Taking a closer look at oral propranolol as first-line treatment in infantile hemangioma

Most cases of infantile hemangiomas do not require therapy due to their tendency to regress spontaneously, but for the few infants with complicated cases, oral propranolol has become the first-line treatment, researchers wrote in a review on infantile hemangioma published in The Lancet.

Led by Christine Léauté-Labrèze, M.D., of Pellegrin Children’s Hospital in Bordeaux, France, researchers reviewed studies published between 2008 and 2015 finding that 2-3 mg/kg of propranolol daily for six months, resulted in a response rate of 96-98% of 1,264 cases. Sixty percent of cases experienced a complete or nearly complete regression.

“Propranolol has been shown to be effective for obstructive, life-threatening airway infantile hemangioma and for ulcerated infantile hemangioma. Its exact mechanisms of action are incompletely understood so far, but propranolol could regulate hemangioma cell proliferation via catecholamines or the VEGF pathway,” the authors wrote in the review, which was published in January.

There has been “tremendous progress” in infantile hemangioma research in the last 10 years. Risk factors have been identified, more is known about its pathophysiology, more clinical presentations have been documented and propranolol has been well-vetted in the scientific literature.

Propranolol has been shown to be effective for the most serious cases. The chief indications for treatment are life-threatening infantile hemangiomas that cause heart failure or respiratory distress; tumors posing functional risks such as visual obstruction, amblyopia or feeding challenges; ulceration; and severe anatomic distortion, especially on the face.

The literature search revealed that the beta-blocker propranolol should be administered as early as possible to avoid potential complications.

Between 20-25% of patients experience the most common side effects of treatment: sleep disorders, somnolence and irritability. Fortunately, side effects are reversible and mostly benign. Less common side effects (>1%) include bronchospasm or bronchiolitis and asymptomatic hypotension. Even more rare are more serious side-effects of bradycardia, complications of undiagnosed atrioventricular blocks, and hypoglycaemia are possible. In most cases, discontinuing the treatment will successfully resolve side effects, but in 10-15% of cases, recurrence after discontinuation occurs - primarily in segmental and deep infantile hemangioma. Temporary discontinuation is recommended in cases of poor oral feeding, diarrhea and obstructive bronchitis.

“Because propranolol is a highly lipophilic β blocker and thus capable of crossing the blood–brain barrier, there are theoretical concerns regarding potentially relevant neurodevelopmental or cognitive side-effects of propranolol,” researchers wrote.

NEXT:  Referring patients

REFERRING PATIENTS

Noting that infantile hemangiomas are the most common soft-tissue tumors of infancy, with a prevalence of 4% to 5% in the overall infantile population, the article advocates close follow-up in the first weeks of life to identify at-risk hemangiomas, because 80% of all hemangiomas reach their final size by 3 months of age.

The most likely triggering factor is hypoxia responsible for the activation of the HIF-1 alpha pathway.

Precursor lesions are either present at birth or develop during the early neonatal period as a pale area of vasoconstriction or a telangiectatic red macule.

“Ideally, a patient with infantile hemangioma who is at risk of complications should be referred to a multidisciplinary team for evaluation and for specific diagnostic measures,” the authors write. These measures include MRI and screening for hypothyroidism or coagulation abnormalities.

There are also several scores to access severity, such as the Hemangioma Severity Scale and the Hemangioma Dynamic Complication Scale.

Other beta-blockers like nadolol, atenolol and acebutolol have also been shown to be effective in treating infantile hemangioma. And because these beta-blockers are hydrophilic and not do cross the blood-brain barrier as does propranolol, they may also be associated with a lower risk of central nervous system (CNS) side effects such as disturbed sleep; bronchospasm and hypoglycemia.

NEXT:  Oral propranolol in practice. Some considerations.

ORAL PROPRANOLOL IN PRACTICE:  SOME CONSIDERATIONS

• Educate parents about the risk of hypoglycemia and respiratory symptoms (wheezing) at each visit.

• To avoid hypoglycemia, the infant should feed regularly.

• Stop propranolol temporarily in cases of poor food intake or wheezing.

• Do not alter dosing for minor side-effects such as cold hands and asymptomatic low diastolic blood pressure.

• To minimize nightmares, avoid giving the treatment after 17:00 hours or reduce dose.

REFERENCE

Christine Léauté-Labrèze, John I Harper, Peter H Hoeger. "Infantile hemangiomas:  An overview," The Lancet. Jan. 12, 2017. http://dx.doi.org/10.1016/S0140-6736(16)00645-0