Volume 194 - Issue 6
Bevacizumab and hereditary haemorrhagic telangiectasia
Authors: Ross P Cruikshank and Boris W Chern
Med J Aust 2011; 194 (6): 324-325. || doi: 10.5694/j.1326-5377.2011.tb02989.x
Published online: 21 March 2011
Published online: 21 March 2011
To the Editor: Hereditary haemorrhagic telangiectasia (HHT) or Osler–Weber–Rendu syndrome manifests as vascular dysplasia involving the nose, skin, lung, brain and gastrointestinal tract. It is an inherited disorder manifesting as unbalanced angiogenesis.1
Bevacizumab is a recombinant, humanised monoclonal antibody that binds to and neutralises vascular endothelial growth factor (VEGF), preventing its association with endothelial receptors. VEGF binding initiates angiogenesis (endothelial proliferation and the formation of new blood vessels). VEGF and transforming growth factor β play a role in the pathogenesis of HHT, with affected patients having increased levels of these factors.2 Anecdotal reports have demonstrated the effectiveness of bevacizumab in patients with HHT. To date, good responses have been documented in patients presenting with epistaxis, haemoptysis, anaemia,3 pancreatic arteriovenous malformations4 and hepatic vascular abnormalities.5
We were referred a 71-year-old man who related a 45-year history of recurrent nose bleeds, pulmonary and gastrointestinal haemorrhage and significant facial and oral telangiectasias. He had a history of multiple hospital admissions for haemoptysis and malaena necessitating blood and iron transfusions. The patient averaged three blood transfusions and four iron infusions a year, and his haemoglobin level ranged from 90 to 120 g/L. The patient also received argon laser treatment for his gastric and duodenal telangiectasias, and was taking bovine colostrum for nosebleeds with minimal effect. Shaving resulted in regular bleeding as a result of his facial telangiectasias.
Because of his significant morbidity, the patient was referred for a trial of bevacizumab therapy and underwent six cycles at 5 mg/kg by means of fortnightly intravenous infusion from March to May 2010.
This treatment has resulted in an effective and tangible response. Since completing the treatment, the patient has been followed up monthly, and he reports only two nosebleeds compared with daily bouts before therapy. Further, the telangiectasias on his face and in his mouth have reduced considerably, and he has had only one gastrointestinal bleed, which occurred after heavy lifting. His haemoglobin level 2 weeks after treatment was 163 g/L and has remained stable since that time.
A follow-up gastroscopy in November 2010 showed that his multiple vascular lesions had reduced to just one angiodysplastic lesion in his gastric body (Box). The only adverse effect he experienced from the bevacizumab was poor sleep with associated tiredness, but the patient was able to tolerate this in light of the amelioration of the symptoms of his HHT. Other reported side effects of bevacizumab such as hypertension, proteinuria and thrombosis did not manifest in this patient.
With growing anecdotal evidence of the effectiveness of bevacizumab in treating symptomatic HHT, an argument for using bevacizumab as an adjunctive or even first-line treatment for HHT is becoming stronger.
References
- Abdalla SA, Letarte M. Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease. J Med Genet 2006; 43: 97-110.
- Sadick H, Riedel F, Naim R, et al. Patients with hereditary hemorrhagic telangiectasia have increased levels of vascular endothelial growth factor and transforming growth factor-b1 as well as high ALK1 tissue expression. Haematologica 2005; 90: 818-828. 0_i1095865
- Bose P, Holter J, Selby G. Bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 2009; 360: 2143-2144. 0_i1095867
- Oosting S, Nagengast W, de Vries E. More on bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 2009; 361: 931. 0_i1095869
- Mitchell A, Adams L, MacQuillan G, et al. Bevacizumab reverses need for liver transplantation in hereditary hemorrhagic telangiectasia. Liver Transpl 2008; 14: 210-213. 0_i1095872