Acta Dermato-Venereologica 97-10CompleteContent | Page 11

1167 SPECIAL REPORT The Role of Topical Timolol in the Treatment of Infantile Heman­ giomas: A Systematic Review and Meta-analysis Maham KHAN 1 , Aaron BOYCE 2 , David PRIETO-MERINO 3,4 , Åke SVENSSON 5 , Emma WEDGEWORTH 2 and Carsten FLOHR 2 1 St. John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK, 2 Unit for Population-Based Dermatology Research, Department of Paediatric Dermatology, St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, 3 Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK, 4 Catedra de Analisis Estadistico y Big Data, Catholic University of Murcia, Spain, and 5 Department of Dermatology, Institute of Clinical Research in Malmö, Lund University, Skåne University Hospital, Malmö, Sweden To date the efficacy and safety of topical timolol in the treatment of infantile hemangioma has not been reviewed and analysed systematically. We collated all published data on the efficacy and safety of topical timolol in the treatment of infantile hemangioma. A total of 31 studies with 691 patients were included. The fixed effects pooled estimate of the response rate defined as any improvement from baseline of infantile hemangioma after treatment with topical timolol was significant (RR = 8.96; 95% CI 5.07–15.47; hetero- geneity test p = 0.99), and the treatment was overall well tolerated. However, the quality of evidence was low to moderate. Topical timolol is an effective treat- ment for small infantile hemangioma, with no signifi- cant adverse effects noted. However, there is still a need for adequately powered randomised controlled trials. Key words: infantile hemangioma; timolol; beta-blocker. Accepted Apr 18, 2017; Epub ahead of print Apr 19, 2017 Acta Derm Venereol 2017; 1167–1171. Corr: Dr Carsten Flohr, Director, Population-Based Dermatology Research Unit, St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foun- dation Trust, Westminster Bridge Road, London SE1 7EH, UK. E-mail: [email protected] I nfantile hemangiomas (IHs) are benign proliferation of endothelial cells arising in the first 8 weeks of life as an area of telangiectasia or discoloration (1). IH are the most common benign tumours of infancy (2). Their life cycle is characterised by an early proliferative phase (6–12 months) followed by gradual involution, leading to complete regression in most cases (5–9 years) (1). The incidence of IH in one-year-old children is estima- ted to be 5 to 10% (3). Preterm infants with a birthweight of < 1,000 g have even a higher risk of 23% (4). There is female preponderance and predilection for Caucasians (5). Positive family history in first degree relatives and periconceptual use of drugs increases the risk of IH (6). Although most hemangioma occur sporadically, autoso- mal dominant transmission has been reported (7). Old maternal age, placenta previa, and pre-eclampsia have been associated with IHs (8).There is an increased risk following amniocentesis and even a greater risk after chorionic villus sampling (CVS) (9). Embolization of angioblasts or endothelial cells from placenta to fetal skin during CVS might lead to multiple hemangiomas on the head, neck and thorax (10). While the majority of IHs regress spontaneously, ap- proximately 10% require intervention (11). Typical indi- cations for oral beta-blocker therapy include functional impairment (e.g. periocular IH causing amblyopia, nasal IH causing nose deformity, lip IH leading to feeding dif- ficulties, and auricular IH causing deafness), and IH in life threatening anatomical locations (lung IH causing respiratory distress, obstructive subglottic IH, large cutaneous IH causing hepatic dysfunction and cardiac insufficiency) (11, 12). However, oral beta-blockers can have potential side-effects, such as a reduction in blood pressure and heart rate, even if the risk is small (13). Therefore, the topical application of a beta-blocker has been suggested as a suitable alternative, in particular for superficial IH (14). In 2010, Guo & Ni (15) presented the first report of successful topical timolol treatment in a resolving IH. Since then, several case reports and case series have claimed efficacy of topical timolol, making this a potential first-line agent for the treatment of superficial IH (13). While there are American and European consensus guid