Burning Mouth Syndrome

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BURNING MOUTH SYNDROME

Philip-John Lamey, BSc, BDS, MBChB

When researching orofacial diseases in a scientific manner, it is fundamentally important that there is agreement on what con- stitutes the condition and what features are necessary for diagnosis. In the case of the condition that we shall call burning mouth syndrome (BMS), the oral mucosa appears clinically normal. Patients, however, say that the areas affected feel burning or hot or occasionally scalded.

Historically this condition was described as

pyrosis,2O, 34, 91 stomatodynia,122 stomato- p y r o s i ~ , ~ ~ ~ sore tongue,52* 58, 131 burning

38, 47, I3O, 174 oral dysesthesia,66, 140

burning mouth condition,” and burning mouth syndrome.60, 95, 136 It is not always clear from these descriptions, however, if the oral mucosa appeared normal in all cases, and therefore articles reporting burning mouth are not referring necessarily to burning mouth syndrome (BMS). When terms other than BMS are used they often include patients who have an obvious clinical abnormality such as geographic erosive lichen p l a n ~ s , ~ ~ or oral candidosi~.~~ In the latter conditions, patients also may complain of a burning sensation but clearly do not have BMS. The history of burning reported by patients with these conditions is different and usually only occurs on eating hot or spicy foods.66 Furthermore, the histopathologic features of these conditions are characteristic, whereas in BMS there are no specific histologic fea-

glossodynia,1-7, 21, 31. 55. 83. 110. 117, 174 glossa-

t u r e ~ . ’ ~ ~ Occasionally such conditions are present coincidentally in patients with BMS, but the diagnosis of BMS should be confined to patients with an apparently normal oral mucosa.

Some discussion has taken place about the nomenclature of BMS and in particular the inclusion of the word syndrome.” By defini- tion, a syndrome is a collection of signs and symptoms, which in BMS is a normal-looking mucosa and a burning sensation. We increas- ingly recognize that BMS also can be associated with burning at other bodily sites and therefore may be as much a systemic condition as a localized oral disorder. Personally, I favor the retention of syndrome.

SITES AFFECTED

The tongue is the most common site to be reported by patients with BMS followed by the upper alveolar region, palate, lips, and lower alveolar region.89 The burning is almost always bilateral and symmetrical. Rarely, other sites such as the buccal mucosa, floor of the mouth, and throat may be affected.

The precise site of burning is important and may help identify precipitating factors. For example, burning at the tip of the tongue in a dentate subject may suggest a tongue thrusting habit. The same complaint in a complete denture wearer may suggest faulty denture design, leading to tongue restriction.

From the Department of Oral Medicine, School of Clinical Dentistry, The Queen’s University of Belfast, Belfast, Northern Ireland

DERMATOLOGIC CLINICS

VOLUME 14 * NUMBER 2 * APRIL 1996 339

340 LAMEY

Burning on the dorsum of the tongue in a denture wearer may suggest a tongue postur- ing habit possibly to help stabilize a nonreten- tive denture. Even if sites such as the lips alone are involved in BMS, the same precipitating factors pertain when more typical in- traoral sites are affected.88

If patients are asked about burning at other body sites they frequently also report burning in the anogenital region.50 Male clinicians are less likely to elucidate this information than their female counterparts. The significance of burning at these other sites is presently unclear, but BMS may be a systemic syndrome.

EPIDEMIOLOGY

There are no global figures available for the prevalence of BMS. In selected populations in the United States attempts recently have been made to estimate the prevalence and distribution of a variety of orofacial pain disorders including BMS.'O'

In Finland, one study of 431 predominantly female subjects reported that 15% had experienced a prolonged oral burning sensation.60 These patients also underwent a thorough clinical examination and about half of the 15% who complained of burning had some demonstrable mucosal abnormality such as geographic tongue, lichen planus, or oral candidosis. It would appear therefore that in a Finnish adult population the prevalence of BMS is around 7%. Women were more frequently affected by BMS than men.

Another study investigated 145 oophorectomized women by means of a postal ques- t i~nnai re .~~ No individual was examined clinically but approximately 18% reported a burning sensation affecting the tongue or lips. It was not possible to determine the true prevalence of BMS, but the survey did show no temporal reduction in the frequency of oral symptoms after oophorectomy. The in- troduction of estrogen therapy did not im- prove the patients' oral symptoms, including burning, leading the authors to conclude that estrogen deficiency following the climacteric produced vasomotor changes that may lead to neurosis.

GENDER EFFECTS

All published studies of patients with BMS agree that the condition is more common in

women than men. The female to male ratio is about 7:1, but this varies with site.89 Burning of the lips alone is even more common in women, with a female to male ratio of 12:1.88

The reason for this sex prediliction has not been explained fully, but several other orofa- cia1 pain syndromes such as atypical facial pain and temporomandibular disorders are also more common in women. The exception to this is periodic migrainous neuralgia, which is more common in men.87

There is broad agreement in the literature that BMS is a condition particularly affecting the middle-aged and elderly p~pu la t ion .~~ The youngest patient in one study was 28 years old. The condition has never been reported in children, which is odd because several of the recognized precipitating factors in BMS also can affect children.6

The mean age of BMS patients is approximately 62 years, and several studies have reported roughly the same figure. Because women of this age would be postmenopausal, early reports highlighted the significance of the climacteric in the etiology of BMS.'jO As is discussed further, however, such hormonal changes are probably of no significance.

SUBTYPES

Several years ago, my colleagues and I proposed a classification of BMS into three sub- t y p e ~ ~ ~ ~ (Table 1). Originally we observed that some patients had burning only occasionally,

Table 1. SUBTYPES OF BURNING MOUTH SYNDROME

Relative Frequency

Type ("/) Symptoms

1 35 Burning present every day, not present on waking but developing as the day goes on, being maximal in the evening

2 55 Burning present all day, every day

3 10 Burning only on some days and tending to affect unusual sites such as buccal mucosa, floor of mouth, and throat

BURNING MOUTH SYNDROME 341

others had it every day, but only as the day went on, and still others had burning all day, every day. We presumed, incorrectly as it transpired, that their different history repre- sented an evolving process, but we subsequently realized this is not the case.89

Type 1 Burning Mouth Syndrome

In this subtype patients have burning every day. The burning, however, is not present on waking, but comes on as the day goes on, being maximal in the evening. Around 35% of BMS patients give this history.


In this subtype patients have burning every day, which is present all day from waking. Approximately 55% of BMS patients give this history.


In this subtype burning is only present on some days, and on others patients are asymptomatic. In contrast to type 1 and type 2 patients, the burning tends to affect unusual sites such as floor of mouth, buccal mucosa, and throat. Around 10% of BMS patients give this history, which previously was reported as atypical burning mouth

Recent demographic data comparing UK and US BMS populations have given almost identical prevalence rates for the subtypes in these two populations.81

The subtypes have merit because they are of prognostic significance and also indicate the necessity for specialist investigations such as patch testing to identify allergic compo- nents to the burning. A recent study of type 3 BMS patients showed that their main precipitating factors were emotional instability and allergic factors.97 It is, however, inappro- priate to patch test all BMS patients. Simi- larly, in evaluation of treatment outcomes, type 2 patients are the most difficult to treat successfully because a high proportion have chronic anxiety, which is the most recalcitrant obstacle to cure.86

It has taken many years to establish BMS as a distinct clinical entity and having done so we are now recognizing that it is not a homoge-

neous condition. If subtyping helps us manage our patients better, then it is useful.

PATIENT EVALUATION

For many BMS patients an oral medicine specialist is not their first port of call. Many have been to their doctor, dentist, general physician, general surgeon, and specialists such as otorhinolaryngologists, to no avail. Of the 700 or so BMS patients who have consulted me, not one has ever heard of any other person with the same complaint. This circuit of referral and feeling that they are the only person in the world with the complaint leads to increasing isolation and in some cases feelings of hopelessness. The complaint itself, that is, ”my tongue is burning or feels on fire,” also sounds (even to the patient) odd, and they don’t want to be labeled as having a psychiatric problem. When numerous generalists and specialists have pro- nounced that their tongue looks normal, this adds to the feeling that they must be imagin- ing it, which of course they are not. In addi- tion, fear that the burning will develop into cancer heightens their concern to seek treatment.

It is clear that BMS patients must be treated in a sympathetic manner. An unhurried clinical environment is helpful, and privacy is essential. All our BMS clinics are run jointly by an oral medicine specialist, a prosthodon- tic specialist, and a clinical psychologist. One of the clinicians is a woman. Having more than one specialist is helpful because, as with all pain clinics, some patients do not take to one clinician, and trust is never established. By having three specialists, including one of their own sex, the patient is likely to trust one of us and feel at ease to discuss causes of stress, tension, or marital disharmony.

Having reassured the patient that he or she is one of many sufferers, it is important to go into the history in detail and subtype the BMS. All patients are asked to quantify the burning using a 0 to 10 visual analog scale in which 0 is no burning and 10 is the worst burning imaginable. Typical pretreatment values are shown in Figure 1. This quantifi- cation also allows the response to treatment to be measured prospectively. Because social circumstances also can influence pain perception, all patients are asked to quantify what we call their home circumstances, that is, how they get along with their family and friends

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40 -

30 - &

= 2 0 -

n 5

10 -

0 -

50 1

Score Known

Figure 1. Reported severity of BMS patients pretreatment.

and their job and financial considerations. A linear analog scale also is used, but in this scale, 10 means everything is perfect and 0 means that things could not be worse. When the patient chooses a score of 6, for instance, he or she is then asked what would have to happen to take their 6 score to 10. I have never had a patient refuse to do this and the results are illuminating, for it identifies exact problems. A typical social circumstances profile is shown in Figure 2. The clinician has not been seen to pry or ask lengthy irrelevant questions about possible stress, but the patient has chosen the score, and the patient has been asked to justify the score including identification of social problems if any.

The general medical and dental history also is assessed, and at the end of the first interview the clinician has a good grasp of the problem, its duration, its subtype, and its severity, and a knowledge of the social circumstances.

Subsequently, many investigations are undertaken, all based on our knowledge of precipitating factors in BMS from the literature.

The plethora of recent reviews on BMS in several languages has not added anything to our knowledge.* It is the relative importance of each individual precipitating factor that is

*References 1, 7, 15, 25, 48, 49, 61, 100, 108, 116, 132, 139, 148.

0 1 2 3 4 5 6 7 8 9 10 Visual Analog Score

Figure 2. Reported home and social circumstances scores by BMS patients at initial presentation.


important. To date, this has been the case in only one prospective

PRECIPITATING FACTORS

The following factors listed are thought to be important in precipitating BMS. They are not presented in any particular order.

Hematinic deficiency states Undiagnosed maturity onset diabetes mel-

Oral candidal infection A degree of xerostomia Denture design faults Parafunctional habits Fear of cancer Allergy to a variety of substances and ma-

Psychological states, particularly chronic

Drug-induced disease

litus

terials

anxiety

Hematinic Deficiency States

It has been known for many years that deficiency states such as sideropenia, iron deficiency anemia, pernicious anemia, and folic acid deficiency could result in oral mucosal discomfort described as a burning sensation.12, 22, 42, 65, 73, lo5, 172 Occasionally, the deficiency states reported were accompanied by visible changes in the affected oral tissues, but the complaint of a burning sensation could be present when no obvious mucosal changes were evident.

The exact mechanism by which a variety of deficiency states can lead to a burning sensation is uncertain. In the case of sideropenia and iron-deficiency anemia, depletion of iron- related compounds such as cytochrome oxi- dase leads to functional epithelial changes. In vitamin B,, and folic acid deficiency oral mucosal morphologic changes similar to those described in bone marrow and red cell precursors have been rep0~ted.I~~

The incidence of deficiency states reported in BMS varies (Table 2). Personally, I believe the incidence data are less important than the fact that deficiency states can precipitate BMS and therefore need to be sought in all cases. In one study of 55 BMS patients,lo5 53% were sideropenic and 4% were low in folic acid. In another study,12 7 of 21 BMS patients were low in vitamin B,, (n = 1) or folic acid (n =

6). In half of these patients, the deficiency state was deemed as the sole cause of BMS because the condition resolved following appropriate replacement therapy. In a subsequent report by the same 40% of 37 patients again were identified as being vitamin B12, folic acid, and iron deficient. Again, hematinic deficiency was thought to be primarily responsible for the BMS as judged by response to treatment.

In an American study, only 1 patient of 57 was found to be hematinically defi~ient.~ That study was not of BMS patients alone, however, but included patients with mucosal disease such as lichen planus.

The rationale for investigating vitamin B12, folic acid, or iron deficiency in BMS patients in some ways reflects what investigations are routinely available. Such data do not exclude, of course, other deficiency states, although assay of those may not be routinely available. One group of vitamins of importance are those of the B complex group. Biskindl6 thought that there was an intimate relationship between vitamin B complex status and levels of estrogen but lacked quantitative data. Nevertheless, one study of 86 postmenopausal patients who presented with oral symptoms including BMS reported one third to respond promptly to vitamin B complex

Table 2. THE RELATIVE IMPORTANCE OF PRECIPITATING FACTORS IN BURNING MOUTH SYNDROME

Factor Percentage of Patients

Hematinic deficiency states Anemia ( 1 Ferritin 6 Folic acid Vitamin B,, 8 Vitamin B,, BPI and B6

Undiagnosed maturity onset 3-5 diabetes

Oral candidal infection

Nil in our clinic

37

32% isolation but only 5% respond to antifungal therapy

Stimulated parotid flow rate reduced in 12%

Variable but only 25% are improved by new dentures of good design

A degree of xerostomia

Denture design faults

Parafunctional habits 20-61 Fear of cancer 20

Psychological state

Drug induced Rare

Allergy 5 Variable and complex but

approximately 36% have marked chronic anxiety

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replacement therapy."O Others also suggested a link between glossodynia and vitamin B complex defi~iency.~,

A fairly recent study quantified vitamin B1, B2, and B, levels in BMS patients and age- and sex-matched control subject^.^, Of 70 patients, 28 were deficient in one or more vitamins. Replacement therapy with vitamin Bl (300 mg daily), vitamin B, (20 mg daily), or vitamin B, (150 mg daily) was given to 28 deficient patients and 27 patients with BMS who had normal levels of vitamins B1, B2, and B,. Eighty percent of BMS patients with proven vitamin deficiency were asymptomatic at 3 months compared with none of the nondeficient group, although 7% of the latter group reported improvement. Others recently have repeated similar studies with disap- pointing results, but the doses of vitamins prescribed were not eq~iva len t .~~

Finally, other deficiency states have been investigated in BMS patients. Zinc levels are equivalent in BMS patients compared with age- and sex-matched control subjects.'06

Undiagnosed Maturity Onset Diabetes Mellitus

One of the first to relate oral symptoms and diabetes mellitus was Sheppard, who reviewed the literature prior to 1942.'33 He considered the link largely a reflection of the preinsulin era and with treatment the oral cavity of diabetics should differ little from nondiabetic subjects.

Other researchers studied the link and suggested the oral cavity to be a sensitive indicator of abnormal glucose tolerance.134, 13s Of 26 patients with abnormal glucose tolerance test results, 9 reported occasional oral burning. In another report, 12 of 45 patients with a variety of oral complaints including burning had abnormal glucose tolerance test results con- sistent with laboratory criteria at that time for diabetes mellitus.2y The technical quality of the latter report was reviewed and urinalysis questioned as a sensitive means of detecting diabetes mellitus or prediabetes.Il7 There are anecdotal reports of "sore tongue" in patients with diabetes mellitus resolving following the institution of glycemic

Unselected patients with various oral complaints have been subjected to glucose tolerance tests.I9 In one study, 30% had abnormal results, but it was thought that early small blood vessel disease precluded resolution of

oral sympt0ms.5~ Other studies have reported more encouraging results.53 Of 43 previously undiagnosed noninsulin-dependent diabetics (NIDD) 16 had BMS, and all resolved following glycemic therapy. A similar result was found in a study in which 4 of 150 BMS patients were found by glucose tolerance test (75 g load) to be NIDD. In that study BMS resolved entirely on instituting glycemic con- t1-01.~~ Another study found 1 NIDD patient in 20 BMS patients, so an overall figure of about 5% of BMS patients being NIDD seems reasonable.'os It should be appreciated that in a UK population 5% is a high figure consider- ing that 1% of the population are known diabetic and 1% undiagnosed. Indeed, a patient is twice as likely to be NIDD when presenting with a variety of oral complaints. In practice, all patients with BMS need diabetes mellitus excluded, preferably by fasting blood sugar estimation.

The relationship between BMS and diabetes mellitus also has been investigated by study- ing diabetic patients for symptoms of BMS. BMS was found in 10% of patients in one study (n = 110) and was the second most common oral complaint after xerostomia in another.12 Various reasons have been proposed to explain the relationship between BMS and diabetes mellitus, including meta- bolic alterations in the oral mucosa, accompanying xerostomia, and oral candidosis.

Denture Aspects

Denture design faults that increase the level of functional stress or restrict normal function of the lingual musculature can lead to BMS.12 Denture-bearing areas of the oral mucosa are subjected to stress for which they were not designed and assume the role of the periodontal membrane on transferring functional forces to the underlying bone.138, 147 His- tologically, such loads produce variable changes in the oral mucosa as little as 1 year after denture insertion.*

In a study of 33 patients with BMS, 50% had an error in denture design that was thought to be related causally to their BMS.*05 In a much larger study of 150 patients of whom 120 were edentulous, 60% had denture design faults, but replacing dentures alone only helped 25% of BMS patientse9 Thus,

"References 3, 26, 68, 76, 79, 109, 111, 114, 118, 156, 157, 161, 162.


even if the patient's BMS is coincidental with complete denture provision, the dentures alone account for BMS only in a quarter of patients. This of course reflects the multifactorial nature of BMS. Good dentures on a com- promised mucosa can produce BMS, good dentures on a healthy mucosa can produce BMS secondary to parafunction, and so on. As well as being of good fit, occlusal errors also can produce a burning sensation,"j5 and the dentures themselves have to be made cor- rectly to maintain the health of the underlying mucous membrane.166

Excess loading on dentures was reported by Thomson145 to produce a burning sensation principally in the palate, but also on the tongue and lips. Symptoms of burning could appear within minutes of denture insertion and be relieved by removing the dentures. Systemic factors such as deficiency states also may have been relevant to his observations, and treatment should aim to deal with excessive load, such as by correcting the vertical dimensions2, lUa or improving the supporting tissues. Parafunctional activity also leads to excessive occlusal loading99 and is probably more common than was realized previously in dentate and edentulous individual^.^'^, 120

Patients who clench or grind their teeth also often thrust their tongue against their teeth, and this can give rise to BMS. Such activity in BMS patients appears to be related to anxiety as detected by the Hospital Anxiety and Depression Scale.9o Others also have linked stress to increased muscle activity and clenching.167, Parafunction may be uncon- scious,17 and if the patients wear dentures with acrylic teeth, wear facets indicate this habit.lU

If BMS patients wear dentures, they may be contributing to their complaint. Careful assessment of the vertical dimension should ensure an adequate freeway space.", 98,

Io4, lUa Similarly, tongue movements should not be restricted. The denture bases themselves should ensure maximal load distribution.14 Underextended denture bases are the most common design and the area available for support can be increased by up to 50% with fully extended bases.145

Salivary Aspects

It is debatable whether salivary gland function reduces with age.13, 30, 41, 69, Few studies have been undertaken in a logical manner

using identical sampling techniques. Salivary gland output does appear related to gland size, and this varies between individ~als .~~

Because BMS occurs predominantly in postmenopausal women, a reduction in salivary flow in this group has been suggested as a possible cause of the burning, but good data are lacking.38 In one study, parotid salivary flow rate (resting and stimulated) was reduced in postmenopausal women, thus lending support to a link with BMS.71 Another study, however, showed no differences in resting mixed saliva between postmenopausal women who had burning tongues and those who did and others have shown similar results.8o Xerostomia itself is multifactorial, and factors contributing to xerostomia also may influence BMS.30 In one study, 40% of BMS patients complained of a degree of xerostomia, but only 12% had reduced stimulated parotid gland Of clinical interest is that the 12% of patients in whom reduced salivary function could be shown said that the burning and dryness were "the same thing." If this is the case, then saliva substitutes may have a role to play in the management of some patients with BMS. Other changes in saliva rather than just the volume of saliva could be important, namely compo- sitional changes. Some authors have claimed elevated protein, potassium, and phosphate levels in women with BMS and a relationship to hormonal status.14 Recent studies have suggested no change in protein profiles between BMS patients and control Our own studies have, however, identified a novel protein in the parotid saliva of BMS patients.126 There is no evidence that BMS is associated with histopathologic changes at least in minor salivary glands.l15 In a study of minor palatine glands in patients with or without the complaint of burning, no histologic changes were found. It was, however, unclear from that study if patients did indeed have BMS.

Microbiologic Aspects

There are few good studies on the oral microflora of BMS patients. What is fundamentally important is that patients can harbor pathogenic numbers of candidal species intraorally, yet have no clinical mucosal changes.57

In health, about 40% of patients harbor candidal species intraorally as assessed by culture of mixed saliva.lo The techniques for candidal isolation are important. Various

346 LAMEY

techniques are in use including 153

imprint cultures: epithelial smears, impres- sion cultures? and the oral rinse technique.125 The oral rinse technique is simpler to perform and is quantifiable, as well as allowing detection of Staphylococcus aureus and coliforms. Application of the oral rinse technique to BMS patients showed a higher prevalence of Candida species and coliforms in BMS patients than control The Candida species most frequently isolated was Candida albicans, and Enterobacter and Klebsiella were the most prevalent coliforms. It is likely that the coliforms were transferred to the mouth via the patients’ fingers, perhaps when investigating the mouth for disease.

Treating BMS patients in which candidal species were isolated (37% of 150 patients) improved symptoms in only 6%.89 Other studies using various isolation techniques claim figures of 10% candidal isolation in glossodynia patients? 13% in burning mouth patients, and 3.5% in a heterogenous group.’”

Overall, it would appear that candidal species play a minor role in BMS. Nevertheless, in one study 5% of patients had sustained improvement following antifungal therapy and confirmed elimination of candid^.^' Can- didal species still should be sought in BMS patients, preferably by using the oral rinse technique.

Allergic Aspects

It previously has been emphasized that even if a patient’s symptoms of BMS began when new dentures were provided, it is not likely that the dentures alone were responsible. Nevertheless, this apparent association led to several publications linking BMS to allergy to polymethyl methacrylate on the as- sumption that allergy to the acrylic resin or metal component of the denture base was present.

It is generally accepted that true allergy to polymethyl methacrylate in acrylic is rare.33 Many reported claims for allergy were dubi- ous both in the clinical complaint and the way in which allergy testing was undertaken. Indeed, contact allergic reactions in the mouth themselves are rare.7o This rarity has been attributed to rapid absorption and dis- persal of potential allergens through the mucosa and to dilution and removal of potential allergens by saliva.45

Some reports of allergy to denture materi-

als have been in patients who complain of a burning mouth, but do not have BMS because they had clinically obvious oral change^.^ At- tempts to reduce residual monomer levels by various means, such as boiling, are largely unsuccessful.9 There are, however, rare cases of true allergy to polymethyl methacrylate in BMS patients who have responded to the provision of alternative denture base materials such as nylon.35 It would appear that such patients give a type 3 BMS history, and that other allergens, such as the constituents of foodstuffs, are more important.97 A recent de- tailed study of type 3 BMS patients suggested that about 50% have allergy as a major precipitating factor, and the other 50% have emotional instability as a major factor. Appro- priate patch testing by a dermatologist experienced in the technique and professional advice on dietary evidence largely resolved their condition. Numerous other substances have been reported as having an association with BMS by being allergenic in susceptible individuals. These substances have included sorbic nicotinic acid epoxy resin (and bisphenol A),155 pyrethroid (an in~ecticide):~ palladium? octyl gallate (an anti~xidant),”~ benzoylperoxide, 4-tolyl dietha- nolamine, N,N-dimethyl-4-t0luidine?~ peanut extract,163 cinnamon adel~de,2~ and nickel

159

Cancerphobia

About 20% of patients with BMS have a strong fear of cancer.89 This fear almost is never volunteered by the patient but should be asked about by the clinician.38 Reassurance that BMS is in no way related to oral cancer can do much to put a patient’s mind at ease. Indeed, the outcome of treatment of BMS patients who are slightly anxious is even better than patients who are not anxious, and this is almost certainly because cancerphobia is producing additional anxiety.86 In type 1 and 2 BMS patients, the presence of symptoms on a daily basis and the possible lack of success in the early consultation period also contrib- ute to the feeling that BMS represents a serious disorder about which the clinician is not telling the patient. Patients who say that they think that part of their mouth looks abnormal have almost certainly been examining it in the mirror and think they notice pathology. Repeated self-examination is almost pathog- nomonic of cancerphobia.


The Climacteric

In 1946, Ziskin and M o ~ l t o n ’ ~ ~ described the typical BMS patient as a postmenopausal woman unduly emotionally disturbed by her oral condition and complaining of ner- vousness, depression, hopelessness, and in- somnia, or alluding to significant cancerphobia. They also stated that younger female patients rendered sterile by oophorectomy also could be affected. It was claimed that lack of female sex hormones produced histologic changes (progressive atrophy) in the oral and vaginal epithelium.lZ2 Primate studies reported reversal of histologic changes in the oral mucosa of oophorectomized mon- k e y ~ ; ~ ~ and Ziskin’” repeated these studies in women. The same group and others showed that although estrogen administra- tion produced histologic changes in the oral mucosa, it did not relieve symptoms of BMS.

Other studies claimed benefit from hormone replacement therapy alone or in combi- nation with vitamin B complex therapy.”O Some authors considered that, although the oral symptoms may be related to the climacteric, they were psychological in origin.71

Menopause clinics have been used to inves- tigate oral symptoms that such patients may have. In one study, 20% of patients had some oral symptoms, but not all had BMS.12 The prevalence of oral symptoms at the climacteric, including a burning sensation, is high.150, 170 Hormone replacement therapy was of doubtful benefit, suggesting that estrogen deficiency is an uncommon cause of BMS.& Some authors have attempted to identify oral nuclear estrogen receptors immunohisto- chemically in an attempt to identify patients likely to benefit from hormone replacement

The present situation is that there is no proven benefit of hormone replacement therapy in BMS.

Psychological Factors

Psychological factors of importance in BMS include simple fear of personality disorders,s6 uncommon depre~sion,’~~ and most significantly chronic anxietyg0 or emotional in~tabili ty.~~ Emotional instability is present in approximately 50% of type 3 BMS patients.97 Such patients can respond quickly to a stressful situation by developing symptoms of BMS, which then resolve when the situation reverts to normal. It is important

when assessing patients’ psychological status to be objective, and many psychological proformas are available to allow the clinician or psychologist to do this. Some proformas, such as the Hospital Anxiety and Depression scale, are quick and simple to complete and have been validated and applied to BMS patients2O One such study emphasized that anxiety was much more common than depression. Others also have noted hypochondriacal tendencies (i.e., anxiety) in their 179 The sources of anxiety are many and various, but include ”dissatisfaction with life.” It is for this reason that, when evaluating patients with BMS, a home circumstances score is used because it is a nonconfrontational means of allowing patients to verbalize their con- cerns and qualify them.

Personality traits in BMS patients have been assessed using Cattell’s 16PF Question- naire.86 This questionnaire is fairly lengthy and requires specialist interpretation. It can, however, highlight personality traits in BMS as shown in Figures 3 and 4. Such individuals tend to be anxious, somewhat introverted and self-reliant, but with low self-esteem. Others have claimed that although BMS patients appear superficially kind and sensitive, they ac- tually show suppressed hostility.18

Schoenberg128 considered depression to be a feature of BMS, but patients in that study were excluded if any organic factor was found. A degree of dependency and ”symptom formation” can develop in BMS patient~:~ and in managing them, such patients should receive attentive listening. Verbal ex- pression was encouraged, as well as offering appropriate explanations to social difficul- ties.31,83 Additional studies, this time using a psychological proforma, highlighted a preoc- cupation with ~ o s s . ~ ~ ~

This range of psychological problems that some BMS patients have emphasizes the need for the clinician to adopt a sympathetic approach with reassurance and avoidance of excessive treatment.12, 56, 78, lo2, lo3 It is still not clear if psychological aspects of BMS are cause or effect, and indeed, some patients may have a chronic pain personality.6o State and trait anxiety are elevated in BMS pa- t i e n t ~ , ~ ~ ~ with figures varying between 44YOZ4 and 62%.86 In the latter study, type 2 BMS patients were more severely psychologically disabled than type 1 BMS patients, and anxiety seemed the most recalcitrant obstacle to cure. Overall, in management there is a re- quirement for an objective assessment of psy-

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Figure 3. Mean profile recorded by Cattell's 16PF Questionnaire Form C for BMS patients (n = 47) compared with age general population. = P <0.001, ** = P <0.01

Stens

Unstable

-Apprehensive

I Casual - Tense

Figure 4. Mean profile recorded by Cattell's 16PF Questionnaire Form C for BMS patients with (0-c [n = 281) and without (0-0 [n = 191) an abnormal psychological profile.


chological status as well as a regimen to cater to psychological as well as medical and dental needs. Clearly life events are important in BMS 86, 149 but it has been claimed recently that BMS symptoms do not necessarily correlate with stressful life events.86

Drug-related Burning Mouth Syndrome

The only drugs of significance in apparently precipitating BMS are angiotensin-con- verting enzyme (ACE) inhibitor^.'^^ Reported cases refer to scalded mouth . syndrome (SMS), but they almost certainly mean BMS. The three drugs involved are all ACE inhibitors and are lisinopril, captopril, and enala- pril. Although the mechanism of BMS induc- tion by ACE inhibitors is not known, it does appear dose related and subsides on reduction or discontinuation of therapy.

Relationship to Systemic Disease

BMS may involve the complaint of burning at other body sites and as such may be a systemic disorder.50 It has also, however, to be borne in mind that accompanying psychiatric problems can produce somatization and result in multiple perceived somatic problems.

Only rarely is BMS a manifestation of underlying organic disease. Two recent reports, however, have associated the complaint of BMS with acoustic n e ~ r o m a ~ ~ and temporal arteritis51 (also known as giant cell arteritis). In the case of temporal arteritis, which affects the same age group as BMSY4 recognition of the underlying disease is important because permanent blindness is a serious complica- t i ~ n . ~ ~ A useful clinical clue to the potential for a patient having giant cell arteritis is that they usually feel systemically unwell at tlie time of presentation.

Associated Sensory Changes

Several groups of investigators have studied sensory changes including taste in BMS patients. In one study, sensory and pain thresholds to brief argon laser stimulation showed abnormal prepain perception and disturbances in the perception of nonnocicep- tive and nociceptive thermal stimuli in pain- affected and normal regions.*41 This suggests

a perceptual deficit unrelated to pathophysio- logic mechanisms in BMS. The authors con- cluded that this alteration in sensory function may be more plausible than a psychological explanation of BMS.

When taste accompany BMS,6I it has been stated that treatment is unsatisfac- tory, but that depression frequently accompa- nies chemosensory distortion.l12 It is not clear from these studies if candidal carriage had been sought or treated. It is common for taste abnormalities to be due to candidal species, even in the absence of clinical changes.

Sensory changes of BMS have themselves formed the basis of attempts to objectively diagnose the condition.27 Thermoesthesiome- try, which, it is claimed, accurately detects surface temperature, showed that in BMS the surface mucosal temperature was lower than in control subjects, and this was attributed to reduced blood circulation in the area. The diagnostic benefit of this test is still to be subject to independent study.

NOVEL TREATMENT OPTIONS IN BURNING MOUTH SYNDROME

Two recent publications have suggested novel ways of treating BMS. These reports are clearly only initial observations but warrant inclusion in any free-thinking academic com- munity.

One study evaluated the use of soft laser therapy in patients with BMS.27 Forty ”stomatopyrosis” and ”stomatodiniae” patients underwent 5 days of therapy for 3 minutes daily on 1 cm2 of oral tissue. The reported response, was complete healing by which one assumes the patients were asymptomatic. No follow-up data were presented.

The second novel treatment involves the use of ca~sa ic in .~~ Capsaicin is a neurotoxin that destroys a major class of nociceptors, primarily C polymodal and some A delta nociceptors. Although a mixed group of ”oral neuropathic pain” patients were described, some would appear to have BMS. Further data on this treatment are required as is de- tailed information concerning patient investigation.

MANAGEMENT PROTOCOL

This protocol is based on scientific evaluation of the known precipitating factors in BMS and is what I follow routinely.

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Hematinic assay of hemoglobin, ferritin, vitamin BIZ, and corrected whole blood folate. Deficiencies detected need investigation for cause prior to supple- mentation. Assay of vitamin B, and vitamin B,. If these are not available, then empirical treatment with vitamin B, (300 mg daily) and vitamin B6 (50 mg every 8 hours). Both are prescribed for 4 weeks or rarely for 8 weeks. Patients should discontinue all self-medication with vitamins. Assay of blood glucose on a morning fasted sample. If results are equivocal, a glucose tolerance test (75 g load) is performed with referral to a physician with an interest in diabetes. Measurement of stimulated parotid flow rate using a Carlsson-Crittenden cup and stimulated with 1 mL of 10% citric acid. Flow of less than 0.7 mL/ min is low, and the patient may benefit from saliva substitutes. An oral rinse for Candida species. The distinction between carriage and infection (without clinical signs) is vague, but in practice all BMS patients in whom Candida is isolated should receive 4 weeks of topical antifungal therapy. Advice on a low carbohydrate diet and denture hygiene also should be given, if appropriate. Reassure about cancerphobia. This may need to be repeated at subsequent vis- its. Objective psychological assessment. For screening purposes the Hospital Anxiety and Depression scale is useful and can be supplemented with others if required. Involvement of a clinical psychologist also can be helpful. If there is a clear psychological problem, then appropriate therapy is needed. Prothiaden (dothiepin), 75 mg nocte, is our drug of choice because it combines anxiolytic and antidepressant properties and is not addictive. The drug should be avoided in patients with car- diac arrhythmias. Assessment of denture status if relevant. The main features of note are restricted tongue space, lack of freeway space, and underextended denture bases. Obvious design features need to be corrected. Inquire about parafunctional habits

10.

In

such as tongue thrusting or tooth clenching. It can be difficult for patients to refrain from such habits. Sometimes sugar-free chewing gum allows patients to break their habit. In type 3 patients who are psychologically normal, patch testing is appropriate. Once identified, avoidance of the relevant allergen(s) usually resolves the complaint, but the patient should realize that this may take several months.

our hands this management protocol renders approximately 7@/0 of patients asymptomatic or greatly reduces their burning score. This protocol fails 28% of patients, however, and indeed made 2% of patients worse. The reason for this may lie in the patients' home circumstances and chronic anxiety. We also should bear in mind that other factors,, possibly organic, which we do not yet know about, also may be important.

PROGNOSIS

It has been stated that there is not a predict- able endpoint in the outcome of treating BMS patients.57 This is certainly the case if not all relevant investigations are undertaken. There can be few conditions more multifactorial than BMS, and we all owe it to our patients to manage them to the best of our ability and take cognizance of our current scientific knowledge. If all investigations are undertaken, it would seem that approximately 70% of BMS patients can be rendered asymptomatic or nearly so by treatment.89 Initially, the follow-up period in that study was 18 months, and longer follow-up data are awaited. In a mixed group of patients reviewed 8 to 10 years after treatment, over 50% of patients still thought they needed treatment and continued to be high consum- ers of healthcare resource^.'^^

In our present state of knowledge, we do not know the long-term prognosis for BMS patients. Spontaneous remission has been claimed>12 but this is not my experience. The application of statistic methods to predict outcome has not proved usefu1.'07, lZ1

CONCLUSION

Our knowledge of BMS has advanced enor- mously in the last 10 years. These advances


have arisen from carefully controlled prospective studies aimed at addressing outcome of treatment. Hypotheses on the role of additional organic causes of BMS should be pur- sued. It is also important for our patients to have a logical scientific approach to care and make sure they benefit from the knowledge we have already. Science cannot replace a caring and supportive clinical approach, but it can help us confirm what we do know and help us understand what we do not.

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Burning Mouth Syndrome