Hereditary haemorrhagic telangiectasia

Learning objectives

Introduction

• Hereditary haemorrhagic telangiectasia (HHT), also known as Osler–Weber–Rendu disease
• Rare autosomal dominant genetic disorder that leads to abnormal blood vessel formation
• Telangiectasia found in the skin, mucous membranes
• Others found in the lungs, liver, and brain
• Most Cerebral AVMs in the HHT population are symptomatic.
• Family history of a parent, sibling or child with same

Aetiology

• A disorder of angiogenesis with abnormal fragile blood vessels
• Mutations in several genes, including the ACVRL1, ENG, and SMAD4 genes
• HHT1 patients more likely to have brain AVMs than HHT2 patients.

Aetiology of stroke

• Bleeding from a cerebral vascular malformations
• Paradoxical embolism through a pulmonary AVM (rare)
• The vessels lack contractile elements and so given direct arterial connection, bleeding from telangiectases can be brisk and difficult to stop. This may be seen with GI Bleeds.

Clinical

• Difficulties with Epistaxis seen in most by adulthood
• GI bleeding, Haematemesis, Melaena, Fe deficiency anaemia often over age of 50
• Haemorrhagic stroke as risk of AVMS
• Mucocutaenous lesions in skin and oral cavity and nose
• Embolic stroke via paradoxical embolism via pulmonary AVM
• Pulmonary AVM can rupture, leading to haemoptysis

Clinical Signs

Types

• Type 1: mutations in the ENG gene. Brain AVMS in 13.4 %
• Type 2: mutations in the ACVRL1 gene. Brain AVMS in 2.4 %
• Juvenile polyposis/hereditary haemorrhagic telangiectasia syndrome is caused by mutations in the SMAD4 gene.

Differential

• Vasculitis rash
• Thrombocytopenia
• Telangiectases of chronic liver disease are spider like with a central core and small vessels radiating outward

Diagnostic clinical criteria

Investigations

• FBC: exclude Fe deficiency anaemia from GI blood loss. ESR, CRP, U&E, LFTs
• Brain Imaging - CT/MRI
• CXR : may show lung lesion ? AVM
• Angiography is AVM suspected. The Spetzler-Martin grade for HHT related lesions is 2 or less in nearly 90% of patients.
• Bubble echo shown to be a sensitive screen for PAVMs and then CT Pulmonary angiogram if positive bubble echo. This avoids radiation in young adults. This may need repeated at 5 year intervals.
• Colonoscopy and upper endoscopy +/- capsule endoscopy. Those with mutations in the SMAD4 gene may be at increased risk for polyps. Alternatively may be done to exclude other cause of Fe deficiency anaemia
• Molecular genetic testing is used to establish the genetic subtype of hereditary haemorrhagic telangiectasia in a clinically affected individual and family, and for early diagnosis to allow for appropriate screening and preventive treatment.

Management

• ABC, Stroke management, Acute management for GI Bleed as needed. Transfusion if needed.
• ENT referral for epistaxis - Laser ablation is usually recommended as the intervention for control of mild to moderate nosebleeds
• Gastroenterology review for GI bleeds. Iron replacement therapy for anaemia.
• Avoid antithrombotic drugs. Antifibrinolytic drugs such as tranexamic acid have been used in select patients
• Genetic counselling.
• Management of Cerebral Arteriovenous Malformations if found. A recent study has found that functional outcomes were not statistically different between those who had surgery and those who didn't on long term follow-up. Link
• Closure of Pulmonary AVM if embolic stroke by Interventional neuroradiology if needed.Any PAVM with a feeding artery > 1–3 mm detected by chest CT should be considered for treatment by transcatheter embolization.

References

• Prevalence and characteristics of brain arteriovenous malformations in hereditary hemorrhagic telangiectasia: a systematic review and meta-analysis. J Neurosurg. 2017 Aug;127(2):302-310.
• MR of hereditary hemorrhagic telangiectasia: prevalence and spectrum of cerebrovascular malformations.
• Surgical Treatment vs Nonsurgical Treatment for Brain Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia: A Retrospective Multicenter Consortium Study.
• Hereditary hemorrhagic telangiectasia: An overview of diagnosis, management, and pathogenesis Genetics in Medicine volume 13, pages 607–616 (2011)

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