Hereditary haemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT) is also known as Osler-Weber-Rendu syndrome.

It is an autosomal-dominant multi-organ vascular dysplasia, characterised by multiple arteriovenous malformations (AVMs) that lack an intervening capillary network. Telangiectasias (small superficial AVMs) are particularly common.

The classic triad on presentation is:

1. epistaxis
2. multiple telangiectasias
3. positive family history

Epidemiology

World wide prevalence 1 to 2 per 100,000. Wide geographic variability. Much higher incidence in certain regions (eg. 1 in 200 in Dutch Antilles, 1 in 3500 in France).

Pathogenesis

Autosomal dominant. Mutations in one of several genes (three known so far). Denovo mutations are rare – almost all have a first degree relative affected.

Clinical spectrum

HHT can involve multiple organ systems. The spectrum includes

• nasal : 90 %
  • telangiectasias of nasal mucosa
  • complications : recurrent epistaxis
• skin & mucosal membranes : 90 %
  • telangiectasias of skin, oral cavity, conjunctivae
  • complications : recurrent bleeding
• pulmonary : 20 %
  • pulmonary arteriovenous malformations (AVM)s
    • 36% of patients with solitary pulmonary AVM have HHT
    • 57% of patients with multiple pulmonary AVMs have HHT
    • complications:
      • pulmonary haemorrhage, haemoptysis (less common)
      • complications of shunting (more common): paradoxical emboli (eg stroke), septic emboli (eg cerebral abscess), hypoxaemia, high-output cardiac failure
• CNS : 5 - 10%
  • cerebral AVMs
  • spinal AVMs or
  • cerebral aneurysms
  • complications : headache, seizures, paraparesis, haemorrhage
  • 1/3 of cerebral complications in HHT are due to cerebral AVMs or aneurysms, and 2/3 are due to paradoxical emboli from pulmonary AVMs
• gastrointestinal tract : 20 - 40%
  • AVMs or angiodysplasia in stomach, small bowel or large bowel
  • complications : recurrent GI bleeding
• liver : 8 - 31%
  • symptomatic liver involvement in HHT is uncommon but does occur. It has been attributed to three distinct clinical subtypes and is believed to be a consequence of the predominant hepatic shunt pattern ².
  • high-output cardiac failure
  • shunting that increases cardiac preload
  • typically arteriovenous or portovenous shunts
  • portal hypertension
    • increased flow into the portal system (arterioportal shunt)
    • hepatic anatomic abnormalities leading to increased intrahepatic resistance
  • biliary disease
    • shunting of the blood away from the peribiliary plexus (arteriovenous or arterioportal shunting)
    • case 3 – extensive arteriovenous shunting lead to biliary necrosis and bile leak.
    • complications : hepatomegaly, right upper quadrant pain, high-output cardiac failure, portal hypertension, mesenteric angina from steal phenomenon

Radiographic assessment

Diagnosis

The presence of 3 out of 4 of the following doagnostic criteria are required 

• recurrent spontaneous epistaxis
• multiple telangiectasias
• visceral AVMs
• first degree relative with HHT

Imaging of visceral AVMs

• lung
  • CXR : well-circumscribed mass (may be lobulated) with enlarged draining vein
  • CT : well-circumscribed vascular mass with enhancing feeding artery and draining vein
  • contrast echocardiography : presence of contrast bubbles in left atrium confirms presence of a shunt
• CNS
  • content required
• gastrointestinal tract
  • CT / CTA
  • conventional angiography
  • endoscopy
  • pill-cam (capsule endoscopy)
  • nuclear medicine GI bleed study for active bleeding
• liver
  • CT / CTA
  • MRI
  • conventional angiography
  • ultrasound

Treatment and prognosis

Treatment of visceral lesions

• lung
  • embolisation
  • surgical resection
• CNS
  • embolisation
  • surgical resection
  • stereotactic radiosurgery
• gastrointestinal tract
  • embolisation
  • surgical resection
  • endoscopic ablation/electrocautery
• liver
  • embolisation
  • surgical resection
  • liver transplantation

Prognosis

• most patients have a normal life expectancy
• 10% die of complications: usually stroke, cerebral abscess or massive haemorrhage.