What is gvhd in mouth

And these can get plugged and inflamed, and cause these little blisters of saliva. They don't actually tend to be very painful, but they can be pretty alarming when they're all over the place.

Again, we saw this in the other picture, but another example where we have this focal area of ulceration in the cheek or what we call the buccal mucosa. And then surrounded by these very prominent red and white changes. And again you can see very similar involvement with the tongue but also the lips. And this was from the group in Seattle. Schubert is an oral medicine specialist, someone I've known for many years, and still sees patients there.

In addition, we've noted that the oral cavity can be the site of persistent activity after resolution of chronic GVHD affecting other sites. And sometimes it might be the only area of involvement. This was a figure that we had published a few years ago in this review article.

But, we can think of, as I've already sort outlined, we can think of the disease in the mouth as three different diseases. One is the disease affecting the mucosa. And the primary symptom with that tends to be what we call sensitivity.

So, even with one of these mouths that I showed you that look like they would have to be incredibly painful, if it were me, I would actually be fine, right now, talking if my mouth weren't dry. And I wouldn't necessarily have a dry mouth just because the inflammation. But, as soon as I went to have breakfast, and I tried to eat those potatoes, I'd probably go from being as comfortable as possible to tears coming out of my eyes just because of the texture, let alone the flavor, the little bit of spice.

And things that we would never even think would bother somebody immediately can become something that they just can't even tolerate. So, the idea of going out to dinner, let alone having someone else cook for you, going to somebody's house for dinner, ends up becoming really very difficult. With a dry mouth there's also increased risk of recurrent yeast infections in the mouth. And I think many of you know that's a common complication also related to just systemic immunosuppression.

But, some of the symptoms can be similar. So, sometimes when somebody just has a very dry mouth, the mouth can actually become very sensitive even though we don't see the typical lichenoid, lacy inflammation patterns. In rare cases I've seen patients where similarly we can see with the skin, where there can actually be deep inflammation into the muscle, and chronic spasm of muscles which can be very painful. But, again, this is not very common. The cheeks and the tongue are most common, lips are really frequently affected.

Again, the sensitivity tends to be the main feature. This affects eating and drinking; in particular tooth brushing. Simply using a children's toothpaste rather than an adult toothpaste for most patients is enough to make things comfortable. So, as long as there's not a minty flavor or any real strong flavor. There's also adult formulated toothpaste like the Biotene toothpaste, some of the Tom's toothpaste that can so be tolerated well.

In some cases, some patients may note that the mouth seems tighter than normal. It may seem like they can't open it. And it's not because there's the sclerotic changes like we talked about, but simply those white changes actually make the tissue thicker than normal; and so it actually will restrict opening a little bit. And simply by treating the mouth, if we can treat it effectively, it can actually treat that very well. We can use gels and we can use solutions.

In most cases, especially for the cases I showed you, we would tend to use solutions just because they're easier to treat the mouth. You can put it all in your mouth, swish around everywhere. We generally recommend upwards of five minutes of swishing, because the contact time is really important.

Otherwise, it's just going on for a minute and then it gets washed away, and then whatever saliva the patient has basically washes everything else away. The solution that we typically start with, and I think is used most widely throughout this country, is called dexamethasone. Dexamethasone is not actually approved for topical use.

So, this is a steroid that's provided in a solution form, so that somebody who otherwise can't swallow pills, for example little children, can swallow this nicely flavored medicine. And we repurpose that as a topical agent. It works very well. It's widely available. So, basically, no matter where somebody lives, it's very easy to get from the pharmacy.

It works well for most patients, but not for all patients. So, sometimes we have to go to these other agents that I have in italics. I have them in italics because they require compounding. These are not commercially available. I can't just prescribe clobetasol as an oral solution for somebody. But, again, for any of you who are familiar with some of these names or have treated skin disease, we use generally the same medications for different areas.

For the skin, we have many formulations of clobetasol. For the mouth, all we have, for example a gel formulation. We can use to treat one area focally. Sometimes I'll use gauze to maybe treat an ulcer very specifically.

But, even that is usually in combination with doing a rinse as well. Some of you, again, may be familiar with this if you've treated the skin. And we use that to treat the lips very effectively. The lips are an area that we try to avoid using topical steroids extensively on, because it can cause irreversible thinning. And the lips are obviously an area that's very sensitive.

That can be a problem with the skin, fortunately it's not something we typically see in the mouth. So, we can actually treat the mouth as aggressively as we need to for extended periods of time.

On occasion, we'll actually have this compounded into a solution as well. And this is actually, this is what we see here. This is actually injecting an injectable steroid directly into the area where the inflammation is. So, basically the idea is I'm injecting just next to this ulcer, delivering the steroid right to the area. And I have many patients that just require this on an ongoing basis; but, manages the condition very well. Here's somebody before they've started doing rinses, after doing the rinses.

They had a sense of tightness, some discomfort. Now their symptoms are significantly improved. Similarly, you can imagine this lip would be very uncomfortable any time anything is touching it. And this is after a few weeks of treatment with a topical tacrolimus; and you can see how well it can respond. Use of a topical steroid increases the risk, because it locally suppresses the immune system in the mouth.

For patients who are also on systemic immunosuppressive therapy it's an additive effect, so they're already at risk to some extent. And then if the salivary glands aren't functioning completely normally, it's potentially another contributing factor.

So, this is a fairly common complication. But, one that we can actually treat very easily, in most cases actually prevent from developing once it's happened. The other potential risk factor is if somebody has a removable denture, that can also contribute to the risk of the infection coming back.

So, disinfecting the denture on a regular basis can be very important, making sure that it's out at night. Management is with antifungal therapy. We have topical and systemic agents. I tend to favor systemic agents. There's always some potential interactions depending on what systemic medication somebody is on. But, especially with fluconazole, which is the most commonly used systemic antifungal agent, that risk is relatively small and it's something that we can monitor.

For the prevention, in most cases I can have somebody on a once a week dose, sometimes twice a week. And that once or twice a week dose will not typically have a significant impact on interacting with other medications. But, it can be very effective in keeping the infection from coming back. And this is something that once I have a patient who has had thrush come back a couple of times, we'll pretty much go to a prophylaxis. So, herpes cold sores that I think most people are aware of.

The primary risk factor is immunosuppression. So, most patients, even fairly young patients, this is an infection that most people are exposed to in childhood, teenage, early adulthood. Once you're exposed, you have it forever. It can reactivate under certain conditions, usually stress, but in particular, suppression of the immune system. And important to remember: that for somebody who is taking their acyclovir regularly, which is supposed to suppress this, we can still, if there's enough suppression, otherwise get what is called a breakthrough infection.

So, you're taking the medicine but you still develop an infection. And so, we have to go up to a higher dose of medication or potentially change the medication.

And so, it's not always the easiest diagnosis to make, especially when somebody has generalized graft-versus-host disease changes. But, if somebody develops fairly acute onset really, really painful symptoms, especially just painful at rest, there's a little ulcer here, and an ulcer here, it probably looks very subtle to you. But it's very painful for this patient, and also this funny, irregular ulcer here on the inner aspect of the lip without any typical associated white changes like we talked about before.

So, the important thing to realize is that saliva isn't purely just water. I think we tend to think of that way. It feels like we have wetness in our mouth.

But saliva, and I'm not going to through this, you have this in your slides, it's somewhat of a technical table, but, it talks about all the various properties and the components of the saliva.

So, it provide lubrication, it has antimicrobial, and actually controls bacteria and fungus in the mouth. There's growth factors, various proteins in the saliva that we don't even really understand exactly what it does. It plays a role in maintaining mucosal integrity. Plays actually an important role in maintaining the health of the teeth.

Has buffering capacities, and actually remineralization. So that just like bone, the teeth are in this constant flux of being broken down and built back up. So in some cases, a patient may not even notice that the mouth feels dry. And yet over a period of time, we may actually start to see changes where we can see that there's cavities developing. Typical symptoms can be dry mouth, some discomfort, sometimes difficulty eating and swallowing just because saliva plays an important role in being able to chew up food and swallow food.

But, what I'll show you in the next slide—and what we're most concerned about—is the risk of caries, dental cavities developing. And they tend to follow a fairly distinct pattern. Areas where food and debris would tend to collect, like along the gum lines and in between the teeth.

And then again, this is an important factor for recurrent yeast infections in the mouth. But, you can see it has almost like a frosted appearance along the gum line. And this is what demineralization looks like. So, even though there aren't actual cavities formed at this point, the hard tissue is actually very undermined. And this is after just not a very long, unfortunately, period of time where we can see the progression of this to the actual cavity.

And with an instrument this would be very soft. And then this is, again, typical pattern. These are more advanced cavities at this point. But, this is very typical pattern of along the gum line, and with almost all teeth being affected. So, obviously we want to be able to intervene at a point before this. But even if it's at this point, it's still a time at which as long as the teeth are salvageable, we want to be aggressive and go in there and treat the teeth, and try and prevent any further advancement.

There are actually some medications that can help stimulate the saliva. But, making sure that there's just good hydration, things like sugar free chewing gum or candy, can help just keep the saliva flowing. Brushing and flossing, having a diet that doesn't promote dental caries is important; avoiding sugary foods, sticky foods. Use of fluoride, both sometimes being applied at the office, like something like fluoride varnish, but, also prescription fluoride at home.

We always struggle a little bit about how much to push this on all transplant survivors, because we know that not every patient is at the same level of risk.

And it's difficult to keep up with all of these preventive instructions that you're given. But, for somebody who has significant dry mouth symptoms, any evidence that there have been changes already with the teeth, we obviously really reinforce this.

Application of topical calcinerium inhibitors is an alternative to locally applied corticosteroids, because long-term use of topical steroids has been associated with atrophy of the lip vermilliomm, but not on oral mucosa.

Frequently it could result in side effect of oral candidiasis and other systemic effects from long- term use of topical potent steroid [15]. When symptomatic oral mucosal GVHD impairs nutrition or communication, viscous lidocaine may provide a topical analgesia and some relief [15,16]. For dry mouth patient can be instructed for frequent water drinking, to use gustatory and mechanical saliva stimulants sugar free chewing gums and candies , to avoid xerogenic medications and to use oral moisturizing agents and saliva substitutes, and also parasympathetic agents e.

Routine dental care, including Professional cleanings, fluoride applications, infections prophylaxis and monitoring for the development of osteonecrosis of the jaw in long-term bisphosphonates users are very important to improve the quality-of-life [15]. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Trends in Transplant 1 DOI: Home Contact Us. About us About Us Providing cutting-edge scholarly communications to worldwide, enabling them to utilize available resources effectively Read More. Open Access News and events Contact Us. For Authors We aim to bring about a change in modern scholarly communications through the effective use of editorial and publishing polices. Read More. Special Issues Frequently Asked Questions. Links Advanced knowledge sharing through global community… Read More.

Take a look at the Recent articles. Oral chronic graft-versus-host disease: A short review Ricardo Hsieh. Key words graft-versus-host disease, oral mucosa, salivary gland Introduction The first Allogeneic Hematopoietic Stem Cell Transplantation allo-HSCT was performed in to treat end-stage leukemia [1], and it has seen a steady increase in the overall success and applicability to treat a wide range of malignancies, including: neoplastic and non-neoplastic hematologic disease and immune deficiency states, and autoimmune disease [].

Chronic GVHD cGVHD Chronic Graft-versus-host disease cGVHD is a major late complication of allo-HSCT, representing a clinical syndrome characterized by complex allogeneic and autoimmune dysregulation of the immune system, leading cause of non-relapse-related morbility and mortality among long-term transplant survivors [11,12]. Oral GVHD clinical features The spectrum of clinical manifestation of oral cGVHD is variable including white papules, plaques, lichenoid hyperkeratosis, erythema, mucoceles, mucosal atrophy, edema, fibrosis, pseudomembrane, ulcerations, bleeding and xerostomia.

Oral GVHD histopathological features Generally, the typical histologic findings are subepithelial lymphocytic infiltration with epithelial changes in the oral mucosa and diffuse lymphocytic infiltration in the salivary glands [10]. Treatment Usually, ancillary therapy is used for symptomatic oral mucosal or erythematous or ulcerative disease in GVHD treatment by using routine systemic drugs, several topical treatments as corticosteroids prednisone, dexamethasone, betamethasone , immunosuppressants ciclosporine, azathioprine, tacrolimus, sirolimus and phototherapy.

All rights reserv For dry mouth patient can be instructed for frequent water drinking, to use gustatory and mechanical saliva stimulants sugar free chewing gums and candies , to avoid xerogenic medications and to use oral moisturizing agents and saliva substitutes, and also parasympathetic agents e.

Conclusion cGVHD is a late complication among patients those undergo allo-HSCT, and it can damage directly to oral mucosa integrity and salivary glands function, interfering their speaking, eating and drinking.

Oral Dis Oral Oncol Dent Clin North Am Despite there being a number of commercially available adjunctive agents intended to improve oral cancer screening eg, toluidine blue vital staining, tissue autofluorescence , none of these has proven benefit over careful examination under adequate white light. Minimal data exist on treatment outcomes, but it appears that these secondary oral cancers may be associated with higher rates of recurrence and poorer long-term survival compared with de novo squamous cell carcinoma of the oral cancer in non-HCT patients.

Although not inherently life-threatening, it is associated with significant morbidity because of pain and dysfunction, restricted oral intake, and secondary complications. Given the absence of oral medicine specialists at many transplant centers and the unfamiliarity with transplantation-associated complications in the community, oral cGVHD is probably underdiagnosed and suboptimally managed.

With a systematic rational approach to the diagnosis and management of oral cGVHD outlined in this manuscript, symptoms can often be well controlled and complications minimized.

In more complicated and refractory cases, however, patients can benefit greatly from referral to an oral medicine specialist. Greater efforts in both educational outreach and clinical research will lead to improved management and better long-term outcomes.

Sign In or Create an Account. Sign In. Skip Nav Destination Content Menu. Close Abstract. Epidemiology of oral cGVHD. Clinical features of oral cGVHD. Mucosal disease. Salivary gland disease. Sclerotic disease. Other associated conditions. Diagnosis of oral cGVHD. Management of oral cGVHD. Oral mucosal cGVHD. Management of candidiasis. Salivary gland cGVHD.

Sclerodermatous oral cGVHD. Long-term complications and surveillance. Dental caries. Squamous cell carcinoma. Article Navigation. How we treat oral chronic graft-versus-host disease Nathaniel Treister , Nathaniel Treister.

This Site. Google Scholar. Christine Duncan , Christine Duncan. Corey Cutler , Corey Cutler. Leslie Lehmann Leslie Lehmann. Blood 17 : — Article history Submitted:. Cite Icon Cite. Figure 1. View large Download PPT. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. Figure 8. Figure 9. Multiple superficial mucoceles of the palate. Figure Sclerotic cGVHD. View Large. No symptoms Mild symptoms with disease signs, but not limiting oral intake significantly Moderate symptoms with disease signs, with partial limitation of oral intake Severe symptoms with disease signs, with major limitation of oral intake.

If after wks still inadequate control, add tacrolimus and use equal parts with clobetasol as a single combined rinse Secondary candidiasis, typically occurs in first week, in addition to treatment most will require prophylaxis. Table 4 Guidelines for screening, prevention, and management of late complications in patients with oral cGVHD. Late complication. Contribution: N. Conflict-of-interest disclosure: The authors declare no competing financial interests.

Search ADS. Quality of life associated with acute and chronic graft-versus-host disease. Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial.

Global and organ-specific chronic graft-versus-host disease severity according to the NIH Consensus Criteria. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Pilocarpine hydrochloride for symptomatic relief of xerostomia due to chronic graft-versus-host disease or total-body irradiation after bone-marrow transplantation for hematologic malignancies.

Salivary gland involvement in chronic graft-versus-host disease: prevalence, clinical significance, and recommendations for evaluation. Subjective reports of xerostomia and objective measures of salivary gland performance.

Development of a Visual Analogue Scale questionnaire for subjective assessment of salivary dysfunction. Using the modified Schirmer test to measure mouth dryness: a preliminary study. Superficial mucoceles in chronic graft-versus-host disease: a case report and review of the literature.

How do we manage oral infections in allogeneic stem cell transplantation and other severely immunocompromised patients? Oral ulcers in kidney transplant recipients treated with sirolimus and mycophenolate mofetil. Calcineurin inhibitor-associated oral inflammatory polyps after transplantation. Oral verruciform xanthoma associated with chronic graft-versus-host disease: a report of five cases and a review of the literature. New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia.

Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Oral epithelial dysplasia and squamous cell carcinoma following allogeneic hematopoietic stem cell transplantation: clinical presentation and treatment outcomes.

National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Pathology Working Group Report. Therapy for chronic graft-versus-host disease: a randomized trial comparing cyclosporine plus prednisone versus prednisone alone.

Vesiculo-erosive oral mucosal disease: management with topical corticosteroids: 1. Fundamental principles and specific agents available. Local drug delivery for oral mucosal diseases: challenges and opportunities. Topical cyclosporin A for treatment of oral chronic graft-versus-host disease. Topical azathioprine in the combined treatment of chronic oral graft-versus-host disease.

Budesonide: a novel treatment for oral chronic graft versus host disease. Chronic graft versus host disease of oral mucosa: review of available therapies. The effect of budesonide mouthwash on oral chronic graft versus host disease. Improvement in oral chronic graft-versus-host disease with the administration of effervescent tablets of topical budesonide: an open, randomized, multicenter study. Treatment of severe chronic oral erosive lesions with clobetasol propionate in aqueous solution.

Successful treatment of oral lichen planus-like chronic graft-versus-host disease with topical tacrolimus: a case report. Severe oral chronic graft-versus-host disease following allogeneic bone marrow transplantation: highly effective treatment with topical tacrolimus.

Oral graft vs.