Graft-versus-Host Disease: Mouth

Dry mouth, mouth sores, reduced saliva production and changes in taste often occur after a stem cell transplant, particularly in patients who have graft-versus-host disease. Learn how to treat these oral complications.

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Chronic Graft-versus-Host Disease of the Mouth

May 3, 2023

Presenter: Jacqueline Mays, DDS, MHSc PhD,  National Institute of Dental, and Cranial Facial Research. National Institutes of Health

Summary: Dry mouth, mouth sores and reduced saliva production are common after a stem cell transplant. Being vigilant about daily mouth care and finding a dentist who is familiar with problems that can arise after transplant are important steps to take to protect your mouth long-term after transplant.

Many thanks to Sanofi® whose support helped make this workshop possible.


  • Mouth sores, changes in taste and reduced saliva production are common after a stem cell transplant.
  • Oral problems can be caused by infection, drugs or chronic graft-versus-host disease (GVHD)
  • An annual screening for oral cancer is vital for stem cell transplant recipients to detect and treat cancer in the mouth.

Key Points:

(03:07): The mouth is a unique and rich environment because it is the gateway to your body with an immune system that protects against infection.

(05:08): Mouth care after transplant is similar to before transplant, although the mouth may be more sensitive, especially if there are mouth sores.

(10:44): If your dentist gives you a blank look after you explain that you are a transplant survivor, he or she may need more education, or you may need to find a different dentist.

(12:53): A good place to look for dentists who treat patients with complex medical history are university clinics.

(13:52): An oral cancer screening is critical for anyone who has been through bone marrow transplant.

(15:40): Some oral complications, such as dry mouth or changes in taste, that occur early after transplant may be caused by drugs such as methotrexate, sirolimus, radiation or viral infections such as herpes simplex virus (HSV) or thrush.

(22:47):  Many patients develop graft-versus-host disease (GVHD) in the mouth that can cause dry mouth, temporary blisters on the roof of the mouth and sensitivity to spicey or acidic foods.

(33:54): The first line of therapy for oral graft-versus-host disease, in almost every case, is swishing the mouth with a steroid rinse such as dexamethasone oral suspension.

(36:31): GVHD can affect the salivary glands and reduce saliva production. Sugar-free gum or candy, frequent sips of water or lubricating rinses can be helpful.

(38:57): If GVHD has reduced the mouth opening, progressive gentle stretching, guided by a physical therapist can help.

Transcript of Presentation:

(00:00): [Lynne Spina]:  Hello. Welcome to the workshop Chronic Graft-versus-Host Disease of the Mouth. My name is Lynn Spina, and I will be your moderator for this workshop.

(00:11): I'd like to thank Sanofi® whose support helped make this workshop possible.

(00:16):  Introduction of Speaker. It is my pleasure to introduce today's speaker, Dr. Jacqueline Mays. Dr. Mays is an immunologist, and a clinical trials dentist. She heads the Oral Immunobiology Unit within the Division of Intramural Research at the National Institute of Dental, and Cranial Facial Research, which is part of the National Institutes of Health (NIH). Her research focuses on how chronic Graft-versus-Host Disease, GVHD, develops after a transplant using donor cells, an allogeneic transplant; the causes of salivary gland dysfunction after transplant; and therapies to improve the treatment of oral GVHD with clinical trials directed toward advancing chronic GVHD therapy. Please join me in welcoming Dr. Mays.

(01:16): [Dr. Jacqueline Mays]: Good afternoon. It's a great privilege to be here, and I want to thank all of you who are watching this session. I have some information that will help you return to a healthy mouth state.

(01:35): Learning Objectives. I will be explaining oral care following transplant. There are oral complications that are both expected and unexpected after transplant; things that can happen in your mouth; signs to recognize chronic graft-versus-host disease (GVHD) in the mouth; different types of oral graft-versus-host disease; and then we'll speak about how we treat those different types of oral chronic graft-versus-host disease.

(02:08): We will evaluate non-graft-versus-host disease, post-transplant complications, and graft-versus-host disease in your mouth, what it looks like, what it feels like, and how to treat them. I will discuss general oral care with a focus on the critical elements post-transplant, as well as how to establish dental care where you actually live; the who, what and when. I also will review the critical role of oral cancer screenings after your transplant.

(02:40): Oral mucosa refers to all the skin inside of the mouth. To go over some terminology so we're all clear on what I'm referencing during this presentation. Within a normal oral cavity, we call the soft, wet tissue that you see everywhere mucosa. When we're talking about oral mucosa, we're talking about all the skin inside your mouth.

(03:07): The oral cavity is a unique and rich environment because it is the gateway to your body. It's not protected or closed off the way your brain is, or separated like your gastrointestinal system is. It is continually interfacing with the outside environment. It's where your food goes in, it's where you breathe the air for the first time. Because of that, your mouth has a build-up of natural defenses, and has a rich immune system that is integrated within these mucosal tissues.

(03:40): As part of this, you have tonsil tissue at the back of the mouth. You also have a robust immune system underneath the tongue. Medications that need to be administered quickly will often be popped under the tongue if they can't go through your venous system. This is called the sublingual immune response.

(04:04): When I talk about buccal mucosa, that is the skin inside your cheeks. You have two cheeks right and left, and there is mucosa covering the inside lining of each of those.

(04:20): You have three sets of major salivary glands. These produce most of that watery saliva that's in your mouth. There's a set of parotid glands higher on your cheeks, and then underneath the chin, there are the sublingual and submandibular glands.

(04:37): Throughout the oral cavity there are about 2,000 to 3,000 minor salivary glands that contribute to saliva production within your mouth. More importantly, they reflect what's happening in your major glands. If we want to see within the tissues, those minor glands are where we will look rather than looking into your major glands, because it reflects the same immuno and pathological states that your major glands are experiencing.

(05:08): How do you take care of your mouth after your transplant? It's the same way that you would take care of it before your transplant. However, you may have to be more thorough about your oral hygiene post-transplant, since you might find that your mouth is sensitive in ways that it wasn't prior to your transplant.

(05:29): When thinking about brushing your teeth, we strongly encourage our patients to use toothpaste with fluoride. Fluoride is a critical molecule that's able to re-mineralize parts of your enamel that might have gotten soft or become destabilized and it's able to restrengthen that enamel. If you have dry mouth or if you're not eating the best diet when you have mucositis (when your mouth is sore and inflamed) after your transplant, fluoride can help restore some of the damage that has happened with your tooth enamel, keeping it strong.

(06:14): Patients who experience a sensitive mouth after transplant may find that they are sensitive to flavors, both in their food as well as in their oral care, such as toothpaste that they weren't sensitive to prior to transplant. Using a fruit flavored or a children's toothpaste may help bridge that span when your mouth is particularly sensitive, so you're not struggling with minty toothpaste and not wanting to brush because your mouth is too sensitive.

(06:46): For sensitive teeth, we also recommend fluoride rinses, which can be prescribed by your dentist, or gels that can be brushed on your teeth at night, or using an over-the-counter desensitizing toothpaste. Some of these brands include Pronamel®, Sensodyne®, and Colgate Sensitive Toothpaste®. The caveat with these desensitizing toothpastes is that, often, you need to use them for several weeks to notice a difference in the sensitivity of your teeth.

(07:35): There are also professional desensitizing treatments that some dentists offer. These include fluoride that's brushed on the teeth, as well as other treatments including laser therapies that can be used to desensitize teeth.

(07:54): For patients with chronic graft-versus-host disease, we sometimes see that as joint mobility becomes impaired with progressive sclerotic chronic graft-versus-host disease, the mechanical act of brushing your teeth becomes challenging. In those cases, I'm an advocate of electric toothbrushes. Any style and brand that works for you is fine.

(08:41): Everybody's favorite topic, flossing your teeth. Flossing removes any “yuck” and/or food particles that are stuck between your teeth. Cavities love to grow within plaque that is left between your teeth; the whole idea behind flossing is to get rid of the debris from between your teeth. This is no less important after your transplant, but it becomes a more complex issue.

(09:08): Many transplant centers recommend not flossing your teeth for a period following transplant to prevent damage to the gingiva. I realize that you can't see this, but I'm pointing at the floss touching the gingiva in this picture, where you can get a bit of tissue damage, allowing bacteria to travel through your circulatory system. Your transplant team wants to prevent exposure to bacteria in your mouth, so they recommend that you avoid flossing for a while.

(09:38): However, sometimes centers forget to tell you when you are allowed to resume flossing. Once you've stabilized post-transplant, unless there's a specific medical reason to the negative, you should be okay to floss your teeth again. There are many ways to clean between the teeth. If you're not using the conventional long floss string, you can use some of the little pick devices that can be found on the shelves in the drugstore next to toothbrushes and toothpaste. Some of them have a string of floss stretched between them, and some of them are little, tiny brushes that you can fit between your teeth.

(10:13): If your teeth aren't too close together, my favorite are water flossers. There are several different brands, all of which shoot a little stream of water at a strong force rate between your teeth and knock out any debris that's there.  This eliminates the mechanical force of a string or brush that may abrade your gingiva and is a very gentle way to clean between your teeth.

(10:44): An issue that we address, since our patients at the National Institutes of Health are often not local, and we are seeing them for their annual transplant follow up, but we're not taking care of their regular dental care.  I often find myself in the situation of helping patients find a dentist in their home community who understands their graft-versus-host disease, their medical situation post-transplant, and who can be of professional assistance to them. Step one is simply to tell your dentist that you're a transplant survivor. If your dentist gives you a blank look, they might need more education, or you might need a different dental office.

(11:29): Next is to show your dentist anything unusual, or new that you see, or feel in your mouth, including mouth ulcers, lumps, and bumps. These things typically will heal within three weeks; you can see that I've got stars on this slide, because that three-week time projection for healing does not include chronic graft-versus-host disease. If you notice anything with your teeth, gums, lips, tongue, and/or cheeks that has changed, you should show your dentist or other health-care provider.

(12:01): Do make sure that you're getting screened for oral cancer. Your dentist should feel underneath your chin, and check your temporomandibular joints, and use a piece of gauze to move your tongue around during the oral cancer screening process. During your regular check-ups, make sure that your dentist is providing your oral cancer screening.

(12:53): A good place to look for dentists who treat patients with complex medical history is with your medical care providers or cancer clinics. University clinics include dental school faculty, or resident practices who can recommend dental professionals who have the time, education, and patience to deal with more complex problems rather than simply drilling and filling teeth.

(13:20): If you need specialty care, oral surgeons are generally well versed in graft-versus-host disease, and other types of pathology. These professionals are often affiliated with a university or other medical center faculty; they may also have private practice clinics.

(13:52): Critical for anyone who has been through bone marrow transplant is to get an annual oral cancer screening. We know that the highest risk for oral cancer in post-transplant patients is in patients who have had a history of chronic graft-versus-host disease. Constant inflammation can increase this risk. I tell my patients that even though the risk is increased with a history of chronic graft-versus-host disease, the risk of oral cancer is still very small. It's something that you should screen for, but not something that you should stay awake worrying about.

(14:31): The most common time for us to identify these types of lesions is at five to 10 years post-transplant. The tongue, especially the lateral borders of the tongue, the sides of the tongue that touch your teeth when you're at rest, are the most common site to find these types of secondary, or subsequent oral cancers.

(14:50): This picture is from one of my patients who had noticed this lesion just two to three weeks prior to the photo. It had probably been there for a time before that, but it didn't become painful until that point. This turned out to be an oral squamous cell carcinoma and required fairly extensive treatment. Again, this is not something that you should stay awake at night worrying about, but it is something that requires regular screening.

(15:18): Most of you, I assume, are past your first 100 days post-transplant, and you may recall mucositis, dry mouth, and oral thrush that may have occurred during that very early peri-transplant period.

(15:40): During the overlap period, we consider drug-induced complications, so things that come from your systemic doses of methotrexate, sirolimus, and other drugs being a bit off in their titration, or viral infections that can sometimes break through, and cause lesions in the oral cavity including herpes simplex virus and human papillomavirus.

(16:05): The later complications, when we think about things that are happening post-transplant, include obvious chronic graft-versus-host disease, which we will discuss shortly in this presentation, as well as secondary oral cancers that can occur during the five to 10 year, or later post-transplant period.

(16:30): Many of you have likely experienced some of these non-GVHD post-transplant complications including loss of or change in taste. Often, this change in taste is tied to your pre-transplant chemotherapy regimens. Specific types of chemotherapy are notorious for causing taste changes. Our patients often report changes in their food preferences after transplant, such as a difference in the way that meat tastes, or how they perceive the texture, or how tomato sauce tastes after transplant. Those things generally resolve with time.

(17:15): You also may have noticed some radiation-induced dry mouth if your pre-transplant regimen included total body radiation, or if some of your cancer therapies included targeted radiation. You may have noticed medication related to oral ulcers, or lesions that were not graft-versus-host disease but did require treatment. Patients, because they are immunosuppressed following transplant, often fight off a number of different infections in the oral cavity that would normally be there as part of the normal oral microenvironment. However, they are able to overgrow and cause problems where they normally would not in a non-transplant patient's mouth.

(18:02): We often see cold sores, mostly coming from herpes simplex virus (HSV) recrudescence, or reactivation, during the immunosuppressed period after transplant. Again, this is a virus that most of us have living in our bodies already, that normally wouldn't cause a problem until you are in an immunosuppressed state.

(18:22): What does HSV look like? Reactivation is common. It usually comes on very quickly and causes tiny oral ulcerations. I like to show this picture on the left because it's unusual to catch these blisters when they're still in blister form, before the roof comes off them, and they just look like tiny ulcers. But they start as these little blisters, until they're unroofed, or they open, and leave behind small punctate ulcers, which can be very painful. This is one way, clinically, that we suspect that these are virus-induced ulcers.

(19:04): To diagnose this, we'll swab the ulcer, and have the lab test for herpes simplex virus DNA and sometimes other types of viral DNA, as well. This is typically managed with lidobenalox - a combination of Maalox®, lidocaine, and Benadryl®, along with systemic antivirals.

(19:28): Another common post-transplant complication that is not graft-versus-host disease is oral thrush, or candidiasis overgrowth. This can occur in pseudomembranous forms like this white furry looking tongue on the left-hand side of the screen, or erythematous. This is the bright red, shiny- looking tongue in the middle; there's another photo of pseudomembranous candidiasis in the back of a throat on the right-hand side of the screen.

(20:03): This occurs when candidiasis, which is a normal component of the flora in your mouth, is allowed to overgrow. Often this happens when patients are on either systemic or topical steroids and can occur when you're on things such as a steroid inhaler, a fluticasone inhaler. When patients go on FAM therapy (Fluticasone®, Azithromycin®, Montelukast®) they sometimes experience trouble rinsing out their mouth in order to get the steroid out after using the inhaler; sometimes thrush can occur at that point.

(20:37): One of the classic clinical signs of candidiasis overgrowth in the oral cavity is a burning feeling in the mouth. Even if all you're doing is drinking water, and that is burning, that's a sign that this might be a fungal related infection. Typically, this is managed with topical antifungals, such as clotrimazole. These medications are put directly onto the tongue and allowed to melt so that it can go directly into the oral cavity. It can also be added to your systemic antifungal prophylaxis if you're still on a systemic antifungal agent.

(21:20): Another non-graft-versus-host disease ulcer that we often see in the oral cavity in our post-transplant patients are mTOR inhibitors or sirolimus induced oral stomatitis. This occurs when excess circulating levels of mTOR inhibitors, such as sirolimus or everolimus; it could be some of these other newer drugs. If the levels become a bit high systemically, this can induce painful aphthous-like ulcers. They have well demarcated borders, and focal erythema, so really clear borders and a bit of redness are typically associated with them.

(22:01): The white arrows in each of these photos point to the ulcers. I know they're difficult to see because they resemble erosions. They're not like those little punctate dots that you saw with herpes simplex virus. They can be small or can be quite large. They are normally managed in a fairly straightforward manner, using topical steroids, “magic mouthwash”, as well as with adjustment of the medication dose that was the cause of this erosion of the oral mucosa.

(22:34): I will now discuss what it feels like when graft-versus-host disease begins within the oral cavity.

(22:47):  Many patients report that one of their first symptoms is dry mouth or temporary blisters on the roof of the mouth; this can occur quite suddenly. Often things have been fine and then they find that their mouth is suddenly so dry that it wakes them up at night. They often need water to properly chew and swallow their food, which wasn't something that they needed to do before. These blisters on the roof of the mouth are called mucoceles. They often occur when immune cells infiltrate into the tissue, squeezing the openings of the salivary glands closed so that the saliva has trouble getting out into your oral cavity. When your salivary glands are attempting to put that saliva out into your mouth, instead it's causing these blisters on the roof of your mouth, as well as, sometimes, on your lower lips.

(23:45): Red or white patches may occur in the mouth that you cannot scrape off. Often, these aren't really the first signs; however, they might be the first signs that patients notice because, when they're looking in the mirror, they notice that there's a white or red patch in an area that was never there before. It's something that's part of your tissue so can’t be scraped away. Mouth ulcers are things that patients will often feel first before they see them. You might notice that it's painful under your tongue when you’re eating. When you look under your tongue, there may be an ulcer there that was previously unnoticed.

(24:33): This also might be accompanied by white lines on the cheek lining, or other mucosal surfaces. Their clinical name is lichenoid striations, or lichenoid patterning. This is one of the diagnostic signs for oral chronic graft-versus-host disease. If we see these within the oral tissues, or within the oral cavity in an allo transplant patient, we know that this is most likely chronic graft-versus-host disease. These can occur on the inside of the cheeks on the gingiva. We sometimes see them on the bottom side of the tongue, on the floor of the mouth, or on the roof of the mouth. They can occur anywhere within the oral cavity.

(25:16): Along with dry mouth, one of the earliest symptoms that patients report noticing is oral sensitivity. They might be eating one of their favorite foods, and suddenly notice that it's painful. They might notice that if food has even a bit of pepper on it, it's too spicy; they often become very sensitive to these types of things. This can include food that we think of as traditionally spicy, such as chicken wings, spicy sauces, citrus fruits, or even acidic foods such as tomato sauce. These are some of the foods that are often early triggers for this type of oral sensitivity with onset of chronic graft-versus-host disease.

(26:06): What does GVHD look like within the oral cavity? I typically think of this as occurring in three separate domains. You've got the mucosal lesions that are very easy to see in the clinic and at home. This includes hyperkeratosis, which are the white and red lesions that we've demonstrated. This picture shows the roof of the mouth. On the left-hand side, there is another photo of the roof of the mouth. Directly under that is the hard palate, showing these lichenoid lesions, the white patterning; you can see that all the openings to the minor salivary glands on the roof of the mouth are somewhat red and irritated. If you go up towards the middle, you can appreciate that the gums of this patient are very affected by the graft-versus-host disease, and are quite red. There's some hyperkeratosis on the bottom part, then there are pseudo membranous ulcerations, which can often be quite large.

(27:08): Often these ulcers really aren't painful if patients are not eating or drinking. It's very different than the virus induced ulcers where this will often be extremely painful. Often these occur in patients who may not even realize that there are ulcers here. The mucoceles that we were talking about earlier, are here on the palate; they can also occur on the lower lip. The tongue here demonstrates this patchy tufted hyperkeratosis.

(27:48): The other two domains where we think of oral graft versus hosts disease occurring include perioral sclerosis, or limited mouth opening. This can be because the temporomandibular joints are affected, or it can be because the skin around the mouth has become so sclerotic that the mouth opening is very limited.

(28:07): Within the salivary glands, we know that immune cells can infiltrate, and start replacing the acinar balloons that make your saliva in the salivary glands, with collagen bundles. The patient’s mouth becomes quite dry; the salivary glands can be targeted by chronic graft-versus-host disease without having oral mucosal involvement. Our worry, when you lose your saliva, is that dry mouth can lead to smooth surface caries [cavities]. The kind of things that you would expect to see in younger children who might be drinking from a bottle, so-called’ baby bottle tooth decay’, can occur in adults with dry mouth.  It occurs in Sjogren's syndrome, and we see it in graft-versus-host disease patients who have really impacted salivary glands.  Sjogren's syndrome is a chronic autoimmune disease where the body’s immune system attacks moisture producing glands, resulting in the deficient production of tears and saliva. This causes salivary and lacrimal glands to become inflamed, thus resulting in a dry mouth and dry eyes.

(28:58): This diagram illustrates that in the group of NIH patients who have had graft-versus-host disease in the mouth for an extended time, and whom we've studied, that you can have each one of these distinct domains: limited mouth opening, oral mucosal lesions, and salivary gland dysfunction, without necessarily having the other associated problems in the oral cavity. This makes it clear to us that different types of oral graft- versus-host disease may need different types of treatment. We know that the underlying pathology is different, and that the prognosis is different.

(29:40): To diagnose graft-versus-host disease in the oral cavity, if we see these lichen planus-like changes, we know that we can confidently diagnose GVHD. If we have at least one of the distinctive manifestations, dry mouth, mucoceles, mucosal atrophies, pseudo membranes and/or ulcerations, we like to confirm with a pertinent biopsy, so we can rule out other possible diagnoses, such as oral infections, drug reactions, or new cancers.

(30:09): These are different ways that the lichenoid lesions might look on cheeks and lips. Within the palate, this shows different ways hyperkeratosis and erythema, or the redness, might look on a palate, and it's showing a different photo illustrating what these mucoceles might look like.

(30:36): Often we see in our GVHD patients that their tongues will atrophy. Your normal papilla on your tongue that helps you to taste might shrink up a bit and your tongue might become a bit shiny. We call this atrophic glossitis. There might sometimes be red and white patches on the tongue, and then, again, this is that patchy tufted hyperkeratosis tongue that looks a lot like candidiasis but is actually not candidiasis.

(31:05): Pseudomembranous ulcerations can also occur anywhere. They often hide beneath a patient’s tongue. We frequently see them on the buccal mucosa, the inside of the cheeks, and then here is a patient that had those across the lower lip.

(31:26): When we diagnose GVHD in the clinic, we often ask patients," Is your mouth suddenly or progressively dryer? Can you chew and swallow food without drinking water? Are you taking any medications that cause dry mouth? Did you have radiation as part of your cancer therapy, or transplant preparation?" In order to clearly diagnose graft-versus-host disease in the salivary glands, a biopsy of the minor salivary glands is needed.

(32:41): The way to keep your mouth in the best shape possible is to brush your teeth, seek routine dental cleanings with endocarditis prophylaxis, antibiotic prophylaxis if that's what your medical team recommends, and to regularly examine your mouth for infection and malignancy.  That is also what your dentist should be checking for. It can also be something that you are simply doing when you're brushing your teeth. Just look at your mouth, see if anything looks a bit different, and let your dentist, or your health-care professionals, know if things do look different.

(33:17): Moving into therapies for changes in the mouth after transplant. Topical therapies for mucositis, which really happen in the early post-transplant period, include cryotherapy, treatments that involve ice chips or other types of cold therapies. Often, we'll use supersaturated calcium phosphate rinses for patients with mucositis. This tends to help support the wound healing process in the mouth. Obviously, adequate pain control is indicated; typically this is done with opioid analgesics.

(33:54): The first line of therapy for oral graft-versus-host disease, in almost every case, is dexamethasone oral suspension. In the United States, this is typically given at 0.1 mg per ml. We know from published data that 29% to 58% of patients will respond to this. You may think that this is a low number, that it won’t be particularly effective, but it is our best first line of therapy because the second line of treatment is not particularly well established.

(34:30): If you're on topical steroids to treat your graft-versus-host disease, the contact time for these medications is critical. You want to make sure that you are using it for the amount of time that is recommended. You don't have to swish these medications as if you're in a Listerine® commercial. I tell my patients to set a timer for two to five minutes, whatever was recommended for your medication, and read your email, or check out your social media, and then when your timer goes off to just spit the medication back into the sink. You want to just make sure that it has enough time to soak into the tissues within your mouth so that you can receive the positive medication effect that it's supposed to.

(35:17): For mouth sores, lichen planus-like changes, we will often use progressively increasing strengths of steroid rinses. Starting with that dexamethasone rinse and then increasing both concentration and strength of the agent.

Occasionally, if patients are particularly steroid sensitive, we'll use calcineurin inhibitor rinses like tacrolimus in a topical oral rinse form. If there are isolated oral ulcers, on your tongue, or on the inside of your cheek, that's when we use a topical steroid gel, tacrolimus gel, or to do intralesional injections of triamcinolone. This is the same medication that a rheumatologist may use for painful joints, but we find that it's particularly effective if it's injected right at the ulcer bed until that ulcer is able to close. One of the important functions of the mucosa in your mouth is to provide that barrier function. For your mucosa to be a protective barrier, all of the ulcers need to be healed.

(36:31): As to aids for dry mouth; this is a particularly important topic for individuals who have salivary glands that are impacted by radiation, chemotherapy, or graft-versus-host disease. Sugar-free gum or candy, especially lemon flavors, can be helpful for dry mouth; I emphasize the sugar-free part. Often, these contain an alcohol-based sugar called xylitol, which is known to reduce tooth decay. If you're looking for sugar-free gum or sugar-free candy, check the label to see if it contains xylitol.

(37:12): Frequent sips of water, which contribute to staying hydrated, can be helpful. Lubricating rinses, including Biotene®, or any number of the other products can also be helpful. These are often very specific to individuals, so if you don't like one, try another. I was joking with a patient yesterday that we really needed a tasting bar in our clinic to see which dry mouth rinse was to their personal preference!

(37:38): There are prescriptions available for patients who are producing enough saliva. These stimulate your cholinergic nervous system and increase the secretions that your body is making. Medications include pilocarpine (Salagen®) or the more specific cevimeline (Evoxac®). These can take a few weeks to become effective. These drugs only work if you have acinar saliva-producing cells left within your salivary glands. Medically they're not appropriate for everybody, so this is a conversation to have with your medical team.

(38:15): I'm beating a dead horse a bit, but fluoride is important. Please check that your toothpaste contains fluoride. This is critical for rebuilding dental enamel that has mild damage. Toothpastes that include active hydroxyapatite, or zinc hydroxyapatite, can also help to rebuild tooth enamel.

(38:39): Your saliva is important for washing that food away from the teeth, buffering acids, and bases in your mouth, and returning calcium to damaged tooth enamel. Unfortunately, dry mouth provides less protection from decay.

(38:57): If you have reduced mouth opening, progressive gentle stretching can maintain or improve your mouth opening. Some aids that may help this include stacked tongue depressors; opening your mouth to a stack of six or seven tongue depressors, and gradually adding one as you're able to open your mouth a bit more. I strongly recommend that this be guided by a physical therapist, or occupational therapist. They can develop a program of extra oral and intra-oral massage to help break up fibrotic tissue and can often be quite helpful in improving oral opening. In severe cases, perioral steroid injections around the edges of the mouth have been helpful for some patients with reduced oral opening. In severe cases, surgical intervention can help to open the mouth a bit further.

We've now reached the Q&A part, and I'm happy to take any questions.

Question and Answer Session

(40:20): [Lynne Spina]:  Thank you Dr. Mays for your excellent presentation. Our first question is, "Do you find pain in the teeth and sensitivity to be a common issue? I was told it was likely caused by teeth clenching or grinding-related and could be resolved by using a night guard and high fluoride toothpaste. It has resolved some but not entirely; it's been about four months.

(41:03): [Dr. Jacqueline Mays]: I would say that you've gotten excellent advice with the mouth guard and the fluoride gel. We see, especially in the early post-transplant period, that our patients develop dental sensitivity, and their teeth will go through periods of sensitivity. Although we don't know why, we do know that it gets better; it sounds like you're getting good care. Until your tooth sensitivity improves, I would take care to avoid anything that is triggering that tooth sensitivity and continue to use your night guard and fluoride.

(41:58): [Lynne Spina]:  "Have you had success with gum graft in patients with oral GVHD who have experienced gum recession?"

42:22): Gum grafting can be complicated while you're still on systemic immunosuppression. One of the things that drugs such as prednisone, sirolimus, tacrolimus doing is reducing the activity of your immune system. We often find that patients, especially those on prednisone, will have trouble healing if they have any regenerative procedure done such as gum grafting.

If you're on an mTOR inhibitor, I would not recommend gum grafting; for example, if you're on sirolimus, since that directly impacts wound healing. If you are off your systemic immunosuppression, we have seen good results in patients who are further out from transplant, in being able to cover up those re-exposed root tissues. In general, gum grafting is really complicated even when done by qualified periodontist in healthy individuals. It has a limited success rate.

Going back to the issue of dental implant placement in post-transplant patients; we have seen that when patients wait until they're off systemic immunosuppression, dental implants can be quite successful. Often, when I'm seeing patients for their annual follow-up, they come to the office with a well-integrated dental implant; we will discuss how that went.

Implants are not always successful, but for patients who have lost teeth secondary to chemotherapy and/or protracted cancer treatments, we have seen that our patients have often done quite well.

(44:57): [Lynne Spina]:   Are there any foods that may aid in developing saliva?

(45:02): [Dr. Jacqueline Mays]: Lemon flavors are sometimes helpful for stimulating saliva flow. Often, when we're trying to collect saliva in the clinic for a patient in a research study, we'll paint their tongue with citric acid. We don't do that in graft-versus-host disease patients, since that can be very painful. Things that have lemon flavors, that little bit of zing that you recognize as citric acid, can help with saliva flow. The mechanical act of chewing can also help with saliva flow. If your muscles can tolerate it, sugar-free gum can be quite helpful in stimulating saliva flow. Drinking lots of water always helps because the more water you have in the body, the more saliva you can make.

(46:00): [Lynne Spina]:   Can you discuss application of dexamethasone for oral GVHD? Is it helpful to gargle, and should it be followed by Nystatin® (an antifungal medicine), to diminish the possibility of fungal infection?

(46:16): [Dr. Jacqueline Mays]: We have a tremendous amount of experience using dexamethasone in graft-versus-host disease patients; it's really the first line of therapy. Most people on this call who have had graft-versus-host disease, have probably also used topical dexamethasone as a swish and spit medication. It's not necessary to gargle. If you're holding it in your mouth, the liquid will allow the steroid to have enough contact with your mucosal tissues. Steroids are lipophilic; they like fats and oils, so they're good at traversing through the oral mucosa. You need to keep that medication in your mouth for a prolonged period of time for it to work. There are medications that medical teams might prescribe as a swish and then a swallow, but that is a very different issue. That's something that should be discussed clearly with your medical team, since then you're increasing your systemic dose of steroids, which is something that needs to be carefully controlled.

(48:07): [Lynne Spina]:  Is a high dose fluoride toothpaste as good as using fluoride gum molds?

(48:20): [Dr. Jacqueline Mays]: Your dentist can make custom fluoride trays for you where they take an impression of your teeth. They can make something that looks like a little Invisalign® tray that you can put fluoride gel in at night, and sleep with that in, so that your teeth get maximum exposure to that fluoride gel. You will get more exposure and, thus, more therapeutic benefit from a fluoride tray than you will from a prescription fluoride toothpaste. However, it depends on your individual situation whether or not you need that additional therapeutic exposure. If you really need intensive support, for patients undergoing head and neck radiation, for example, they really need those fluoride trays. If patients are suffering from dry mouth and have decay associated with that dry mouth, I will try to get them to use fluoride trays so that they can try to repair some of that dental damage.

(49:59): [Lynne Spina]:  Can decalcification of teeth, and gum recession after transplant be prevented?

(50:10): [Dr. Jacqueline Mays]: Yes, to an extent. This is a tricky question, since you are asking both about gum recession and about tooth decay. Tooth decay can be prevented with good oral hygiene, often with fluoride supplementation, so that if a bit of damage happens to the enamel, it can be re-mineralized and reversed.

The question about gum recession is a much different question, since this is soft tissue. We know that when patients are on, for example, high doses of prednisone for an extended period of time, there is often a recession in their gingiva. That really can't be prevented, absent not being on those high doses of prednisone for a long time that's needed systemically to treat graft-versus-host disease as well as other conditions. As much as we would like to prevent gum recession, that's not always something that we can prevent. If gum recession is occurring from periodontal disease, or gingivitis, those are a bit more preventable with regular cleaning, perhaps seeing a periodontist every three months. In our transplant patients, we see that the gum recession is usually more related to systemic medications.

(51:46): [Lynne Spina]:  Do you have any specific recommendations for frequency of teeth brushing, and frequency of dental visits when dealing with GVHD?

(51:58): [Dr. Jacqueline Mays] I would love it if everybody was able to brush their teeth after each time they eat. Practically speaking, if you can brush in the morning and in the evening, that is good. For frequency of your regular dental visits, I would like everyone to visit their dentist at least once a year so that you can get that oral cancer screening. We generally recommend a dental cleaning every six months. It's easier if you can catch problems when they're small. I have some patients who have many dental challenges, who go every three months for a cleaning to help keep things under control and maintain  good oral hygiene.

(53:15): [Lynne Spina]:  How do I get rid of mouth ulcers? I know you mentioned something in your presentation as it relates to treatment, but can somebody get rid of the mouth ulcers themselves?

(53:32): [Dr. Jacqueline Mays]: It depends on what the ulcers are from. If they are ulcers related to graft-versus-host disease, topical treatment will often help. Treatments can include topical dexamethasone or a steroid gel that goes directly onto the ulcers, whether it is a triamcinolone gel, or a clobetasol gel. Sometimes we'll apply that and may cover it with a piece of gauze for about 15 or 20 minutes, so that the steroid can get to the ulcer. If they are longstanding oral ulcers, sometimes they're more chronic type of oral ulcerations in the mouth that no longer hurt. They've been there for so long that the tissue has curled under and it's not healing properly. In those patients, we will often inject steroids directly into the ulcer base to try to get that ulcer to heal, so that the mucosal barrier function can be restored in those patients.

(54:55): [Lynne Spina]:  If you see oral GVHD resolve with the use of Rezurock®, or Jakafi®, is it gone? Or do you watch for possible flareups?

(55:04): [Dr. Jacqueline Mays]: We always watch for possible flareups. We have seen excellent results with Rezurock. In clinical trials, we've seen oral graft-versus-host disease improve quite a bit in many of our patients. The caveat to that is that it's still a new drug. We haven't seen many patients with chronic graft-versus-host disease when they start this. What I'm telling you is very anecdotal but, with graft-versus-host disease, there's always that question whether it's completely burned out, or if it's going to flare up again. Often, with the oral cavity, we keep treating the flares until they stop occurring. Unfortunately, I can't give you any remarkable hope about this being the one drug that will eradicate GVHD in the oral cavity for good.

(56:05): [Lynne Spina]: Last question; I've had my transplant five years ago, and now have GVHD, and a numb tongue. What causes this? What can I do to treat it? Is it common?

(56:23): [Dr. Jacqueline Mays]: A numb tongue is not common, but you're not the first patient that I've met who has a numb tongue with graft-versus-host disease. Depending on exactly the type of numbness… if it's like a numb sensation or if it is simply altered trouble tasting anything that's making the tongue feel numb, it remains a tricky question, to which I don't have a stock answer. If the tongue numbness is secondary to graft-versus-host disease, GVHD treatments may help. It's possible that it's more of a neurologic manifestation of the graft-versus-host disease or other conditions. I would recommend seeing an oral facial pain specialist who can guide you through some less common treatments for that numb tongue.

(57:37): [Lynne Spina]:  I'd like to tell everybody out there who is dealing with GVHD that BMT InfoNet has a directory of GVHD specialists. It's on our website,; go to the tab that says find treatment; you will find dentists that are versed in treating GVHD. On behalf of BMT InfoNet, and our partners, I'd like to thank Dr. Mays for a very helpful presentation. And thank you, the audience, for your excellent questions. Please contact BMT InfoNet if we can help you in any way.

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