UPMC HHT Center of Excellence Brings Multidisciplinary Expertise to a Complex, Multisystem Disease

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder of abnormal vascular development that results in mucocutaneous telangiectasias and arteriovenous malformations (AVMs) affecting the lungs, brain, liver, and gastrointestinal tract. Clinical severity of HHT varies, and patients may present with anything from recurrent epistaxis to life-threatening complications.

In many cases, clinicians recognize the diagnosis. The more persistent challenge is determining how to evaluate and manage the disease longitudinally once it is identified.

Diagnosis of HHT is based on the Curacao criteria. The criteria are spontaneous recurrent epistaxis; mucocutaneous telangiectasias at characteristic sites including the lips, fingertips, and oral mucosa; pulmonary, cerebral, hepatic, or gastrointestinal arteriovenous malformations; and a first-degree family history of HHT. Three or more criteria makes a definitive diagnosis. Two criteria are a possible diagnosis warranting further evaluation.

“Recognition of HHT is generally not the problem,” says Quyen Nguyen, MD, assistant professor, medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, and adult clinical director of the UPMC HHT Center of Excellence. “The bigger issue is that clinicians who are not specialists in this disease often don't know how to navigate the findings or triage them appropriately once the diagnosis is made. That can lead to real problems downstream because some of the complications of this disease can be quite severe if undertreated or underrecognized.”

About the UPMC HHT Center of Excellence

The UPMC HHT Center of Excellence brings together specialists across pulmonary medicine, interventional radiology, otolaryngology, neurology, gastroenterology, hematology, and genetics to evaluate and manage patients with known or suspected HHT. The program includes both adult and pediatric clinical care, with coordination between teams when patients transition across age groups or require family-based evaluation. It has been accredited as a HHT Center of Excellence by Cure HHT since 2015.

The program is led by Dr. Nguyen and Adam Fish, MD, assistant professor of radiology. Dr. Fish is an interventional who leads the pulmonary arteriovenous malformation program at UPMC.

The center’s clinical work is supported by translational and basic science research led by Beth Roman, PhD, associate professor and vice chair of research in the Department of Human Genetics at the University of Pittsburgh.

Patients are evaluated through a structured process that includes confirmation of diagnosis, screening for organ involvement, and development of a lifetime management plan based on the presence and relative risk of AVM.

“Many physicians in the community have some familiarity with this disease, but not the full picture and not all of the resources to manage it,” Dr. Fish says. “What our center provides is a network of specialists who all speak the language of HHT, know the most current guidelines, are actively involved in developing them, and who are studying the disease to bring new insights into the clinic.”

The UPMC HHT Center continues to assess patients over time, repeating imaging when indicated, evaluating for recurrence after intervention, and identifying new arteriovenous malformations as the disease evolves.

“This is not a one-time evaluation. Patients require ongoing reassessment because new findings can emerge and previously treated lesions can recur,” Dr. Nguyen says.

Recognizing HHT

HHT patients typically reach a specialist through one of three pathways, each with distinct diagnostic and management pitfalls.

The most straightforward is the patient with a known family history. Variable expressivity within families is significant, and a mild phenotype in one family member does not predict disease severity in the next. Patients in this group are often under triaged because prior family experience with a less severe presentation can lead to an underestimation of individual risk.

The second is an incidental pulmonary AVM identified on imaging obtained for unrelated reasons. Clinicians unfamiliar with HHT may monitor a stable lesion rather than treat it. These lesions carry embolic risk independent of interval growth or size, and observation does not mitigate that risk. AVMs in HHT do not behave like aneurysms and cannot be treated, monitored, or evaluated in a similar manner

The third is the patient whose individual findings are nonspecific in isolation: recurrent nosebleeds, exertional dyspnea, cutaneous telangiectasias, or a family history of early or unexplained stroke. No single feature is diagnostic. The constellation is. ENT is a common entry point given the prominence of epistaxis, and primary care and internal medicine physicians frequently encounter the full picture first.

“One of the reasons this diagnosis gets missed is that patients often enter the system through one symptom at a time. They may see ENT for recurrent nosebleeds, another physician for anemia, or have an AVM found incidentally on imaging, but those findings are not always connected into a single diagnosis when they are evaluated separately,” Dr. Fish says.

Managing the Disease

Epistaxis is the most visible feature of HHT, but pulmonary AVM carry the greatest potential for serious complications. As right-to-left shunts, these types of AVM can allow embolic material to bypass pulmonary filtration and enter the systemic circulation, which can lead to ischemic stroke or brain abscess. This risk accumulates over time and may be present in patients who are otherwise asymptomatic. Over a lifetime, the risk of stroke or brain abscess in patients with untreated pulmonary AVMs approaches 50%.

“A significant number of patients with HHT present with their first stroke or brain abscess as a direct consequence of an undetected pulmonary AVM,” Dr. Nguyen says. “Preventing those outcomes is really the central purpose of our Center. Yes, recurrent nosebleeds and other symptoms are important to deal with because of their impact on quality of life, but first and foremost, we have to manage the stroke and abscess risk. Those are what catastrophically debilitate or kill people.”

At UPMC HHT Center, the team approaches pulmonary AVMs based on embolic risk rather than symptom status or interval change. Lesions are evaluated for treatment based on size, anatomy, and degree of shunting, with the understanding that absence of symptoms does not indicate absence of risk.

“The goal is not a stable lesion. The goal is no lesion and it’s not really open to clinical debate at this point. As long as that AVM is present, the patient remains at risk for paradoxical embolization, and that risk does not go away because the lesion hasn’t changed on imaging or because the patient is asymptomatic,” Dr. Fish says.

Pregnancy substantially elevates the risk of AVM rupture in women. Increased blood volume, elevated cardiac output, and hormonal effects on angiogenesis contribute to the dynamic, and most AVM ruptures occur in the second and third trimesters. Women with known or suspected HHT should be screened for pulmonary AVMs before pregnancy. If prior screening has not occurred, evaluation during pregnancy is indicated to identify lesions that may require intervention.

Also, any patient with a known or suspected pulmonary AVM should receive prophylactic antibiotics before dental and medical procedures until their pulmonary AVM status has been formally evaluated and cleared.

The UPMC HHT Center also sees patients who have been mismanaged in the opposite direction, with screening protocols that do not reflect the natural history of pulmonary AVM.

“We have seen patients receiving CT imaging every six months because the managing physician was not familiar with how these lesions actually behave,” Dr. Nguyen says. “That dynamic carries its own clinical and radiation exposure consequences that have to mitigated.”

Pulmonary AVM embolization at an UPMC HHT Center differs from general interventional radiology practice. Technique and device selection directly affect rates of persistence and recurrence. Incomplete occlusion of the feeding artery or failure to address the full vascular architecture can result in continued shunting or recanalization, sometimes through recruitment of adjacent vessels.

Patients referred after prior embolization frequently require reassessment to determine whether residual flow persists and whether additional treatment is necessary.

In his interventional radiology practice, Dr. Fish uses 3D-printed anatomic models of pulmonary AVMs, produced through the UPMC 3D Printing Program, for procedural planning and patient education. The UPMC 3D Printing Program’s medical director and founder is Anish Ghodadra, MD, associate professor, radiology, with whom Dr. Fish collaborates. These models allow detailed visualization of feeding vessels and nidus anatomy before intervention and inform device selection and access strategy in more complex lesions. Following treatment, patients undergo longitudinal follow-up to assess for residual flow and recurrence.

The UPMC HHT Center also has a defined framework to determine which patient findings require intervention and in what order.

“We have a systematic approach that sequences interventions appropriately,” Dr. Nguyen says. “Addressing a pulmonary AVM before it causes a stroke takes precedence over managing the epistaxis, even when the nosebleeds are what brought the patient in.”

While patients often present with multiple manifestations simultaneously, the UPMC HHT Center team prioritizes treatment based on embolic risk and the potential for serious complications rather than symptom severity alone.

Refer a Patient and Learn More About the UPMC HHT Center

The UPMC HHT Center of Excellence currently follows approximately 150 adult patients and adds roughly 25 new patients per year. Referral is appropriate for patients with:

• Recurrent epistaxis accompanied by systemic features such as dyspnea, cutaneous telangiectasias, or a family history of HHT or unexplained early stroke.
• Patients with an incidental pulmonary AVM identified on imaging.
• Patients with a confirmed or suspected HHT diagnosis who have not undergone comprehensive evaluation.

To refer a patient to the UPMC HHT Center of Excellence, please call 412-648-6161 or email us at PittHHT@upmc.edu. Please mention if the patient is under the age of 18 so we can coordinate care with our pediatric HHT colleagues.