Hereditary hemorrhagic telangiectasia
Updates to Article Attributes
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:
- epistaxis
- multiple telangiectasias
- 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). DenovoDe novo 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
-
pulmonary arteriovenous malformations (AVM)s
-
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
- Increased incidence of capillary telangiectasia and developmental venous anomalies
-
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 diagnosis is a clinical diagnosis and based on the presence of 3 out of 4 of the following doagnosticdiagnostic criteria are(the Curacao criteria) is required
- recurrent spontaneous epistaxis
- multiple mucocutaneous telangiectasias
- visceral AVMs
- first degree relative with HHT
Imaging of visceral arteriovenous malformations
-
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 the left atrium confirms presence of a shunt. Characteristically, this occurs late (after several cardiac cycles), indicating a pulmonary shunt rather than intracardiac shunt.
-
CNS
-
content requiredMR: 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
- 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.
-</ol><h4>Epidemiology</h4><p>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).</p><h4>Pathogenesis</h4><p>Autosomal dominant. Mutations in one of several genes (three known so far). Denovo mutations are rare - almost all have a first degree relative affected.</p><h4>Clinical spectrum</h4><p>HHT can involve multiple organ systems. The spectrum includes</p><ul>- +</ol><h4>Epidemiology</h4><p>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).</p><h4>Pathogenesis</h4><p>Autosomal dominant. Mutations in one of several genes (three known so far). De novo mutations are rare - almost all have a first degree relative affected.</p><h4>Clinical spectrum</h4><p>HHT can involve multiple organ systems. The spectrum includes</p><ul>
-<a href="/articles/pulmonary_arteriovenous_malformation">pulmonary arteriovenous malformations (AVM)s</a><ul>- +<a href="/articles/pulmonary-arteriovenous-malformation">pulmonary arteriovenous malformations (AVM)s</a><ul>
-<li>pulmonary haemorrhage, <a title="Haemoptysis" href="/articles/haemoptysis-1">haemoptysis</a> (less common)</li>- +<li>pulmonary haemorrhage, <a href="/articles/haemoptysis-1">haemoptysis</a> (less common)</li>
- +<li>Increased incidence of capillary telangiectasia and developmental venous anomalies</li>
-<li>complications : hepatomegaly, right upper quadrant pain, high-output cardiac failure, <a href="/articles/portal_hypertension">portal hypertension</a>, mesenteric angina from steal phenomenon</li>- +<li>complications : hepatomegaly, right upper quadrant pain, high-output cardiac failure, <a href="/articles/portal-hypertension">portal hypertension</a>, mesenteric angina from steal phenomenon</li>
-</ul><h4>Radiographic assessment</h4><h5>Diagnosis</h5><p>The presence of 3 out of 4 of the following doagnostic criteria are required</p><ul>- +</ul><h4>Radiographic assessment</h4><h5>Diagnosis</h5><p>The diagnosis is a clinical diagnosis and based on the presence of 3 out of 4 of the following diagnostic criteria (the Curacao criteria) is required</p><ul>
-<li>multiple telangiectasias</li>- +<li>multiple mucocutaneous telangiectasias</li>
-<li>CT : well-circumscribed vascular mass with enhancing feeding artery and draining vein</li>-<li>contrast echocardiography : presence of contrast bubbles in left atrium confirms presence of a shunt</li>- +<li>CT: well-circumscribed vascular mass with enhancing feeding artery and draining vein</li>
- +<li>contrast echocardiography : presence of contrast bubbles in the left atrium confirms presence of a shunt. Characteristically, this occurs late (after several cardiac cycles), indicating a pulmonary shunt rather than intracardiac shunt.</li>
-<strong>CNS</strong><ul><li>content required</li></ul>- +<strong>CNS</strong><ul><li>MR: cerebral and cerebellar AVMs typically in superficial locations.</li></ul>