|Year : 2015 | Volume
| Issue : 1 | Page : 2-8
Burning mouth syndrome: An update
Vijay Kumar Ambaldhage1, Jaishankar Homberhalli Puttabuddi2, Purnachandrarao Naik Nunsavath3
1 Department of Oral Medicine and Radiology, P M Nadagouda Memorial (PMNM) Dental College and Hospital, Bagalkot, India
2 Department of Oral Medicine and Radiology, Jagadguru Sri Shivarathreeswara Dental College and Hospital, Mysore, Karnataka, India
3 Department of Oral Medicine and Radiology, SIBAR Institute of Dental Sciences, Takkellapadu, Guntur, Andhra Pradesh, India
|Date of Web Publication||1-Dec-2014|
Vijay Kumar Ambaldhage
Department of Oral Medicine and Radiology, PMNM Dental College and Hospital, Bagalkot - 587 101, Karnataka
Source of Support: None, Conflict of Interest: None
Burning mouth syndrome (BMS) is characterized by an oral burning sensation in the absence of any organic disorders of the oral cavity. Although the cause of BMS is not known, a complex association of biological and psychological factors has been identified, suggesting the existence of a multifactorial etiology. It is observed principally in middle-aged patients and postmenopausal women and is characterized by an intense burning type of pain, preferably on the tongue and in other areas of the oral mucosa. As the symptom of oral burning is seen in various pathological conditions, it is essential for a clinician to be aware of how to differentiate between symptom of oral burning and BMS. This article provides an overview of the literature on this syndrome with special reference to the etiological factors, clinical aspects, diagnostic criteria that should be followed and the therapeutic management with reference to the most recent studies.
Keywords: Glossodynia, glossopyrosis, glossalgia, stomatodynia
|How to cite this article:|
Ambaldhage VK, Puttabuddi JH, Nunsavath PN. Burning mouth syndrome: An update. Indian J Pain 2015;29:2-8
| Introduction|| |
Burning mouth syndrome (BMS) is a chronic orofacial pain condition characterized by deep burning pain of the oral mucosa in absence of identifiable local or systemic pathology, lasting at least 4-6 months.  It is associated with burning, stinging, and/or itching of the oral cavity in the absence of any organic disease and most often involves the tongue with or without extension to the lips and other parts of oral mucosa.  It can be accompanied by dysgeusia (distortion in sense of taste) and subjective xerostomia (dry mouth). It is observed principally in middle-aged patients and postmenopausal women.  Probably of multifactorial origin, and often idiopathic, with a still indefinite etio-pathogenesis in which local, systemic and psychological factors are implicated. Currently there is no consensus on the specific treatment of the condition.  This article provides an overview of the literature on this syndrome with special reference to the etiological factors, clinical aspects, diagnostic criteria that should be followed and the therapeutic management with reference to the most recent studies.
The BMS has been defined principally by the quality or location of the pain. The International Association for the study of Pain (IASP) defines BMS as "A pain of at least 4-6 months duration located on the tongue or other oral mucosal membranes associated with normal clinical or laboratory findings". 
The International Headache Society (IHS) in the International Classification of Headache Disorders-II classifies BMS in the category of cranial neuralgias and central causes of facial pain within the subcategory of central causes of facial pain. According to the IHS, burning mouth syndrome is "an intraoral burning sensation for which NO dental or medical cause is found". 
The BMS is also called as Stomatodynia, Stomatopyrosis, Oral dysesthesia, Sore mouth and Sore tongue. The most affected area is the tongue (tip and lateral borders) thus denominated the terms Glossodynia (painful tongue), Glossopyrosis (burning tongue) and Glossalgia. ,
Authors prefer to use the term 'syndrome' to refer to this entity due to the frequent association of burning sensation in oral cavity with other symptoms like xerostomia and taste alterations in the absence of any organic disease and the complexity surrounding the condition of the patient. 
Burning mouth syndrome is a debilitating medical condition affecting nearly 1.3 million of Americans. The true prevalence of BMS is difficult to establish due to the lack of accurate diagnostic criteria in many of the published series that do not distinguish between the symptom of oral burning and the BMS. Thus the prevalence varies between 0.6-15% in general population.  The female/male ratio of occurrence of BMS is 7:1. The prevalence of BMS increases with age in both males and females, mainly affecting the middle aged females in the fifth to seventh decade of life.  Its prevalence is estimated 18-33% in postmenopausal women. 
The condition affects multiple sites in the oral cavity, but the tip of the tongue is the most common location (71%) followed by lips (50%), lateral border of tongue, (46%) and palate (46%). 
A typical patient with BMS is postmenopausal woman of age fourth to sixth decade with various medical comorbidities. Patients usually complains of the classic triad of chronic oral mucosal burning pain associated with dysgeusia and xerostomia with no visible disease in the oral mucosa for 4-6 months duration.  Clinical presentations may vary as some patients can be oligosymptomatic (pain and dysgeusia or xerostomia) or monosymptomatic (pain only).  In general, 63% of patients report accompanying dry mouth, 60% of patients may report bitter/metallic taste, and 35% may complain of altered taste perception. 
Pain characteristics in BMS
The patients usually complaint of chronic pain of 4-6 month duration, burning or scalding type, sometimes itching sensation or numbness of the tongue and other oral mucosal surfaces.  The onset of pain can be either gradual and spontaneous or sudden and related to a precipitating event such as any dental procedure. Typically pain is localized to tongue and sometimes involving other mucosal surfaces also like palate, lip, buccal mucosa and floor of mouth. The pain will be continuous or intermittent, mild to moderate in intensity, localized to the oral cavity and does not radiate to other regions of face. The pain typically relieves on intake of food or liquids, which is in contrast to burning symptom in other diseases; in which the pain aggravates. Patients do not normally wake up during the night, but do find it difficult to get to sleep. ,
Review of systems may be remarkable for headache, chronic fatigue, gastrointestinal and urogenital symptoms, insomnia, mood changes, irritability, anxiety and depression. Physical examination and laboratory analysis are classically unremarkable in primary BMS. However, they can be abnormal in secondary BMS. 
According to Scala A et al., BMS classified into two types: 
- Primary BMS/idiopathic BMS: for which NO organic local/systemic causes are identified.
- Secondary BMS: resulting from local/systemic pathological conditions and thus this form responds well to the etiology-directed therapy.
According to Lamey and Lamb (1994) the BMS can be divided into three clinical types depending on the diurnal fluctuations of symptoms. 
- Type 1: it is characterized by progressive burning type of pain. Patients wake up without pain, which then increases gradually throughout the day. Affects approximately 35% of patients. This type may be associated with systemic diseases, such as nutritional deficiencies.
- Type 2: in this the symptoms are constant throughout the day and patients find it difficult to get sleep. Affects 55% of patients. These patients usually present associated psychological disorders.
- Type 3: symptoms are intermittent, with atypical location and pain. Constitutes 10% of patients. It seems that contact with oral allergens could play an important etiologic role in this group.
The BMS is a primary diagnosis. Several factors are reported as being associated with burning mouth symptoms, including xerostomia, allergies to dental restorative materials, oral candidiasis, systemic nutritional deficiency (e.g. vitaminB1, B2, B12, folic acid and zinc), diabetes, hormonal disturbances, oral ulcer and periodontitis. Nonetheless, diagnosis of BMS requires the exclusion of secondary causes.
Diagnosis of BMS may be complex for three main reasons  :
- BMS is positively defined only by symptom(s) without regard to signs or etiologies.
- The symptomatic triad rarely occurs simultaneously in same patient.
- Overlapping or overwhelming stomatitis may confuse the clinical presentation.
As a result, clinicians can arrive at a diagnosis of BMS by matching specific details of the main complaint with clinical oral findings that exclude oral mucosal changes, the only exception being the presence of stomatitis, which requires proper and prompt management.
The diagnostic Criteria developed by Scala for the diagnosis of burning mouth syndrome are as follows  :
- Daily deep burning sensation of the bilateral oral mucosa.
- Burning sensation for at least 4-6 months.
- Constant intensity or increasing intensity during the day.
- No worsening on eating or drinking. Instead the burning sensation may reduce.
- No interference with sleep.
- Dysgeusia and/or xerostomia.
- Sensory or chemosensory alterations.
- Mood changes or psychopathological alterations.
The symptom of "oral burning" sensation might be associated with a large number of local and systemic factors. But, the term "burning mouth syndrome" or a true "BMS" should be applied only if burning sensation occurs in clinically healthy oral tissues in the absence of all aforementioned known local and systemic factors. The various conditions in which patients feels the symptom of oral burning are summarized in [Table 1].
Xerostomia is a concomitant symptom in patients with BMS, prevalence varying between 34 and 39%, while Grushka et al., found that this is equal to or greater than 60%. In contrast, some authors consider that the composition (increased concentrations of K+, Na+, Cl-, Ca+2, immunoglobulin A, amylase) of the saliva could play a major role in the pathogenesis of BMS. 
A study was done to assess the efficacy of anti-xerostomic topical medication (urea 10%) in patients with BMS by Luciana A da Silva et al. The patients were evaluated before and after treatment with the xerostomia questionnaire and quantitative sensory testing. The results showed no differences between control and BMS groups and both exhibited an association between reported improvement and salivation. There was an improvement in chewing and generalized pain complaints, supporting the role of saliva in oral health and the patho-physiological effects of local chronic pain. 
Cavalcanti et al., found no difference in the presence of Candida albicans between BMS and control patients. Thus, candidiasis has not been confirmed as an associate etiological factor for BMS. 
Some authors have pointed out a possible relationship between diabetes mellitus and BMS, since this syndrome is found in 2-10% of diabetic patients. Although Sardella et al., did not found this relationship; burning sensation could be a symptom of an undiagnosed diabetes mellitus and perhaps the control of diabetes leads to the improvement or cure of burning sensation. ,
Deficiency disorders have always been referred as cause of burning symptom. Nutritional deficiencies have been claimed to cause oral mucosal burning in 2-33% of patients. Zinc deficiency may cause organic effects such as lingual papillary atrophy, resulting in dysgeusia and glossodynia.  Tanaka et al., noted improvement in symptoms following zinc intake and further clinical improvement when zinc was associated with B12 vitamin and iron. 
BMS may change the individual's general and psychological well being, reducing the quality of life, even though it is not clear if psychopathologic distress is related to this syndrome or it is a result of the chronic oral burning symptoms that these patients suffer. Some studies have reported that people with BMS experience adverse life events more frequently than people without BMS, which may be a risk factor for developing BMS. Hakeberg et al., focusing on psychological aspects of women with BMS, observed that all patients in their study had gone through situations of great stress or disappointment in their lives leading to chronic oral pain. 
A study by Bakhtiari S et al., to correlate between BMS and anxiety in the elderly inmates of sanitaria in Tehran showed that highly significant differences in anxiety scores between the case and control groups. They evaluated the state and trait anxiety using Cattell Anxiety Scale. The trait anxiety scores or anxiety were significantly higher in BMS patients than the controls. 
An clinical study by Tatullo M et al., to assess the correlation between the BMS and oxidative stress, in which Oxidative stress assessment was performed by means of an integrated analytical system. Study results indicated that female patients affected by BMS show significantly different oxidant capacity and biological antioxidant potential as iron-reducing activity levels, similar to those present in oxidative stress condition with respect to the general population. Thus confirming the effectiveness of antioxidant treatments in these patients to prevent or decrease the onset of oxidative stress. 
There is evidence of a possible relationship between BMS and psychogenic factors, as shown by Sardella et al. More recently several authors have investigated the trigeminal somatosensory system in order to detect neurogenic abnormalities. These studies suggest peripheral alterations in the function of this system with the presence of abnormal reflex. 
Calcitonin gene-related peptide (CGRP) is one of the neurotransmitters found in the nerve fibers of the nervous system that is involved in salivary secretion and plays an important role in the development of pain and hyperalgesia. Supporting this interpretation, some studies showed that the use of neuroprotective/neurotropic drugs improved the symptoms in patients with BMS. However, Zidverc-Trajkovic et al., found no elevated levels of CGRP in the saliva of patients with BMS, which seems to demonstrate the trigeminal nerve degeneration in this syndrome. 
Gao et al., found anxiety, depression and somatization symptoms to be the most common psychological problems in BMS.  Bergdahl et al., demonstrated that patients with BMS exhibited low levels of socialization and high levels of anxiety and health status concern when compared to a Control Group.  It has been shown that BMS exerts a negative impact on the quality of life of affected individuals. According Lσpez-Jornet et al., patients with BMS have poorer scores on all scales that measure quality of life. 
More recently, a beguiling hypothesis has been proposed that burning mouth syndrome is associated with an alteration of gonadal, adrenal and neuroactive steroid levels. Woda et al., suggested that chronic anxiety or stress results in a dysregulation of adrenal steroids. A reduction in adrenal steroids may lead to an altered production of neuroactive steroids in skin, mucosa and the nervous system.  The relationship with menopause is proven by the suggestion that the dramatic fall in gonadal steroids that occurs at that time further alters the production of neuroactive steroids. 
Since both BMS and vulvodynia occur more frequently in menopausal women, estrogen deficiency could be considered as a common pathological mechanism of these clinical conditions. Estrogen receptors are also identified in both the tongue and the vaginal mucosa besides having microscopic similarity. However, hormone replacement therapy (HRT) has not been majorly found to be useful and thus estrogen deficiency is generally not accepted as underlying etiology of BMS. 
According to Bergdahl and Bergdah, the chronic use of systemic drugs may be a significant factor for BMS.  Hugosson and Thorstensson, in a study involving patients with BMS and a control group, have observed that 87.5% of the patients with the syndrome were taking one or more drugs; 44% were psychotropic drugs, 25% were digestive disorder drugs, 25% were lung disorder drugs and 6.2% were supplemental vitamins. 
In a study by Cavalcanti et al., found that 80.6% of the patients with BMS were chronic users of systemic drugs, among which 35.5% were benzodiazepines, 19.35% were other antidepressants and 38.7% were antihypertensive drugs. Some drugs, like antihypertensive agents, are frequently associated with the beginning of symptoms compatible with BMS. 
Although the relationship between BMS and Parkinson's disease (PD) is not universally accepted, the comorbidity has been suggested. BMS is frequent among patients with PD. In a study of 115 patients with PD, burning mouth happened in 24% of them, incidence prevalence 30 times greater than expected by chance only.  It is hypothesized that Levodopa may play a role in the development of BMS in patients with PD. 
It is judicious for the clinician to obtain a clear and detailed medical/dental history as well as perform a thorough oral clinical examination including any laboratory studies indicated. A neurological examination can be useful although, unless there are marked deficiencies, the lack of baseline data can present a problem. If all other causes of oral burning symptom are ruled out and/or the patient fails to respond to a normal course of treatment then a diagnosis of primary BMS is reasonable.
The initial step in management is to identify primary versus secondary BMS. The objective of management for secondary BMS should initially be directed at treating the causative local or systemic disease and withdrawing the use of offending medications (such as ACE inhibitors). This etiology-directed therapy typically gives a good response. The cure for primary BMS, however, remains obscure despite attempts with wide variety of medications. 
There is no universally accepted management protocol for primary BMS due to unknown specific mechanisms underlying the syndrome. Researchers have tried wide variety of drugs including antidepressants, anxiolytics, anticonvulsants, antioxidants, local anesthetics, NSAID's, hormone replacement therapy, antimicrobials, mucosal protectants, salivary stimulants (sialogogues) and herbal supplements.  Various alternative treatment modalities have also been implicated, which includes: lasers, acupuncture, behavioral therapies, yoga, relaxation therapy, meditation, group psychotherapy, electroconvulsive therapy etc.  [Table 2].
Alpha lipoic acid (ALA) is a powerful neuroprotector that prevents damage to nerve cells by free radicals. It regenerates other antioxidants such as vitamins C and E, thus increasing levels of intracellular glutathione. Due to its antioxidant properties ALA significantly reduces the symptoms in the majority of patients with idiopathic dysgeusia and reduces the symptoms of peripheral neuropathy in diabetics. Several studies suggest ALA can improve the symptoms in BMS.  Recent randomized double blind placebo controlled trial by Lopez D et al., showed that use of gabapentin alone (300 mg daily) or in combination with ALA (600 mg daily) was beneficial in reducing symptoms in 50% and 70% of patients with BMS, respectively, compared to placebo (15%). ,
Clonazepam lozenges (oral dissolution of 1 mg tablets for 3 min with subsequent expectoration three times a day) are beneficial in patients with predominantly primary BMS. A randomized controlled study of topical clonazepam reported a reduction in pain intensity in 66% of patients after 2 week and 29% after 6 months. ,
Efficacy of capsaicin, a desensitizer of neural receptors for inflammation, has been evaluated in several studies. Systemic capsaicin 0.25% capsules three times daily showed dramatic improvement (93%) in patients with severe BMS in duration of 1 month. Side effects includes gastric pains in 32% of the patients and thus may long term use of this medication is not possible.  Capsaicin oral rinse may be beneficial in treating primary BMS with reported reduction of burning sensation in over 75% of the patients after 2 months of therapy without significant side effects. 
Capsaicin receptors have both efferent and sensory activities. These receptors are found in the C-polymodal nociceptors, which regulates the events associated with neurogenic inflammation. These receptors are activated by receiving afferent signals and simultaneous release of neuropeptides from the same nerve endings . Thus, capsaicin acts by depletion of substance P. ,
Pramipexol is a non-ergotic dopaminergic agonist, with predilection to dopaminergic D-2 receptors. The dopaminergic and nigrostriatal pathways are important on pain modulation. Non-specific disturbances on the dopaminergic system have been documented in patients with BMS. The association of BMS with PD and the improvement with amisulpiride suggests that dopaminergic dysfunction in BMS. All these facts support the use dopaminergic agonists such as pramipexol in treating BMS. ,
Psychiatric interventions show great promise in treating patients with BMS. In an study by Bergdahl J et al., Weekly one-hour sessions of cognitive behavioral therapy lasting for 12-15 weeks significantly reduced oral burning symptom in all study patients compared to placebo control group, with an estimated 27% of patients remaining symptom-free at 6 month follow-up. 
There is no consensus in the literature concerning the best treatment approach. Conservative management such as low doses of antidepressants, benzodiazepines and topical clonazepam or capsaicin application are some of the modalities that have been evaluated. There is insufficient evidence to understand the real cause and to provide accepted guidance for an effective treatment of BMS. Furthermore, it is important that in most of the patients the disease is self-limiting, not exceeding three years, regardless of the treatment modality used. 
| Conclusion|| |
The symptom of oral burning is a very frequent complaint a dental clinician can come across in daily clinical practice and is seen in wide variety of oral and systemic disorders. The BMS diagnosis will be defined only after excluding all possibilities of oral mucosa diseases, contact allergy reactions and all other possible causes of referred pain or burning sensation. Due to the multifactorial etiology of this condition (local, systemic, psychogenic and neuropathic), clinicians should better opt for an integrated treatment effectively carried out by a multi professional team in order to manage all symptoms related to BMS.
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[Table 1], [Table 2]