Shanna Spring MD
University of California, San Francisco, CA and The
Hospital for Sick Children, Toronto, ON
Ilona J. Frieden MD
Birthmarks and Vascular Anomalies Center
and Division of Pediatric Dermatology, Benioff
Children’s Hospital, University of California, San
Francisco, CA
and Division of Pediatric Dermatology, Benioff
Children’s Hospital, University of California, San
Francisco, CA
Infantile hemangiomas (IH) are among the most common
vascular lesions of infancy. The incidence rate of infantile
hemangiomas is approximately 4.5%, with virtually all IH
presenting before the age of 3 months.1 Various hypotheses
have been proposed regarding their pathogenesis. These include
placental embolization, somatic mutation of an endothelial
type cell, stimulation of endothelial progenitor cells by
hypoxia and mediation of growth by aberrant growth factors
(ie, VEGF).2 Risk factors include female sex, Caucasian race,
prematurity, low birth weight, and multiple gestations. Maternal
risk factors include advanced maternal age, placenta
previa, and pre-eclampsia.3
The natural history of infantile hemangiomas has been well
characterized, most typically with early proliferation followed
by gradual involution. Not all IH require treatment as most
resolve without significant sequelae, but a significant minority
require active intervention. Indications for treatment include
ulceration, potential for permanent disfigurement and functional
compromise. The challenge in treating IH is to identify
which are likely to cause long-term complications or sequelae
and to intervene before permanent damage has been done.
An approach to risk stratification can help in decision making
regarding which IH can be left to involute on their own and
which require active treatment (Table 1).4
Management
The management of IH has been revolutionized by the serendipitous
discovery by Léauté-Labrèze et al of the dramatic
responses of infantile hemangiomas to beta blockers. The
focus of our discussion of the various treatment options for
IH emphasizes the approach to management in the “post-propranolol
era†beginning in 2008 when this treatment option
became available. A key management of therapy is timing.
Many hemangiomas have reached their maximum growth
very early, by 5 to 7 weeks of age. Most have completed or
nearly completed growth by 3 months of age. For those that
need treatment, “the sooner the better†to prevent complications
or permanent scarring. Using knowledge of growth
characteristics, the optimal time for referral for consideration
of treatment is 4 weeks of age5!
Topical and Local Therapies
Topical and local therapies are an appropriate choice for
small, localized and relatively superficial IH (eg, low to moderate-
risk category). Timolol maleate, a topical beta blocker,
is gaining popularity in the treatment of superficial hemangiomas.
We typically use the gel forming solution (0.5%).4
Timolol is FDA-approved for the treatment of glaucoma in
infants. It is not approved for IH but there are hundreds of
reports (in case series and case reports) of its use with largely
favorable reports in pre-selected patients (where topical
therapy might make a difference). It works more slowly than
oral propranolol, with benefits often visible in a few weeks
and continued improvement for several months. Theoretical
side effects are similar to oral beta blockers, but have rarely
been reported.4 Treatment should be limited to 1 drop BID
to TID in order to minimize the risk of systemic absorption,
especially on mucosal or ulcerated surfaces.6
Intralesional triamcinolone (TAC) is helpful in the treatment of
certain IH, particularly small to medium-sized facial IH (eg, lip