BURNING MOUTH SYNDROME (BMS) NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH Burning mouth syndrome (BMS) is a painful,

, frustrating condition often described as a scalding sensation in the tongue, lips, palate, or throughout the mouth. Although BMS can affect anyone, it occurs most commonly in middle-aged or older women. BMS often occurs with a range of medical and dental conditions, from nutritional deficiencies and menopause to dry mouth and allergies. But their connection is unclear, and the exact cause of burning mouth syndrome cannot always be identified with certainty.

Signs and Symptoms

Moderate to severe burning in the mouth is the main symptom of BMS and can persist for months or years. For many people, the burning sensation begins in late morning, builds to a peak by evening, and often subsides at night. Some feel constant pain; for others, pain comes and goes. Anxiety and depression are common in people with burning mouth syndrome and may result from their chronic pain. Other symptoms of BMS include: tingling or numbness on the tip of the tongue or in the mouth bitter or metallic changes in taste dry or sore mouth.

Causes
There are a number of possible causes of burning mouth syndrome, including: damage to nerves that control pain and taste hormonal changes dry mouth, which can be caused by many medicines and disorders such as Sjgrens syndrome or diabetes nutritional deficiencies oral candidiasis, a fungal infection in the mouth acid reflux poorly-fitting dentures or allergies to denture materials anxiety and depression. In some people, burning mouth syndrome may have more than one cause. But for many, the exact cause of their symptoms cannot be found.

Diagnosis
A review of your medical history, a thorough oral examination, and a general

medical examination may help identify the source of your burning mouth. Tests may include: blood work to look for infection, nutritional deficiencies, and disorders associated with BMS such as diabetes or thyroid problems oral swab to check for oral candidiasis allergy testing for denture materials, certain foods, or other substances that may be causing your symptoms.

Treatment
Treatment should be tailored to your individual needs. Depending on the cause of your BMS symptoms, possible treatments may include: adjusting or replacing irritating dentures treating existing disorders such as diabetes, Sjgrens syndrome, or a thyroid problem to improve burning mouth symptoms recommending supplements for nutritional deficiencies switching medicine, where possible, if a drug you are taking is causing your burning mouth prescribing medications to relieve dry mouth treat oral candidiasis help control pain from nerve damage relieve anxiety and depression. When no underlying cause can be found, treatment is aimed at the symptoms to try to reduce the pain associated with burning mouth syndrome.

Helpful Tips
You can also try these self-care tips to help ease the pain of burning mouth syndrome. Sip water frequently. Suck on ice chips. Avoid irritating substances like hot, spicy foods; mouthwashes that contain alcohol; and products high in acid, like citrus fruits and juices. Chew sugarless gum. Brush your teeth/dentures with baking soda and water. Avoid alcohol and tobacco products. NIH Publication No. 10-6288 Reprinted March 2010

Burning Mouth Syndrome AAFP (American Academy of Family Physician)

MIRIAM GRUSHKA, M.SC., D.D.S., PH.D., William Osler Health Center, Etobicoke Campus, Toronto, Ontario, and Yale University School of Medicine, New Haven, Connecticut JOEL B. EPSTEIN, D.M.D., M.S.D., University of British Columbia, Vancouver, British Columbia, and University of Washington, Seattle, Washington MEIR GORSKY, D.M.D., Tel Aviv University, Tel Aviv, Israel.
Am Fam Physician. 2002 Feb 15;65(4):615-621. Patient Information Handout

Burning mouth syndrome is characterized by a burning sensation in the tongue or other oral sites, usually in the absence of clinical and laboratory findings. Affected patients often present with multiple oral complaints, including burning, dryness and taste alterations. Burning mouth complaints are reported more often in women, especially after menopause. Typically, patients awaken without pain but note increasing symptoms through the day and into the evening. Conditions that have been reported in association with burning mouth syndrome include chronic anxiety or depression, various nutritional deficiencies, type 2 diabetes (formerly known as non insulin-dependent diabetes) and changes in salivary function. However, these conditions have not been consistently linked with the syndrome, and their treatment has had little impact on burning mouth symptoms. Recent studies have pointed to dysfunction of several cranial nerves associated with taste sensation as a possible cause of burning mouth syndrome. Given in low dosages, benzodiazepines, tricyclic antidepressants or anticonvulsants may be effective in patients with burning mouth syndrome. Topical capsaicin has been used in some patients.

Burning mouth syndrome has been defined as burning pain in the tongue or oral mucous membranes, usually without accompanying clinical and laboratory findings. In the past few years, some
1,2

investigators have disputed this definition, arguing that it is too restrictive and suggesting that the syndrome may exist coincidentally with other oral conditions.
3

There has also been no clear consensus on the etiology, pathogenesis or treatment of burning mouth syndrome. As a result, patients with inexplicable oral complaints are often referred from one health care professional to another without effective management. This situation not only adds to the health care burden of these complaints but also has a significant emotional impact on patients, who are sometimes suspected of imagining or exaggerating their symptoms.
4

This article provides updated information on burning mouth syndrome and presents a new model, based on taste dysfunction, for its pathogenesis. Current treatment options are discussed, although data on the effectiveness of these treatments remain limited.

Epidemiology
Based on the makeup of most studies published to date, oral burning appears to be most prevalent in postmenopausal women. It has been reported in 10 to 40 percent of women presenting for treatment of menopausal symptoms. These percentages are in contrast to the much lower prevalence rates for oral burning in epidemiologic studies (0.7 to 2.6 percent). The reason for the gender difference between study populations (approximately 85 percent of study subjects have been women) and epidemiologic studies (which demonstrate a more equal distribution of oral burning in men and women) may be related to the definition used in each study design.
5 6 7

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 time of onset to a dental

procedure, recent illness or medication course (including antibiotic therapy). Regardless of the nature of pain onset, once the oral burning starts, it often persists for many years.
8

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. Facial skin is not usually affected. No correlation has been noted between the oral sites that are affected and the course of the disorder or the response to treatment.
5

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. 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. Earlier studies frequently minimized the pain of burning mouth syndrome, but more recent studies have reported that the pain ranges from moderate to severe and is similar in intensity to toothache pain.
8 2 9

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. No clinical factors predicting recovery have been noted.
5,10

Most studies have found that oral burning is frequently accompanied by other symptoms, including dry mouth and altered taste. Alterations in taste occur in as many as two thirds of patients and often include complaints of persistent tastes (bitter, metallic, or both) or changes in
5

the intensity of taste perception. Dysgeusic tastes accompanying oral burning are often reduced by stimulation with food. In contrast, application of a topical anesthetic may increase oral burning while decreasing dysgeusic tastes.
5,8

Etiologic 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 only small groups of patients. With the recently increased understanding of the role that taste damage plays in the pathogenesis of burning mouth syndrome, many of these etiologies can now be viewed as part of a larger model of disease.
PSYCHOLOGIC DYSFUNCTION

Personality and mood changes (especially anxiety and depression) have been consistently demonstrated in patients with burning mouth syndrome and have been used to suggest that the disorder is a psychogenic problem. However, psychologic dysfunction is common in patients with chronic pain and may be the result of the pain rather than its cause.
11

The reported success of biobehavioral 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. 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 benzodiazepines on taste-pain pathways.
12 13,14

SYSTEMIC AND LOCAL FACTORS

Although burning mouth syndrome has not been linked to any specific medical condition, associations with a wide variety of concurrent health conditions and chronic pain conditions, including headaches and pain

in other locations, have been documented. Patients with burning mouth syndrome often have high blood glucose levels, but no consistent or causal relationship has been documented. Nutritional deficiencies (vitamins B , B and B , zinc, etc.) are other findings that are not consistently supported by the literature.
15 1 2 6 5

Despite reports suggesting a significant relationship between burning mouth syndrome and mucosal ulcerative or erosive lesions, periodontitis and geographic tongue, most studies have reported no significant changes in intraoral soft or hard tissues. Similarly, chemical irritation and allergic reactions to dental materials and galvanic currents between dissimilar metals have not been found to be important causes of burning mouth syndrome.
16 8,9 16

HORMONAL CHANGES

Hormonal changes are still considered to be important factors in burning mouth syndrome, although there is little convincing evidence of the efficacy of hormone replacement therapy in postmenopausal women with the disorder. 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.
5 17 8

DRY MOUTH

It is not surprising that dry mouth has been suggested as an etiologic factor, in view of the higher incidence of this problem in patients with burning mouth syndrome. However, most salivary flow rate studies in affected patients have shown no decrease in unstimulated or stimulated salivary flow. Studies have demonstrated alterations in various salivary components, such as mucin, IgA, phosphates, pH and electrical resistance. 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
8,9 5 5 6

interactions between the cranial nerves serving taste and pain sensation.
18

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. There is an increased prevalence of so-called supertasters (persons with enhanced abilities to detect taste) among patients with burning mouth syndrome.
19

Supertasters would be more likely to be affected by burning pain syndrome because of their higher density of taste buds, each of which is surrounded by a basket-like collection of the pain neurons of the trigeminal nerve (cranial nerve V). This model would also explain the lack of effect of hormone replacement therapy once neural damage has already occurred.
20

Other investigations have found that the ability to detect bitter taste decreases at the time of menopause. This reduction in bitter taste at the chorda tympani branch of the facial nerve (cranial nerve VII) results in intensification of taste sensations from the area innervated by the glossopharyngeal nerve (cranial nerve IX) and the production of taste phantoms. It has been suggested that damage to taste might also be associated with loss of central inhibition of trigeminal-nerve afferent pain fibers, which can lead to oral burning symptoms.
21 22 19

OTHER POSSIBLE CAUSES

Case reports have linked burning mouth symptoms to the use of angiotensin-converting enzyme (ACE) inhibitors. Once these medications were reduced or discontinued, oral burning was found to remit within several weeks. Interestingly, loss of taste sensation has also been reported with the use of ACE inhibitors.
2325 23

Candidal infections are also purported to cause burning mouth syndrome. Although candidiasis can cause burning pain, its prevalence has not been found to be increased in patients with the disorder compared with control populations.
5,8

Management
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 with eating, oral dryness that waxes and wanes with the burning, and the frequent presence of taste disturbances. Even when a patient reports typical features of burning mouth syndrome, other potential causes should be ruled out (Table 1).
8

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 disturbance and salivary function. Referral to a subspecialist with expertise in this area may be beneficial in particularly difficult cases.
TABLE 1

Possible Causes and Management of Burning Mouth Symptoms

Condition Mucosal disease (e.g., lichen planus, candidiasis) Menopause Characteristic pattern Variable pattern Sensitivity with eating Onset associated with climacteric symptoms More than one oral site usually Management Establish diagnosis and treat mucosal condition. Hormone replacement therapy (if otherwise indicated) Oral supplementation

Nutritional deficiency (e.g., vitamins B , B

1 2

or B , zinc, others)
6

Dry mouth (e.g., in Sjgren's syndrome or subsequent to chemotherapy or radiation therapy); altered salivary content Cranial nerve injury

affected Possibly, mucosal changes Alteration of taste Sensitivity with eating

High fluid intake Sialagogue

Variable pattern Usually bilateral Decreased discomfort with eating Onset related to time of prescription

Medication effect

Central pain control: benzodiazepine, tricyclic antidepressant, gabapentin (Neurontin) Local desensitization: topical capsaicin If possible, change medication.

The treatment of burning mouth syndrome is usually directed at its symptoms and is the same as the medical management of other neuropathic pain conditions (Table 2). Studies generally support the use of low dosages of clonazepam (Klonopin), chlordiazepoxide (Librium) and tricyclic antidepressants (e.g., amitriptyline [Elavil]). Evidence also supports the utility of a low dosage of gabapentin (Neurontin). Studies have not shown any benefit from treatment with selective serotonin reuptake inhibitors or other serotoninergic antidepressants (e.g. trazodone [Desyrel]. .)
26 13 27 28 29

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. The beneficial effects of tricyclic antidepressants in
3

decreasing chronic pain indicate that, in low dosages, these agents may act as analgesics.
30

Topical capsaicin has been used as a desensitizing agent in patients with burning mouth syndrome. However, capsaicin may not be palatable or useful in many patients.
31

TABLE 2

Medical Management of Burning Mouth Syndrome

Exampl es of specific agents Amitripty line (Elavil) Nortriptyl ine (Pamelo r) Clonaze pam (Klonopi n) Chlordia zepoxide (Librium) Comm on dosage range* 10 to 150 mg per day

Medicat ions Tricyclic antidepr essants

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

Benzodi azepins

0.25 to 2 mg per day 10 to 30 mg per day 300 to 1,600 mg per day Variabl e (next column )

Anticon Gabape vulsants ntin (Neuront in) Capsaic Hot pepper in and water

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 doses 5 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 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 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.

*Burning mouth pain usually responds to dosages in the lower part of the given ranges. Some patients empirically appear to respond better to low-dose combinations of the medications in this table.

Burning Mouth Syndrome emedicine 5 januari 2009 Background

Burning mouth syndrome (BMS) is an idiopathic condition characterized by a continuous burning sensation of the mucosa of the mouth, typically involving the tongue, with or without extension to the lips and oral mucosa. Classically, burning mouth syndrome (BMS) is accompanied by gustatory disturbances (dysgeusia, parageusia) and subjective xerostomia. By definition, no macroscopic alterations in oral mucosa are apparent. Burning mouth syndrome (BMS) occurs most frequently, but not exclusively, in peri-menopausal and postmenopausal women. See the following illustration.

A 29-year-old female presents with tongue irritation. A diagnosis of benign migratory glossitis (geographic tongue) is made by the appearance. The portions of the tongue with atrophic filiform papilla are symptomatic to acidic foods.

Burning mouth syndrome (BMS) is a clinical diagnosis made via the exclusion of all other causes. No universally accepted diagnostic criteria, laboratory tests, imaging studies or other modalities definitively diagnose or exclude burning mouth syndrome (BMS). Various attempts to classify burning mouth syndrome (BMS) based on etiology and symptoms have been made. In a classification by etiology or cause, idiopathic burning mouth syndrome (BMS) is considered primary BMS (or "true BMS"), whereas secondary BMS has an identifiable cause. For the purposes of this article, we will use these terms.

Another classification of burning mouth syndrome (BMS) is based on symptoms, stratifying cases into 3 types, as follows:[1] Type 1 burning mouth syndrome (BMS): Patients have no symptoms upon waking, with progression throughout the day. Nighttime symptoms are variable. Nutritional deficiency and diabetes may produce a similar pattern. Type 2 burning mouth syndrome (BMS): Patients have continuous symptoms throughout the day and are frequently asymptomatic at night. This type is associated with chronic anxiety. Type 3 burning mouth syndrome (BMS): Patients have intermittent symptoms throughout the day and symptom-free days. Food allergy is suggested as a potential mechanism. Burning mouth syndrome (BMS) is likely more than one disease process, and the etiology may be multifactorial. The ambiguous definition of burning mouth syndrome (BMS) makes evaluation of prognosis and treatment difficult.

Anatomy and Physiology

The oral cavity is comprised of mucosa, glands, muscle, teeth and sensory receptors. The sensory capabilities of the oral cavity include pain, temperature, proprioception, light touch, vibration, and taste. Efferent innervation supplies muscles of mastication, the tongue, and autonomic reflexes. Below is an overview of the neuroanatomy, with particular paragraphs highlighting the most relevant elements. Somatosensory innervation Somatosensory innervation is provided by the maxillary (V2) and mandibular (V3) branches of the trigeminal nerve and the glossopharyngeal nerve (IX). The V2 branch supplies the following: Hard and soft palate Mucosa of the maxillary vestibule Upper lip Maxillary teeth Maxillary periodontal ligaments Maxillary gingiva The V3 branch supplies the following: Buccal mucosa Anterior two thirds of the tongue (lingual branch)

Mandibular teeth Mandibular periodontal ligaments Mandibular gingiva Anterior mandibular vestibule Lower lip The glossopharyngeal nerve innervates the following: Posterior third of the tongue Posterior wall of the pharynx Pertinent to burning mouth syndrome (BMS), the lingual branch of the mandibular nerve (V3) supplies the anterior two-thirds of the tongue. It has superficial and deep fibers, which have small receptive fields and low thresholds, creating a highly sensitive sensory field. Pain and temperature in the mouth are sensed by both simple free nerve endings and by more organized nonmyelinated endings. Sensory innervation of the periodontal ligaments provides proprioceptive information about pressure on the teeth and oral stereognosis (perceiving the form of an object) as well as jaw opening and salivation reflexes. In general, the anterior and midline portions of the oral cavity tend to be more sensitive than the posterior and lateral aspects to discriminatory touch and warm temperatures. Cold temperatures are perceived more uniformly throughout the mouth. Trigeminal neuroanatomy The trigeminal nerve enters the brainstem at the pons and bifurcates in the principal sensory nucleus. There, the different types of fibers in the trigeminal nerve follow different courses, as follows: Discriminatory tactile fibers synapse in the principal sensory nucleus, cross midline, and ascend in the medial lemniscus to the ventroposterior medial nucleus of the thalamus (VPM). Afferent proprioceptive fibers of V3 from masticatory muscles (masseter, temporalis, medial and lateral pterygoids) pass through the principal sensory nucleus. Their cell bodies are located in the mesencephalic nucleus superior to the principal sensory nucleus, and they synapse in the motor nucleus medial to the principal sensory nucleus. Nociceptive (pain and temperature) fibers pass through the principal sensory nucleus and descend before synapsing in the large spinal trigeminal nucleus of the medulla. The spinal nucleus contains 3 subnuclei from cranial to caudal: oralis, interpolaris, caudalis. Generally, pain fibers synapse in the subnucleus caudalis prior to crossing and ascending in the spinothalamic tract.

Of importance with respect to burning mouth syndrome (BMS), the spinal nucleus may be important in central sensitization of peripheral trigeminal nerve fibers via alterations in NMDA (N-methyl D-aspartate) receptors. Taste Chemoreceptors for taste are supplied by the chorda tympani branch of the facial nerve (VII) to the anterior two thirds of the tongue, while the posterior third of the tongue and pharynx are supplied by the glossopharyngeal nerve (IX). The chorda tympani is probably most responsible for taste alterations in burning mouth syndrome (BMS). A small population of taste receptors on the soft palate is supplied by the greater superficial petrosal nerve branch of the facial nerve. The larynx bears some taste receptors that are innervated by the superior laryngeal nerve. Trigeminal nerve (V) endings also supply some sensation of taste. They respond more to chemically active compounds such as ammonia, menthol, and capsaicin. Noxious stimuli can stimulate salivation and the cough reflex via these trigeminal afferents. Salivation Mechanical and gustatory stimuli incite parotid, submandibular, and sublingual salivary flow. In particular, stimulation to the anterior tongue is effective in activating submandibular and sublingual glands, while posterior lingual stimulation is more effective at engaging parotid flow. Ions present in saliva, particularly sodium, produce continual low-level stimulation of taste receptors. In theory, the content of saliva may affect sensitivity of taste receptors. This may explain how medications and metabolic conditions alter taste perception (dysgeusia) or produce novel tastes, such as bitter or metallic tastes in the mouth (parageusia.) Acute decreases in the quantity of saliva do not appear to affect gustatory sensitivity; however, chronic deprivation (as in Sjgren Syndrome or after radiation therapy) does appear to result in decreased sensitivity of receptors by trophic effects.

Pathophysiology
The pathophysiology of burning mouth syndrome (BMS) is not understood. It was originally considered a psychogenic illness; however, a neuropathic mechanism for burning mouth syndrome (BMS) is currently favored. This is based on objectively measured abnormalities of physiologic responses of the trigeminal nerve in burning mouth syndrome (BMS) patients.[2, 3] There is also evidence to suggest histopathologic changes in nociceptive fibers in BMS patients.[56] The differentiation between a peripheral versus a central

etiology has not been determined. There is evidence[50] to suggest that anxiety is associated with BMS but whether it is a cause or the result of intractable symptoms has not been elucidated. One small study proposed that unilateral chorda tympani (taste) hypofunction results in lingual nerve (somatosensory) hyperfunction by disruption of a centrally mediated equilibrium between the two.[4] Observation in other conditions has shown that when a sensory circuit loses afferent signals that hyperactivity may result in hallucinatory sensations. Examples of this include phantom limb sensation following amputation and tinnitus in hearing loss. It would tend to account both for pain and for gustatory disturbances in burning mouth syndrome (BMS). Metallic or sour tastes are considered symptomatic manifestations of an understimulated gustatory circuit while understimulated sensory circuitry manifests burning sensations. The cause of this proposed neuropathy is unknown. Studies focusing on trigeminal nerve alterations have found both hypersensitivity and hyposensitivity as well as large and small fiber neuropathy.[5, 3, 2, 6] These studies suggest that burning mouth syndrome (BMS) may have multiple etiologies producing similar symptoms. Xerostomia in burning mouth syndrome (BMS) is likely related to neuropathy, rather than glandular dysfunction. In studies of burning mouth syndrome (BMS) patients in comparison to controls, differences in salivary content have been documented, but no differences in salivary quantity or flow have been identified.[7, 8] Burning mouth syndrome (BMS) has been associated with oral parafunctional habits such as bruxism, clenching, and tongue thrusting. The bruxism and clenching are increased with anxiety, which is also associated with burning mouth syndrome (BMS). Although psychogenesis is no longer regarded as the primary cause, it may exacerbate symptoms. Whether burning mouth syndrome (BMS) has a neurologic abnormality in common with parafunctional behaviors has yet to be adequately investigated.

Epidemiology
Good epidemiologic data documenting incidence and prevalence of burning mouth syndrome (BMS) are lacking. Statistical values vary widely and are likely affected by variable definitions of burning mouth syndrome (BMS).

The overall prevalence is roughly 4%.[9] Women are 3-7 times more likely than men of a similar age to experience burning mouth syndrome (BMS) symptoms.[9, 10] Burning mouth syndrome (BMS) is rarely observed in patients younger than 30 years of age and prevalence may increase from 3- to 12- fold with increasing age.[9] No racial or ethnic predilections have been reported. BMS is associated with a higher incidence of GI and urogenital disease, the significance of which is still unclear.[57]

History
History is the cornerstone of diagnosis. Although burning mouth syndrome (BMS) is a diagnosis of exclusion, several elements are supportive: Bilateral mouth discomfort (burning/pain) Pain deep in the oral mucosa Symptoms present for at least 4-6 months Xerostomia Dysgeusia Symptoms that are nearly constant throughout the day No clear precipitating factors Alleviated or aggravated by drinking/eating Mood or personality disruptions The absence of any of the above symptoms does not exclude a diagnosis of burning mouth syndrome (BMS). See the image shown below.

A 55-year-old female with tongue burning for 15 months. The history for cancer risk factors was negative. Examination failed to reveal any systemic or local causes. Diagnosis of burning mouth syndrome (BMS) was made, and the patient received no medical treatment except for serial examinations.

Classically, 3 major symptoms are associated with burning mouth syndrome (BMS): pain, dysgeusia, and xerostomia. These occur nearly

continuously for at least 4-6 months. The complete triad (pain, dysgeusia, xerostomia) is most commonly found in peri-menopausal and postmenopausal women, while other populations may have fewer symptoms. Pain Pain is typically the major symptom. The pain is described as burning, scalding, tingling, or numbness. It is bilateral, typically involving the anterior two thirds of the tongue or tip. The hard palate mucosa and lips may also be involved. The buccal mucosa and floor of the mouth are atypical sites. In patients with dentures, alveolar ridges/gingiva are common sites. Involvement of the throat may be suggestive of allergy or gastroesophageal reflux disease (GERD). The pain may be mild to severe. It may be constant or worse at the end of the day with no pain on waking. It may or may not interfere with sleep, typically it does not. Food and drink may or may not exacerbate symptoms. Hot, acidic or spicy foods typically aggravate pain in patients who report worsening of symptoms with ingestion. Speaking may also exacerbate pain in select individuals. Dysgeusia Dysgeusia is present in up to 70% of cases and may take the form either of a persistent taste in the mouth or altered perception of tastes. Dysgeusic tastes may be bitter, metallic, or mixed. Alterations may take the form of decreased perception of sweetness or intensified sensation of sweet or sour flavors. Xerostomia Xerostomia is a symptom in up to 64% of patients. Patients may not volunteer symptoms of xerostomia but affirm it on direct questioning. Xerostomia in burning mouth syndrome (BMS) is unlikely to be objectively confirmed by quantitative tests of salivary function. Some evidence suggests differences in salivary composition;[7, 8] however, this relationship to symptoms of pain or dysgeusia is not clear. Other associated symptoms and conditions Burning mouth syndrome (BMS) may be associated with various other nonspecific symptoms.[11, 12] Elicit information about bruxism or clenching, which may cause headache, ear, temporomandibular joint pain, or myofascial pain in masticatory, neck, shoulder, and suprahyoid muscles that can be associated with burning mouth syndrome (BMS). Patients may

not be aware of these parafunctional behaviors, but bruxism can be observed by family members during sleep, particularly if it is loud. The patient may also notice clenching if made aware. Other signs of bruxism include worn tooth enamel, tooth sensitivity, or superficial ulceration of buccal mucosa. Tongue thrusting in patients with burning mouth syndrome (BMS) may be identified by having the patient swallow a liquid while smiling; leakage through the teeth is suggestive. Patients or family members may also report puckering or tightening of the lips during swallowing. Mood and emotional disturbances have been associated with burning mouth syndrome (BMS). In particular, patients may note anxiety, irritability, mood changes, and other symptoms consistent with depression, including changes in appetite and decreased desire to socialize. These symptoms have not been studied in relation to sleep disruption in patients with burning mouth syndrome (BMS). Whether mood symptoms are predisposing factors or are caused by the disorder is unclear.[13] Excluding secondary BMS Because burning mouth syndrome (BMS) is a diagnosis of exclusion, inquiring about symptoms or history that may be consistent with other disorders is important. Symptoms suggestive of other underlying conditions include fatigue, hot flashes, irregular periods, vaginal dryness, mood swings, irritability, weight loss or gain, skin and nail changes, heartburn, polyuria, polydipsia, numbness or tingling in any other area of the body, neurologic symptoms, fevers, lymphadenopathy, cough, shortness of breath, or lightheadedness. A thorough review of medical history for menopause and climactic symptoms, diabetes, thyroid disorders, anemia, vitamin deficiencies, GERD, use of dental prostheses, and neurologic and connective tissue disorders may be helpful. Reviewing medications that may cause xerostomia as well as medications implicated in BMS-like symptoms such as ace-inhibitors, angiotensin receptor blockers, and antiretrovirals is important. Reviewing diet, alcohol consumption, tobacco, or other chew products for possible reversible causes of BMS-like symptoms is helpful. Some tooth pastes or mouth rinses containing mint flavoring may also cause or aggravate burning mouth syndrome (BMS) symptoms.

Physical Examination

In true (idiopathic) burning mouth syndrome (BMS), no clinically evident lesions should be in the oral cavity, including the most symptomatic areas. A thorough examination should be conducted to investigate alternate diagnoses. Head and neck examination Oral inspection may identify any areas of atrophy (see first image below), erythema, leukoplakia (see second image below) erosion, or ulceration (see third image below). Bimanual palpation of the tongue, tonsils, and floor of the mouth aid in evaluating deep tissues

for masses or infections. A 29-year-old female presents with tongue irritation. A diagnosis of benign migratory
glossitis (geographic tongue) is made by the appearance. The portions of the tongue with atrophic filiform papilla are symptomatic to acidic foods.

A 60-year-old male with a 2-week history of tongue and mouth burning. The lateral
tongue was positive for C. albicans fungus inflammation. The black arrow identifies a white tongue lesion. The patient was treated with oral clotrimazole.

 A 63-year-old female presents with tongue discomfort lasting 6 months. She had a
right tongue squamous cell carcinoma that extended to the regional lymphatics. She was treated with combined modality therapy.

Dental examination may reveal damage to enamel or worn teeth (a sign of bruxism/clenching) or protrusion of the front teeth/malocclusion (a sign of tongue thrusting). Palpation of the jaw, muscles of mastication, neck, shoulder, and suprahyoid muscles for tenderness suggests temporomandibular joint disorder or bruxism. Palpation for submental, submandibular, cervical, and supra/infraclavicular lymphadenopathy may identify signs of possible infection or neoplasm. Palpation of the thyroid gland may suggest thyroid disease. Other Examination of the skin and nails may indicate possible nutritional deficiencies. Examination of the joints and skin may suggest connective tissue diseases. A complete neurologic examination with particular attention to sensory disturbances may be supportive of a systemic disorder, such as diabetes or B12 deficiency.

Proposed Etiologies
No consensus exists regarding a definitive cause. Rather, burning mouth syndrome (BMS) appears to be multifactorial in origin. Many of the currently proposed etiologies describe secondary, rather than primary burning mouth syndrome (BMS). Endocrine Menopause, whether surgical or physiological, is associated with a higher

prevalence of burning mouth syndrome (BMS), and, while the mechanism is unclear, hormonal alterations in oral mucosa have been suggested as a cause. Estrogen has documented effects on oral mucosa, and deprivation may lead to atrophic changes thereby altering stimulation of the nerve endings within the epithelium.[14] Alternatively, atrophic epithelia may be more prone to inflammation. Peripheral neuropathy secondary to diabetes mellitus is a cause of secondary burning mouth syndrome (BMS).[15] Immunologic An immunologic mechanism for burning mouth syndrome (BMS) has been suggested by the observation of elevated serum ESR and salivary IgA in burning mouth syndrome (BMS) patients compared with controls.[16, 17] Allergies are infrequently identified in patients with burning mouth syndrome (BMS) but have been suggested as a cause of Type 3 burning mouth syndrome (intermittent symptoms). However, typically they are associated with signs of mucosal irritation. Suggested irritants include dental materials such as mercury (present in amalgam), methyl methacrylate, cobalt chloride, zinc and benzoyl peroxide.[18] Components of lotions such as petrolatum cadmium sulfate, octyl gallate, benzoic acid, and propylene glycol have been implicated. Food allergens include peanuts, chestnuts, cinnamon, and sorbic acid.[1] Nicotinic acid has also been suggested. Nutritional Deficiencies of B vitamins 1, 2, 6, and 12, as well as zinc[54] , folate and iron, have been suggested as causes of secondary burning mouth syndrome (BMS), either from direct neurologic damage or in relation to anemia. Neuropsychiatric Anxiety, if present, is usually considered an exacerbating factor, rather than a cause of the chronic pain picture of burning mouth syndrome (BMS).[9] Cases of spontaneous resolution of symptoms after positive life events have been reported. Patients with burning mouth syndrome (BMS) may also have increased salivary cortisol relative to controls, indicative of higher levels of stress.[19] A proportion of patients have anxiety centered around concerns of cancer, or cancerphobia.[20] At this point, the nature of the association between burning mouth syndrome (BMS) and anxiety is not clear.

Endogenous or reactive depression has been implicated; however, depression is strongly associated with anxiety.[9] Whether depression is directly connected to burning mouth syndrome (BMS) is unclear. Serotonin deficiency has been suggested as a possible mechanism for sensory alterations in burning mouth syndrome (BMS) because of its role in the descending inhibition of pain. In addition to serotonin, alterations in dopamine transmission and nigrostriatal pathway abnormalities have been suggested as a root cause for the dysesthesia.[21] Whether parafunctional habits relate to dopamine transmission is unclear. Infectious Oral infection has been explored, and a few microbes have been identified to be potentially more prevalent in burning mouth syndrome (BMS) patients without visible mucosal lesions: Candida, Enterobacter, Fusospirochetals, Helicobacter pylori, and Klebsiella. Of note, candidal infections may not always produce visible lesions.[52] Iatrogenic Various cases of drug-associated burning mouth syndrome (BMS) have been reported. ACE inhibitors and angiotensin receptor blockers are perhaps the most commonly noted in case reports.[22, 23, 24] This may be the product of an inflammatory reaction generated by increases in bradykinin (similar to the mechanism by which angioedema may result). The mechanism as it relates to burning mouth symptoms has not been determined, but kallikrein, a molecule active in the kinin pathway, may be increased in the saliva of burning mouth syndrome (BMS) patients, resulting in increased inflammation.[7] Other drugs that have been reported are the antiretrovirals nevirapine and efavirenz.[25, 26] No clear mechanism has been proposed. L-thyroxines have also been implicated in burning mouth syndrome (BMS), although whether the medication itself or the underlying hypothyroidism is the cause is unclear.[27] Topirimate, a common treatment for trigeminal neuralgia, has been reported to cause BMS-like symptoms.[57] Burning mouth syndrome (BMS) symptoms have been noted in patients with dental prostheses.[28] Local trauma (particularly in patients with parafunctional habits) has been proposed as a mechanism of secondary burning mouth syndrome (BMS). As mentioned above in Immunologic etiologies, contact dermatitis due to materials used in prostheses may also be a mechanism.

Differential Diagnosis
Distinguishing primary (idiopathic) burning mouth syndrome (BMS) from secondary burning mouth syndrome (BMS) is important. The following conditions may produce BMS-like symptoms: Candidiasis[52] Sjgren Syndrome Scleroderma GERD Anemia Diabetes Vitamin deficiency (B1, B2, B6, B12, folate, iron) Hypothyroidism Multiple sclerosis Anxiety Dehydration Mouth breathing/nasal obstruction Alcohol-based mouthwash Medication reaction (eg, ACE inhibitors, ARBs, antiretrovirals, psychotropic, anticholinergic, clonazepam,[29] chemotherapeutic agents) Radiation-induced stomatitis Aphthous stomatitis Contact stomatitis Erosive lichen planus Pemphigoid Pemphigus Geographic tongue Mandibular fracture Neoplasia Impacted teeth Infections of bone, teeth, or implants Ciguatera neurotoxin exposure[30] Chewing tobacco use Areca nut extract exposure[31] Leukoplakia Bacterial infection[32]

Laboratory
No laboratory tests diagnose burning mouth syndrome (BMS), but the patients history and examination may indicate the need for any of the following studies:

CBC count Serum B vitamin levels Serum folate Serum ferritin Serum blood glucose (fasting or glucose tolerance test) Urine analysis for glucose TSH T4 Thyroid binding globulin Antithyroperoxidase antibodies Antithyroglobulin antibodies Antimicrosomal antibodies LH FSH Sialochemistry ESR Anti SS-A, Anti SS-Ro, Anti SS-B, Anti SS-La antibodies RF ANA

Imaging
Imaging is rarely indicated but may be useful to identify specific causes of secondary burning mouth syndrome (BMS), as follows: CT scans of the head may be useful if a mass lesion is suspected. MRI of the head, brain, and/or spinal cord may assist in diagnosing mass lesions (either neoplastic or infectious) or neuropathies such as multiple sclerosis. Thyroid echography is useful if gross thyroid lesions are suspected.

Other Diagnostic Tests and Procedures

The patients history and examination should direct the use of the following tests: Bacterial culture (especially anaerobes) KOH of lingual scraping Fungal culture Biopsy of tongue or mucosa Sialometry Schirmer's test Laryngoscopy or endoscopy if reflux is suspected.

 Lumbar puncture with gel electrophoresis Patch testing for methylmethacrylate mercury, cobalt chloride, benzoyl peroxide, petrolatum cadmium sulfate, octyl gallate, benzoic acid, propylene glycol, peanuts, chestnuts, cinnamon, sorbic acid, and nicotinic acid among others.

Treatment & Management

Studies of burning mouth syndrome (BMS) have focused more on etiology than treatment. Currently, no definitive cure exists; many treatments have been tried with variable success. Attempting combinations of therapies may be appropriate; in particular, cognitive therapy may be synergistic with other agents. Additionally, it may be worth empirically treating for other conditions that cause secondary burning mouth syndrome (BMS) based on the nature of symptoms or exam findings. Because burning mouth syndrome (BMS) is a chronic pain syndrome, patients must have realistic expectations of the natural course of their condition. For patients with primary burning mouth syndrome (BMS), an estimated 50-66% may have improvement in symptoms after 6-7 years.[9] A small study of 32 patients reported near universal improvement in symptoms within 16 weeks for patients receiving ongoing multidisciplinary treatment.[53] Spontaneous remission is rare but does occur in roughly 3% of patients.[33] These findings are similar to other idiopathic chronic pain syndromes and support the idea that treatment should be individualized based on symptoms. Continued follow-up is also likely help patients with management of symptoms. The following treatments for primary burning mouth syndrome (BMS) have been suggested with variable evidence to support their use[34] : Clonazepam (low-dose) dissolvable wafers (may be better than tablets)[35] Alpha lipoic acid[35] Intermittent oral capsaicin[36] Psychotherapy (cognitive behavioral modification, relaxation)[35] Topical capsaicin[1] Hormone replacement therapy SSRIs Tricyclic antidepressants Oral lidocaine Near infrared irradiation of the stellate ganglion, to inhibit sympathetic discharge and improve blood flow to the tongue in glossodynia (still

experimental)[37] Laser therapy[38] Topiramate[39] Olanzapine[40] acupuncture (to increase microscopic blood flow, small, uncontrolled study)[55] Treatments for secondary burning mouth syndrome (BMS) include the following: Discontinuation of medications that may cause xerostomia, such as anticholinergics or psychotropics Substitution of medications that may cause oral burning (If an ACE inhibitor, ARB, or antiretroviral is suspected, trying another medication in the same class is reasonable.) Adjustment of levothyroxine dosing Oral nystatin Abstinence from smoking and oral tobacco use Avoidance of allergens Adjustment of dentures (refitting and/or substituting materials) Chewing sorbitol-containing gum to stimulate saliva Pyridostigmine, Pilocarpine, or other sialogogues B vitamin supplementation Zinc supplementation[54] Iron supplementation Folate supplementation Neuropathic analgesics

Medications
Clonazepam (oral or wafers) Diazepam Amitriptyline Nortriptyline Doxepin Fluoxetine Paroxetine Sertraline

Chlordiazepoxide Capsaicin (oral or topical) Olanzapine (case report with low dose) Topiramate (case report)