Discussion
This study documented a wide variation in the treatment of infantile
hemangiomas. A consistent theme is that each patient and each IH are
unique. The clinical practice guidelines are based on available data,
and on expert opinions in the absence of data. With the publication of
additional high quality studies and the widespread use of beta blockers
for the management of IH, updated clinical practice guidelines may be
indicated.
Ongoing studies continue to demonstrate the safety and efficacy of
propranolol as well as other beta-blockers including
atenolol,18,19 nadolol,20 and
topical timolol.21 Most studies have used a goal dose
of 2 – 3 mg/kg/day of propranolol.15 Three mg/kg/day
is superior to 1 mg/kg/day,9 but little data exist
comparing 2 mg/kg/day to 3 mg/kg/day.22 In fact, doses
of 2.5 – 3 mg/kg/day may increase toxicity without added
benefit.12,23,24 Early initiation of propranolol
(before 10 – 12 weeks of age) improves outcomes compared to an older
age of initiation.25,26 Current literature suggests
that propranolol is effective and well tolerated in infants younger than
five weeks corrected gestational age.27 Depending on
response, most experts recommend continuing propranolol until age 12
months, and sometimes longer.15,28 The CPG recommends
a baseline echocardiogram for patients with PHACE syndrome, but does not
address the indications of an echocardiogram for other
patients.15 Obtaining a baseline electrocardiogram is
rarely helpful in otherwise well infants.29 Five or
more cutaneous IH is associated with IH of the liver, and it has been
recommended that such patients undergo ultrasound of the
liver.30 However, at least one study found that liver
ultrasound rarely affects clinical management, and that it may be safely
omitted in the absence of concerning signs or symptoms such as lethargy
or poor feeding.31
The FDA’s recommendation for monitoring patients is currently based on a
clinical trial which had strict criteria and oversight, including
intermittently monitoring heart rate and blood pressure for two hours
after the first dose and when increasing the dose.9For propranolol, peak plasma concentrations occur 1 – 4 hours after a
dose. Consumption of protein-rich foods increases the bioavailability by
about 50% with no change in time to peak
concentration.32 At least one large study suggests
that at home initiation and dose escalation may be safely
done.33 In addition, guidelines from Britain,
Australia, and North America state that in children without risk
factors, outpatient initiation without monitoring may be safely done
with initial doses of 1 mg/kg/day.34-36 At home
initiation and dose escalation, including by telehealth encounters,
became more common for non-high risk patients during the COVID-19
pandemic.34 When therapy has been completed, some
clinicians may discontinue propranolol abruptly,36although it has been suggested that it be tapered (for example, over two
to four weeks), to potentially lower the risk of rebound
growth.28,37 Despite evidence that most patients can
be safely started on propranolol at home, many practitioners continue to
monitor patients in the clinic or in the hospital when initiating or
increasing the dose of propranolol, and some still get routine cardiac
assessments and lab work.
Areas identified for future research and discussion include the optimal
dose of propranolol (including for ulcerated IH, which may respond
better to a lower initial dose (≤1 mg/kg/day) of
propranolol38), the optimal duration of therapy, which
patients truly benefit from ultrasound of the liver, how patients should
be monitored, how often to see patients in follow-up, which patients
should get additional work up (such as an echocardiogram), and how
propranolol should best be discontinued (tapered or stopped abruptly).
Limitations of this study include a small sample size which is heavily
biased towards PHOs and pediatric cardiologists. Few dermatologists and
other providers responded, which could impact results since
dermatologists, particularly the Hemangioma Investigators Group
(https://www.hemangiomaeducation.org/) have been leaders in the
treatment of infantile hemangiomas. Thus, analysis of variations in
practice between specialties could not be reliably performed. Published
guidelines suggest that dermatologists are more comfortable with
outpatient initiation and dose escalation of beta
blockers.34-36
In conclusion, this study demonstrates wide practice variations in
managing infantile hemangiomas. Further research is indicated to address
these variations and develop additional/updated evidence-based
guidelines.
Acknowledgements: The authors thank Christine Rodgers and Janet
Tooze for assistance with the REDCap survery.