Hereditary Hemorrhagic Telangiectasia (HHT)

Key Features

• An autosomal dominant disorder of development of the vasculature

• Recurrent epistaxis

• Mucocutaneous telangiectases

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

Clinical Findings

• 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

Diagnosis

• 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

Treatment

• 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