Reply to Fernández-Fernández

Dr Fernandez-Fernandez¹ is right in raising the important new data regarding anti-angiogenic strategies in hereditary haemorrhagic telangiectasia (HHT), data which were published too late for inclusion in our review.² Although the gene mutations inform us that HHT is a disorder caused by aberrant signalling by the transforming growth factor (TGF)-β superfamily, the context in which the gene mutations are deleterious, when functioning apparently perfectly well for the vast majority of vessels, has always proved tantalising. In 2009, there has been a resurgent interest in the role of angiogenesis in provoking or unmasking an HHT phenotype, with animal models particularly implicating a role for aberrant angiogenesis during wound healing.³ Pathogenesis-based treatment strategies based on case reports using anti-VEGF (bevacizumab/Avastin),^{4, 5, 6} interferon,^{7, 8} and thalidomide^{9, 10} are being assessed in ongoing clinical trials at HHT centres. For any efficacious agent, side-effect profiles are likely to be crucial in determining whether the use of any efficacious agents can become more widespread within the HHT patient population. In 2009, encouraging data were also reported for two better-tolerated agents, N-acetyl cysteine (trial data for 600 mg tds)¹¹ and tamoxifen (randomised placebo-control trial data for 20 mg/day).¹² These have been introduced into specialised HHT practice, reflecting the rapidly advancing field.