Diagnosis and Management of Infantile Hemangioma

Overview of the Literature
We identified 24 studies (three RCTs, one cohort study, and 20 case series) reporting
outcomes and/or harms following corticosteroid use in children with IH. 40,107-129 One RCT and
one case series 120,122 likely report on a subset of the same children; however, the extent of
overlap is not clear. Three RCTs 107,108,122 and one retrospective cohort study 40 addressed
corticosteroids and included a total of 239 children (age range 1-72 months) with IH in multiple
anatomic sites. Studies were conducted in India, 122 Canada, 107 Pakistan, 108 and Turkey. 40 Two
studies included children with cutaneous IH, and IH types across all studies included superficial,
deep, and mixed.
Comparative studies and case series assessed oral methylprednisolone, oral prednisolone,
intravenous methylprednisolone, topical mometasone furoate, topical betamethasone, topical
clobetasol, topical halobetasol, intralesional betamethasone, and intralesional triamcinolone
acetonide and compared one agent to another or various doses of agents. One RCT included an
observational/conservative control group. 108 Only one RCT explicitly noted that assessors were
blinded to treatment status. 107 Treatment duration (where clearly reported) in comparative studies
ranged from 3 weeks to 12 months. We rated one RCT as good, 107 one as fair, 122 and one as
poor 108 quality and the cohort study 40 as fair quality for effectiveness outcomes. We considered
the cohort study and one RCT 40,122 as poor quality for harms reporting and two RCTs as good
quality for harms reporting. 107,108
In our network meta-analysis, oral steroids had a mean estimated expected clearance rate of
43 percent (95% BCI: 21% to 66%). Intralesional triamcinolone had a rate of 58 percent but with
wide confidence bounds (95% BCI: 22% to 93%). Thus, there is adequate evidence to support a
moderate strength of evidence for oral steroids to have a modest effect on clearance rates and
low SOE for intralesional steroids to have a modest (albeit larger) effect relative to control with
wide confidence bounds.
We also report harms from two RCTs 98,100 and five cohort studies 96,97,130-133 that compared
steroids with propranolol (effectiveness outcomes reported in Effectiveness and Harms of Beta-
Blockers Compared With Other Active Modalities section below). These studies were conducted
in the U.S., 97,98 Canada, 96 India, 100 , the Netherlands, 131 Germany, 132,133 and Egypt 130 and included
308 children with IH (age range=1 to more than 9 months). We rated these studies as good 98 and
poor 96,97,100,130-133 quality for harms reporting.
Twenty case series provided harms data on corticosteroids. 109-121,123-129 Children in case series
(n=3508) ranged in age from 0 to 19 years and typically had IH in multiple anatomic sites. Nine
case series were conducted in the United States, three in India, two in the U.K., two in China,
and one each in Qatar, Israel, Thailand, and the Netherlands. Four studies reported on only
orbital or periocular IH. 111,121,127,128 Treatment duration was frequently not reported. We rated all
case series as poor quality for harms reporting.
Steroids were consistently associated with clinically important harms including Cushingoid
appearance, infection, growth retardation, hypertension, and mood changes that may be
important in making treatment decisions. The SOE is moderate for the association of steroids
with these clinically important harms.
25