Oral Propranolol in the Treatment of Proliferating Infantile Haemangiomas

British Society for Paediatric Dermatology Consensus Guidelines

L. Solman; M. Glover; P.E. Beattie; H. Buckley; S. Clark; J.E. Gach; A. Giardini; I. Helbling; R.J. Hewitt; B. Laguda; S.M. Langan; A.E. Martinez; R. Murphy; L. Proudfoot; J. Ravenscroft; H. Shahidullah; L. Shaw; S.B. Syed; L. Wells; C. Flohr

Disclosures

The British Journal of Dermatology. 2018;179(3):582-589. 

In This Article

Abstract and Introduction

Abstract

Background: Infantile haemangiomas (IH) are the most common vascular tumours of infancy. Despite their frequency and potential complications, there are currently no unified U.K. guidelines for the treatment of IH with propranolol. There are still uncertainties and diverse opinions regarding indications, pretreatment investigations, its use in PHACES (posterior fossa malformations–haemangiomas–arterial anomalies–cardiac defects–eye abnormalities–sternal cleft and supraumbilical raphe) syndrome and cessation of treatment.

Objectives: To provide unified guidelines for the treatment of IH with propranolol.

Methods: This study used a modified Delphi technique, which involved an international treatment survey, a systematic evidence review of the literature, a face-to-face multidisciplinary panel meeting and anonymous voting.

Results: The expert panel achieved consensus on 47 statements in eight categories, including indications and contraindications for starting propranolol, pretreatment investigations, starting and target dose, monitoring of adverse effects, the use of propranolol in PHACES syndrome and how to stop treatment.

Conclusions: These consensus guidelines will help to standardize and simplify the treatment of IH with oral propranolol across the U.K. and assist in clinical decision-making.

Introduction

Infantile haemangiomas (IH) are the most common vascular tumours, affecting around 4% of infants.[1] They are more common in premature or low-birthweight infants, females and white people.[2] Placental anomalies are an important risk factor.[1] IH typically appear in the first few weeks of life and grow rapidly for the first few months. However, slow proliferation can continue for the first 6–12 months.[3] Owing to their spontaneous involution, the majority of IH do not require treatment. Nonetheless, about 15% of IH result in complications, such as obstruction of airway and vision, ulceration or disfigurement, and require therapeutic intervention.[4] In 2008, the first report of the successful use of propranolol radically changed the treatment of IH. Since then, propranolol has become the first-line therapeutic agent in the management of complex IH.[5] Studies have shown that propranolol is a safe and effective treatment for IH in most patients.[6–9]

The exact mechanisms of action of propranolol on IH are still not completely understood. Recent studies have offered evidence for variety of mechanisms, including pericyte-mediated vasoconstriction,[10] the inhibition of vasculogenesis,[11,12] catecholamine-induced angiogenesis-[13,14] and downregulation of the renin–angiotensin–aldosterone axis.[15]

Despite the high frequency of propranolol use and potential complications, there are currently no U.K. guidelines for the treatment of IH with propranolol. Our recent European treatment survey indicated differing approaches to the management of IH, for instance with regard to pretreatment investigations, treatment dose, length of treatment, use in PHACES (posterior fossa malformations–haemangiomas–arterial anomalies–cardiac defects–eye abnormalities–sternal cleft and supraumbilical raphe) syndrome and cessation of treatment.[9] In addition, many U.K. dermatology departments have formulated their own propranolol guidelines for the treatment of IH. U.S. and European roundtable expert consensus statements published in 2013 and 2015 have provided guidance on best practices to standardize the approach to the use of propranolol for treatment of complicated IH, but the European recommendations did not include a survey of current practice, and the U.S. recommendations did not follow a Delphi and anonymous voting approach.[16,17]

The purpose of the British Society for Paediatric Dermatology (BSPD) guidelines is to provide evidence-based guidance on the use of propranolol in the treatment of IH, with a view to assisting clinical decision-making and standardizing care. These guidelines are based on an international survey of how oral propranolol is currently used in clinical practice, a systematic review of the literature and a Delphi consensus process to produce specific guidance for practising clinicians.[9]

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