Jason M. Tanzer, DMD, PhD
Among the most prominent and troublesome features of Sjögren’s syndrome is xerostomia, a sense of dry mouth. While sensing dryness, patients seem as much to sense lack of lubrication in the mouth, as though the mucous membranes of the lips, cheeks and tongue fail to smoothly slide over the surfaces of the palate and teeth. Some patients tolerate this discomfort and both they and their health care providers often dismiss it as “growing older”. In the early stages of Sjögren’s syndrome it can be difficult to actually measure, under ordinary clinical conditions, a decrease of saliva flow for individual patients. Only later in the course of Sjögren’s does it become relatively easy for the clinician to document the dryness, by the dental mirror sticking to the cheeks or by making actual measurements of the rate of saliva flow upon standardized stimulation of secretion. The problem is further confused by the typically oscillating character of Sjögren’s, with periods of improvement and of worsening. When the patient is persistently and measurably dry, therefore, it is clear that Sjögren’s is relatively advanced and that a lot of salivary gland functional deficit (manifested as decreased flow rate of saliva) has already occurred.
Commonly, it is not until this state that the patient first presents to the dental health care provider and a tentative differential diagnosis–a list of possible explanations of a troublesome dry mouth symptom–is formulated. (If the patient had a predominance of eye complaints or joint complaints, they might have gone first to their ophthalmologist, rheumatologist, or primary care physician to seek diagnosis and help.)
Mouth complaints are usually voiced to the dentist, in the following way: “My mouth is dry; it hurts, sometimes it burns; I can’t speak; I can’t chew; I can’t swallow my food without drinking at the same time; the corners of my mouth are red and sore; and my teeth are rotting (breaking, cracking, or decaying, or my fillings are falling out).” If the patient has already lost many teeth, the complaint often is that “I can’t tolerate my dentures.”
These complaints reflect at least two kinds of interrelated problems: 1) lack of flow and lubrication by saliva, with apparent loss of body defense molecules and buffers contained in saliva, and loss of the flushing of food and bacteria from the mouth; 2) infections (colonization) of the mucous membranes of the mouth by yeast and of the tooth surfaces by bacteria which become strongly decay-causing when the mouth is dry.
This article is addressed to the issue of the discomfort of the mouth and yeast infections, their diagnosis and management. It centers on the topic of oral mucositis, inflammation of the mucous membranes of the mouth.
It is not totally clear why patients with dry mouths develop oral mucositis and variable sensations of soreness. There is, however, no evidence that different microorganisms live on the mucous membranes or teeth of Sjögren’s patients than in non-Sjögren’s patients. Some subtle ecological shifts may occur, however, because of the compromise of the host (patient) in the form of decreased amount of saliva flow, and decreased delivery of anti-yeast molecules to the oral environment. Indeed, it appears that yeast (usually an organism called Candida albicans) may increase in the mouth in this opportune time.
Fundamental to the management of dry mouth and its associated discomfort is frequent sips or sprays of water, or use of diet soda or other sugar-free drinks, to keep the mucosa hydrated. Fruit juices contain sugars and are a real risk for tooth decay complications, as is sugar-containing soda. Use of alcohol or mouth rinses containing alcohol is contraindicated because alcohol dries and damages the mucous membranes.
In some diseases Candida infections of the mouth present as a thick white membrane-
Unfortunately, these signs can be confusing and cannot, by themselves, be taken as diagnostic of Sjögren’s syndrome. A large variety of medications also induce dryness and, depending on the constancy of that dryness, mucosal changes. Some other diseases can affect the salivary glands. Also, changes of the mucosal surface, of the tongue especially, can result from other phenomena, some of which are essentially normal. A high percentage of normal people have what has been called a geographic tongue. Clearly, the oral mucosa needs to be looked at by trained eyes, and the best ones to critically look, undoubtedly, are those of the dentist, who looks and works in mouths every day.
Virtually all humans have some Candida in the mouth; they are normal inhabitants. They are found in higher numbers between upper removable dentures and the palate, especially when the denture is worn at night and when it is not carefully cleaned or disinfected. But Candida numbers appear to increase in Sjögren’s and the host’s tissues seem intolerant to them. In addition, the corners of the lips, and sometimes the entire surface of the lips become colonized by them and become inflamed, conditions called angular cheilitis (or perleche) and cheilitis, respectively. Scraping or scrubbing of the mucosal surfaces that evidence erythema with atrophy and examination of the scrapings microscopically or after culture on special diagnostic media reveals the presence of Candida. This, coupled with the complaint of soreness or burning of the mouth operationally give the diagnosis of Candida mucositis and justify anti-Candida treatment. A positive laboratory report for yeast alone, without evidence of chronic erythematous/atrophic mucositis, does not justify the diagnosis of Candida mucositis and treatment with an anti-yeast antibiotic.
Before discussing antibiotic treatment, it needs to be stated that a significant number of people who do not have Sjögren’s syndrome have a phenomenon called burning mouth syndrome, also referred to by a lot of other names. Some of these patients have oral yeast infections; but most have neither erythematous/atrophic mucosal changes nor do they appear to have a mucosal yeast infection. Importantly, it is the minority of burning mouth syndrome patients who also have Sjögren’s.
It also needs to be recognized that a variety of medications and conditions foster yeast infections of mucous membranes, with or without concurrent Sjögren’s syndrome. For example, prolonged use of an antibiotic for a bacterial infection, especially one like tetracycline which inhibits the growth of a wide spectrum of bacteria but which does not inhibit growth of yeast, reduces the natural competition between yeast and bacteria in the mouth. Consequently, yeast on the mouth, throat, or genital mucous membranes have a special opportunity to flourish and “opportunistic” yeast infections are commonplace during antibiotic treatment. They almost always subside when the antibiotic is discontinued. The other common conditions in which yeast flourish on mucous membranes involve compromise of the immune (body defense) systems of the host–for example, as seen in poorly-controlled diabetes, in use of prednisone or other steroids, in use of medications used to control severe immunologic states such as graft rejection, and in AIDS. (People with yeast infections of mucous membranes who have Sjögren’s shouldn’t conclude that they have AIDS!)
There are some reasonable guidelines which can be suggested for the use of anti-yeast antibiotics in Sjögren’s. Nonetheless, patients shouldn’t be making diagnostic and treatment decisions themselves, for several reasons, but especially because the guidelines described below are not appropriate for those situations in which yeast infections occur in the bloodstream, which are life-threatening situations requiring different anti-yeast medications. A health care professional should be consulted to determine the necessary treatment.
The most established and probably the least expensive of the anti-yeast medications appropriate for the treatment of oral Candida mucositis are nystatin and clotrimazole. There are potential pitfalls in their use, but some sense can be made of the way they seem best prescribed.
First, both nystatin and clotrimazole are remarkably safe, with almost no adverse drug interactions. One needs to be assured of normal liver function before taking clotrimazole. Both drugs need to be used for a long period of time in order to have reasonable certainty of suppression of the yeast infection. Because the underlying problem of oral dryness and associated compromise of the host does not change as a result of using anti-yeast medication, the patient is likely to relapse, to have another oral yeast infection in the future. However, often patients unwisely stop using medications as soon as they begin to feel better. This frequently leads to early relapse. On/off self-medication is unwise and counterproductive.
A goal in the delivery of anti-yeast medications is to keep the drug at the affected site, in this case the mouth’s mucosal surfaces, for a long time with each dose. A swishand-swallow anti-yeast mouth rinse makes limited sense. Similarly, the use of special anti-yeast medications that get into the bloodstream and are relatively toxic also makes little sense, except in cases of life-threatening yeast infection of the blood. Even if anti-yeast medications were secreted into saliva from the bloodstream, they wouldn’t likely work in Sjögren’s patients whose salivary glands are not working properly. Therefore, there is little doubt that topical treatment using a suckable dose delivery form is likely to be the best.
Neither nystatin nor clotrimazole taste good. This leads to a significant problem for patients who have teeth. Manufacturers want to mask the flavor of these drugs. They do it with sucrose or glucose, common, inexpensive, and generally safe sugars. However, both of them promote tooth decay, the other big oral problem for Sjögren’s patients. For example, nystatin syrup is a 50% solution of sucrose containing nystatin. Furthermore, using a syrup hastens the swallowing of the medication. This puts it where it usually isn’t needed, in the stomach. Nystatin pastilles are sucrose hard candies containing nystatin. Clotrimazole is compounded into a suckable troche with glucose. (There would be tremendous virtue in having pleasant tasting sugar-free anti-yeast troches for Sjögren’s sufferers.) As an alternative approach, the patient could be sucking on Nystatin Vaginal, a form of nystatin made without sugar, and originally made for the control of vaginal candidiasis. It doesn’t taste great, but I have only once had a patient who refused to use it. Patients don’t complain of the nystatin taste very much and there is no reason to have philosophical problems with oral use of something called Nystatin Vaginal.
However, to use either of the now readily available, suckable sugar-containing products without the simultaneous use of intensive topical fluoride gel therapy to inhibit tooth decay is to invite worsening of what may already be a bad tooth decay problem in the setting of the chronic oral candidiasis of Sjögren’s patients. The patient needs a dentist to integrate the prescription fluoride gel and to manage the diet so as to minimize the risk for tooth decay, as well as to establish the diagnosis of oral Candida mucositis and the management of anti-yeast therapy.
Of course, if the patient no longer has her/his own natural teeth, this concern about sucking on hard candy is irrelevant. It should be remembered that Sjögren’s patients have compromised salivary flow. As such, anything they put in their mouths remains there for a long time because it can’t be washed away rapidly by saliva. This is good with respect to delivering an anti-yeast medication where the goal is to keep the medication in contact with the oral mucosa for a long time, but it is bad when the thing put in the mouth is sugar which is fermentable to acid by the oral bacteria that live on the teeth. This is why using candy or other sweets by a Sjögren’s patient and the resultant aggressive tooth decay often become the biggest oral problems in Sjögren’s.
It is the nature of yeast infections that they are not quickly suppressed. In one good study, to achieve reliable suppression of oral yeasts nystatin needed to be used twice daily for 60 days in the form of a lozenge. Typically, clotrimazole is used for 14 days, 5 times a day. In the case of Sjögren’s patients, the dwell time can be especially long, a virtue, because not much saliva may be available to dissolve the troche. If it doesn’t dissolve at all, however, it can’t work, and occasional tiny sips of water may be needed.
If the troches are chewed on, their benefit is diminished because the medicine is cleared from the mouth too fast. Should the patient wear a removable denture, it needs to be removed during the time when the troche is being sucked to allow the anti-yeast antibiotic access to all of the Candida-infected sites in the mouth. But the denture itself also has to be disinfected, otherwise it will just recontaminate the mucous membranes that the patient has been trying to treat. There are two good ways to do this. The first step in both is to soak the denture in ordinary denture cleaner that can be bought in any drugstore or supermarket and to clean it carefully and completely with a soft toothbrush. (If tartar has accumulated on the denture, help from the dentist will be required to remove it.) Then, after thoroughly rinsing away the denture cleaner, the denture has to be soaked in disinfectant which kills yeast. A good one is Zephiran chloride, diluted 1 part to 750 parts with water, soaked for at least 1 hr. This has to be gotten from a drugstore. An alternative in those cases where there are no metal parts to the removable denture is diluted bleach, diluted 1 part per 100 parts of water, about 1 teaspoonful per cup of water. The denture should not be soaked for more than 1 hr. (Longer soaking in bleach or use of higher concentrations of bleach could change the color of the denture. Use of bleach on the metal parts of a denture may corrode them.) After disinfection, the dentures have to be thoroughly rinsed in water before putting them back into the mouth. Dentures should not be worn at night. They should be soaked during that time in ordinary supermarket-available denture cleaner.
Angular cheilitis represents an infection by bacteria and yeast of the tissue folds at the corners of the mouth. It is worse in patients who have lost their natural teeth and either have no dentures or whose dentures do not hold the mouth open sufficiently. As a result, the creases where the upper and lower lips meet are exaggerated, and the area is maintained moist from the mouth (even in Sjögren’s patients) and from the lip itself when a break in the mucous membrane or skin occurs there. Some topical ointments, such as Mycology II, can help suppress this problem. These contain nystatin and a low dose of a steroid which reduces the local inflammation. While an anti-yeast ointment would seem adequate, the inclusion of the steroid seems to be helpful. The ointment is applied after meals.
Treatment of Candida-associated angular cheilitis will usually be unsuccessful in the long run unless the oral Candida mucositis is also suppressed and dentures are disinfected, otherwise the mouth contents simply reinfect the lips. Dry, cracking lips need to be cared for with ordinary lip balms or vaseline. If they are colonized by yeast, they first need to be treated with an anticandidal. Long-term successful management of the problem also requires that the patient’s occlusion (“bite”) be maintained either by adequate repair of existing teeth or by making adequate dentures.
Over the years I have seen a number of situations in which patients with the problem of a dry, sore/burning mouth have made bad choices for themselves, or their physicians or dentists have made bad choices, and have faced treatment dilemmas. Among them–advice to suck on hard candies; placement of topical or ingested tetracycline; use, in certain ways, of some medications that make the mouth drier. Often, patients must use a variety of other medications for problems other than Sjögren’s. A few examples follow which should help the reader focus on this issue.
Benadryl (diphenhydramine) is an antihistamine, commonly used for hay fever. It is also a mild topical anesthetic, and when used in a mouth rinse, it is effective in transiently palliating sore or burning mouth symptoms. For this purpose it is usually formulated in a 1 to 1 mixture with either kaopectate or Maalox. It is intended to be spit out. The kaopectate coats the oral mucosa, so it also tends to be soothing and keeps Benadryl around in the mouth for awhile. However, it makes no sense for a sore mouth Sjögren's patient to be swallowing Benadryl, because it is an antihistamine. Like other antihistamines, when absorbed into the bloodstream from the gastrointestinal tract, it powerfully inhibits salivary secretion. Ask any hay fever sufferer who uses antihistamines whether they get a dry mouth. The thing that a Sjögren’s patient surely doesn't need is more oral dryness.
Unfortunately, many important medications have the undesired side effect of reducing the flow of saliva. For the Sjögren's patient, they further dry the mouth. Some are used for regulating high blood pressure, controlling chronic diarrhea, helping with emotional problems, or controlling allergies to dust and pollen. There literally are over one hundred medications that can cause dryness. It is very important that patients inform their dentists of the use of all medications so that, where possible, ones that have diminished salivation-inhibiting properties can be tried. Obviously, this will require close consultation between the dentist, internist, psychiatrist or other relevant health care provider. However, patients should not on their own stop taking medications which are prescribed for them when they learn that they have Sjögren's. Similarly, they should inform all of their health care providers that they have Sjögren's syndrome.
Fluocinolone and triamcinolone are steroids which can be very useful as topical rinses, ointments, and creams. They can alleviate a lot of discomfort. But they carry some risks. Long-term use on surfaces, for example, make those surface membranes, either skin or mucosa, atrophic, i.e., less structured, more fragile, and less resistant to infection. Indeed, one of the several risks of long-term use of steroids is increased risk of various infections, including yeast infections.
One musn’t be too dogmatic. For example, infection and inflammation of the eyelids is rather common among Sjögren's patients. It is often effectively treated by ophthalmologists with systemic (taken internally) tetracycline. But this treatment fosters Candida mucositis. It is, therefore, important for the dentist and the ophthalmologist to be in communication, to be monitoring the mouth and eye problems, and to adjust treatment in accordance with the status of oral Candida mucositis and/or eyelid bacterial infection. Therapy can be adjusted and it may be necessary to simultaneously use both tetracycline and an anti-yeast topical in the mouth.
It is clear that patients with sore or burning mouths are intolerant to acidic foods (fruit juice, tomatoes, salad dressings) and to alcohol. They have to adjust their diets. While it is theoretically a good strategy to put patients onto chlorhexidine mouthrinse (a good and safe antiseptic) to control oral yeast infections and to suppress dental plaque, the only chlorhexidine rinse available in the U.S. (Peridex) contains alcohol. It is the rare Sjögren’s patient who can tolerate it. Additionally, almost all of the fluoride mouth rinses which can be purchased without a prescription in the supermarket or drugstore contain substantial amounts of alcohol and will increase mouth discomfort. It is better to use an alcohol-free fluoride gel which is a more potent tooth decay inhibitor than fluoride-containing (or fluoride-free) mouth rinses.
In summary, the sore mouth of Sjögren's, if established to be associated with yeast infection, probably will resolve with adequate anti-yeast treatment. It can be suppressed and palliated (made less troublesome, if not cured) with topical agents. The patient must be aware of the risk of tooth decay, potentially an even more frustrating and surely a more expensive problem. The management of the sore mouth (or tooth decay) problems must not be seen in isolation but must be an aspect of the comprehensive care of the Sjögren's syndrome patient.
Jason M. Tanzer, DMD, PhD is Professor and Head, Division of Oral Medicine, Department of Oral Diagnosis, School of Dental Medicine; Professor, Division of Clinical Microbiology, Department of Laboratory Medicine, School of Medicine, University of Connecticut Health Center, Farmington, CT. This article was published in the July/August 1994 issue of The Moisture Seekers â Newsletter.
Bennett JE. Fungal infections, Chap 151, . In: Harrison's Principles of Internal Medicine, Volume 1, Wilson JD et al, editors, McGraw-Hill, p743, 1991.
Budtz-Jargensen E, Stenderup A, and Grabowski M. An epidemiologic study of yeasts in elderly denture wearers. Comm Dent Oral Epidemiol 3:115, 1975.
Daniels TE. Oral manifestations of Sjögren's syndrome. In: Sjögren's syndrome. Clinical and immunological aspects. Talal N, Moutsopoulos HM, and Kassan SS, editors. Springer-Verlag, Berlin p 15, 1987.
Fox PC, vender Ven PF, Sonies BC, Weiffenbach DM, and Baum B. Xerostomia: Evaluation of a symptom with increasing significance. JADA 110:519, 1985.
Grushka M and Sessle BJ. Buming mouth syndrome. Dental Clin N Amer. 35(1):171, 1991.
Hemandez YL and Daniels TE. Oral candidiasis in Sjögren's syndrome: Prevalence, clinical correlations, and treatment. Oral Surg Oral Med Oral Path 68:324, 1989.
Xu T, Levitz SM, Diamond RD, and Oppenheim FG. Anticandidal activity of major human salivary histatins. Infect Immun 59:2549, 1991.
Table 1. Prevalence of Signs and Symptoms in Sjögren’s Syndrome
|Sign or symptom||% of patients|
|Nocturnal fluid ingestion||45|
|Tongue and mouth burning||26|
|Difficulty eating dry foods||17|
From Vivino, FB, Huan CH: Arthritis Rheum 1993.2
Based on a total of 58 patients.
Table 2. Subjective Oral Dryness Symptoms
|Symptom||Percent of Patients|
|Difficulties eating dry foods||52|
|Dryness of the tongue||52|
|Sensitivity to acids||52|
|Sensitivity to spicy foods (hot)||48|
|Pain/swelling of salivary glands||38|
|Altered bitter taste||24|
|Taking drug associated with infection†||19|
†Glucocorticosteroid and immunosuppressant.
Data were collected with a questionnaire completed by the patient.
Adapted from the Journal of Rheumatology 1998; 25:5