Your Mouth and Chronic GVHD

GVHD and your mouth:  Symptoms, Appearance and Therapies


  • Jacqueline Mays, DDS, MHSc, PhD, The National Institute of Dental and Craniofacial Research, National Institutes of Health
  • Stephanie Tsai, MD, Loyola University Chicago Medicine, Hematology/Oncology 

This is a recording of a workshop presented at the 2019 GVHD Summit. 

Presentation is 37 minutes, followed by 21 minutes of Q&A. 


Oral GVHD is a treatable condition which can impact the salivary glands, cheeks, tongue, lips and other areas of the mouth. Regular evaluations with an experienced dentist are key to finding relief and solutions.


  • See your dentist regularly starting 100 days - 6 months after transplant to monitor for problems
  • Any lumps, bumps or ulcers in your mouth, lips, cheeks or tongue that do not heal within three weeks need to be evaluated.
  • Many non-GVHD oral complications are brought on by radiation, steroids, immunosuppression and chemotherapy.

Key Points: 

05:17 A healthy mouth is less likely to develop problems.

05:56  Use children’s fruit favored toothpaste if you are sensitive to mint.

07:39  Use an electric toothbrush if you have limited joint mobility.

11:25  Do regular oral cancer screenings using but avoid a the VELscope if you have GVHD.

14:41  Individuals with GVHD have a higher risk of developing oral cancer 5-10 years after transplant.

24:32  GVHD can shut down salivary glands and cause dry mouth.

29:18  GVHD of the tongue can appear white and cannot be wiped away.

32:05  Topical treatments such as rinses are only effective on 29-58% of patients.

37:26  Physical therapy is very successful for reduced oral opening.

47:21  Ibrutinib or Imbruvica are new oral drugs which can be used to treat chronic GVHD in many parts of the body.

Transcript of Presentation 

 [Moderator] So my name is Jackie foster, I'm with Be The Match and I am so happy to be here this morning to introduce our speaker and panelist. I will be your moderator. This session is designed to be interactive. So while Dr. Mays is presenting, there'll be plenty of time for questions at the end and we encourage everyone to use a microphone because this session is being recorded. So we want to make sure that we capture everyone's great questions and all the great answers.

So I'm going to introduce our speakers. Dr. Mays is an immunologist and clinical trials dentist whose research focuses on chronic GVHD in the salivary glands and oral mucosal. She heads the oral immuno-biology unit within the oral and pharyngeal cancer branch of the division of intramural research at the National Institute of Dental and Craniofacial Research.

She's joined by Dr. Tsai who's an Assistant Professor in the hematopoietic stem cell transplant program at Loyola University. And she specializes in blood and bone marrow disorders and stem cell transplantation. Please join me in welcoming Dr. Mays and Dr. Tsai.

01:09         [Mays] We'll put this on, can everybody hear me okay? Wonderful. Well, I want to thank you all for spending an hour of your time with us this morning. I'm hoping that this will be informative. Please, if there's something that you really wanted to know about, ask a question if I don't cover it specifically. And I also wanted to thank the BMT InfoNet for putting on this phenomenal symposium today, it's such a tremendous collection of knowledge. I really admire the work that they are doing.

So I have been seeing transplant patients at the National Institutes of Health since 2011 in our dental clinic. I'm going to go over the key points for the day while I still have all of your attention at the beginning. So these are the things that I really want you to remember when you walk out of this room in about 50 minutes.

02:09         So one of the most important things you can do for yourself after transplant is to continue seeing your dentist regularly after your transplant is stabilized. So typically this is around day 100, certainly by six months. If your transplant team has told you that you shouldn't go back and see the dentist, clarify with them. Sometimes these are misunderstandings that last for years. And there's nothing sadder to me than seeing somebody come three years post-transplant and saying that they're not allowed to see the dentist with a mouth full of cavities. So please return to regular dental care as soon as possible.

Call your dentist or let your transplant team know if you start to notice changes within your mouth. This includes teeth that hurt, this includes sensitivity to new types of foods, whether it's too spicy things, too minty things or just something that feels like it's different in your mouth.

And finally, and this is not a really exciting key point, but take care of your mouth by brushing and flossing every day. We know that clean mouths develop fewer problems. This is not to say that you can prevent graft-versus-host disease by brushing and flossing, but some infections and other things can certainly be improved with a healthy mouth.

03:26      Overview of Presentation:  Okay. So what are we going to talk about today? We are going to discuss taking care of your mouth, that includes your teeth and your soft tissues. We'll talk about establishing community dental care, so the who, the what and the when. I'm going to talk about the importance of oral cancer screenings and having those done at least on a yearly basis. We'll touch a little bit on some non-GVHD post-transplant complications, so things that you might be seeing in your mouth that are not necessarily graft-versus-host disease. And then finally we'll hit the big topic of the day. So graft-versus-host disease, what it feels like, what it looks like, and things that can be done to treat it in your mouth.

04:09      The Oral Cavity is the Gateway to the Body : We know that the oral cavity is the gateway to the body, it's not just your teeth. You've got a lot of soft tissues in there and we know that a lot of those soft tissues have a lot of immune cells in them.

So your mouth is constantly subject to these micro traumas. So every time you eat a piece of crusty bread when you brush your teeth, when you bite your cheek, when you burn the roof of your mouth with some hot food, we know that these sort of constant bits of damage are things that your immune system has evolved to not have a big response to, but they're always there.

There's microbiome in your mouth. So there's like a normal bacterial flora in your oral cavity and there's also saliva. So there's a lot of things going on in your mouth and when those become dysregulated and when you start having graft-versus-host responses in your body, it's not too surprising that the oral cavity is one of the number one targets or the mouth is one of the number one targets of that disease.

05:17      Ways to Take Care of Your Mouth:  Number two, second to skin, keeping the data in mind. So one of the most important things you can do at home is taking care of your mouth. And I don't normally include lectures on brushing and flossing in my shtick, so this is a new component for me too, but it's really important. So check your toothpaste that you're using at home, make sure that it's toothpaste that has fluoride in it. So any standard toothpaste will have fluoride in it, but sometimes some of the more specialty toothpaste, especially things like Tom's of Maine, you can sort of end up with something that doesn't have fluoride in it.

05:56      Your teeth are made up of enamel crystals, and when those crystals become de-mineralized just because of again, daily damage. So eating acidic foods or having your bacteria produce a little bit of acid, those crystals can become de-mineralized. And having fluoride in your toothpaste helps to stabilize those crystals and repair some of that damage. So it's sort of like vitamins for your teeth. So check, make sure that your toothpaste has fluoride in it. If your mouth is very sensitive, using fruit flavored or children's toothpaste can be tremendously helpful in aiding you and keeping up that brushing. So there are fruit flavor toothpaste, Tom's of Maine makes a strawberry toothpaste. Children's toothpaste often comes in non-mint flavors, things like Sparkle Fun that can be helpful if you're really sensitive to mint.

06:50      If your teeth are sensitive, using a fluoride rinse or a desensitizing toothpaste can be helpful. There's some names up on the slide. So things like Sensodyne Pronamel, Colgate Sensitive, you'll see an overwhelming number of options if you walk through the dental care aisle at CVS. These can be helpful. I will caution you that they take about a month to really start working well. So they plug up openings in the outside of your tooth so that the nerves inside your teeth are less exposed to the external environment that they can help over time. Your dentist can also do some professional desensitizing treatments. There are several options. So there are some things that can be painted on the teeth, including just a fluoride treatment can help with sensitive teeth.

07:39      And also to help with brushing if you have limited joint mobility, if your wrists or your elbows are challenged, using an electric toothbrush can help a lot, or if you're just lazy like I am. Because with these electric toothbrushes really all you have to do is hold them there and they do a lot of that work for you, then you don't have to do this brushing back and forth motion. So that can help quite a bit.

Cleaning between your teeth is something that nobody really likes to do, flossing is a little bit tricky, but it's important to get bacteria plaque and food bits out from between your teeth. There are a number of aids that have been developed to help with this because everyone recognizes that using a piece of string and figuring out exactly how to manipulate that is not the world's easiest thing to do. Some things that can help include these little plastic pics. So these have a piece of floss suspended between them, and with these all you really have to do is pop it between your teeth and that can help with the flossing.

There are also a number of different styles of these floss picks. So these have little rubberized tips that will help to clean between your teeth. And then if you want to get really fancy there's a device called a Waterpik that shoots a little stream of water between your teeth. And this can flush out bacteria and food particles from between your teeth and also from the [inaudible 00:09:10] sulcus, which is that little pocket between your gum tissue and your tooth.

So this is a hippopotamus sized Waterpik, the part that you can't see in this picture is in this gentleman's other hand, he actually has a hose with a sprayer on the end. So this is helping him to clean out in between the hippopotamus's teeth. So I don't necessarily recommend that, but it's important to take care of your mouth even for zoo animals.

09:43      How to Find a Good Dentist:  So how do you find a dentist? A lot of times post-transplant I find that my patients have moved, their dentists has maybe retired and they're left without dental care. Oftentimes that's the point at which people stop seeing a dentist. If you do have a regular dentist when you go back and when you're able to pick up care again after transplant, tell your dentist that you're a transplant survivor. They may not know that anything has changed or anything is different, but they should be aware that there are some additional things that they need to screen for. Show your dentist anything unusual or new that you see or you feel in your mouth. Normally we say that lumps, bumps and ulcers inside your mouth should heal up within three weeks. And I have these little stars here to remind myself to give you the disclaimer that that time projection of things healing within three weeks unfortunately doesn't include Graft-versus-host disease lesions. So we don't expect those to heal in three weeks.

10:46      But anything that's really not an issue that's just sort of coming and going should heal up within three weeks. And if it doesn't you should definitely show one of your care providers. And this includes not only things on your teeth but things in your gums, your lips, your tongue and your cheeks. And ask your dentist while you're there if they're doing an oral cancer screening. So oral cancer screenings involve a feeling or palpating the lymph nodes, sort of in the head and neck to see if there's any immune response happening. Moving the tongue back and forth so that you can see all of the surfaces, especially the sides and taking a careful look at all of the soft tissues.

11:25      So this can be happening without you really realizing what's going on, but make sure that you ask them also to remind them that they really need to do a good job with the oral cancer screening.

11:39      Like a VELscope, like the UV light.

11:48      So it can show changes in the tissue, it can show areas that need to be watched carefully. The data are sort of mixed on whether the VELscope helps at all, which is also why I don't have a slide about that today. So it's not something that you would necessarily need to seek out. It's a useful tool to show changes in the tissue. When we use it with patients who have Graft-versus-host disease however in the oral cavity, a lot of things will light up because there are a lot of tissue changes in the mouth, right? So I don't necessarily recommend that you need to have a cancer screening with one of these fancy things. Sometimes if you have a dentist looking with his or her sharp eye that's better in these situations.

12:34      So as you probably know by now, not every dentist appreciates your complex medical history and your needs regardless of whether or not this is somebody who went to elementary school with or whether it's your uncle who you've seen for dental care your entire life. If your dentist isn't a good fit or they don't seem to really understand what you need, feel free to interview other dental offices. So this involves calling them up and not just finding out if they take your medical and your dental insurance, but also asking them if the dentists have experienced treating medically complex patients, if they have any experience with hospital dentistry, which is where dentists often will get experience with patients who have a little bit more complicated medical histories.

And also what their overall philosophy is with respect to preventative care. So if this is a dental office that is really focused on cosmetic dentistry, that's not necessarily the place you want to go. You don't need your teeth whitened and straightened you need somebody who's going to make sure that everything is healthy and take care of any problems as they're coming up.

A good place to find a dental office with this sort of philosophy is at a university setting. So either attached to a dental school faculty practice, so this is where the professors and instructors from the dental school will see patients or they're more advanced practice residents. These are both good places to find dental care. I appreciate that not everybody is close to a university dental practice. But a lot of medical center clinics will also have dental clinics within that medical center. And this is another good place where you can sort of do one stop shopping, right. So that when you're there to see your transplant physicians, you're also able to pick up your six month cleaning.

14:41      Annual oral cancer screenings. We know that the patients post-transplant who are at highest risk of developing an oral cancer after transplant are those with a history of oral Graft-versus-host disease. These tend to pop up five to 10 years post-transplant. The tongue is the most common site. This is one of my patients who noticed the lesion about two to three weeks before we saw him and at that point it was relatively advanced. So this is not to scare you. Your risk of oral cancer is still quite low, but it's about double that of the general population. Anyways, so frequent screenings, very good idea.

15:21      Early Post-Transplant Complications in the mouth:  Timing of post-transplant complications in the oral cavity, early after transplant, which you're all past at this point. We see mucositis, dry mouth and oral thrush overlap. We tend to see drug induced complications and also viral infections that will pop up in the oral cavity. And then later on we tend to see graft-versus-host disease popping up. And then much, much later we see these secondary oral cancers.

15:52      Oral complications other than graft-versus-host disease:  I'm going to talk a little bit about non graft-versus-host disease post-transplant complications. These include infections, these include cold sores which is much like an infection because it's a virus reactivating in your mouth. I'm going to talk about those in a little bit more depth.

Radiation induced dry mouth is something that can result if you had total body irradiation as part of your conditioning regimen or if you had targeted, had an echo radiation at some point along your cancer therapy journey.  Unfortunately this isn't something that we're great at treating, there are a couple of clinical trials trying to correct this radiation induced dry mouth. But your salivary glands are quite sensitive to radiation and we can talk more about that moving forward. If anybody has questions medication related oral ulcers or lesions and loss or change in taste.

16:49      So loss or change in tastes will typically correct itself within the first year post-transplant. And we know a lot of times this comes from the chemotherapeutic conditioning regimens pre transplant. But finding a very creative dietitian if you do have a lot of changes in taste can help you to find a diet that you enjoy despite your taste changes.

17:19      So what does it look like when you have a recurrence or reactivation of herpes simplex virus? This is quite common post-transplant in the setting of immunosuppression. Here we've got these little pus jewels that are still intact. They're fluid filled and this is what they look like on the inside of the oral mucosa. These are often characterized by being exquisitely painful, so they pop up very quickly. They're incredibly painful. We diagnose them using a little swab that we send for detection of the viral DNA. And typically it's managed with systemic antiviral medications on top of the antiviral medications that you're already taking.

And then sort of a rinse that we colloquially call magic mouthwash. It's also light up Benelux I see some smiles out there I think some of you might have it in your bathrooms at home. But this is lidocaine, Benadryl and Maalox all mixed together. Just sort of numb and sooth your oral cavity.

18:25      Oftentimes we will also see overgrowth of a fungi called candidiasis. Everybody has this naturally in their oral cavity. Once your immune system gets thrown off balance or your mouth gets thrown off balance, it can overgrow. This isn't because your mouth is dirty, it's just because the immune system isn't doing its job and keeping everything in check.

A lot of times it will look like this white coating. Sometimes you get erosion of the tissues that are involved. So these are one of the classic tests for this just to see if the white stuff will wipe away. If it does, this is typically thrush or the candidiasis overgrowth, another form of it however you can see that there's no white stuff on this tongue. But this is erythematous candidiasis. So it's once the fungus gets sort of within those tissues, you no longer see that white coating on them, it can just be red.

One of the clinical hallmarks here is that your mouth will burn. So burning the mouth is almost always a sign that there's an overgrowth of candidiasis. Fortunately, it's something that we're very good at treating. Typically we treat this either with a rinse or more effectively with like a little B in that you put on the back of your tongue and let melt with an antifungal medication in it.

19:51      Sirolimus or mTor Inhibitors can cause oral complications:  For those of you on sirolimus or other mTOR inhibitors we know, and we see very clearly in the clinics that if your systemic levels of that sirolimus get to be too high you almost always will develop an oral ulcer. These look a little bit different than GVHD ulcers and with the ... It's a little bit bright in here, but there's one ulcer here. And then here is, so this is on a lower lip of the patient. And then here this is showing up on the bony Ridge behind the teeth. So these also tend to be very painful they have clean borders. You might have a little bit of redness, but really it'll pop up as an isolated lesion.

So to manage these we typically will give topical steroids so something like a dexamethasone again, this magic mouthwash and also the dose of sirolimus so that you're back within therapeutic ranges and not with concentrations that are above and beyond.

20:58      Oral GVHD can cause a dry mouth or blisters on roof of mouth:  So back to the main topic, symptoms of graft-versus-host disease. What does this feel like in your mouth when it starts? One of the first signs often will be dry mouth or blisters that are temporary on the roof of your mouth. So these are those mucus seals that can pop up. And they sort of come and go these little blisters. We know that you might start seeing red or white patches in your mouth that you can't scrape off. I'm not recommending that if you see something in your mouth, you try to like scrape it away, please don't do that. But these are things that will pop up and they don't really go away.

21:39      Oral GVHD can cause food sensitivities:  You might notice sensitivity in your mouth too spicy foods, citrus foods, acidic foods mint in your toothpaste. So things like a flake of pepper that never bothered you before, it might start to be incredibly not necessarily painful but uncomfortable.

21:54      You may notice white lines on the inside of the cheek lining or any of your other mucosal surfaces. So these can show up on your lips, they can show up on your tongue and they can show up under your tongue and they can be everywhere. And this is the real diagnostic sign. So if your doctor sees that inside your mouth, they'll call it chronic graft-versus-host disease immediately. Mouth ulcers as we've discussed, mouth ulcers don't always mean that it's graft-versus-host disease, but that in combination with these other signs can indicate graft-versus-host disease.

22:26      Picture of GVHD in the mouth:  So what does it look like? There are a lot of pictures on this slide. And these are fairly severe cases, so they may be quite a bit worse than what you might see in your own mouth.

So we see changes in the palate. So this is hyper keratosis, so this is like a thickening of the tissues that then look quite white because there there's extra thick epithelium there. These are those like annoyed lesions. So those white Lacy like lesions and they show up actually a little bit better in this picture. So this is the classic diagnostic sign for oral graft-versus-host disease.

You may see hyper keratosis or this epithelial thickening in different places in the mouth. Here it's on the tongue here, it's on the pallet. These are those mucous seals that I was talking about, those blisters that come and go often times when you're either eating or thinking about food and those will show up because you have minor salivary glands in your lower lip. And also up there on the junction of the hard and soft palate and they are trying their best to make saliva and pump it out into your mouth.

But because of the inflammation, the salivary gland duct is actually pinched, closed. So these vessels are typically filled with saliva that just can't quite make it out into your oral cavity, which is why they sort of come and go.

And then redness will oftentimes be seen this is on the gum tissue. So another type of graft-versus- host disease is when the period oral tissues are affected. So this results in reduced oral openings. So you know that you can maybe take as big of a bite of a sandwich as you could before or you might have to cut your food into smaller pieces in order to be able to eat it. This isn't strictly oral graft-versus-host disease. A lot of times it's because the skin is so affected around the mouth. And then we also know that salivary glands are significantly affected.

24:32      GVHD can damage salivary glands:  And the salivary glands contain acinor tissue, that's what actually makes the saliva and pushes that out into your mouth. We know that when cGVHD starts their T-cells all around in your salivary glands unfortunately they drive a fibrosis of the glands much like the fibrosis that we see on other parts of the body that are affected by graft-versus-host disease. And once that salivary gland tissue is gone, it's no longer able to make saliva.

This particular patient you can appreciate that her gum tissue looks pretty normal. But it looks quite dry and this is because she had very severe salivary gland graft-versus-host disease. But her oral mucosa was perfectly fine. Fortunately she also had excellent oral hygiene, which is not always the case.

When your mouth becomes dry or your saliva is not there to protect it anymore. So normally our saliva functions to wash food away from our teeth. And also to re mineralize our teeth and sort of correct some of those daily damages that are done. When it's no longer there, our teeth are really susceptible to things like these smooth surface cavities. So it's not easy necessarily to keep your teeth clean between your teeth or where they're touching, but it's relatively easy to keep your teeth clean sort of in the front flat areas and when we start seeing decay in those areas, we know that something is really out of whack.

26:07      Oral GVHD is three distinct diseases:  I've touched on this a little bit, but we think of oral graft-versus-host disease really is three distinct diseases. When we look at our patient cohorts of patients that we've seen at the National Institutes of Health who have chronic GVHD and oral Graft-versus-host disease we see that the phenotype of this disease falls in three different domains. We see patients with oral mucosa lesions that overlap a little bit. So this is like a 3% overlap with patients that have salivary gland dysfunction. And there's a little bit of overlap patients who have limited mouth opening.

26:44      So these really seem to be sort of different manifestations of GVHD. And different types of oral graft-versus-host disease may require different types of treatment. And we also suspect that the underlying pathology is different.

27:05      Hos is graft-versus-host disease diagnosed in the mouth? So how is graft-versus-host disease diagnosed? We've talked about this actually quite a bit in these slides, but if your doctor sees these like annoyed lesions anywhere in your mouth that's enough for them to call a graft-versus-host disease. Or if they see one of what we call a distinctive manifestation. This includes dry mouth, this includes those mucus seals, those little blisters on the roof of your mouth, atrophy or shrinking of the mucosal tissues, pseudo-membranes.

27:35      Mouth ulcers caused by GVHD:  And this is something I didn't mention. But when graft-versus-host disease begins to ulcerate in the oral tissues, the T cells are actually attacking the junction between the epithelium and the oral mucosa. So those all sort of start by separation of the tissues. And then the epithelium will lift away. But before it lifts away, it leaves a pseudo membrane. So that's why even if it looks like there's not necessarily an ulcer in there, you might see a big white patch that's quite tender. And that's because it's tissue, it's just about to turn into an ulcer.

So that's student membranes and then frank ulceration so after those ulcers are uncovered. And following the criteria strictly, it requires a pertinent biopsy or other relevant tests that can rule out other possible diagnoses these include oral infections, drug reactions, and potential new cancers. And those are all things that we talked about in the previous part of this talk.

So looking at these lichenified lesions, again, I'm just seeing some of the different forms of them. This is the inside of a cheek. This is on the upper lip of a patient and this is a somewhat different form on inside that the cheek tissue once again, the pallet can start to look quite different. And if you sort of tilt your chin up and look in the mirror, you can see what the roof of your mouth looks like. So this is that ptosis. This is a fairly severe set of mucus seals on the roof of the mouth of this patient. And then we will often see a lot of redness of tissues.

29:18      GVHD can affect the tongue:  Tongues can look quite different, You can have loss of the sort of taste buds on the surface of your tongue. As you can see in this patient and you've got some of this whiteness showing up to, and this is whiteness that doesn't wipe away. So this is cGVHD hyper keratosis. And then here you've got sort of patchy red and white. And here you've got a really sort of unusual tufted appearance on the surface of the tongue. And this also isn't thrush but it can sort of mimic that but it's being caused by graft-versus-host disease. So this is looking a little bit more closely at these pseudomembranous ulcerations. They can occur anywhere from across the lower lip underneath the tongue they can sometimes hide there and on the cheek.

I shouldn't mention that oftentimes graft-versus-host disease ulcers are not terribly painful compared to other ulcers that we see in the mouth. Oftentimes the main problem with them is if you're eating a piece of crusty bread or something else that irritates them that's when there'll be painful. They won't be painful on their own.

30:34      Diagnosing salivary gland cGVHD is a little bit trickier. So the only real way to do this according to diagnostic criteria is to take a biopsy of the salivary gland tissue. That's not always feasible. You obviously don't always want to do that. But we can get pretty close to figuring out what's going on with a set of clinical questions.

So asking is your mouth suddenly dryer? And is your mouth progressively drier? So has your cGVHD is advancing as your mouth getting drier and drier? Asking if you can chew and swallow food without also drinking water. So if you can do that, it's a sign that things are sort of okay, but if you always need a sip of water in order to swallow any food you know that your saliva is not doing its job.

There are a lot of reasons to have dry mouth, not justg graft-versus-host disease. So there are a number of medications that can cause dry mouth especially antidepressants. Our sort of classically known for causing dry mouth. So if you're a sudden onset dry mouth is coupled with medication changes, that can be the reason. So it's important to sort of to have your doctors look carefully. At the timing of medication changes and dry mouth.

31:46      Radiation can affect salivary glands:  Did you have a radiation, either total body radiation or head and neck as part of your cancer treatment? Again, I mentioned that this can damage salivary gland tissue and sometimes that damage starts a little bit later after the radiation. So this is not Graft-versus-host disease. It is a cancer side or cancer therapy side effect.

32:05       So how do we treat Graft-versus-host disease? We know that a lot of our topical therapies for oral Graft-versus-host disease, have limited efficacy. It's really helpful if you're able to work with somebody to sort of go through the available treatments to figure out what works for you and what doesn't work for you. The first line of treatment will always be dexamethasone oral suspension. So we know from clinical trial data that it's only even partially effective in 29 to 58% of patients. So that's pretty low right?

So that's for one out of two patients, it might work a little bit. We know that we need better treatments and that's one of the things that I do in my day job to try and find things that are going to work a little bit better than dexamethasone rinse for your oral cGVHD.

An option is to use a calcineurin inhibitor rinse. Unfortunately, this has to be compounded and can be somewhat expensive. So this is a tacrolimus rinse. We know that it doesn't work much better than dexamethasone rinse. The data show that dex rinse actually works a little bit better but especially if your transplant team is really concerned about conserving that graft versus tumor effect of your transplant and not putting you on any steroids, which some of our teams are very concerned about that in those cases we'll try and use a tacrolimus rinse to treat any oral lesions that we see.

33:32      Treatment for isolated ulcers:  There we go, I think my battery is dying on the pointer. So for isolated oral ulcers we do have a number of relatively decent options. You can apply a steroid gel to those ulcers directly so you can dry it with gauze, put the medication on, and sometimes that direct targeted therapy will help a little bit more. We can also do direct injection of triamcinolone. So this is a steroid that rheumatologists will often inject into joints, but it's really effective if you have an ulcer that's resistant to healing to do that.

34:20      Treatment for dry mouth:  For dry mouth there are a number of lubricating agents that can help, some people like them more or less than others. So these include dry mouth rinses and they'll help for a little bit, but you have to keep sort of using them. You can use salivary stimulants, so sugar-free gum and lozenges.

And I should've put this up here, actually I think I have it in some of the other slides, but if you find sugar-free gum or candies with something called xylitol in it, this is an alcohol-based sugar. This can help to stimulate your salivary flow without adding extra sugar tier to your oral cavity.

35:03      Treatment for difficulty opening the mouth:  With reduced oral aperture or reduced closing or opening, progressive stretching regimens can help. In more severe cases, surgeons may be willing to do sort of peri-oral steroid injections, and in very severe cases, we've needed to do surgical intervention to sort of open up the mouth a little bit more.

Preventative measures. We spend a lot of time talking about dental and oral hygiene, getting routine dental cleanings with possible antibiotic coverage if your medical team wants that, and then continually surveilling your mouth for infections and malignancies.

35:47      Aids for dry mouth. So this is the sugar that I was talking about, this xylitol and it's found in a lot of sugar-free gum and candies. And it's recommended because the data show that it can actually help to reduce tooth decay because it changes the way your bacteria are metabolizing the sugar. Lemon flavors can also stimulate saliva, so things like lemon drops, especially if you find some that are sugar-free, frequent sips of water and staying well hydrated can help with dry mouth. And then again using these lubricating rinses such as Biotene, some people find that that improves sort of their comfort level.

There are also prescription medications that for some patients can stimulate saliva production if you still have intact tissue within your salivary glands. These include Pilocarpine and Cevimiline, and there are things that should be managed by your physician. They may take a few weeks to take effect so if you try them, give it a good three to four week trial before you decide that it's either working or not working. And as I mentioned, they really only work if you still have saliva producing cells left in your glands. They're not appropriate for everybody if you have cardiac issues, that's definitely something that makes these medications not a good fit.

37:11 Fluoride is important. Check your toothpaste, does it contain fluoride. It re-mineralizes dental enamel that has mild damage. If you have a dry mouth, you've got less saliva and less protection from decay.

37:26      Physical therapists can help if you have difficulty opening the mouth:  And this is my last slide. If you have reduced oral opening, there are some things that can help. Progressive gentle stretching can help maintain or improve mouth opening. Some of the things that can help with this are having a stack of tongue depressors and maybe every couple of weeks adding one more tongue depressor to your stack to maintain the opening of your mouth and maybe stretch it just a little bit.

And physical therapists and occupational therapists can really help in these endeavors. So they have a number of other devices that can help with oral opening. In severe cases as I mentioned, steroid injections in the tissues around the mouth or surgical interventions maybe wanted. So with that, we'll open up the floor for questions, and hopefully some of this was helpful. So we've already got our first-

Question & Answer Session

38:18 [Moderator] Thank you very much, thank you Dr. Mays for this great presentation. So I just want to remind everyone that we are audio recording this, so if you raise your hand, I'll get you the mic so you can ask your question to the mic, and we've got Dr. Mays and Dr. Tsai that we can ask questions of. So here I'll start with you.

38:36      [Audience] Difficulty Eating:  I can't eat at all, and haven't been able to for a year and a half. My mouth is extremely dry and this grit is in my mouth. And if I tried to put food in my mouth, it's like trying to eat straw. Have you ever heard of anything like that? I've been to a few doctors but nobody seems to know what to do.

39:00      [Mays] So you're not alone, it's not a common story, but it is a story that I hear on a regular basis. Are you able to eat like pureed foods or things like smoothies?

39:13      [Audience] I choked down boost that everything tastes terrible.

 [Mays] Okay.

 [Audience] I choked down boost, I have tried smoothies, the ice texture bothers me too.

 [Mays] Okay. So nothing cold then?

 [Audience] You know, I can't find anything that works. I can't even try like soup or anything like that, I can't. Everything just tastes like straw. And then if it's food you have to chew, I can't stand it in my mouth.

 [Mays] I wish that I had a magic solution for you and I'm happy to talk with you a little bit more afterwards about some specific things that might help. So this is, it's severe and you know that.

 [Audience] Yeah, it's bad. I mean it's been going on and nobody, I've been to a couple, I went to Seattle and they can't figure out what to do either. So if you know something[inaudible 00:40:20].

 [Mays] So find me afterwards and we can maybe talk about some things that could help.

 [Moderator] Okay. Other questions?

40:33      [Audience] Sensitivity to Spices: I have a real sensitivity spice in my mouth and I do the dexamethasone swish and I've got little like lesions, I can feel them if they're harder, I want to scrape them off like you said-

 [Mays] Don't scrape them off.

 [Audience] I know I shouldn't do that but, is there any kind of treatment that can work. Ketchup makes my head sweat, just a little of ketchup, I mean, it's like that crazy.

[Mays] You know tomato is really acidic and tomato sauces and ketchup is really acidic.

 [Audience] Okay. So it's acidic more than it's-

 [Mays] Just because kids like ketchup doesn't mean that it doesn't have any sort of-

41:11      [Audience] Toothpaste Recommendations  Right, and mint toothpaste I can do it for 15 seconds and then it just burn [inaudible 00:41:16] that was in my mouth. But I find that the kids' toothpaste don't have enough grit in them if you want to say that[crosstalk 00:41:25]-

 [Mays] You don't feel clean afterwards.

 [Audience] No.

 [Mays] Yeah.

 [Audience] So any thoughts on that that can help me out?

 [Mays] So you've asked several questions. The toothpaste bit, we can troubleshoot somewhat. So Tom's of Maine makes a strawberry toothpaste that may or may not help a little bit. You could always add maybe like a little bit of baking soda if the grit is really what you're missing in the children's toothpaste. I also don't appreciate the Sparkle Fun flavor, but there are different children's toothpaste as long as they have fluoride in them. And also Sensodyne and I think a couple of the other dry mouth companies make a very mild mint toothpaste that really doesn't have much mint in it at all. So that might help if you really want that sort of clean feeling that we're all socialized to expect from our toothpaste for it to really feel clean.

Now going back to the spicy food and bothering you in the dextrins, it's possible that you can increase the frequency of your dextrin use and this is something you should obviously discuss with your doctor that prescribed it. They can also have a higher strength dextrins compounded for you. So this is available over, it's just by prescription in Canada, but in the United States we have to have a compounding pharmacy make it for us. And this is a 0.4 milligrams per ML dexamethasone. It has to be refrigerated, which is not amazing, but it does tend to help a little bit more than standard dextrins. And if you have specific areas of your mouth that are more sensitive than others, those might be good candidates to try like a gel or an ointment on to sort of get that specific area. If it's your entire mouth, that's a lot to try and put a steroid ointment on, and I don't necessarily recommend that because you'll end up swallowing a lot more than will actually make its way through your tissues.

43:30      [Moderator] Hey, another question?

 [Audience] Yeah.

 [Moderator] Go ahead, will be back there then we come here.

43:35      [Audience] Problem swallowing pills:  Thank you. First of all, I'd like to thank you for saying Sparkle Fun out in a room of grownups because that's my go to a toothpaste after much trial and error. I don't know if this is going beyond your area of expertise, but I had pretty bad oral GVHD with a sensitivity to spicy foods and all that. The dexamethasone doesn't seem to be helping, but I keep taking my swishes, but a bigger problem that I've been having in the last year or so is a problem with swallowing my pills. I'm a transplant survivor, so I take a lot of pills and some of them I can't get in liquid form and I've choked on them repeatedly in scary ways.

 [Audience] And I actually had a, they stuck a tube down my throat and found fleshy webs that were apparently caused by GVHD. And they just did some surgery on those suckers with their scope, they knocked them out and he said, Oh, well we found these things and now they're gone, but they could come back I gather without me noticing. And I'm wondering if you know anything about these fleshy webs in the throat and whether there's any preventative measures or any kind of self, because I just knew they were there because I was choking on my pills and that's not a good place to be.

 [Mays] Right. So we see this in our patients, especially our more advanced GVHD patients and Dr. Tsai this is probably a good one for you to take.

 [Tsai] So first of all, oral and oropharyngeal GVHD can occur by itself or in the setting with other organ systems involved. And so first question is that your only manifestation of GVHD or do you have any other symptoms?

 [Audience] I got all the symptoms, but that's the only one that I can see causing me to die imminently as fixating on a pill that I can't seem to swallow, and can't get in any other form. So it's kind of like top of the list at the moment.

 [Tsai] So are you taking your pills with something like applesauce or pudding to help kind of guide it down?

 [Audience] Yeah, I try to wash it down with liquids, but ... Yeah, since they knocked the fleshy webs out, I don't choke as often, and I try to soften up the caplets a little bit. So I'm working around but I gather these webs could come back.

46:39      [Tsai] Recommendations for Difficulty Taking Pills Yeah. So we can get at treating the GVHD. Symptomatically people do find that sometimes taking pills with applesauce or pudding is easier than with just the liquids as one. Secondly is working with your doctors to see, are you crushing some of them into applesauce and taking that way or are you just swallowing them all whole. That's another thing to look at as far as how you're taking your medications. As far as the GVHD itself, especially if you are having other organ systems, but even for oral GVHD, there are systemic therapies that we can give to treat GVHD.

47:21      [Tsai] New Treatments for GVHD In the past year or two is actually the first time in history that two medications have been approved for the treatment of GVHD. One is for more acute GVHD, one is for chronic GVHD. Your manifestations are typically what we consider chronic GVHD. So the medication that we can prescribe that can be beneficial is a pill called Ibrutinib or Imbruvica. Are you on other treatments for GVHD other than the localized therapies which she's kind of talked extensively about?

 [Audience] I am on tacrolimus and I had to get back on prednisone, but I'd love to get off the prednisone, and I tried Jakafi until that study came out saying it was linked to more lymphoma, which I don't need any more of at the moment or ever again. But yeah, Ibrutinib is the one medication that I've talked about with my oncologist as a systemic treatment for GVHD, but I didn't like the sound of some of the side effects to be honest with you. But I'd love to hear from other people if they have tried Ibrutinib. But yeah, some of the bleeding through the pores and stuff like that, that doesn't sound great. So I've just kinda been living with the chronic GVHD trying to figure out, okay, well what's top of mind to get rid of next as far as medications go or symptoms that I just can't live with.

 [Tsai] So the Jakafi you speak of that as the medication that's been approved for acute GVHD, for chronic GVHD, it's Ibrutinib. The GVHD is essentially an inflammation, inappropriate response to the immune system. It can take time for things to calm down. We typically consider that people are going to be on treatment for GVHD for one year, three years, sometimes even longer than that, it can take time. It's a bit of a gradual process, but it is possible that after a period of time, after things have calmed down, that you can actually start cutting back on treatments.

There is a possibility that you're on certain treatments for a period of time and sometimes it needs to be interrupted and that's okay and you go back on it. But these treatments are pretty young such as the Ibrutinib, it's possible that after several years if you're doing fine, you would be able to come off with it. In general, I would say in my experience it's overall pretty well tolerated. There are definitely instances where we've had to discontinue it for certain side effects, but I would say majority of people actually can tolerate it for at least some period of time.

50:31      [Audience] Thank you very much.

50:32      [Moderator] I want to make sure we get those questions here, so over to you.

50:35      [Audience] Ear Nose and Throat problems Pretty much the same thing, just going down my throat, I've had it for a long time and I just wonder if I did everything you said with the oral surgeons and the dentists. They saw something at an oral surgeon, another one and they were pulling on it and it seemed like that flared up from everybody pushing on it, like it was tissue paper. Now I have a big scar, hard time breathing.

 [Mays] So pushing on like your tissues.

 [Audience] I can barely hear you.

 [Mays] Pushing on your cheek tissues?

 [Audience] My hearing is going too.

 [Mays] All of the hearing is going. Pushing on your cheek tissues or down your throat?

 [Audience] Well, down my cheek but it feels like this is tightening like he was talking about-

 [Mays] Right.

 [Audience] If it's going down. I've been doing this for a long time, 20 years.

 [Mays] That's a long time. So sometimes, I mean, oral surgeons won't really do, they're not necessarily trained to treat anything in the throat. So ENT doctors, ear, nose and throat doctors are really the ones who will run the scopes and look for this webbing. Obviously if you do have a lot of sort of manipulation of your tissues when you have graft-versus-host disease that can cause inflammation and sort of exasperate things. We've seen that, that that our patients come in, they get an exam and then they'll develop a new ulcer.

 [Audience] It just seems after doing this all this time that the doctors push you down the row and like you'd say, go see this doctor, go see the next one. We saw three oral surgeons, we've seen the two different dentists and the other one you mentioned that for the ear-

 [Mays] The ear, nose and throat doctor. Yeah.

 [Audience] And they just say, let's just watch it, You've done dexamethasone, that's kind of scary that 20 years ago that's the same process that[crosstalk 00:52:44]-

 [Mays] It hasn't changed in the last 20 years?

 [Audience] Yeah.

52:47      [Mays] So there are treatments and your transplant physicians or whoever is following your GVHD may be willing to start this, but there are medications that you can swallow. So more topical medications sometimes, they'll set up a regimen where you're actually swallowing your dextrins or something like Budesonide that's suspended in corn oil. You have to work with your physicians though because it's, when you swallow these things, they get into your systemic sort of system, they're no longer a topical treatment. So they need to adjust your other medications in, in response to that.

 [Audience] Okay. Electric toothbrush-

 [Mays] Electric toothbrush fluoride.

 [Audience] Yeah. It takes you a week to get used to that splatter in the mirror.

 [Mays] Thank you.

 [Moderator] One other question. Is there anybody that could have had one more question?

 [Audience] I have.

53:39      [Audience] Excess Mucus and Dry Mouth:  I also have all this phlegm in my throat. Do you know what could be causing that? I mean, it started a few months ago and I've asked my doctors and I don't know, and I'm like, I've asked the dentist, they don't know.

 [Mays] You described your mouth being really dry, right?

 [Audience] It's dry and-

 [Mays] And if you are really dry this could sort of be, normally the mucus that's in your throat and in your mouth would be counteracted by the watery components of your saliva that are helping to wash it away. So sometimes we see in patients with dry mouth that everything is sort of condensing and it's harder to clear those components away. And Dr. Tsai, I don't know if you have any insight on this.

 [Tsai] So it just started, you said a couple months ago.

54:30      [Audience] Well, actually it's probably been about six months now. I mean, the months are starting to just flow together from one thing to another and live alone this bad, I mean it's just whatever, but it makes it hard to swallow with all that phlegm in there, and I can't seem to get rid of it.

 [Tsai] Do you get a sense that it's more in the back of your mouth or more down?

 [Audience] It's like right here.

 [Tsai] Right there. Certainly, as you mentioned with dryness you make secretions from your mouth all the way down to the end of your GI track and so you can get ... GVHD can affect the consistency of it so it can be thickened. I think it's important to make sure that you don't have some new infectious process that could be contributing to it. I mean, it doesn't sound like it, but if it's a change it's certainly worth looking into.

 [Audience] I know my salivary glands are damaged and I didn't even have a radiation. They're damaged and-

 [Tsai] We can see it occur just from the chemotherapy also, it's certainly not limited to the people who've received radiation. I mean if you have not seen an ear, nose, throat doctor, it might be helpful to have them look down further to see what-

 [Audience] I went to one and he told me to keep going to the doctors until I find somebody who could help me.

 [Tsai] Did he actually take a look though?

 [Audience] Not really, no.

56:02      [Tsai] Yeah. So it kind of goes back to something she touched upon, which is trying to see physicians who have some experience with the complexity of patients such as you all have. People who kind of see the normal stuff may not have such experience like

 [Audience] He was recommended by my oncologist. They called him and then I was like, I'll go back to him.

 [Tsai] I've certainly had experiences also where I've sent the patient somewhere hoping to get more help from the specialist and it doesn't quite happen, and so then I will refer them to someone else. It happens sometimes.

 [Audience] Yeah. Okay.

 [Mays] So I just wanted ... As you are talking are you able to like gargle with anything? So gargling with saltwater may help to sort of break up some of that mucus and sort of give it a little bit of physical sort of agitation. And that's something that you can do as many times a day as you, whatever is tolerable. So room temperature might be best, but if it's a little bit warm you'll be able to get the salt to dissolve in it and you can make your own salt water at home. Just a teaspoon of salt and a glass of tapped water, stir it up and gargle with that. That may help a little bit, don't use anything minty, no mouthwash.

 [Audience] The guy in Seattle thought I had a[inaudible 00:57:31] burning down. He also said it's very complex and we can't ... You never know.

 [Mays] Yeah, I mean it's possible there's a neuropathic component to sort of the change in sensation that you're describing.

 [Audience] He gave me some Doxepin to start trying with the normal mouth wash. It numbs it but then he said it might break the nerves

58:01      [Mays] In my experience Doxepin is an outstanding and very bad tasting numbing agent, but I'm not familiar with it, it's used to help nerves regenerate.

 [Moderator] Great. Thank you. Thank you to our speakers Dr. Mays and Dr. Tsai. And this concludes the time for this session, so next sessions we'll be starting shortly. Thank you very much.


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