Hereditary Haemorrhagic Telangiectasia

HHT, Osler-Weber-Rendu disease, Osler-Weber-Rendu syndrome

Hereditary haemorrhagic telangiectasia is a genetic disorder that affects blood vessels throughout the body, causing them to form abnormally and bleed easily. While frequent nosebleeds are the most common sign, this condition can also affect the lungs, brain, liver, and other organs, sometimes leading to serious complications.

Table of contents

• What is Hereditary Haemorrhagic Telangiectasia?
• Who Gets This Condition?
• What Causes HHT?
• Signs and Symptoms
• How is HHT Diagnosed?
• Treatment and Management
• Can You Pass HHT to Your Children?

What is Hereditary Haemorrhagic Telangiectasia?

Hereditary haemorrhagic telangiectasia is a condition that affects how blood vessels form in your body. In a healthy circulatory system, blood flows from the heart through arteries at high pressure, then passes through tiny vessels called capillaries (the smallest blood vessels that connect arteries to veins), and finally returns to the heart through veins at much lower pressure. This normal flow allows oxygen to reach your body’s tissues safely.^[1]

In people with HHT, some blood vessels develop abnormally. Instead of having normal capillaries, the blood flows directly from arteries into veins. These abnormal connections are called arteriovenous malformations, or AVMs for short. When these malformations are small and occur near the surface of the skin or inside the nose, they are called telangiectases (the singular form is telangiectasia).^[2]

Because blood moves directly from high-pressure arteries into thinner, less elastic veins without the normal cushioning effect of capillaries, these abnormal blood vessels become strained and enlarged. They are fragile and can easily burst, causing bleeding. The location of these abnormal vessels determines what symptoms a person experiences and how serious the complications might be.^[1]

Who Gets This Condition?

HHT affects men, women, and children from all racial and ethnic groups around the world. It is believed to affect between 1 in 5,000 and 1 in 10,000 people, though many cases go undiagnosed because symptoms can be mild or mistaken for other conditions.^[2][4]

Because HHT is a genetic disorder, it runs in families. If you have a parent or sibling with HHT, there is a higher chance you might have it too. However, the severity of symptoms can vary greatly, even among members of the same family. Some people have mild symptoms that cause little disruption to daily life, while others develop more serious complications.^[1][3]

What Causes HHT?

HHT is caused by changes, called mutations (alterations in genes that can affect how the body functions), in certain genes. These genes normally provide instructions for making proteins that are found in the lining of blood vessels and help them develop properly. When one of these genes is mutated, the protein either is not made at all or does not work correctly, leading to the formation of abnormal blood vessels.^[2]

About 90% of people with HHT have mutations in one of two genes: ENG or ACVRL1. Mutations in the ENG gene cause HHT type 1, while mutations in the ACVRL1 gene cause HHT type 2. A small percentage of people have mutations in other genes, including SMAD4, which causes a form of HHT that can also involve growths in the digestive tract.^[2][3]

The different types of HHT can have slightly different patterns of symptoms. People with type 1 tend to develop symptoms earlier in life and are more likely to have blood vessel malformations in the lungs and brain. Type 2 and type 3 may carry a higher risk of liver involvement. Women with HHT are more likely than men to develop lung malformations with type 1 and are also at higher risk for liver problems with both type 1 and type 2.^[2]

Signs and Symptoms

The symptoms of HHT vary widely from person to person, depending on where the abnormal blood vessels develop in the body. Symptoms usually begin in childhood or during the teenage years, but they can start at any age.^[1][6]

Nosebleeds

Frequent nosebleeds are the most common sign of HHT, occurring in more than 90% of people with the condition. These nosebleeds happen because of abnormal blood vessels in the lining of the nose. They may begin in childhood and can be very frequent—some people experience nosebleeds every day. The loss of blood from repeated nosebleeds can lead to anaemia (a condition where the blood has too few red blood cells, causing tiredness and weakness) if the lost iron is not replaced through diet and supplements.^[1][3][6]

Visible Red Spots on the Skin

Many people with HHT develop small red or purple spots on the skin, usually during adolescence or later. These spots are telangiectases—abnormal blood vessels just under the surface of the skin. They are delicate and may lighten briefly when you press on them. These spots most commonly appear on the fingertips, hands, face, lips, inside the mouth, and on the lining of the nose. Sometimes they also form on the ears.^[1][4][6]

Internal Bleeding

Abnormal blood vessels can form in the digestive system, particularly in the stomach and intestines. About 70% of people with HHT have telangiectases in the gut, and these can bleed, leading to anaemia. Bleeding from the digestive tract is rarely seen before age 50.^[3][5]

Complications from Larger Arteriovenous Malformations

When AVMs form in major organs like the lungs, brain, liver, or spinal cord, they can cause serious problems. About 15 to 30% of people with HHT have AVMs in the lungs, and more than 10% have them in the brain.^[8]

Lung AVMs can cause shortness of breath, low blood oxygen levels, blue discoloration of the skin, coughing up blood, and fatigue. Without the normal filtering action of capillaries, small blood clots, bacteria, or air bubbles can pass through the lungs into the rest of the body, potentially causing strokes or brain abscesses (pockets of infection).^[1][3][4]

Brain AVMs can cause headaches, seizures, strokes, dizziness, or double vision if they bleed or compress nearby tissues.^[1][4]

Liver AVMs are found in more than 70% of people with HHT, though only about 8% develop symptoms. When the liver is severely affected, it can lead to heart failure because the heart must work much harder to pump blood through the abnormal vessels.^[3]

How is HHT Diagnosed?

HHT is often diagnosed based on clinical information rather than laboratory tests. Healthcare professionals use a set of criteria called the Curaçao criteria, which include four features:^[3][8]

• Frequent nosebleeds that happen without an obvious cause
• Multiple telangiectases in typical locations (such as the lips, inside the mouth, on the fingers, or on the face)
• Arteriovenous malformations in internal organs (such as the lungs, brain, liver, or digestive tract)
• A first-degree relative (parent, sibling, or child) who has been diagnosed with HHT

If a person has three or more of these features, the diagnosis is definite. If they have two features, the diagnosis is possible. However, these criteria are less helpful in children because many of the signs of HHT develop later in life. For this reason, children of a parent with HHT should be considered to have the condition unless genetic testing proves otherwise.^[8]

Genetic testing can provide a definitive diagnosis at any age if it identifies a mutation in one of the genes known to cause HHT. This testing is especially useful for children and young adults who may not yet have developed obvious symptoms.^[3][4]

Screening for Complications

Once HHT is diagnosed or suspected, screening tests are recommended to check for AVMs in the lungs, brain, and other organs, even if there are no symptoms. Finding these malformations early can help prevent serious complications.^[3][8]

For the lungs, an echocardiogram (an ultrasound test of the heart) with bubbles injected into a vein can detect abnormal blood flow. CT scans (computed tomography scans, which are detailed X-ray images) can confirm the presence and location of lung AVMs.^[9]

For the brain, MRI (magnetic resonance imaging, which uses magnets and radio waves to create detailed pictures of the inside of the body) is recommended. Children with possible or confirmed HHT should be screened for brain AVMs in the first six months of life or at the time of diagnosis.^[8][9]

Screening for liver involvement may be done with ultrasound or MRI.^[9]

Treatment and Management

There is currently no cure for HHT, but there are many effective treatments to manage symptoms and prevent complications. Treatment should ideally be coordinated at a specialized HHT centre where experts from multiple medical fields work together.^[3][9]

Managing Nosebleeds

For mild nosebleeds, keeping the inside of the nose moist with saline sprays, gels, or ointments can help. Humidifying the air at home may also reduce the frequency of nosebleeds.^[3][6]

If nosebleeds are severe or frequent, several treatments are available. Laser therapy can be used to destroy telangiectases inside the nose. This treatment is usually temporary, and repeat procedures may be needed. In more severe cases, surgery such as skin grafting may be considered.^[3][6]

Medications that reduce bleeding, such as tranexamic acid (a drug that helps blood clot better), may be helpful. Some people benefit from hormone treatments with estrogen-like drugs, though more research is needed to understand the long-term effects.^[9][10]

Treating Anaemia

Because bleeding from the nose and digestive tract can lead to anaemia, many people with HHT need to take iron supplements. In some cases, intravenous iron infusions (iron given directly into a vein) are more effective than pills. Blood transfusions may be necessary if blood loss has been significant.^[3][6]

People over 35 years of age with HHT should have their blood count checked annually to monitor for anaemia.^[8]

Treating Arteriovenous Malformations

Lung AVMs are usually treated with a procedure called embolisation (a minimally invasive procedure that blocks the blood flow to an abnormal blood vessel), even if they are not causing symptoms. During this procedure, a tiny plug is placed inside the artery supplying the abnormal vessel, blocking its blood supply. This prevents complications such as strokes or infections. Embolisation is preferred over surgery because it is less invasive.^[3][6]

People with lung AVMs, whether treated or not, should use antibiotic prophylaxis (antibiotics taken before certain procedures to prevent infection) before dental work or other procedures that could introduce bacteria into the bloodstream. This helps prevent brain abscesses. They should also avoid scuba diving and make sure that any intravenous lines have air filters to prevent air bubbles from entering the bloodstream.^[8][3]

Brain AVMs may be treated with surgery, embolisation, or radiation therapy, depending on their size and location. Not all brain AVMs require treatment, and decisions are made on an individual basis.^[3][6]

Liver AVMs are often monitored without treatment. If they cause heart failure or other serious symptoms, medical management is the first approach. In severe cases, liver transplantation may be necessary.^[3]

Emerging Treatments

Research has shown promising results with a medication called bevacizumab, which targets a protein called VEGF (vascular endothelial growth factor, a substance that promotes the growth of blood vessels). Bevacizumab may help reduce nosebleeds and bleeding from the digestive tract in people with severe HHT. However, more research is needed to fully understand how well it works and what side effects it may cause with long-term use.^[9][13][14]

Can You Pass HHT to Your Children?

HHT is inherited in what is called an autosomal dominant pattern. This means that if you have HHT, each of your children has a 50% chance of inheriting the condition. You only need one copy of the altered gene from one parent to develop HHT.^[1][4]

If you have HHT or a family history of the condition and are planning to have children, genetic counseling can help you understand the risks and options. Early diagnosis and monitoring of children who inherit HHT allows for screening and treatment to prevent serious complications.^[3][4]

Women with HHT who become pregnant are considered at higher risk for complications such as bleeding or stroke, and should receive care from specialists familiar with the condition throughout pregnancy and delivery.^[6][11]