients to pediatricians and pediatric cardiologists.
Still, it is possible for dermatologists to successfully treat their smallest patients with oral propranolol, according to Dr. Drolet and Ilona J. Frieden, MD , professor of dermatology and pediatrics at the University of California, San Francisco.
In interviews, the two pediatric dermatologists spoke about the challenges and benefits of treating hemangioma patients with oral propranolol solution, which was approved by the Food and Drug Administration in 2014 for “proliferating infantile hemangioma requiring systemic therapy.” It is the only FDA-approved systemic treatment for this indication.
“It’s more complicated than many conditions we see, but most dermatologists should be able to use [propranolol] comfortably,” Dr. Frieden said. “The tricky part is understanding which hemangiomas need treatment with propranolol and which ones can be left to resolve spontaneously. That requires judgment and understanding that a time frame is involved. There is a window of opportunity for making more of a difference.”
The oral form of the drug was used off label to treat patients with hemangioma after a French dermatologist discovered in 2007 that it could effectively treat the condition. A topical form of propranolol is also used for hemangiomas that do not require systemic treatment.
Prior to about a decade ago, Dr. Drolet said, steroids were used to treat severe hemangiomas with limited success.
In general, infantile hemangiomas “have a natural course of gradually involuting even without treatment,” Dr. Frieden noted. But the most severe cases can produce functional impairment, scarring, and anatomic distortion.
Dr. Drolet said she considers treatment if hemangioma threatens a vital function (hearing, sight, breathing) or can lead to pain, infection, or scarring.
One challenge for dermatologists is that standard of care treatment with oral propranolol requires in-office cardiac monitoring, especially as the dose is increased over the first week or two of treatment.
“I don’t think most dermatologists are comfortable taking a heart rate and blood pressure in an infant,” said Dr. Drolet, who is director of the birthmarks and vascular anomalies section at Children’s Hospital of Wisconsin, Milwaukee. Instead, they tend to refer patients to a pediatrician or pediatric cardiologist.
Her clinic hired a cardiac nurse to train the staff in how to take heart rate and blood pressure in babies. “Partnering with cardiology was really important for us,” she commented. “We worked really closely with our pediatric cardiology team to gain that expertise for our staff to assess that. You have to be pretty comfortable with it. If you’re not, you’re going to have to find someone else.”
Another option for dermatologists, Dr. Frieden said, is to focus on heart rate alone since blood pressure in infants is difficult to measure. “It’s not FDA sanctioned, but many people seem to do that and it’s OK,” she said.
Dr. Frieden and Dr. Drolet provided the following recommendations about treating babies with oral propranolol:
• Caution parents about side effects. Cardiac side effects have been “extraordinarily rare,” Dr. Drolet said. “We have seen problems with wheezing and, very rarely, severe hypoglycemia,” which can be prevented by educating the family. While it’s uncommon for the medication alone to produce wheezing, this may occur when a respiratory infection and propranolol combine to stress the body, she noted.
In some cases, physicians prescribe albuterol for wheezing without realizing that it will interact with propranolol, she added. “One is a beta-blocker, and the other is a beta-antagonist. They completely cancel each other out.”
To prevent hypoglycemia, Dr. Frieden said she recommends that children be fed every 6 hours if they’re under 6 months old or every 8 hours if they’re over 6 months of age. And Dr. Drolet said she advises parents to stop propranolol when their infants are sick.
A major focus of an educational video provided by Dr. Drolet’s clinic is advising parents “to stop the medication if the infant is not eating regularly, vomiting, or has diarrhea. It interferes with how you respond to low blood sugar if you’re not eating,” she said. “That surprised us. Now that we’ve been teaching parents about when to call us, that’s been pretty preventable.”
Minor side effects include cold hands and feet and sleep disturbances such as sleepiness and apparent nightmares, Dr. Frieden pointed out.
• Monitor guidelines regarding safety and protocols. “Over time, we’re getting more and more expertise,” Dr. Drolet said. For example, her clinic no longer performs ECGs on babies who take the medication because research has suggested they are not needed.
• Spend time developing an education program for parents. Dr. Drolet’s clinic provides the educational video to teach parents about how oral propranolol is used. “We haven’t done that for any other drugs,” she said. “But we want to make sure we aren’t overdosing it. We’ve been very careful about our parent education to prevent that.”
Guidelines on the diagnosis and management of infantile hemangioma were published in 2015 in Pediatrics ( 2015 Oct;136:e1060-104 ).
Dr. Frieden has consulted for Pierre Fabre Dermatologie, the manufacturer of the oral propranolol product, marketed as Hemangeol . Dr. Drolet has received an investigator-initiated grant from the company.