2005

Mayo Clinic Designated Center for
Excellence for Diagnosis and Treatment of
Hereditary Hemorrhagic Telangiectasia

Points to Remember

• Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder that affects approximately 1 in 5,000 people.
• HHT presents with a wide array of common symptoms that range in severity.
• The most common symptom is frequent nosebleeds. The most dangerous complications of HHT are transient ischemic attacks, stroke, seizures, right to left shunting through the heart, shortness of breath, and low oxygen levels.
• Various procedures are available to treat HHT, but currently there are no medical treatments.
• Mayo Clinic's new HHT center coordinates comprehensive care for HHT patients. It is 1 of 9 Centers of HHT Treatment Excellence in North America.

Scope of Problem

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic abnormality of the blood vessels that affects an estimated 1 in 5,000 people worldwide. It is occasionally referred to by its older name, Rendu-Osler-Weber syndrome. As a result of 1 of 3 gene mutations identified to date, HHT patients lose capillary network connections between veins and arteries in multiple organ systems, including, but not limited to, brain, lungs, nose, gastrointestinal tract, and liver.

Symptoms therefore vary in both kind and severity, but the most common symptom is recurrent, severe nosebleeds. Coupled with the fact that HHT is uncommon, the array of symptoms and involvement of multiple organ systems can make the diagnosis and treatment of HHT challenging. Complications of HHT include transient ischemic attacks and stroke, as well as shortness of breath and low oxygen levels, primarily due to arteriovenous malformations (AVMs).

HHT Symptoms and Criteria for Diagnosis

Three of the following 4 criteria must be met for a definitive diagnosis of HHT. If 2 of the 4 criteria are met, the patient is suspected of having HHT. The criteria include the following:

• Telangiectases, or red pigmentation spots, usually appearing on the lips, tongue, nasal mucosa, or fingertips.
• Visceral involvement resulting in AVMs in the brain, lungs, liver, or gastrointestinal tract. Gastrointestinal tract bleeding usually does not appear until the age of 50 years or older and is caused by the development of telangiectases in the gastrointestinal tract. AVMs in the lung can cause right to left shunting, which can result in low blood oxygen levels and also contribute to brain abscess, stroke, or seizures.
• Epistaxis. HHT patients' nosebleeds range from irritating to severe nosebleeds, which contribute to anemia and limit lifestyle. A severe nosebleed can last 2 hours or more and may occur daily and require blood transfusions. Most patients with this severity and frequency of nosebleeds develop them by the age of 19 years.
• Family history of any of the above conditions. A high degree of clinical suspicion is warranted whenever a patient presents with severe, recurrent nosebleeds or a family history of them. The typical HHT patient often initially seeks help for nosebleeds, yet is unaware of any other organ system involvement. If the physician does not consider the possibility of HHT, he or she will fail to screen the brain with MRI or the chest with CT or check liver function with blood testing or abdominal CT looking for blood vessel abnormalities in the liver. The diagnosis will then be missed, and the patient will continue to be at risk of developing preventable complications related to HHT.

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A New Approach: Comprehensive, Coordinated Care at Specialty HHT Center

Specialty HHT centers are uniquely suited to fully address all organ systems involved in HHT. This coordination of care concept originated about 10 years ago at Yale University. Since then, a network of 9 Centers of Excellence in North America has evolved through the HHT Foundation International. The distinction as a Center of Excellence recognizes depth and breadth of medical knowledge, clinical care experience, and multidisciplinary expertise available to coordinate and integrate the many procedures and subspecialty consults an HHT patient may require.When HHT is suspected, a physician at an HHT center performs the following during the initial evaluation:

Before (above) and after (below)

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HHT patients lose capillary network connects between veins and arteries in multiple organ systems. Systems required for diagnosis include visceral involvement resulting in AVMs such as those shown here in the lung before and after treatment with coils.

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• A thorough medical and family history is taken, looking for such symptoms as inherited patterns of severe nosebleeds, early stroke, brain abscess, and pulmonary AVMs.
• The presence of telangiectasia is noted; the clinician listens for mention of early stroke or other evidence of AVMs in the medical history.
• A transthoracic contrast echocardiogram is ordered to check for right to left shunting in the heart from an intrapulmonary source, and a chest x-ray and brain MRI examinations are ordered as well to determine if AVMs are present.
• If the chest x-ray film or echocardiogram shows abnormalities suggestive of pulmonary AVM or right to left shunting, a CT scan of the chest is performed to look for pulmonary AVMs. If the CT scan shows pulmonary AVMs, a pulmonary angiogram and coil embolization are scheduled.
• Blood tests are usually done to evaluate hemoglobin, liver enzyme, and iron levels.
• If the patient is diagnosed as having HHT, the HHT specialists recommend that all first-degree family members be screened for HHT
• Genetic testing is now available and may be a reasonable option for the patient and for other family members. Genetic testing may be
  useful in making the diagnosis of HHT in the absence of symptoms, especially in children. Genetic counseling is also provided.

Treatments Available

No proven medical therapies are available for HHT. Tamoxifen and hormone therapies have been tested, but more data are necessary before their use becomes standard practice. The comprehensive approach of HHT Centers of Excellence therefore relies on treatments specific to each organ system. For example:

• Nosebleeds may be relieved by use of laser cautery or skin grafting by specialists in the otolaryngology department.
• Pulmonary AVMs may be treated with coil embolizations if the feeding artery is more than 3 mm in diameter. This involves specialists in pulmonary medicine and interventional radiology.
• Brain AVMs may be treated with stereotactic surgery with specialists from neurology and neurosurgery.
• Liver AVMs are difficult to treat. Embolization is not recommended because it too often leads to complications and does not appear to be safe. Liver transplantation has been performed safely in a small number of patients with HHT, which involves specialists from hepatology and transplant surgery.
• Contrast echocardiogram with bubble study can document right to left intrapulmonary shunt. If a right to left shunt is identified, patients should take prophylactic antibiotics before dental work to minimize the chance of brain infection (abscess).
• Telangiectases of the gastrointestinal tract are difficult to treat. Patients may have AVMs bleeding at a site that can be treated with laser surgery. Patients may also require blood transfusions and iron supplementation. Specialists from gastroenterology and hematology perform these procedures.