Hereditary Hemorrhagic Telangiectasia (HHT)

An autosomal dominant disorder of development of the vasculature

Recurrent epistaxis

Mucocutaneous telangiectases

Visceral arteriovenous malformations (AVMs) (especially lung, liver, brain, bowel)

Epistaxis may begin in childhood or later in adolescence

Punctate telangiectases of the lips, tongue, fingers, and skin generally appear in later childhood and adolescence

AVMs can occur at any age in the brain, lungs, and liver

Bleeding from the gastrointestinal tract

• Due to mucosal vascular malformations

• Usually not a problem until mid-adult years or later

Pulmonary AVMs can cause

• Hypoxemia (with peripheral cyanosis, dyspnea, and clubbing)

• Right-to-left shunting (with embolic stroke or brain abscess)

The criteria for diagnosis require presence of three of the following four features:

• Recurrent epistaxis

• Visceral AVMs

• Mucocutaneous telangiectases

• Being the near relative of a clearly affected individual

Mutation analysis can be used for presymptomatic diagnosis or exclusion of the worry of HHT

Contrast MRI of the brain should be obtained in all patients in whom HHT is suspected

Contrast echocardiogram

• Detects most pulmonary AVMs when "bubbles" appear on the left side of the heart after 3–6 cardiac cycles

• When findings are abnormal, obtain a high-resolution CT angiogram to localize pulmonary AVMs

MR or CT arteriography detects AVMs

Molecular analysis used to identify three genes that can cause HHT:

• ENG

• ALK1

• SMAD4

Prenatal diagnosis through mutation detection is possible

Embolization is indicated for patients who have AVMs with a feeding artery of 2 mm diameter or greater

Embolization of pulmonary AVMs with wire coils or other occlusive devices reduces the risk of stroke and brain abscess

Treatment of brain AVMs reduces the risk of hemorrhagic stroke

All patients with HHT with evidence of a pulmonary shunt should practice routine endocarditis prophylaxis

All intravenous lines (except those for transfusion of red blood cells and radiographic contrast) should have an air-filter to prevent embolization of an air bubble

After successful embolization of all treatable pulmonary AVMs, the CT angiogram should be repeated in 6 months and 3 years

A person with a negative contrast echocardiogram should have the test repeated every 5 years

Any person with a pulmonary AVM, even an embolized one, should utilize routine endocarditis prophylaxis

Anti-estrogenic agents (eg, tamoxifen), thalidomide, or anti-vascular endothelial growth factor agents (eg, bevacizumab) may reduce epistaxis and gastrointestinal bleeding and improve hepatic shunting

However, two randomized, controlled clinical trials of intranasal bevacizumab therapy failed to show an improvement in epistaxis