burning mouth syndrome: diagnostic appraisal and management strategies

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Saudi Dental Journal, Volume 19, No. 3, September - December 2007

SAUDI DENTAL JOURNALSAUDI DENTAL JOURNAL

Burning Mouth Syndrome: Diagnostic appraisal and management strategies

Sukumaran Anil, BDS, MDS, PhD, FICD, FPFA *Mohammed Nasser Alsqah, BDS **R. Rajendran, BDS, MDS, PhD ***

*Associate Professor, Division of Periodontics**Intern ***Professor, Division of Oral PathologyCollege of Dentistry, King Saud UniversityP.O. Box 60169, Riyadh 11545, Saudi Arabia

INTRODUCTION

Burning mouth syndrome (BMS) has been defined as pain of a burning nature in the tongue or oral mucous membrane, usually without accompanying clinical and laboratory findings.1,2 Other terms that are applied to this condition include burning lips syndrome, scalded mouth syndrome, stomatodynia, glossodynia, and glossopyrosis.3,4 There has also been no clear consensus on the etiology, pathogenesis or treatment of burning mouth syndrome.5 As a result, patients with inexplicable oral complaints are often referred from one health care professional to another without effective management strategies. This situation not only adds to the health care burden but also has

a significant emotional impact on these patients, who are sometime suspected of deducting or exaggerating their symptoms.

Epidemiology Based on the data accrued so far, oral burning appears to be most prevalent in postmenopausal women.6 It has been noted in 10 to 40 percent of women reported for treatment of menopausal symptoms.7

These percentages are in contrast to the much lower prevalence rates reported for oral burning in epidemiologic studies (0.7 to 2.6 percent),8,11 The Incidence and prevalence of BMS vary according to diagnostic criteria, and many studies

Address reprint request toDr. S. AnilAssociate Professor and ConsultantCollege of Dentistry, King Saud University P.O. Box 60169, Riyadh 11545, Saudi ArabiaE mail: [email protected]: www.perio.in

Burning mouth syndrome (BMS) is a disorder that is characterized by a burning sensation of the oral cavity in the absence of visible local or systemic abnormalities. Affected patients often present with multiple oral complaints, including burning, dryness and taste alterations. The exact cause of burning mouth syndrome often is difficult to pinpoint. Conditions thathave been reported in association with burning mouth syndrome include chronic anxiety or depression, various nutritional deficiencies, type 2 diabetes and changes in salivary function. Studies have pointed to dysfunction of the cranial nervesassociated with taste sensation as a possible cause of burning mouth syndrome. Since burning mouth symptoms may arise as the result of a number of etiologic factors, diagnosis and management of the patient with BMS should involve consideration of all possible causative factors. Hormone replacement therapy, benzodiazepines/ anti-convulsants, anti-depressants, analgesics, capsaicin, alpha-lipoic acid and cognitive behavioral therapy etc. have all been used in the management of BMS. The present review outlines various aspects of BMS, updates current knowledge on the disease, and provides guidelines for successful patient management.

REVIEW ARTICLE

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included people with the symptom of burning mouth rather than with burning mouth syndrome.9

Pain Characteristics In more than one half of patients with burning mouth syndrome, the onset of pain is spontaneous, with no identifiable precipitating factor. Approximately one third of patients relate the time of onset to a dental procedure, recent illness or medication course. Regardless of the nature of pain onset, once the oral burning starts, it often persists for many years.10

The burning sensation often occurs in more than one oral site, with the anterior two thirds of the tongue, the anterior hard palate and the mucosa of the lower lip most frequently involved.6 In many patients with the syndrome, pain is absent during the night but occurs at a mild to moderate level by middle to late morning. The burning may progressively increase throughout the day, reaching its greatest intensity by late afternoon and into early evening.10 Patients often report that the pain interferes with their ability to fall asleep. Perhaps because of sleep disturbances, constant pain, or both, patients with oral burning pain often have mood changes, including irritability, anxiety and depression.2 Little information is available on the natural course of burning mouth syndrome. Spontaneous partial recovery within six to seven years after onset has been reported in up to two thirds of patients, with recovery often preceded by a change from constant to episodic burning.6 Most studies have found that oral burning is frequently accompanied by other symptoms, including dry mouth and altered taste.6

Etiologic Factors - Systemic and Local Factors Because of a long-standing difficulty in understanding the pain of burning

mouth syndrome and its complex clinical picture, a number of etiologies have been suggested. However, each of these postulated causes explains the pain in isolated groups of patients. With the recently increased understanding of the role that taste damage plays in the pathogenesis of burning mouth syn-drome, many of these etiologies can now be viewed as part of a larger spectrum of disease. Etiological factors can be divided into local, systemic and psychological (Table 1).

Local Causes of Burning Mouth Syndrome Although many predisposing factors have been attributed to BMS, none are free from controversies.

Table 1. Common conditions associated with burning mouth syndrome

LocalCandidiasis Lichen planusErythema migrans Parafunctional habits

Denture problems Gastro-oesophageal reflux disease

Systemic Conditions

Diabetes mellitus Medications (such as captopril)

Dry mouth -Xerostomia Menopause Deficiency States

Vitamin B FolateIron

PsychogenicCancerophobia DepressionAnxiety HypochondriasisStress

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Candidiasis Pseudomembranous and erythematous candidiasis have been associated with BMS.5 The pseudomembranous type is easily recognized by white, slightly elevated plaques that have a milky appearance and can be rubbed off, it is most commonly found on the cheeks and palate. The erythematous type is characterized by flat, red changes of the

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mucosa, tongue, and palate. The diagnosis of candidiasis is often presumptive, made on the response to antifungal therapy and rarely based on cytologic or histologic studies. Gorsky et al.11 reported that in patients with BMS having no clinical signs of candidiasis, 86% improved after using antifungal lozenges and 13% had complete elimination of their symptoms.

Oral Cancer Glossodynia may be caused by oral cancer, which is normally present on the lateral borders of the tongue or the oropharynx. Carcinomas of the oral cavity can also present with itching or burning as the premonitory symptom. Premalignant entities such as leukoplakia or erythroplakia may also present with burning or painful sensation.12

Dental Causes A faulty denture design may promote the burning sensation due to an increased level of functional stress to the circum oral or lingual musculature. Main and Basker 13 found ill-fitting dentures to be the single greatest contributor to BMS in their patient population. BMS patients were found to have significantly less daily denture use, reduced tongue space, incorrect placement of the denture occlusal table, and increased denture vertical dimension.14 However, in the majority of patients in whom denture abnormalities were adequately corrected, the burning mouth symptoms persisted.15

A similar controversy attributes the cause of burning mouth to an allergic response to the denture materials. Methyl-methacrylate monomer and other products used in denture fabrication have been shown to produce positive skin reactions to patch testing.16 If erythema of the mucosa exists, the construction of new dentures using different material, such as metal alloys, has been shown to

result in a partial or even total relief of symptoms. However, in the absence of oral lesions which could indicate contact dermatitis, the substitution of materials in general has not been shown to alleviate BMS.17

Hypersensitivity to mercury was found to be one of the most common medical diagnoses concomitant with BMS.18 In addition to mercury, other metals used in dental restorations are gold, palladium, zinc, tin, gallium, indium, cobalt, chrome, nickel, iron, and silicon. Although hypersensitivity to these materials has been reported, their precise role in the causation of symptoms of BMS is not absolutely clear. The symptoms of galvanism may resemble those of BMS, and they require consideration.12 Treatment would involve the elimination of one of the metallic restorations or using synthetic nonconductive materials wherever applicable.

Lichen Planus The symptoms of burning and pain occur most often with erosive lichen planus.19 The diagnosis is made by histological examination. Local or systemic corticosteroid therapy is frequently helpful in the acute phase of erosive lichen planus. The incidence of malignant transformation of erosive lichen planus varies from 0% to 10%.

Systemic Causes of Burning Mouth Syndrome Various systemic factors have been associated with BMS, although many of these conditions require further study to verify the correlation. There is a predilection for BMS to occur in menopausal and postmenopausal women,7 however, there have been varied opinions regarding the hormonal role in BMS. Oral discomfort, including burning mouth, is one of the two most common oral manifestations of menopause.20 Basker et al.21 reported that

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26% of patients evaluated for menopause experienced some oral symptoms, one-third of these describing BMS. Yet in early studies, neither topical nor systemic hormonal replacement therapy has been shown to be effective.22,23 In a recent study, hormone-replacement therapy was found to be efficacious in BMS patients who had demonstrated nuclear estrogen receptors on immunohistochemical assay, and ineffective in those patients who did not have the receptors.24 Therefore, hormone modifications may have a role in selected patients with BMS.

Iron and Vitamin B Complex Deficiency Glossodynia may be one of the symptoms of deficiency states especially iron, Vitamin B and folic acid. The diagnosis can be made by estimation of hemoglobin content, serum iron, ferritin level and iron binding capacity. The treatment is by iron replacement therapy. Lamey et al.25 found replacement therapy of vitamin B1, B2 and B6 effective in treating BMS in 88% of patients. However, in another study of therapy-resistant BMS patients, vitamin B replacement therapy was unsuccessful.26 The definitive role of B complex vitamins in the etiology of BMS remains unclear. A deficiency of folic acid may lead to burning mouth associated with angular cheilitis and glossodynia.27 The tongue shows varying degrees of papillary atrophy which progresses until the surface of tongue is smooth and shiny. The diagnosis is done by RBC morphology and serum folate level. Likewise, niacin deficiency causes generalized erythema of the oral mucosa along with papillary atrophy. A proper diagnosis can be made by the measurement of niacin level. It is treated with niacin and vitamin B-complex vitamins.27

Diabetes Mellitus Glossodynia may be one of the symptoms of diabetes, which is often

associated with xerostomia and candidiasis. There also may be diabetic neuropathies, which manifest in the head and neck region contributing glossodynia.21,28

It has been suggested that diabetics are more susceptible to the Candida infections which may cause the burning mouth.5 While some found that the symptoms of BMS in diabetic patients did not decrease after glucose control,12 others found that in many cases, diabetic treatment resolved the oral symptoms.28

Psychologic Dysfunction Personality and mood changes have been consistently demonstrated in patients with burning mouth syndrome and have been used to suggest that the disorder is a psychogenic problem.29 How-ever, psychologic dysfunction is common in patients with chronic pain and may be the result of the pain rather than its cause. Browning et al.30 concluded that 44% of burning mouth patients had an associated psychiatric disorder. Lamb et al.31 indicated that 60% of burning mouth patients has had psychological factors and anxiety was most difficult to control. Glossodynia may be a symptom of cancer-phobia. Reassuring the patients after a proper diagnosis is often helpful in relieving the symptoms. The treatment of psychogenic Glossodynia is anxiolytic/antidepressant drugs or by referring the patient for psychiatric consultation. The reported success of bio-behavioral techniques in the treatment of burning mouth syndrome may be related more to an improvement in pain-coping strategies than to a “cure” of the disorder.32 Similarly, the usefulness of tricyclic antidepressants and some benzodiazepines may be more closely related to their analgesic and anticonvulsant properties, and to the possible effect of benzo-diazepines on taste-pain pathways.33

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Hormonal Changes Hormonal changes are still considered to be important in burning mouth syndrome,6 although there is little convincing evidence of the efficacy of hormone replacement therapy in postmenopausal women with the disorder.24 Approximately 90 percent of the women in studies of the syndrome have been postmenopausal, with the greatest frequency of onset reported from three years before to 12 years after menopause.10

Dry Mouth (Xerostomia) Dry mouth has been suggested as an etiologic factor, in view of its higher incidence in patients with burning mouth syndrome.10,14 Glass34 suggests that xerostomia is a local contributing factor in the development of BMS, and other authors also found a higher or lower percentage prevalence of xerostomia in burning mouth syndrome patients.35,36 However, most salivary flow rate studies in affected patients have shown no decrease in unstimulated or stimulated salivary flow.6 Studies have demonstrated alterations in various salivary components, such as mucin, IgA, phosphates, pH and electrical resistance.6 The relationship of these changes in salivary composition to burning mouth syndrome is unknown, but the changes may result from altered sympathetic output related to stress, or from alterations in interactions between the cranial nerves serving taste and pain sensation.7 Although there is no effective treatment, saliva substitute and fluoride gel should be prescribed for the relief of these oral symptoms.

Taste Function The role of taste in burning mouth syndrome is not straightforward, although recent studies by one set of investigators demonstrated a possible relationship between taste activity and the disorder.37,38

Diagnosis of BMS History taking is the key to diagnosis of BMS. Both diagnosis and management may be difficult because patients often present with multiple oral complaints, may be focused on their symptoms and may be anxious or depressed, which intensifies the pain experience. The diagnosis is based on clinical characteristics, including either a sudden or intermittent onset of pain, bilateral presentation, a progressive increase in pain during the day and the remission of pain with eating and sleeping. The clinical history is helpful in diagnosing burning mouth syndrome. Most patients with the disorder report an increase in pain intensity from morning to night, decreased pain while eating, oral dryness that waxes and wanes with the burning, and the frequent presence of taste disturbances.39 Even when a patient reports typical features of burning mouth syndrome, other potential causes should be ruled out (Table 2).

If burning persists after management of systemic or local oral conditions, a diagnosis of burning mouth syndrome can be considered, and empiric treatment for sensory neuropathy may be offered. Although not widely available, specific techniques can be used to test for taste disturbances and salivary function. Referral to a specialist with expertise in

Table 2. Investigations and assessment which might currently be considered in patients with symptoms of a burning mouth

Detailed history and clinical examination Blood test- to exclude anaemia Iron, vitamin B12 and red cell folate levels – to

exclude deficiency Random blood glucose levels – to exclude diabetes

mellitus Measurement of salivary flow – to exclude dry mouth Autoantibody assay-to exclude Sjogren’s syndrome Oral biopsy – for definitive oral diagnosis Assessment of denture fitness and function Psychological assessment – to investigate possible

roles of depression or anxiety

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this area may be beneficial in particularly difficult cases.

Management of BMS Owing to the large variety of associated factors, the protocol for BMS management is complex. Although many drugs, medications, and miscellaneous treatments have been proposed in BMS,40 the management of this syndrome is still not satisfactory, and there is no definitive cure.41,42 In the absence of any identifiable cause(s) of the burning sensation, pharmacologic therapy has been suggested. Medications used for BMS include antifungals, antibacterials, corticosteroids, analgesics, sialagogues, vitamin and mineral replacements, hormone replacements, benzodiazepines, antidepressants and antihistamines.43 BMS patients have shown a good response to long-term therapy with systemic regimens of anti-depressants44 and anxiolytics.45 In addition, some patients undergoing topical capsaicin administration have experienced a partial or even complete remission of their pain.46

Information for Patients and Psychological Support Patients with BMS often feel that they have insufficient information about the condition and verbal reassurance should be reinforced with well-supported documents. Patients must be made aware, instead, that their pain is “real”, the syndrome is common in middle-aged/elderly individuals, and is often linked to some identified conditions. Precautionary measures, such as abstaining from smoking and specific food allergens, should also be suggested. Drugs able to induce either BMS 47,48 or xerostomia 49 should be avoided as well. Some explanatory leaflets or booklets may be helpful for this purpose. When evidence of a psychogenic pain component is

detected, specialists should also provide patients with adequate psychological support. This preliminary counseling, in fact, can have a great impact on the patients’ attitude and may often result in long-term beneficial effects.50

Causative Therapy in BMS Subjects with BMS should be treated for the precipitating factors of this disorder. Depending on the type of salivary dysfunction, xerostomia is controlled with saliva substitutes or saliva-stimulating agents.51,52 Saliva substitutes have some properties similar to those of the salivary glycoproteins.53 Active stimulation of salivation may be obtained by means of chewing gums or sweets, whereas passive stimulation is achieved through specific cholinergic drugs (sialagogues), such as pilocarpine.33,52 Pyridostigmine is of greater benefit, since it is longer-acting and associated with fewer side-effects. Parafunctional habits are treated by a biofeedback technique 54 and/or restoration of proper bite. Muscular tension/pain and temporomandibular joint mobilization are managed by means of physical relaxation training and physical therapy, respectively.55 Peri-/post-menopausal women with BMS should be referred to a gynecologist for proper administration of conjugated estrogens and medroxyprogesterone acetate, which in fact, may relieve oral symptoms in this subgroup of BMS patients.24 Vitamin B complex replacement therapy (pyridoxine, riboflavin, thiamine, etc.) may yield a good response 25 in very few cases of patients with nutritional deficiency.26

As mentioned previously, the different types of responses to etiology-directed therapy in BMS might be related to the type(s) of neuropathic change(s) underlying the syndrome. In non-responding cases, local and/or systemic predisposing factors may have caused an irreversible

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Table 3. Supportive therapy of Burning Mouth Syndrome Medications (Dosage) Prescription

Tricyclic antidepressantsAmitriptyline (Elavil) Nortriptyline (Pamelor)

10 mg at bedtime; increase dosage by 10 mg every 4 to 7 days until oral burning is relieved or side effects occur

BenzodiazepinesClonazepam (Klonopin)

Chlordiazepoxide (Librium)

0.25 mg at bedtime; increase dosage by 0.25 mg every 4 to 7 days until oral burning is relieved or side effects occur; as dosage increases, medication is taken as full dose or in three divided doses5 mg at bedtime; increase dosage by 5 mg every 4 to 7 days until oral burning is relieved or side effects occur; as dosage increases, medication is taken in three divided doses

AnticonvulsantsGabapentin (Neurontin)

100 mg at bedtime; increase dosage by 100 mg every 4 to 7 days until oral burning is relieved or side effects occur; as dosage increases, medication is taken in three divided doses

Capsaicin

Rinse mouth with 1 teaspoon of a 1:2 dilution (or higher) of hot pepper and water; increase strength of capsaicin as tolerated to a maximum of 1:1 dilution.


neuropathic damage/defect, and thus patients should be additionally treated with a therapy targeted to the neuropathic damage. Recently, a three- to four-week regimen of alpha-lipoic acid (ALA) has been claimed to provide a slight to decisive pain reduction in BMS patients.56,57 Based on the currently reported efficacy of ALA in treating neuronal damage,58 especially in diabetic neuropathy,59 this drug might be particularly indicated in BMS subjects who show lack of response to etiology-directed therapy. Further investigation, however, is mandatory for better defini-tion of the role of this drug in BMS.

Supportive Care in BMS: The Control of Pain and Associated Symptoms The supportive treatment of burning mouth syndrome is usually directed at its symptoms and is the same as the management of other neuropathic pain conditions (Table 3). Studies generally support the use of low dosages of clonazepam (Klonopin),3 chlordiazepoxide (Librium) 33 and tricyclic antidepressants (e.g., amitriptyline [Elavil]) 60 . Evidence also supports the utility of a low dosage of gabapentin (Neurontin).39 Studies have not shown any benefit from treatment with selective serotonin reuptake inhibitors or other serotoninergic antidepressants (e.g. trazodone [Desyrel].61

Although benzodiazepines might exert their effect on oral burning by acting as a sedative-hypnotic, this possibility appears to be unlikely because the maximal effect of clonazepam is usually observed at lower dosages.45 The beneficial effects of tricyclic antidepressants in decreasing chronic pain indicate that, in low dosages, these agents may act as analgesics. Topical capsaicin has been used as a desen-sitizing agent in patients with burning mouth syndrome.46 However, capsaicin may not be palatable or useful adjunct in many patients.

Antidepressants: For many years, low dose tricyclic antidepressants (TCA’s) including amitriptyline, desipramine, nortriptyline, imipramine and clomipramine remained the treatment of choice in the management of BMS.60,61 The choice of these medications was based on the effectiveness of the tricyclic antidepressants as analgesics.

Benzodiazepines: There are several published reports that both chlordiazepoxide and clonazepam, GABA (gamma-amino butyric acid) receptor agonists, may be effective for some orofacial pain conditions including BMS.3,33 These drugs are believed to facilitate the inhibitory actions of GABA.

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Woda et al.3 additionally demonstrated the possibility of a topical effect of clonazepam in reducing oral burning in approximately 2/3 of their BMS patients. These studies also suggest no particular benefit to increasing doses of clonazepam beyond what appears to be its “window” of activity in BMS.

Capsaicin: Capsaicin desensitization is an effective oral analgesia when painful lesions are present.46 According to our hypothetical model, capsaicin would not be expected to be effective in reducing BMS since the burning is a central and not a peripheral sensation. This is in contrast to atypical odontalgia, in which peripheral triggers in the periodontal membranes of the affected teeth do appear to respond to capsaicin desensitization and/or topical anesthetic with temporary relief of pain.62,63

Alpha-Lipoic Acid Alpha-lipoic acid (ALA) significantly reduces symptoms of burning mouth syndrome (BMS).57 The improvement in symptoms was maintained for at least ten months after discontinuing treatment with ALA in the majority of cases. ALA is a potent antioxidant that protects the body against damage from free radicals. It has been used to treat radiation sickness and complications of diabetes, and has been investigated as a possible anti-HIV medicine. ALA helps to conserve other antioxidants, such as vitamins E and C, and increases cellular levels of glutathione, another potent antioxidant. The benefits of ALA may be due to its ability to neutralize free radicals and prevent damage to nerve cells. However, more research is needed to clarify its mechanism of action in the treatment of BMS. Cognitive behaviour therapy (CBT) has been shown to have some benefit in this condition but is complex and clinically intensive. This involves the identification

of maladaptive thought processing and its attempts to change this in a positive way.50,64 Successful treatment of BMS patients with combined psychotherapy and psycho-pharmacotherapy has also been reported.65

SUMMARY

Burning mouth syndrome is a painful and often frustrating condition. The burning sensation may affect the tongue, the roof of the mouth, the gums, the inside of the cheeks and the back of the mouth or throat. The exact cause of burning mouth syndrome often is difficult to pinpoint. The disorder has long been linked to a variety of other conditions: menopause, diabetes, nutritional deficiencies, tongue thrusting, disorders of the mouth (oral thrush and dry mouth), acid reflux, cancer therapy (irradiation and chemotherapy) and psychological problems. Burning mouth syndrome remains a fascinating, though poorly understood, condition in the field of oral medicine. New evidence for the neuropathic basis of this syndrome is emerging. As a result, a subgroup of BMS cases may fall into the category of nigrostriatal dopaminergic disorder. In the remaining group of patients, in whom there are clear precipitating local factors, BMS might be considered as a consequence of selective damage (trauma/ chemo-mechanical irritation) to the nerve fibers of the trigeminal nervous system.

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burning mouth syndrome: diagnostic appraisal and management strategies

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