Hereditary Hemorrhagic Telangiectasia (HHT)

What HHT is

In HHT, a gene change disrupts the signaling that guides blood vessel growth. Some arteries connect directly to veins, without capillaries in between. Small connections form telangiectasias: thin-walled red spots that bleed easily. Larger ones form arteriovenous malformations (AVMs) in internal organs.

Three genes cause most cases:

Symptoms

Nosebleeds

Spontaneous, recurrent nosebleeds (epistaxis) are the first sign in more than 90% of people, often starting in childhood or the teens. They tend to become more frequent with age and range from a few drops to daily, heavy bleeds.

Telangiectasias

Small red or purple spots, 1 to 3 mm, that blanch with pressure. They appear on the lips, tongue, face, fingertips and ears, usually from the 30s onward.

Gastrointestinal bleeding

Telangiectasias in the stomach and small bowel cause slow, often hidden bleeding in about a quarter of people, usually after age 50. It shows up as iron deficiency anemia or dark stools.

Organ AVMs

• Lungs (in up to about half with HHT1): may cause breathlessness, low oxygen and clubbed fingers, but often no symptoms. The main danger is that small clots or bacteria bypass the lung filter, causing stroke or brain abscess.
• Brain (about 10%): usually silent; can bleed and cause stroke or seizures.
• Liver (common in HHT2): often silent; may cause high-output heart failure, pulmonary hypertension or liver problems.
• Spine: rare.

How HHT is diagnosed

Curaçao criteria

1. Spontaneous, recurrent nosebleeds
2. Multiple telangiectasias at typical sites (lips, mouth, fingers, nose)
3. Internal AVMs (lung, brain, liver, spine) or GI telangiectasias
4. A first-degree relative with HHT

3 or 4 criteria mean definite HHT; 2 means possible HHT. Children may not yet meet the criteria, so genetic testing is useful when a family mutation is known.

Tests

• Genetic testing for ENG, ACVRL1, SMAD4 and less common genes.
• Bubble contrast echocardiogram: screens for lung AVMs; a CT scan confirms and sizes them.
• Brain MRI: screening for brain AVMs, typically once in adults and in children.
• Blood count and iron studies: checked regularly.
• Endoscopy: for unexplained anemia; colonoscopy screening for those with SMAD4.
• Liver Doppler ultrasound or CT: if liver AVMs are suspected.

Treatment

Nosebleeds

• Keep the nasal lining moist with saline sprays and gels; humidify the bedroom.
• First aid: sit up, lean forward and pinch the soft part of the nose for 10 to 15 minutes.
• Tranexamic acid tablets can reduce bleeding frequency.
• ENT procedures: laser or radiofrequency ablation, sclerotherapy, septal dermoplasty, or nasal closure (Young's procedure) for severe cases. Avoid nasal cautery that is not HHT-specific, and avoid nasal packing that is not dissolvable when possible.
• Bevacizumab, an anti-blood-vessel-growth medicine given by IV infusion, reduces severe nosebleeds and GI bleeding. Pomalidomide has shown benefit in trials and is used in some specialist centers.

Anemia

Iron tablets, or IV iron if tablets are not enough. Blood transfusion for severe anemia.

Lung AVMs

Embolization: a catheter blocks the feeding artery with coils or plugs. It is recommended for AVMs with feeding arteries of about 2 to 3 mm or more. People with lung AVMs, even treated ones, should take antibiotics before dental work and other procedures with a risk of bacteria entering the blood, and use air filters on IV lines.

Brain and liver AVMs

Managed by specialists. Brain AVMs may be treated with surgery, embolization or radiosurgery. Liver AVMs are usually managed medically; transplant is rare.

Medicines and lifestyle

Blood thinners and antiplatelet drugs are not automatically ruled out, but the decision must balance bleeding risk. Avoid unnecessary NSAIDs and aspirin, which increase bleeding. Scuba diving is unsafe with untreated lung AVMs.

HHT and pregnancy

Most people with HHT have uneventful pregnancies, but lung AVMs can enlarge and bleed. Screening for lung AVMs before or early in pregnancy is recommended, and delivery should be planned with a team aware of HHT.

Outlook

With screening and treatment, most people with HHT have a normal or near-normal lifespan. Nosebleeds and anemia can significantly affect quality of life, but newer treatments have improved control. Because HHT is inherited, family members should be offered testing and screening.

Frequently asked questions

What are the first signs of HHT?

The first sign is usually frequent, spontaneous nosebleeds, often starting in childhood. Red spots on the lips, tongue and fingers appear later, usually in adulthood. Some people are first diagnosed after a stroke, brain abscess or unexplained iron deficiency anemia.

Is HHT life-threatening?

It can be if lung or brain AVMs go undetected, because they can cause stroke, brain abscess or serious bleeding. With screening, embolization of lung AVMs and treatment of anemia, most people with HHT live a normal lifespan.

How is HHT inherited?

HHT is autosomal dominant: an affected parent has a 50% chance of passing it to each child, regardless of sex. Severity can differ greatly even within a family. Genetic testing can identify the family's variant so relatives can be tested.

What helps HHT nosebleeds?

Daily nasal moisturizing with saline and gels, humidified air, and tranexamic acid help many people. For frequent or heavy bleeds, ENT laser treatment, sclerotherapy or bevacizumab can be effective. Ask for an ENT surgeon experienced in HHT.

Why do people with HHT need antibiotics before dental work?

Lung AVMs let blood bypass the lungs, which normally filter out bacteria. Bacteria released during dental work can travel straight to the brain and cause an abscess. A single dose of antibiotics before the procedure reduces this risk.