1167
SPECIAL REPORT
The Role of Topical Timolol in the Treatment of Infantile Heman
giomas: A Systematic Review and Meta-analysis
Maham KHAN 1 , Aaron BOYCE 2 , David PRIETO-MERINO 3,4 , Åke SVENSSON 5 , Emma WEDGEWORTH 2 and Carsten FLOHR 2
1
St. John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK, 2 Unit for Population-Based Dermatology
Research, Department of Paediatric Dermatology, St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust and
King’s College London, 3 Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London,
UK, 4 Catedra de Analisis Estadistico y Big Data, Catholic University of Murcia, Spain, and 5 Department of Dermatology, Institute of Clinical
Research in Malmö, Lund University, Skåne University Hospital, Malmö, Sweden
To date the efficacy and safety of topical timolol in
the treatment of infantile hemangioma has not been
reviewed and analysed systematically. We collated all
published data on the efficacy and safety of topical
timolol in the treatment of infantile hemangioma. A
total of 31 studies with 691 patients were included.
The fixed effects pooled estimate of the response rate
defined as any improvement from baseline of infantile
hemangioma after treatment with topical timolol was
significant (RR = 8.96; 95% CI 5.07–15.47; hetero-
geneity test p = 0.99), and the treatment was overall
well tolerated. However, the quality of evidence was
low to moderate. Topical timolol is an effective treat-
ment for small infantile hemangioma, with no signifi-
cant adverse effects noted. However, there is still a
need for adequately powered randomised controlled
trials.
Key words: infantile hemangioma; timolol; beta-blocker.
Accepted Apr 18, 2017; Epub ahead of print Apr 19, 2017
Acta Derm Venereol 2017; 1167–1171.
Corr: Dr Carsten Flohr, Director, Population-Based Dermatology Research
Unit, St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foun-
dation Trust, Westminster Bridge Road, London SE1 7EH, UK. E-mail:
[email protected]
I
nfantile hemangiomas (IHs) are benign proliferation
of endothelial cells arising in the first 8 weeks of life
as an area of telangiectasia or discoloration (1). IH are
the most common benign tumours of infancy (2). Their
life cycle is characterised by an early proliferative phase
(6–12 months) followed by gradual involution, leading
to complete regression in most cases (5–9 years) (1).
The incidence of IH in one-year-old children is estima-
ted to be 5 to 10% (3). Preterm infants with a birthweight
of < 1,000 g have even a higher risk of 23% (4). There is
female preponderance and predilection for Caucasians
(5). Positive family history in first degree relatives and
periconceptual use of drugs increases the risk of IH (6).
Although most hemangioma occur sporadically, autoso-
mal dominant transmission has been reported (7). Old
maternal age, placenta previa, and pre-eclampsia have
been associated with IHs (8).There is an increased risk
following amniocentesis and even a greater risk after
chorionic villus sampling (CVS) (9). Embolization of
angioblasts or endothelial cells from placenta to fetal
skin during CVS might lead to multiple hemangiomas
on the head, neck and thorax (10).
While the majority of IHs regress spontaneously, ap-
proximately 10% require intervention (11). Typical indi-
cations for oral beta-blocker therapy include functional
impairment (e.g. periocular IH causing amblyopia, nasal
IH causing nose deformity, lip IH leading to feeding dif-
ficulties, and auricular IH causing deafness), and IH in
life threatening anatomical locations (lung IH causing
respiratory distress, obstructive subglottic IH, large
cutaneous IH causing hepatic dysfunction and cardiac
insufficiency) (11, 12). However, oral beta-blockers can
have potential side-effects, such as a reduction in blood
pressure and heart rate, even if the risk is small (13).
Therefore, the topical application of a beta-blocker has
been suggested as a suitable alternative, in particular for
superficial IH (14). In 2010, Guo & Ni (15) presented
the first report of successful topical timolol treatment
in a resolving IH. Since then, several case reports and
case series have claimed efficacy of topical timolol,
making this a potential first-line agent for the treatment
of superficial IH (13).
While there are American and European consensus
guid