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(e.g. 1 in 200 in Dutch Antilles, 1 in 3500 in France).
Pathogenesis
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.
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; 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
- symptomatic liver involvement in HHT is uncommon but does occur
Radiographic assessment
Diagnosis
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
- 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 -
characteristically, this occurs late (after several cardiac cycles), indicating a pulmonary shunt rather than intracardiac shunt
.
- presence of contrast bubbles in the left atrium confirms presence of a shunt
-
CNS
- MR: cerebral and cerebellar AVMs typically in superficial locations
.
- 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
- 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). 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>- +</ol><h4>Epidemiology</h4><p>World wide prevalence 1 to 2 per 100,000. Wide geographic variability. Much higher incidence in certain regions (e.g. 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>
-<li>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 <sup>2</sup>.</li>- +<li>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 <sup>2</sup>
- +</li>
-<li>case 3 – extensive arteriovenous shunting lead to biliary necrosis and bile leak.</li>- +<li>case 3 – extensive arteriovenous shunting lead to biliary necrosis and bile leak</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>- +<li>contrast echocardiography<ul>
- +<li>presence of contrast bubbles in the left atrium confirms presence of a shunt</li>
- +<li>characteristically, this occurs late (after several cardiac cycles), indicating a pulmonary shunt rather than intracardiac shunt</li>
- +</ul>
- +</li>
-<strong>CNS</strong><ul><li>MR: cerebral and cerebellar AVMs typically in superficial locations.</li></ul>- +<strong>CNS</strong><ul><li>MR: cerebral and cerebellar AVMs typically in superficial locations</li></ul>