Hereditary Hemorrhagic Telangiectasia · What Is It, Causes, Signs and Symptoms, Treatment, and More

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a genetic disorder that affects blood vessel formation in multiple organs of the body. It is characterized by the presence of multiple vascular lesions, including arteriovenous malformations (AVMs) and telangiectasias. Both AVMs and telangiectasias are abnormal connections of blood vessels that lack capillaries between arteries and veins. AVMs are typically larger and develop in internal organs (e.g., liver, lung, and brain), whereas telangiectasias are smaller and occur in mucocutaneous surfaces like the skin, nose, or gastrointestinal tract. 

Normally, arterial blood is a high-pressure system, and as it goes through the capillary bed, pressure decreases until blood eventually drains into the lower-pressure veins. With AVMs, high-pressure arterial blood flows directly into a low-pressure vein without having to squeeze through the capillary system, which puts increased pressure on the vein walls. The weakened blood vessels are more prone to rupture and bleed, resulting in the signs and symptoms of HHT. 

Hereditary hemorrhagic telangiectasia affects all sexes equally and can occur in people of all ages and ethnic groups.  

Signs and symptoms of HHT are related to the presence of telangiectasias and arteriovenous malformations (AVMs). Telangiectasias are small malformed blood vessels found on the skin and mucous membranes. They can be seen as pink to red spots that blanch with pressure and typically appear on the lips, tongue, face, and fingers. Telangiectasias can also develop on the nasal and gastrointestinal mucosa, where they can cause recurrent nosebleeds and GI tract bleedings (e.g., melena, hematochezia). Many individuals with HHT develop iron deficiency anemia due to chronic bleeding, which may result in skin pallor and fatigue.  

While AVMs can form anywhere in the body, they most often develop in the lungs, brain, and liver. If an AVM ruptures in the brain, it can cause a hemorrhagic stroke. Depending on the location, this can cause several neurological complications, like headaches, seizures, sensory loss, or motor weakness. In the lungs, AVMs can interfere with gas exchange, causing decreased oxygen levels and shortness of breath. Additionally, if the artery leading into a pulmonary AVM is large enough, small blood clots can travel through the AVM and go to the brain, causing an ischemic stroke. If a pulmonary arteriovenous malformation ruptures, it might also result in hemoptysis, or coughing up blood. Finally, in older individuals, AVMs can lead to heart failure due to increased heart strain by needing to pump extra blood through the low-resistance pathway of the AVM instead of through the tissue’s capillaries. 

Diagnosis of HHT is based on a set of clinical criteria, which includes the presence of recurrent nosebleeds, telangiectasias, AVMs in internal organs, and a family history of HHT. If HHT is suspected, the diagnosis might involve several imaging techniques, such as angiography, which is a type of X-ray used to examine blood vessels, CT scans, and MRI. In individuals with GI bleeding, an upper endoscopy or a colonoscopy may also be performed to locate and identify the source of bleeding. 

Sometimes, a definitive diagnosis of HHT cannot be made based solely on clinical criteria. In these cases, genetic testing may help confirm the diagnosis by identifying specific gene mutations. It is important to know that a negative result does not necessarily rule out the condition, as up to 15% of individuals with suspected HHT may have gene mutations that have not been identified yet.  

Treatment for HHT is aimed at managing symptoms and preventing complications, as there are currently no curative treatments for the disease. Management is carried out by a multidisciplinary team at specialized HHT centers, including otolaryngology (ENT) specialists, dermatologists, hematologists, neurosurgeons, gastroenterologists, and pulmonary specialists. 

Since the most common symptom of HHT is nosebleeds, management of nosebleeds is key to treatment. For some people, these may be an uncommon, easily managed occurrence, while others may have multiple nosebleeds daily. Mild nosebleeds can be stopped by pinching the nose for at least 10 minutes while sitting upright. If this fails, the bleeding may be stopped by applying a cotton pledget soaked in a vasoconstrictor like phenylephrine inside the nose or by cauterizing the bleeding site. Laser therapy and systemic treatments, like antiangiogenic medications (e.g., bevacizumab), may be considered to help reduce the frequency of bleeding episodes. In cases where other treatments have not been effective, surgery may be performed to control the nose bleeds.  

The decision to treat AVMS is mainly based on their location. Some AVMs, like those located on the brain, may be treated even if the person doesn’t have symptoms because of the risk of bleeding. Treatment strategies include surgical resection and radiosurgery, where beams of radiation are directed at the AVM, causing the blood vessels to scar and close off. Alternatively, AVMs may be treated with endovascular embolization, where a catheter is used to obstruct the vessels.  

Finally, individuals affected by HHT who have frequent mucosal bleeding may be given iron supplements to treat or prevent anemia.