Diagnosis and Management of Infantile Hemangioma

Propranolol Versus Other Active Modalities
• In network meta-analysis, oral propranolol was associated with a mean estimate of
expected clearance of IH of 95% (95% BCI: 88% to 99%) compared with a lower rate for
oral steroids (43% [95% BCI: 21% to 66%]), while in head-to-head comparisons three
small studies found propranolol was more effective than corticosteroids, and two did not
find a significant difference in effectiveness between the two therapies. Combined effects
from individual studies and network meta-analysis conferred moderate SOE for the
superiority of propranolol over steroids at achieving IH clearance.
• In one cohort study comparing the effects of intralesional steroids and oral propranolol on
vision outcomes, improvement in amblyopia did not differ between agents, but fewer
children receiving propranolol required additional treatments or had side effects than
those receiving steroids.
• Propranolol combined with pulsed dye laser (PDL), either concurrently or sequentially,
was more effective than propranolol alone in one study.
• In a study comparing oral propranolol with intralesional bleomycin, 6 of 10 children in
each arm had at least 75 percent clearance of IH.
• One study found that patients who received propranolol had a lower likelihood of
subsequent laser treatment than those who received other interventions.
• Propranolol was associated with faster healing of ulceration versus historical treatments
including laser and antibiotics.
Oral Propranolol Versus Other Beta-Blockers or Dosage Forms
• Other oral beta-blockers (atenolol, nadolol) investigated in three studies were reported to
be effective in promoting IH resolution and potentially associated with fewer adverse
events than propranolol (low SOE for no difference in response of IH to propranolol,
nadolol, or atenolol).
Timolol Versus Placebo/Observation or Other Active Modalities
• In our network meta-analysis, topical timolol had a mean expected clearance rate of 62
percent (95% BCI: 39% to 83%) compared with 6 percent (95% BCI: 1% to 11%) for
placebo or observation (low SOE for effectiveness of timolol versus placebo or
observation).
• Topical timolol 0.5 percent maleate gel promoted improvement of superficial IH without
reported adverse effects in four comparative studies (low SOE for lack of association
with harms). Studies reported effectiveness at 24 weeks with the noticeable change in IH
lesions occurring approximately 12 to 16 weeks after initiation of treatment.
Overview of the Literature
We identified a total of 81 studies (nine RCTs, 14,17,92,93,98-100,102,104 16 cohort studies, 95-
97,101,103,105,106,130-133,144-150
and 56 case series 16,18,151-205 ) addressing beta-blockers including
propranolol, atenolol, nadolol, and timolol. Comparative studies addressed the following
interventions and comparators: propranolol compared with observation or placebo arms,
propranolol compared with other active modalities (e.g., steroids), oral propranolol compared
with other beta-blockers or dosage forms, and timolol compared with observation/placebo or
another modality (e.g., laser). Comparative studies included a total of 1539 children between the
ages of less than one month to 9 years. We considered four RCTs to be good quality and five as
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