Hereditary haemorrhagic telangiectasia (HHT) affects approximately 1.5 million individuals worldwide, results from a germline loss-of-function gene variant (‘mutation’) usually in ENG, ACVRL1 or SMAD4, and causes a spectrum of vascular malformations, including mucocutaneous telangiectasia and visceral arteriovenous malformations (AVMs). 1–3 Expert consensus informs clinical management, 1 as randomised control trial (RCT) evidence for local and systemic approaches is limited. There is RCT evidence for tamoxifen and tranexamic acid, but management of severe haemorrhage causing transfusion-dependent iron deficiency anaemia remains challenging. Here, international guidance 2 proposes intravenous bevacizumab (monoclonal anti-vascular endothelial cell growth factor (VEGF), but this is not well supported by RCT evidence, 4 nor approved for HHT in the United Kingdom. There is an urgent need for new treatments.

At our institution, prospective characterisation of more than 1000 HHT patients over 24 years enables recognition and validated categorisation 5 when expected patterns are not followed. For the case presented, patterns of HHT nosebleeds and anaemia at clinical review differed markedly from multiple previous assessments, and on direct questioning, a relevant new drug was noted to have been taken for an unrelated gynaecologic low-grade cancer. Following a failure of cytotoxic drugs and hormone therapy, the MEK inhibitor trametinib 6 was given continuously, and the tumour has responded for more than 2 years. The initial dose of trametinib (2 mg/day) was not well tolerated due to hand oedema and it was reduced to 1 mg/day. This was well tolerated, with only Grade 1–2 adverse events (intermittent finger swelling) described at 10 and 18 months. The patient described no other adverse events, none of the lethargy, paraesthesia or pains described by HHT patients on other anti-angiogenics, and at 2 years there was continued regression of tumour deposits.