From migraines to strokes to brain bleeds, the symptoms of HHT are varied. Diagnosis is often delayed, yet early care can prevent both bothersome and deadly side effects.
March 9, 2020 - By Tracie White
Jennifer Cook has dealt with migraine headaches and nosebleeds since she was in junior high school, but it wasn’t until much later in life, after two small strokes in her 40s, that she discovered these seemingly disconnected ailments — including strange, little red dots on her hands and face — were all symptoms of a genetic disorder running rampant through three generations of her family.
“We all started to connect the dots,” said Cook, 48, of Sacramento, referring to about a decade ago, when her father was the first in the family diagnosed with hereditary hemorrhagic telangiectasia, or HHT, a little-known disorder causing malformed blood vessels that can affect the skin and other organs. Since then, her aunt, sister, two of her brothers and two of her daughters also have been diagnosed.
“It was so shocking to find out,” said her daughter Nina Murphy-Cook, 23, also of Sacramento, who was diagnosed four years ago. “Bloody noses, headaches and strokes in really young people. Literally, we had no idea. We all got those little red spots on the skin. My mom just called them Irish moles and said it was just something our family gets.”
Cook and her daughter, now patients at Stanford Health Care’s recently designated HHT Center of Excellence, are under the care of a multidisciplinary team of specialists that includes interventional radiologists, neurosurgeons, pulmonologists, otolaryngologists, hematologists, gastroenterologists and a genetic counselor. The team members diagnose, prevent and, if necessary, treat the disparate problems that can result from this often undiagnosed and misdiagnosed disease.
“If people get diagnosed and treated, they can have a normal life expectancy with this disease,” said Edda Spiekerkoetter, MD, associate professor of pulmonary and critical care medicine and director of the Stanford HHT center. “Otherwise, they’re susceptible to chronic, dangerous illnesses without even knowing there are treatments that can prevent them from happening.” Key to solving this problem is better educating the public, including doctors, on how to recognize the symptoms. She’s educating primary care physicians, otolaryngologists and dentists, in particular, to serve as frontline screeners: They can keep an eye out for the hallmark red dots, called teleangiectasia, in the oral cavity and on lips and ask about nosebleeds, which are extremely common in patients.
HHT causes abnormal connections, called arteriovenous malformations, to develop between arteries and veins. They can cause all sorts of problems. These deformed vessels grow most commonly in the nose, lungs, brain, gut and liver and can cause brain bleeds, nosebleeds, strokes, gastrointestinal bleeding and heart failure. The malformationsgrow in place of smaller vessels called capillaries, which normally connect arteries and veins. Capillaries are responsible for oxygen uptake into the blood and filter small particles circulating in the blood. Bypassing the capillary bed, these larger, malformed vessels allow small blood clots, bacteria and air bubbles to circulate throughout the body unfiltered. This can lead to strokes or a reduction of oxygen in the blood, which can lead to shortness of breath and exhaustion.
To prevent complications from these deformed vessels in the lungs, you need an interventional radiologist to step in; to prevent brain bleeds, you need a neurosurgeon; abdominal bleeds and anemia can be controlled by a gastroenterologist and hematologist; and otolaryngologists can help prevent severe nosebleeds, Spiekerkoetter said. While HHT is rare — affecting an estimated 1 in 5,000 people — 90% of cases go undiagnosed, Spiekerkoetter said. Patients often don’t get diagnosed until after a serious event, such as a stroke.
“This disease is as common as cystic fibrosis, but the tragedy is that it’s not well-known,” said Marianne Clancy, executive director of CureHHT.org, a nonprofit patient advocacy group that has certified 28 centers of excellence in North America, including Stanford’s, for treating the disorder. Each center requires a multidisciplinary team with expertise in diagnosing and treating the various parts of the body that can be damaged by HHT.
“On average, it takes 27 years from the first symptom before a diagnosis,” she said. “Patients can be misdiagnosed with colon cancer from gastrointestinal bleeding. Many are misdiagnosed with asthma due to the lung arteriovenous malformations. Some end up in the ER throwing up blood. No one thinks to piece all these things together.”
Nosebleeds occur in 90% of patients; they cause a lot of social embarrassment and can lead to transfusion dependence, Clancy said. Anemia occurs in 50%. The deformed blood vessels are present in about 23% of patients and can result in stroke, and arteriovenous malformations in the lungs grow in about 50% of patients, she said.
Both Cook and her daughter know firsthand how difficult it can be to deal with just the routine nosebleeds that usually accompany this disease.
“When I was a sophomore in high school, after I had my tonsils out I got this horrible bloody nose,” Murphy-Cook said. “It was like a faucet of blood. I lost so much blood I was hospitalized. It was crazy, absurd. I thought it was just a post-op problem at the time, but it was probably the HHT.”
Treatment can prevent serious side effects
Children of a parent with the illness have 50-50 odds of being born with the disease. Genetic tests can diagnose it in more than 85% of patients, and imaging tests can both locate and measure any arteriovenous malformations. If found early enough, treatment can prevent the serious side effects.
At the Stanford center, different specialists treat the diverse symptoms, but the most serious concerns are the often silent malformations that nobody knows are there until they cause a serious event such as a stroke, Spiekerkoetter said.
“We have people come in to see our specialists to have their symptoms, such as nosebleeds and anemia, treated,” she said. “We screen patients for additional arteriovenous malformations in the organs which allows us to prevent the more severe complications, such as strokes or head bleeds. And we suggest genetic testing to determine who else in the family might carry the disease.”
While adult patients are seen at Stanford Health Care, children are seen at Stanford Children’s Health. The care of children is coordinated by David Stevenson, MD, professor of pediatrics and co-director of the center. Spiekerkoetter and her colleagues are also developing mouse models of the disease to better understand its biological underpinnings.
After genetic tests uncovered their HHT, Cook and her daughter underwent imaging tests, which identified malformations in their lungs. Murphy-Cook’s are small and don’t require any treatment for now. She’ll return for more tests in three years to monitor their growth. Cook’s malformations, though, were large enough to require treatment. She underwent a nonsurgical, catheter-based procedure by an interventional radiologist at Stanford Health Care, who inserted tiny plugs in the vessels of her lungs to block blood flow through the malformations with the aim of preventing future strokes.
“My strokes were small this time and didn’t cause any permanent damage except some mild memory loss,” Cook said. “I remember my grandmother used to get bloody noses so bad she always put a tissue up her nose. She didn’t know she had this. She had a couple of small strokes and then finally had a more serious one that she died from. Some people just don’t want to know, but I wanted all my kids tested and hope they get their kids tested too. It’s so important to know.”
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