β-blocker therapy for infantile hemangioma

ABSTRACT

Introduction

Fifteen percent of proliferating infantile hemangioma (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.

Areas covered

The demonstration of a hemogenic endothelium origin of IH, with a neural crest phenotype and multi-lineage differentiation capacity, regulated by the renin-angiotensin system, underscores its programmed biologic behavior 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, acebutolol, nadolol, intralesional propranolol injections, topical propranolol and timolol, and oral captopril.

Expert opinion

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.

KEYWORDS:

• Β-blockers
• infantile hemangioma
• hemogenic endothelium
• stem cells
• propranolol
• acebutolol
• nadolol
• atenolol
• timolol
• renin-angiotensin system
• inhibitor
• captopril

Declaration of interest

Swee T. Tan is an inventor of a provisional patents Treatment of Vascular Anomalies (PCT/NZ2017/050032), 2016; and Methods and Compositions for the Treatment of Hemangioma (PCT/NZ761251), 2020. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. There are no other financial, commercial, or other relationships of a declarable nature relevant to this manuscript. None of the authors received any grants, fellowships, commercial assistance, or financial sponsorship to write this paper.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper has not been funded.