β-blocker therapy for infantile hemangioma

Abstract

15% of proliferating infantile haemangioma (IH) require intervention because of the threat to function or life, ulceration or tissue distortion. Propranolol is the mainstay treatment for problematic proliferating IH. Other β-blockers and angiotensin-converting enzyme (ACE) inhibitors have been explored as alternative treatments. The demonstration of a haemogenic endothelium origin of IH with a neural crest phenotype and multi-lineage differentiation capacity, regulated by the renin-angiotensin system, underscores its programmed biologic behaviour and accelerated involution induced by propranolol, other β-blockers and ACE inhibitors. We review the indications, dosing regimens, duration of treatment, efficacy and adverse effects of propranolol and therapeutic alternatives including oral atenolol and acebutolol, nadolol, intralesional propranolol injections, topical propranolol and timolol, and oral captopril. Improved understanding of the biology of IH provides insights into the mechanism of action underscoring its accelerated involution induced by propranolol, other β-blockers and ACE inhibitors. More research is required to understand the optimal dosing and duration, efficacy and safety of these alternative therapies. Recent demonstration of propranolol’s actions mediated by non-β-adrenergic isomer R-propranolol on stem cells, offers an immense opportunity to harness the efficacy of β-blockers, to induce accelerated involution of IH, while mitigating their β-adrenergic receptor-mediated adverse effects.