preroll: The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education, ACCME, to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 credit. Physicians should claim only the credit commensurate with the extent of their participation in this activity.  

Melanie Cole, MS (Host): Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole. And we have a panel for you today to highlight hereditary hemorrhagic telangiectasia. Joining me is Dr. Jeb Justice. He's the Chief of the Division of Rhinology and Skull Base Surgery at the University of Florida College of Medicine and Co-Director of the UF HHT Center of Excellence, and he practices at UF Health Shands Hospital. And Dr. Ali Ataya. He's an Associate Professor of Medicine in

the University of Florida Division of Pulmonary Critical Care and Sleep Medicine, Director of the Pulmonary Hypertension Program and Co-Director of the UF HHT Center of Excellence. He is also practicing at UF Health Shands Hospital.

Doctors, thank you so much for joining us today. Dr. Ataya, I'd like to start with you. Can you give us a little bit of an overview of the prevalence of HHT and how it varies across populations? Are there specific age groups or demographics more commonly affected by it? Kind of set the table for us.

Dr. Ali Ataya: Thanks for having us, Melanie. So, hereditary hemorrhagic telangiectasia, or HHT, is a genetic disorder that is inherited in an autosomal dominant fashion. That means every parent has a 50% chance of passing on the gene to the future generation if they have it. It doesn't discriminate between geographic areas, sexes, or race. And we believe the prevalence around one per 5,000 may actually carry one of these different genetic mutations that may cause this disease and can cause so much variable presentations among patients and families.

Melanie Cole, MS: Well, thank you for that. So Dr. Justice, speak a little bit about the underlying pathophysiology that we know, with a focus on these vascular abnormalities that make this such an interesting condition.

Dr. Jeb Justice: Sure. Also, thanks for having us. So with respect to the pathophysiology, the simple way to think about it is that there are abnormal blood vessels that are formed. We could get into the nuts and bolts of it. It has to do with the TGF beta pathway and it disrupts the endothelial cells inside the vessels. And this can happen anywhere in the body, really. The most common symptom is going to be nosebleeds. And so, that's why an Ear, Nose and Throat doctor would be involved.

And the other way to think about it is that when these vessels form, when they're small in the nose, we call them telangiectasias. If they're larger on different parts of the body, they can be called arteriovenous malformations or AVMs. But the clinical manifestation has to do with the lack of a capillary bed. So, you have a high flow coming from the arterial side straight into small venules that don't have a smooth muscle that can help them withstand higher pressure. And so, that pressure tends to make these vessels crack and bleed. And then, you get into a vicious cycle where the scabs fall off too early and they bleed again. And it's actually the airflow through the nose that is one of the inciting factors that causes the vessels to form and crack and bleed. Well, we know that because there's a rare, rare surgery that thankfully we don't have to perform very much. But if we can actually suture the nostrils closed and stop the airflow, then the telangiectasias go away and the bleeding stops.

Melanie Cole, MS: That is so interesting. Now, Dr. Justice, sticking with you for a second here. I'd like you to speak about the epistaxis and why this is such a prominent feature. You just mentioned a rare surgery and you were briefly touching on some of the clinical manifestations. I'd like you to speak about some of the others and really how you see in your practice every day that patients living with this how it affects their quality of life, because it's not just the nosebleeds. There are other manifestations. So, speak about the whole situation.

Dr. Jeb Justice: Sure. So, the nosebleeds, we think of it as kind of the cardinal symptom because some studies have shown 96% of patients with HHT will have nosebleeds, and they can start at a young age. They do get worse with age. But you can imagine a lot of these patients bleed every day, multiple times a day. So, think about that, how that would reduce someone's quality of life. It's hard for them to go out in public. It's hard for them to go out and have meals or dinner or do activities, because even when they're not bleeding, they're worried about having a bleed. And there's a stigma attached to that, right?

If you see somebody in a restaurant whose nose is bleeding spontaneously, there are certain potential judgments that one might have about that. So, it's really important that we plug these patients in with support systems, whether that's family, friends, or similar patients, because bleeding from your nose every day and not being able to stop it is a pretty tough thing to have to deal with.

Dr. Ali Ataya: Yeah, I'd like to add to that, that these bleeds can be very, very dramatic. Obviously, it varies from patient to patient, but we see patients who bleed profusely for over half an hour almost every day. And you can imagine how this can impact their quality of life. And we're not sure why exactly that they start off mild in young children and they get worse over time, whether it's aging or other environmental factors. But a lot of our patients tend to live with this and deal with it for most of their life, that they don't actually seek help. They just say, I'll just manage. But it's so important for them to see someone who specializes in ENT with the different treatments, like Dr. Justice, because we can significantly improve their quality of life.

Melanie Cole, MS: I'm glad you made that point, Dr. Ataya, because I'm not sure that people realize or even referring physicians would realize that this is something that can be managed by the multidisciplinary approach. And we're going to get into that. But before we do, Dr. Ataya, speak about some of the interventions that are commonly used to manage this and alleviate some of these symptoms.

Dr. Ali Ataya: Well, whenever we encounter these patients, the first thing we stress to them is about trying to humidify their nasal passages, especially with people with less severe bleeding. And we're talking about using nasal sprays, a humidifier at night, very simple interventions that can make quite a bit of a difference. And a lot of our patients notice that their bleeds get worse with the change in seasons, the cold air and so on. So clearly, as Dr. Justice alluded to, is that doing certain surgeries where we reduce the dry air or turbulent air that goes into the nose can impact the bleeding. And for those who have more significant bleeding, you know, we first try to do some medical interventions at the same time having seen by a multidisciplinary team between myself and Dr. Justice to figure out what works best for the patients. No two patients will have the same response to different medical interventions or surgical interventions. So, we try to find the right combination for them, what fits best. So, we tend to prescribe a medication called doxycycline. It's an antibiotic routinely available that may play a role in having what we say, anti-angiogenesis effects, where it can prevent the production of new blood vessels. And we've seen a dramatic improvement in some of the nosebleeds in some of our patients. And if that doesn't work, we escalate to other medications like tranexamic acid and, in severe situations, IV infusions with bevacizumab. But I think Jeb can speak more to the surgical interventions as well that we resort to for some of these patients.

Dr. Jeb Justice: Absolutely. So, Dr. Ataya is right. We always try medical therapy first. If that fails or if the patient's bleeding is quite severe, thankfully now there's multiple techniques we can do. When I was training 15, 18 years ago, we basically told patients, you know, "We can pack your nose, we can cauterize, or we can do a laser," and that was about it. Packing's uncomfortable. Cauterization can cause what we call collateral damage, you know, of some of the normal structures inside the nose. Overly aggressive cauterization can cause a hole in the septum called a nasoseptal perforation, which can sometimes be a problem for patients. And then, the laser works well for more milder cases or smaller vessels. But the lasers, you know, it's a little bit of a burdensome setup. There's risk to the people in the room. We have to have eye protection and stuff like that. And the laser didn't really work well for the more severe bleeds or the larger vessels. So thankfully now, there's a couple other procedural techniques or surgical techniques, you know, most of them we do in the operating room, but some of the procedural techniques we can do in the clinic as well as long as we think it's a safe situation, safe patient to do it in. So, there are irrigating bipolar cauteries, which are much more gentle and don't cause as much tissue damage or collateral damage.

There are also radiofrequency ablation devices that ablate or remove the offending vessels in a similar way that the irrigating bipolar cautery does, but the newer and more exciting thing that we're able to offer is called sclerotherapy. Sclerotherapy has been around for varicose vein treatment and lymphatic malformation treatment for decades, really, and in general is quite safe. But it was only applied to HHT patients probably about 10 or 15 years ago. And it involves mixing a detergent or sclerosing agent with air to make a foam that then we inject directly into the vessels. That foam causes endothelial cell disruption and causes the vessel to collapse on itself. And it's really nice because you can offer it in the clinic or in the operating room. And it doesn't cause the collateral damage that some of the other techniques have. And it seems that when we do this sclerotherapy, there's less chance of new vessels growing back in the same spot, which they do tend to grow back after cauterization. So, we work with the patients really closely. We talk to them about the pros and the cons, the risk, benefits of each technique and kind of work with them in a shared decision-making model to try and allow them to pick what they think is going to be best for them.

Dr. Ali Ataya: I believe sclerotherapy is becoming more and more popular. We have patients who even travel from out of state to come and request to have this treatment, because not many providers even are able to offer it in the nose. So, a lot of HHT patients seem to prefer it as a treatment choice once they've had it as well.

Dr. Jeb Justice: That's a great point. The HHT community is a really close-knit community, whether that's with their national or international organization, Cure HHT, as well as through social media. And so, the patients really do communicate with each other and support each other. And so, when there's new treatments like that, they really try to get the word out, which is nice.

Melanie Cole, MS: Dr. Ataya, as we're speaking about this multidisciplinary approach, who are all the specialists that get involved as you educate and support patients and their families regarding management and any lifestyle modifications, precautions you'd like to mention that you speak with patients about, but who else are they seeing to help them manage all of the conditions that go along with HHT?

Dr. Ali Ataya: We're very fortunate here at UF to have access to so many specialists in different fields and we ask them for their expertise based on the patient's needs. So, we are able to offer patients the whole gamut of treatments for their entire manifestations of the disease. The majority of our patients usually see me and Dr. Justice most of the time, especially for their first visit. We try to time our appointments, so for new patients who come to UF to get diagnosed or to establish care. We try to arrange a whole day of testing for them to see myself and Dr. Justice the same day or on back-to-back days with all the testing that they need so they have a comprehensive visit.

And based on the patient's needs, we routinely work with different specialists. The most common are our Hematology specialists, because these patients tend to have severe iron-deficiency anemias and require iron transfusions. We work with geneticists as well at our center. With our pediatric colleagues for children who have HHT, even though we tend to see pediatric and adult patients as well. And of course, for those with brain manifestations, we have our Neurosurgical colleagues. And those with lung and liver manifestations, we work with Interventional Radiology as well as Hepatology and GI. So, patients can have access to all specialists based on their needs.

Melanie Cole, MS: I'd love to give you each a chance for a final thought. So Dr. Ataya, starting with you here, what would you like referring physicians to know about the program for HHT at the University of Florida College of Medicine and the Center of Excellence and when you feel it's important that they refer.

Dr. Ali Ataya: I think any patient where there is a suspicion of having HHT, unexplained nosebleeds unexplained AVMs in internal organs, I think consideration of this disease and referral to our center is important. Not all families who carry the gene have the same manifestations. So, one may tell me, "Well, my relative had this different combination of manifestations while I don't, so I can't have the disease." well, without genetic testing to confirm that, sometimes that may not be accurate.

So, we try to be very accessible to the community physicians in our state and other centers. So, I would ask them to feel free to reach out to us if they have any questions. And genetic testing nowadays is so accessible and affordable that we can even work on mailing out genetic test kits to patients before they see us to help get the diagnosis confirmed when suspected early on. And of course, with access to a multidisciplinary team, we can make sure we take care of our patients and their families. And as I tell all my patients, patients with HHT live complete lifespans and we want them as long as they get appropriate screening. And so, it's important that they get plugged in early with an HHT Center of Excellence and the Cure HHT community is a fantastic one for a supportive system.

Melanie Cole, MS: Dr. Justice, last word to you. What would you like referring physicians to know and where do you see this going in the future? Give us a little blueprint for future research and the key takeaways from this really interesting episode today.

Dr. Jeb Justice: Absolutely. So, I echo everything Dr. Ataya said. I think a couple other things that we try to be as accessible as possible. Any referring position could reach out to us anytime and we'd be happy to try our best to expedite the referral. And you mentioned research, which is super important. Like people have started to prescribe doxycycline. It works in some people and not in others. It's very interesting and we're not really sure why. We don't have a good way to predict right now when we first meet a patient based on their clinical findings or their genetics of who's going to respond to doxycycline or even some of the other treatments. The different genetic variations seem to manifest differently in patients, but it doesn't seem so far, at least with nosebleeds, to predict response to treatment.

The other thing too is, you know, Gainesville's a small town. Most of our patients come from a long way away within the state of Florida and within the Southeast regionally. And it is very important that we continue to work with the local referring physicians, because sometimes the patients can get their treatments, right? If they need Avastin infusion, they can typically get that at home without having to drive up here to have those repeated infusions. And so, we try to work really well with the referring people, especially when they are from a good distance away.

So, you know, these patients are dealing with nosebleeds or dealing with, sometimes pulmonary hypertension and other symptoms, and then add to that the fact that they have to sometimes drive four or five, six hours, one way to come see us. You can imagine how stressful this would be to try to get topnotch care. And so, we want people to know that we'll try to be as accessible as possible and work closely with the referring physicians to give the patients the best care possible.

Melanie Cole, MS: That's great information. Thank you so much, doctors, for joining us today. To learn more about this and other health care topics at UF Health Shands Hospital, please visit innovation.ufhealth.org. And to listen to more podcasts from our experts, you can always visit ufhealth.org/medmatters. That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. Please remember to subscribe, rate and review UF Health MedEd Cast on Apple Podcasts, Spotify, iHeart and Pandora. I'm Melanie Cole. Thanks so much for joining us today.