Oral Health after Treatment: Navigating Graft-versus-Host Disease, Medications and Infections

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[00:01] Moderator: Hello, and welcome to the workshop, Oral Health after Treatment: Navigating Graft-versus-Host Disease Medications and Infections.

My name is Penina Seidman, and I will be your moderator for this workshop. Before we begin, I would like to thank Incyte, who helped make this workshop possible.

It is my great pleasure to introduce today's speaker, Dr. Jacqueline Mays. Dr. Mays heads the Oral Immunology Unit within the Division of Intramural Research at the National Institute of Dental and Craniofacial Research at the National Institutes of Health. She's an immunologist and a clinical trials dentist whose research focuses on chronic GVHD and salivary glands and oral mucosa.

Please join me in welcoming Dr. Mays.

[00:46] Dr. Mays: Thank you so much, Penina, and thank you to you and Sue and Marla who have done such a phenomenal job putting this symposium together. It's a real privilege to be able to speak with you all today. Thank you to everybody who's logged in and to everybody who will watch the recording of this session. I sincerely hope that it is useful for you.

I plan to tell you about general oral care after transplant, things that can happen in your mouth, following transplant: what chronic graft-versus-host disease looks like in the mouth different forms that it can take and treatments that we commonly and less commonly use for the treatment of graft-versus-host disease.

[01:26] Overview of Presentation. Importantly, and number one principle that we'll talk about today is taking care of your mouth.

We'll discuss how to establish community dental care, including the who, the what, and the when. We'll talk about oral cancer screenings, which are particularly critical after transplant. We'll talk about non-GVHD post-transplant complications, so things that can happen in your mouth following your transplant that are not chronic graft-versus-host disease.

Finally, we'll spend some time talking about graft-versus-host disease in your mouth, so what it feels like, what it looks like, and the available treatments.

[02:09] The oral cavity is the gateway to the body. It's a tremendous environment that serves as the portal that you use to eat, to speak, and, to some extent, to breathe, so it includes all of this mucosal tissue that covers the surface.

[02:22] Shown on this slide is a type of epithelium, just like your skin, but it's obviously specialized because it's on the inside of your mouth. It is wet and has a local biofluid that we call saliva.

Your oral cavity has its own microbiome, with unique populations of bacteria, and immune tissues are plentiful within the oral cavity. Your tonsils are right at the back of your throat, sort of at the entrance to that pharynx. And then you're able to generate a wonderful immune response underneath your tongue, in that sublingual space, where the epithelium is very, very thin.

[02:57] On a daily basis, one of the most important things you can do is to simply take care of your mouth.

Brushing means using toothpaste with fluoride in it or with one of the more advanced calcium compounds. This fluoride acts as essentially a vitamin to support your dental enamel. If the enamel has broken down a little bit because of acid that's produced by the bacteria in your mouth, the fluoride is able to replace the calcium in the enamel structure and re-harden the enamel, kind of as a kind of cleanup crew.

If you have a sensitive mouth after transplant, whether or not you have graft-versus-host disease, there is now a plethora of fruit-flavored toothpaste. We always used to recommend children's toothpaste. The problem with children's toothpaste is it has a little bit less fluoride in it, so I like to recommend one of the many, many fruit-flavored toothpastes that don't involve mint at all.

[03:59] If you walk into your local drugstore or wherever you buy your toothpaste, you'll find half an aisle full of different non-mint flavors of toothpaste. 

If you have sensitive teeth, it's highly recommended on a regular basis that you get some extra support from extra fluoride. This could be a fluoride rinse or gel, or something you get from your dentist with a prescription.

It could also be a desensitizing toothpaste such as Sensodyne, Pronamel, or Colgate Sensitive. And professional desensitizing treatments that are available in the dental office. These are things that you would want to ask your community dentist about.

[04:50] I always recommend to our post-transplant patients, whether or not you have limited joint mobility, but particularly if you have limited joint mobility that you use an electric toothbrush. This can be any type of electric toothbrush from the drugstore. The more expensive your toothbrush is, the quieter it is, but it really doesn't make it any more effective. The toothbrush shown on this slide is a $20 or $30 model that you can get from Amazon. It simply vibrates and helps to really power the plaque off of your teeth and keep them a little bit cleaner. It multiplies your effort in brushing your teeth.

[05:38] Taking care of your mouth also includes flossing. Flossing is a great way to get the plaque and the food out from between your teeth. Sometimes, especially if patients have been on prednisone, your gums will shrink back a little bit, which enables food to get caught more frequently between your teeth, so cleaning between your teeth becomes a lot more sensitive.

• Using traditional floss, I like to take a nice long piece, wrap it around my middle fingers, and then use your pointer fingers and your thumb to manipulate that between your teeth. We know that this is not the easiest technique to master, especially not if you have other challenges or mobility issues. 
• Alternatively, I strongly encourage the use of floss picks or any other aid that's shown on this slide to help you clean between your teeth. 
• There's also something called a Waterpik or other brand of electric flosser that will shoot a little stream of liquid, such as water or an antibacterial mouth rinse. This is sort of like a power wash that targets between your teeth.

All of these options can be very helpful for getting the food and the bacteria out from between your teeth.

[07:02] Of course, we recommend seeing your dentist on a regular basis. Following your transplant, as soon as you're cleared by your medical team for regular dental care, it's recommended that you return to your every six-month schedule for regular cleanings and checkups, primarily because problems that are small are much easier to fix than problems that have been ongoing unchecked for several years.

You probably had a dentist before transplant. Hopefully you saw a dentist right before your transplant. That might have been at your cancer center, or it might have been somewhere else. It might not have been where you get your regular care. But I always recommend that you tell your dentist you're a transplant survivor and that you show your dentist anything unusual or new that you see or feel in your mouth.

In general, mouth ulcers, lumps, or bumps should heal within three weeks. That's sort of our general rule of thumb. Anything that lasts a little bit longer probably needs to be checked out. I also strongly recommend every six months when you're in, do ask for an oral cancer screening. This is something that the dentist may or may not tell you she or he is doing, but it's when they take a piece of gauze, wrap it around your tongue and move everything all around so that they can see into all of the nooks and crannies in your mouth. Unfortunately, if you have GVHD in your mouth, that is not expected to heal within three weeks.

[08:40] Not every dentist will appreciate your complex medical history and needs. If your dentist is not a good fit, feel free or please, please interview other dental offices. Talk to the staff, find out who is good at taking the time that's needed to treat patients who might have a little bit more complex medical history than your standard, every six month cleaning in an adult. You can always ask: “Do you have experience treating medically complex patients?” That's the lingo in the dental world.

A good place to look is always the universities. Dental school faculty, resident practices that you can go to for your regular care in your area, or clinics that are at a medical center are all good options, because seeing transplant is less common in the community than it is in a university setting.

[09:51] I strongly encourage you to get at least an annual oral cancer screening. This is not something that I want you to stay awake at night worrying about. We know that after transplant, patients have a higher risk of oral cancers, although it's still a very, very small risk. The highest risk is in patients who have had a significant oral graft-versus-host disease history with a lot of inflammation in the mouth for a long time. We typically start seeing these five to 10 years post-transplant, typically oral squamous cell carcinomas, and often on the tongue.

[10:29] This picture is one of my patients who presented at five years post-transplant with a new oral squamous cell carcinoma. He had noticed it two to three weeks prior to coming in to see us at the NIH. I suspect it had probably been there for a lot longer, but it's difficult to always notice new things that are in your mouth. These are often painful, so that is one thing that will often differentiate these types of lesions from something else in your oral cavity.

[11:06] It’s always helpful to know when to expect some of these things or maybe when to watch out for some of these things. I hesitate to say expect because they are not going to occur in every patient and they're becoming more and more rare as we advance our own expertise in the world of transplant care patients.

In the early days post-transplant, that first 100-day post-transplant period, what we often see in the oral cavity is mucositis. We will see patients reporting dry mouth, and this can be from a number of things. We see patients who develop oral thrush, which is candidiasis. We always have a little bit of yeast in our mouth, and the most common strain is Candida albicans. When you're immunosuppressed, that yeast can overgrow, and that is what we call thrush.

In the overlap period, we start to see drug-induced complications. Sometimes this is because of challenges with dosing methotrexate and sirolimus. Sometimes because of immunosuppression we start to see viral infections breaking through, including herpes simplex virus and human papillomavirus.

In the later stages, approximately 100 days post-transplant or later, we start to see signs of chronic graft-versus-host disease. This can include dry mouth oral ulcers, white lacy lesions that we'll talk about in more detail a little bit later in the slides.

Much, much later we start to see secondary cancers, five to ten years post-transplant.

[13:00] Apart from GVHD, patients may also experience dry mouth, ulcers, infections, cold sores, or mucositis. Non-GVHD post-transplant complications can include loss or change in taste, or dysgeusia. The way that your food tastes can change because of your pre-transplant chemotherapy. It's something that gets better over time, so every month we typically see improvements in this.

You can experience radiation-induced dry mouth if you did have pre-transplant irradiation or radiation at some point during your cancer therapy.

We also see medication-related oral ulcers or lesions. Sometimes we do a biopsy to differentiate these from graft-versus-host disease. Sometimes based on your medical history, it's pretty straightforward to diagnose what's going on with those lesions.

And of course, there are the infections. Sometimes we'll see a superficial bacterial or viral infection in your mouth, just like the rest of your body during an immunosuppressed state because you're more susceptible to infections that your body in a normal healthy state would fight off. 

I've included cold sores as its own line because this is, of course, a viral infection. We see them quite often after transplant, especially if patients are on high-dose prednisone or another steroid, where we see this sort of recrudescence of the herpes simplex virus. Unfortunately, it never really goes away. It lives dormant in your trigeminal ganglia, right by sort of your jaw joints, and can come back if you're in an immunosuppressed state.

[14:43] How do we treat mucositis?

Mucositis is something that can happen early post-transplant, and it also may be something that you experienced prior to your transplant during chemotherapy.

Oftentimes we'll administer something called cryotherapy. This has different formats, the simplest of which is sucking on ice chips. There are medications such as super saturated calcium phosphate rinses which are very thick and help to soothe tissues and reduce inflammation. There are adherent mucosal barriers which are gels that coats the inside of your mouth and help protect that very, very fragile mucosal tissue from being disrupted by your tongue and allow you to eat more easily. Pain control is really important in mucositis. We want you to be able to eat because getting that nutrition into your body is really critical for being able to heal.

[15:51] A newer therapy that's being used at many centers is red light therapy, also called photo biomodulation. It's administered with different protocols but, basically, it's a very intense red light, usually between 660 and 860 nanometers, administered a few times a week. It helps to reduce the inflammation in your oral cavity and promote healing.

[16:20] Moving on to some of the photos of what some of these things look like. Herpes and thrush are other common oral problems after transplant. This is a picture of very early recurrence of herpes simplex virus (HSV). This type of reactivation is very common. You can see on the corner of this patient's lip there are active vesicles. 

This is something that you'll see very early. Oftentimes we see them after they've already popped because they are quite fragile, and these ulcers are exquisitely painful. They tend to be very small. You can see on the inside of this lip where some of these vesicles have popped. We often suspect HSV if the vesicles are very, very painful. To diagnose this, we can swab, just take a little Q-tip and send it to the lab to look for the DNA from that virus.

HSV is managed using systemic antiviral treatments along with lidocaine/Benadryl/Maalox, which is a numbing agent and sort of a soothing agent. It's a mouthwash that's mixed up by your pharmacy to soothe that area and allow you to get good nutrition.

[17:29] Here are images of oral thrush or candidiasis overgrowth. This can occur as a pseudomembranous or an erythematous form, which can look like some white stuck-on material in your mouth. On the rightmost side of the slide, we see it on a tongue. The erythematous form is here in the middle tongue, and something that has gotten within that tissue is shown at the back of the throat on the rightmost side of the slide.

Typically the white stuck-on appearing kind will wipe off with a piece of gauze. The classic sign that this is candidiasis versus something else is that the tongue will burn, especially if you drink a sip of water, something that normally would not irritate your oral cavity at all. This is managed using topical antifungals, oftentimes antifungal medications that melt on your tongue but also potentially your systemic antifungal medication.

Something else we commonly see are medication induced ulcers and lesions in patients that are on sirolimus or another mTOR inhibitor (the same class of medication). You can develop some oral ulcers or less commonly an oral stomatitis. Because of excess circulating levels of these drugs, including sirolimus, you can develop painful aphthous-like ulcers which oftentimes look a little bit like a cold sore. They have well-demarcated borders, and there are white arrows in each of these pictures that are pointing to the ulcers.

We recommend for treatment of these topical steroids, again, that magic mouthwash, that lidocaine/Benadryl/Maalox, and most importantly, adjustment of the sirolimus dose. If the sirolimus dose is not adjusted so that the blood levels are within therapeutic levels – this would be done by your medical team – then those ulcers will continue to be there.

[19:47] Graft-versus-host disease can begin as dry mouth, blisters, and sensitivity to spicy foods., oftentimes this will begin as dry mouth or temporary blisters on the roof of the mouth. You might have heard these called mucoceles. These are little blisters that you can feel with your tongue on that roof of your mouth and sometimes on your lower lip also. You can develop red or white patches in your mouth that you can't scrape away. Unlike the candidiasis that we talked about, which you can often scrape away or wipe away with a piece of gauze, these hyperkeratotic (white) patches from GVHD can't be wiped away with a piece of gauze.

Mouth ulcers are often not the first thing that you experience with graft-versus-host disease, but they certainly are something that is part of the disease course. One of the earliest signs will often be these white lacy lines on the inside of your cheek. Sometimes this can be on your lips, which is a little bit easier to see than all the way in the back of your mouth, but they're often there.

Along with dry mouth, one of the first symptoms that people tend to experience is oral sensitivity to spicy foods, citrus flavors, and acidic foods like tomato sauce. Things that would have never bothered you in your pre-transplant life will suddenly be too painful to put in your mouth, or at least highly irritating to put in your mouth.

[21:17] More advanced oral GVHD may involve white lacy lichenoid-pattern lesions. This is what oral graft-versus-host disease looks like in the mouth, and these are slides showing a mild or moderate presentation, and then a moderate to severe presentation, showing all of the different parts of the oral cavity. 

The hard palate or the roof of the mouth is up on the upper left-hand side. 

The inside of the cheeks or the buccal mucosa is the next set of photos, and here you can see, unfortunately, these white lacy lichenoid-pattern lesions that we were talking about. Sometimes these will progress to be pretty big ulcers on the inside of your cheek. Oftentimes these aren't painful simply because of the way the GVHD progresses, but they can be quite big and very sensitive if they're poked either with your tongue or with food while you're eating.

Moving down, we've got different ways that the gingiva (your gums) can look. A lot of times it just looks very, very red, but sometimes we do see that the gingiva will sort of turn white. Less often we see that there are ulcerations, but that's possible.

Moving over to the other side of the slide, there are many different ways that tongues can look if affected. Sometimes we see some building up of this white tissue, this hyperkeratosis. Again, on the lips, we can see these white lacy lesions, and sometimes ulcerations on the external lips as well.

[22:58] We often think about GVHD, oral graft-versus-host disease, as three distinct diseases. These include: 

1. the oral mucosal disease, which I just showed you detailed photos of; 
2. salivary gland dysfunction, which is very dry mouth because your salivary glands, which make your saliva, are no longer working; and 
3. limited mouth opening.

Limited mouth opening usually is not because of anything that's happening actually inside your mouth; rather, it's because the skin on the outside of your mouth or, less often, your temporomandibular joints that are sort of that hinge jaw joint are being affected by the graft-versus-host disease, tightening up and limiting the amount that your mouth can open. These manifestations need different treatments. The underlying pathology is different, and the prognosis is different for them as well.

GVHD may be diagnosed through the presence of dry mouth, blisters, shrinkage of normal tissue, and white patches in the mouth. Diagnostic criteria are the criteria that your doctor will use to diagnose graft-versus-host disease in your mouth. If they see those white lacy changes in the mouth, that is a definite oral graft-versus-host disease diagnosis. Diagnosis can also be made by at least one distinctive manifestation that's either confirmed by the biopsy or other relevant tests to rule out other causes.  These manifestations include:

• Dry mouth.
• Blisters or fluid-filled lumps on your inner cheek, lips, or floor of the mouth.
• Loss or shrinkage of normal tissue, so things kind of shrinking away and looking a little bit different.
• White patches on your mouth, anywhere on your mucosa i.e., the lining of your mouth.

Additionally, before we call something GVHD, we generally want to exclude infections in the mouth, drug reactions, or new cancers. Once those things have been excluded, generally treatment for graft-versus-host disease can be started.

[25:21] What do these diagnostic features look like? This is a closer view of these lichenoid lesions; these white lacy lesions. To the left is a view on the inside of the cheek. On the right-hand side on the top is a view of an upper lip. There's a much more subtle view of the inside of the cheek, which is a little bit harder to see. If you're at home looking in your mirror, this is something that would be a little bit more challenging for you to see on your own in your own oral cavity.

Oftentimes we see changes to the roof of the mouth. On the hard palate, we can see white hyperkeratosis caused by your epithelium growing a little bit extra and making a thick white covering.

We see these mucoceles. If you look closely at the right-hand side top photo, you can see these little blisters which happen because there's inflammation in your tissues that pinches off the opening for your minor salivary glands that are in the roof of your mouth. Then the saliva that's supposed to be making your mouth feel nice and moist isn't able to get into the oral cavity, it’s stuck.

These mucoceles are full of saliva, but if you pop the mucoceles, they can easily get a secondary bacterial infection, so I recommend leaving them alone. They are irritating, but they wax and wane. When you're thinking about food or eating, oftentimes these mucoceles appear because your mouth is trying to make saliva, but they will go away and come down in size within an hour or two.

The bottom right picture of the palate is showing erythema, a red and irritated looking roof of the mouth.

[27:16] Oral GVHD may also involve shrinkage and other changes in the tongue. The next slide is looking at different tongues in GVHD. Oftentimes when we see atrophy of the tongue or shrinking away of that tissue, you can have loss of your taste buds. On a normal tongue, there's often like almost a furry appearance and rough texture on your tongue. With graft-versus-host disease we see a smoothing away of those taste buds, shown in the first photo, called atrophic glossitis. 

We can also see again, in the middle photo, this patchy hyperkeratosis, a patchy shrinkage of those taste buds on the tongue combined with white patches showing up on the tongue.

Less common, but we do see this, is patchy tufted hyperkeratosis on the dorsal tongue, shown on the last photo, where the epithelium on taste buds is growing unchecked and making these fluffy white things. This looks like candidiasis, does not wipe away, so it does not need to be treated like thrush.

[28:25] Oral ulcerations are often discovered when patients report pain in the mouth.There are different types of ulcerations. One of the things that I always like to do when I'm seeing my post-transplant patients is to ask if anything in your mouth hurts. Some of these ulcers can be quite small or very hidden.

If you look at this first picture on the left-hand side, this is a pseudomembranous ulceration that was under this patient's tongue. These can hide from us if we're not looking really carefully, but if it's in your mouth, you will probably know that it's there because these will hurt if anything is bumping against them.

Ulcers like this one on the right top on the lip are very easy to see. You'll also know that that is there. I want to stress that graft-versus-host disease is not an infectious disease. It's not like having an HSV, like a herpes ulcer on your lip. This is not something that you can give to somebody else. You can't infect somebody else with graft-versus-host disease, even if you have lesions in your mouth.

In the bottom right photo, much more subtle, is this little bump with another ulceration, that was very hidden between the lip and the teeth.

[29:41] Salivary gland graft-versus-host disease is more challenging to diagnose than mucosal GVHD in the mouth, which very easy to see. To find out if GVHD is affecting your salivary glands, i.e., the structures that are producing the saliva in your mouth, we will ask you if your mouth is suddenly drier. Is it progressively drier? Did the dryness happen right away, or has it been happening over time? Can you chew and swallow food without drinking water? Are you taking medications that cause dry mouth? Many different types of medications can cause dry mouth as a side effect. Finally, did you have radiation? Total body radiation or radiation targeted to the head and the neck can have a long-lasting impact on salivary gland tissue, which is very sensitive to radiation.

To definitively know if there is GVHD in your salivary glands, we can take a local biopsy from your lower lip to see under the microscope whether there is graft-versus-host disease versus something that's medication-induced or radiation-induced.

[31:17] There are various topical therapies for graft-versus-host-disease mouth sores.

If there are lichen planus-like changes, you'll most likely be started on a steroid rinse. The most important thing with these steroid rinses is that you keep them in your mouth for at least two minutes, maybe longer. You do not need to act like you're trying out for a Listerine commercial, but you do need to hold that medication in your mouth for two to five minutes. You can do something else like watch some videos, answer emails from friends, but hold it in your mouth for that amount of time – use a timer – before you spit it out, because you want the medication to have time to actually get into your tissues.

Other treatments include calcineurin inhibitor rinses or tacrolimus rinses. These are generally compounded by your pharmacy for patients who can't tolerate steroid rinses or shouldn't have steroid rinses.

If you have isolated oral ulcers, we will try to use topical treatments like topical steroid gels and tacrolimus gel as spot treatments

If nothing is working, we can inject steroids directly at the base of those ulcers and kind of try to force them to heal. In some countries, not the United States, unfortunately, you can use autologous blood products to seal these off and encourage healing.

Topical anesthetics are very important to use in conjunction with these agents: one, so that you can tolerate whatever topical treatment you are using, and two, so that you can continue to eat.

We know that we need better therapy for oral graft-versus-host disease. This keeps me awake at nighttime. There are two clinical trials in the United States that are currently open. Both are relatively specialized. The first one on the left-hand side of this slide is for patients who have medically induced xerostomia, or dry mouth, testing the use of mesenchymal stromal cells to restore salivary gland function. This trial is specifically at the University of Wisconsin Madison.

There is an additional trial testing the use of red light therapy to treat mucosal chronic graft-versus-host disease, with open sites in New York City and Pittsburgh, PA. 

[34:07] There are several remedies for persisting dry mouth. What to do if your mouth is dry?

I recommend either chewing or sucking on sugar-free gum or candies. If you use full sugar candies, gums, or lozenges, this will hypercharge decay in your mouth, so you want to make sure that whatever you're putting in your mouth is sugar-free, especially if you're going to be sucking on it for a long amount of time. Xylitol is an alcohol-based sugar that can also reduce tooth decay. You can look for it in your sugar-free gum or candy. 

Lemon flavors can stimulate saliva. Mint can too, but in the setting of graft-versus-host disease, oftentimes that's not a flavor that can be tolerated.

We recommend frequent sips of water and staying really well hydrated.

Some patients find relief from lubricating rinses such as Biotene, which is essentially like chapstick for the inside of your mouth. It’s a lubricating agent that will work for a little bit and might help you feel a little bit more comfortable.

There are actually a whole host of dry mouth rinses on the market. Find one that works for you and try, if you can, to get either your medical center doctors or your dentist to give you some free samples so you can try out some different brands.

There are prescription medications that can stimulate saliva production from intact salivary glands. Two of these drugs are pilocarpine (Salagen) or cevimeline (Evoxac). These will take a few weeks to show an effect and will only work if you still have saliva producing cells left in your glands, so they're also not appropriate for everybody. For patients with cardiac conditions, they're definitely not recommended. Talk to your medical team if you think that you would like to try a medication for your chronic dry mouth.

I said it before, I'll say it again: Fluoride is important. Please check your toothpaste and ensure that it does contain fluoride. Fluoride rebuilds dental enamel that has mild damage. There are also some newer generation products on the market that contain something called nano-hydroxyapatite, abbreviated nHA or ZnHA, that can also help to rebuild tooth enamel.

Saliva will typically wash away food from the teeth. It buffers the acids and the bases in the mouth, and it returns calcium to damaged tooth enamel. If you have dry mouth, that equals less saliva, and unfortunately that equals less protection from decay, so you really need to bring in the big guns to help protect your teeth.

[36:50] For reduced mouth opening, progressive gentle stretching can help improve or maintain mouth opening. You can see a physical therapist who is trained in helping to support mouth opening therapy. You can also at home use stacked tongue depressors; if you can fit three in your mouth, bite on those three for a couple minutes every day, then see if over time you can add four and then five and then six, to help maintain and increase your mouth opening. 

In severe cases, perioral steroid injections can be done. These are steroid injections around the outside of your mouth to help reduce the inflammation that is sort of helping to keep your mouth closed. 

Surgical intervention is an option we prefer not to use, but it is something that's available.

[38:07] These are the key points.

• See your dentist regularly after your transplant has stabilized for cleanings and screenings.
• Call your dentist if you notice any problem or change in your mouth, especially if something lasts longer than three weeks. 

I will caution you here. If you have symptoms that you think are graft-versus-host disease, don't wait three weeks to see if it goes away. Just call your transplant team and let them know that you've got changes in your mouth. GVHD can start as a dry, sore mouth, and early treatment we know is more successful, and rinses and aids are available to make eating more comfortable.

• There are other infections and issues that can happen in your mouth after transplant that are not graft-versus-host disease, so many treatments are available for these issues.
• Finally, take care of your mouth by brushing and flossing every day.

We know that a healthy mouth is less likely to develop problems, but unfortunately, it cannot prevent every challenge.

Question and Answer Session

[39:14] Moderator: Dr. Mays, thank you so much for an excellent presentation and also for rolling with the punches as we had some technical issues there. We really appreciate you so much. We have a number of excellent questions in the chat.

[39:33] Regarding finding the right provider for oral health,how do you know if a more community-based or small-town dentist is sufficient to help you monitor for GVHD? Can you go a little bit deeper into some of the questions you might want to ask that provider? If you are diagnosed with oral graft-versus-host disease, do you need to change providers?

[40:07] Dr. Mays: This is tough to navigate, because not everybody lives close to a major medical center that has a dental clinic. 

A good indication of whether your dentist is sufficient is whether you're able to see the same provider sort of every time, if you have a dedicated dentist who sees you in that office; this will happen more in privately owned offices versus corporate clinics. It helps if you're able to actually have a relationship with that provider, they actually know your name, and they're able to spend more than 30 seconds taking a look when you are there.

There are dental specialists that are a little bit more well-versed in some of these issues, within a dental specialty called oral medicine. I think the American Academy of Oral Medicine has a provider directory where you can put in your address and see if there's anyone in your local area. Unfortunately, there are not a lot of these providers in community clinics. 

A really wonderful tool that the BMT InfoNet has developed is a provider directory. Because you're all here, I'm guessing that you're relatively familiar with the resources from this great organization. They have a provider directory where you can go in and enter your area and look for the specialists that you need. These are all people that have been vetted to have expertise, mostly in graft-versus-host disease, but of course, in post-transplant care, and might be able to help you if you do get that diagnosis of graft-versus-host disease and want to see a provider.

You will always need a regular community provider for your cleanings and your dental screenings and to take care of a broken tooth or any other sort of run-of-the-mill dental problems.

[42:35] Moderator: There are other symptoms that people are experiencing such as texture changes to saliva or overproduction of saliva. Are there recommendations that you have for those?

[42:55] Dr. Mays: Regarding texture changes, we know that oftentimes after transplant the character of saliva changes but we haven't been able to quantify that in the lab very well. I think it has something to do with the mucins which are the sticky, thicker parts of your saliva, which aren't being made in the same way anymore. Whereas your saliva should be coating your mouth, again, kind of like that chapstick for the inside of your mouth, it just isn't working well anymore. If you feel like you have enough saliva to chew and swallow food without drinking water, but you still feel like your mouth is dry, this is pretty common.

We see a disconnect between patients’ reports of dry mouth versus actual measurements of the amount of saliva that you can make, like spitting in a tube for five minutes; oftentimes these things don't match up. We know that your experience as a patient is not always the same as what we can measure and put a number on in our clinics.

In this case, I would recommend some of the dry mouth products. They may be helpful. In addition, getting good nutrition will support your body to regenerate and rebuild itself.

[44:11] Regarding the overproduction of saliva, we have seen some patients become saliva super producers when there is a lot of inflammation in the oral cavity. These are people that can give me a whole tube of saliva in 20 minutes, which is very unusual. Oftentimes they'll have a lot of inflammation in their mouth, but not always. If this is the case, you probably can manage it the way you're already managing it, either swallowing on a frequent basis or spitting, unless you have a job that involves speaking. I had a wonderful patient who was a music teacher and she really struggled because she needed to sing on a regular basis with her students, and this was a problem because she was making too much saliva. There are medications that are sort of the inverse of the ones that I talked about that can reduce your secretions. These are anticholinergic medications. I would not generally recommend them unless you were in a desperate situation, simply because it will impact every exocrine gland in your body, your tears and your saliva and other things. I would recommend trying to develop some strategies to just sort of get rid of that saliva on a regular basis, whether you're spitting it out or whether you're swallowing it. I hope that it's not a permanent situation. There are things providers can do with salivary glands to reduce the amount of saliva that they're producing, but again, nobody would be very enthusiastic about doing that because we want to make sure that you've got enough saliva to function on a daily basis.

[46:10] Moderator: We have a few folks who are experiencing loose teeth or bone changes to their jaw, to their teeth. What would you recommend for them to help prevent that from getting worse or to manage loose teeth overall?

[46:38] Dr. Mays: We do see sometimes when patients have been on high-dose prednisone, sometimes you'll get a shrinkage of your gums, less so your bone, but sometimes that shrinkage of your gum tissues will loosen the teeth a little bit, because the gums are not doing their job anymore. Sometimes that improves after you're off those prednisone pulses, and sometimes it does not. 

If your teeth are loosening, then one, see your dentist. Two, tell them about the loose tooth situation. There are things that can be done. If things are really loosening, something that might be done is placement of a permanent retainer on the back of your teeth on like a sort of flexible retainer that's bonded to the back of your teeth to help sort of stabilize everything so that you can get some healing around those teeth and have them ideally tighten up a little bit. 

Of course, you want to make sure that it's not because of periodontal disease or another inflammatory condition that can be managed by either your community dentist or by a dental specialist like a periodontist, where they'll do sort of deep cleanings and make sure that they're getting that bacterial biofilm, hopefully to a healthier state on your roots of your teeth.

[48:28] Moderator: We have some questions in the chat about, are there any known oral issues that happen after autologous transplant or after CAR-T therapy?

[48:57] Dr. Mays: The question is whether we see signs of conditions similar to GVHD that happen either after auto transplant or CAR-T-cell therapy.

Generally, full disclosure, I do not see very many auto transplant patients. Typically, any of these side effects can be seen in auto transplant patients. If you had some of the same types of conditioning, such as chemotherapy or radiation, to get your body ready for that auto transplant of your own cells, your cells won't be attacking your tissues, but you certainly can have side effects longer term from chemotherapy, such as taste changes. Something that we would expect from radiation would be fibrosis within the tissues or sort of tightening up of those tissues, either around the oral cavity or potentially in your joints and possibly also dry mouth. This is one of the reasons that we will often take a small lip biopsy in the setting of dry mouth because there are so many things that can cause it.

[50:18] CAR-T-cells are a different beast simply because there are so many different flavors of CAR-T-cell therapies out there. Some of what you're experiencing could indeed be because of the conditioning prior to your CAR-T-cell regimen, and some of it could be side effects because of the specific target of your CAR-T-cell or off-target effects from that CAR-T-cell therapy. Without knowing exactly which therapy you got and what those targets were, it's difficult to say exactly what the situation could be.

[51:13] Moderator:

We have some questions about self-advocacy and how to know what to ask for. Some participants have doctors who have not pointed out these things that folks should be looking for in their own oral health and specifically with the pictures that you showed. Others are experiencing some of these symptoms that you describe and that you've shown in the pictures, but their providers are telling them not to worry about that. Finally,what should they do if they think that they have an issue, they're feeling a symptom, but they don't know where to turn?

[52:05] Dr. Mays: I hope that you are with a transplant team that will listen to you and listen to your symptoms. Sometimes the philosophy at different transplant centers is that if something isn't painful, it doesn't need to be treated, so if you see some of these white lesions in your mouth, but you're not having any symptoms, that it's not something that needs to be treated. And indeed, it might be something that comes; it stays for a few months, and then it will go away on its own.

But especially if you are experiencing symptoms or if you feel like you've got mouth changes happening, please continue to point this out to your providers. At our specific medical center, I would have more specific advice of how to navigate this. It's hard to know because every medical center is set up a little bit differently and everyone's post-transplant care is set up a little bit differently, but you are your best advocate and you know your body better than anybody else.

It might help to have a caregiver help to advocate for you. Sometimes they can make some contacts that might be difficult to do on your own because you are managing so many things all at once after transplant, especially if you have medical complications.

So this would be my advice:  Be persistent. Have faith in your ability to know your own body and maybe get somebody to help advocate for you. When they're making those appointments, tell the scheduler or the nurse or the patient care coordinator that you have mouth changes and ask if there is a dentist you can see, or an NP who's really good with mouth stuff. Oftentimes, dermatologists are able to recognize and treat oral mucosal conditions, so that might be an option.

Different people are more and less comfortable that others with looking in the mouth, but it is a continuation of the skin so I consider that a fair game question to ask your dermatologist.

Another thing to consider with the overproduction of saliva is that some sort of neuropathy that might be involved. We know that nerve damage can happen either as a result of conditioning, medication, and other things pre- and post-transplant, so neuropathy is definitely a component of graft-versus-host disease and post-transplant complications. We also know that nerves control the production of saliva, the movement of your tongue, and other things. So neuropathy is something to consider with your medical team.

[55:06] Moderator: Closing. On behalf of BMT InfoNet and all of our partners, I want to thank Dr. Mays for her very helpful presentation and her answers.

And thank you to the audience for being here with us on a Sunday and for your excellent questions.