Hereditary hemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare inherited disorder characterised by abnormal blood vessel formation in the skin, mucous membranes, and organs including the lungs, liver, and central nervous system.

Epidemiology

Worldwide prevalence ~1.5 per 100,000. Wide geographic variability with a much higher incidence in certain regions, e.g. 1 in 200 in Dutch Antilles, 1 in 3500 in France.

Clinical presentation

TheAlthough the disease has a broad clinical spectrum, the classic clinical triad at presentation is epistaxis, multiple telangiectasias, and positive family history. 

The diagnosis is a clinical diagnosis (Curacao criteria) based on the presence of 3 out of 4 of the following ⁸:

• recurrent spontaneous epistaxis
• multiple mucocutaneous telangiectasias
  • characteristic sites include: oral cavity, lips, fingers and nose
• positive family historyvisceral AVMs

Pathology

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. Mutations have been found in one of several genes (three known so far). De novo mutations are rare, almost all have a first-degree relative affected.

Hereditary haemorrhagic telangiectasia can involve multiple organ systems. The spectrum includes:

• nasal: 90%
  • telangiectasias of nasal mucosa
  • complications: recurrent epistaxis
• skin and mucosal membranes: 90%
  • telangiectasias of skin, oral cavity, conjunctivae
  • complications: recurrent bleeding
• liver: 71-79%^5,7
  • 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)
    • 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
• gastrointestinal tract: 20-40%
  • AVMs or angiodysplasia in the stomach, small bowel or large bowel
  • complications: recurrent GI bleeding
• pulmonary: 20%
  • pulmonary AVMs
    • 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 (e.g. stroke), septic emboli (e.g. cerebral abscess), hypoxaemia, high-output cardiac failure
• CNS: 5-10%
  • cerebral AVMs, spinal AVMs or cerebral aneurysms
  • complications: headache, seizures, paraparesis, haemorrhage
  • one-third of cerebral complications in HHT are due to cerebral AVMs or aneurysms, and two-thirds are due to paradoxical emboli from pulmonary AVMs
  • increased incidence ofcapillary telangiectasia and developmental venous anomalies

Radiographic assessmentfeatures

Imaging of visceral arteriovenous malformations

• lung
  • chest x-ray: 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 the left atrium confirms the presence of a shunt
    • characteristically, this occurs late (after several cardiac cycles), indicating a pulmonary shunt rather than intracardiac shunt
• CNS
  • MR: cerebral and cerebellar AVMs typically in superficial locations
• 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; recanalisation occurs in up to 20% post 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