Hereditary haemorrhagic telangiectasia: From symptomatic management to pathogenesis based treatment

I read with interest the article ‘Hereditary haemorrhagic telangiectasia: a clinical and scientific review’ by Govani and Shovlin.¹ As the authors show in Table 2, treatment of patients with hereditary haemorrhagic telangiectasia (HHT), currently, is primarily symptomatic, without alteration of the underlying pathological process. HHT is a disorder of unbalanced angiogenesis. The vascular endothelial growth factor (VEGF) is upregulated in patients with HHT,² and this factor induces angiogenesis by stimulation of endothelial cell proliferation and migration. Likewise, it stimulates expression of matrix metalloproteinases, which are needed for the degradation of the extracellular matrix in the angiogenic process. In recent years, antiangiogenic drugs have been incorporated into the treatment of HHT. Owing to the important role of VEGF in HHT, drugs against this factor, such as bevacizumab, have been used with favourable outcome in this process.^{3, 4, 5} Lenalidomide, a derivative of thalidomide, proved to be useful in a patient with chronic gastrointestinal bleeding as well as sudden massive life-threatening bleeds.⁶ These clinical observations opened the door to the investigation of pathogenesis-based treatment. From a theoretical standpoint, it might be of interest to evaluate other drugs with fewer side effects.⁷ For example, doxycycline is considered to inhibit angiogenesis through the inhibition of matrix metalloproteinases, and matrix metalloproteinases are increased in some patients with HTT.⁸ This antibiotic appeared to be beneficial in other disorders with unbalanced angiogenesis⁹ or increased activity of matrix metalloproteinases.¹⁰ Against this background, I believe that it might be of interest to investigate whether doxycycline might have a role in the treatment of some patients with HHT.