Burning Mouth Syndrome


Article Author:
Gregory Bookout


Article Editor:
Radley Short


Editors In Chief:
Jeff Thompson


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
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Pritesh Sheth
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Richard Ciresi
Hajira Basit
Phillip Hynes
Kavin Sugumar


Updated:
3/9/2019 8:25:45 PM

Introduction

Burning mouth syndrome is a condition characterized by extremely painful burning sensation of the tongue and mucosal tissue of the mouth, lips, and/or palate that lasts from days to weeks or months. The condition is idiopathic in nature, and the underlying pathophysiology is not well understood. The disorder was originally described in Europe during the early 1800s and initially named by the French. Patients with burning mouth syndrome commonly experience changes in gustatory sensitivity and function, dysgeusia, and/or parageusia. The condition is usually seen in females, typically in the peri-menopausal and post-menopausal periods. The diagnosis is made clinically, and other etiologies of mouth pain, tongue discoloration, and changes in gustatory sensation must be investigated and ruled out. 

Burning mouth syndrome can be both a primary syndrome, with no preceding etiology or arise after previous mucosal pathology. Studies have shown an association of burning mouth syndrome with Axis I and Axis psychiatric disorders.[1]. Along with association with psychiatric illness, structural and functional changes in the nervous system and disruption of circadian rhythm are thought to play a role in the etiology. Disruptions in the Circadian rhythm affect pain perception and mood and can disrupt the hypothalamic-pituitary-adrenal axis.[2] Burning mouth syndrome can be categorized into three categories based on the temporal distribution of symptoms, and suggested associated condition. 

  • Type 1 typically has no symptoms on waking and progressively worsens throughout the day with variable nighttime symptoms. It may be related to nutritional deficiency or diabetes or share common symptoms.
  • Type 2 is associated with chronic anxiety and displays symptoms through the day. However, these patients often are spared nighttime symptoms.
  • Type 3 displays intermittent daytime symptoms and may have periods without any symptoms. Food allergy is thought to be a potential underlying mechanism. [3]

Etiology

The etiology behind burning mouth syndrome is not well understood. The condition can arise with no history of pathology of the oral cavity or follow infection or other abnormality within the oral cavity. Multiple theories exist regarding the underlying etiology, and most believe the condition to be multifactorial. The condition, as previously stated does have a higher prevalence in peri- and postmenopausal women which supports the theory that estrogen plays a role in the underlying process. Decreased levels of estrogen can lead to the atrophy of oral mucosal tissue which may leave the area more susceptible to inflammatory change and the development of symptoms of burning mouth syndrome. In some cases, the infection may precede the development of symptoms, and certain pathogens are more commonly found in patients actively suffering from burning mouth syndrome including Candida, Enterobacter, Fusospirochetal, Helicobacter pylori, and Klebsiella. Diabetes mellitus and associated peripheral neuropathy may also cause symptoms related to burning mouth syndrome, although the underlying mechanism is neuropathy in this case. Immunologic factors tied to burning mouth syndrome include a correlation with elevated sedimentation rate and increased salivation; elevated salivary IgA has been found in patients with the condition. There is an association with certain irritants, including dental materials such as mercury, amalgam, methyl methacrylate, cobalt chloride, zinc, and benzoyl peroxide.[4] In addition, certain food allergies including peanuts, sorbic acid, chestnuts, and cinnamon have an association.[5] As previously stated, there is a connection with patients with neuropsychiatric conditions such as major depression, chronic anxiety, and mood disorders. The most common association is with a major depressive disorder, and it may follow acute symptoms or share an association as a comorbid condition at some point in the patient's life.[1] Other causes include the presence of orthodontic equipment, possible prescription drug adverse effects, increases in bradykinin as well as comorbid dermatologic conditions.[2] Overall the disease comprises a spectrum of symptoms both in severity and temporal occurrence and may have multiple associations with the above conditions.

Epidemiology

Burning mouth syndrome is much more common in females than males, 3 to 7 times higher occurrence in females. It has a strong association with advancing age in both sexes. The highest prevalence in females occurs in the perimenopausal and postmenopausal periods. The condition is essentially non-existent in children and rarely seen in those under age 30. Occurrence in males is rare before the fifth decade. There is a 3- to 12-fold increase in prevalence with advancing age. Overall, the prevalence of burning mouth syndrome is not well documented but is thought to be around 4%.[6]

Pathophysiology

The pathophysiology behind burning mouth syndrome is poorly understood and may be related to both psychogenic and neuropathic pathways. As previously discussed, disruptions in circadian rhythm, chronic anxiety, disruptions in the hypothalamic-pituitary-adrenal axis, irritants, infections, immune, diabetes, and other factors all have been thought to be contributing factors. The underlying mode of the pain conduction is likely along the trigeminal distribution, and some studies have cited evidence of histopathologic changes in nociceptive nerves in patients displaying symptoms. Studies also show changes in perception of taste and hot and cold sensation which may have reflex hyperfunction to closely related nerve hypofunction. One study showed a link between hypofunction of the chorda tympani, resulting in reduced taste while hyperstimulating the lingual nerve and causing symptoms. Other theories include mechanisms similar to phantom limb syndrome as well as small fiber neuropathy. Xerostomia in burning mouth syndrome is thought to be related more to neuropathy as opposed to a glandular issue. Mechanical damage from bruxism, clenching, and tongue thrusting may initiate symptoms, and psychiatric conditions most likely exacerbate symptoms.[7]

Histopathology

Some studies have indicated histopathologic changes to nociceptive nerve fibers in the oral cavity such as dysplasia, although symptoms can occur without evidence of histologic alteration. There are no known histopathologic findings exclusive to burning mouth syndrome.

Toxicokinetics

It has been postulated that burning mouth syndrome symptoms may have an association with certain medications, specifically ace inhibitors and angiotensin blockers, resulting in increased bradykinin in a similar mechanism to the development of secondary angioedema. Although the mechanism is not well understood, increased levels of kallikrein, which is an active molecule in the kinin pathway, may be elevated in the saliva of patients with burning mouth syndrome and lead to inflammation. Anti-retrovirals such as efivirenz and nevirapine have an association, but the underlying mechanism is not understood. Other drugs with association include levothyroxine, topiramate, and dental prostheses are associated with burning mouth syndrome. However, the underlying mechanisms are not fully understood. Irritation to tissue and underlying nerves via either contact dermatitis or direct nerve irritation may partially explain the mechanism.[8]

History and Physical

Burning mouth syndrome is a diagnosis of exclusion. When taking a history, it is important to first rule out organic causes of oral pain. Investigate the onset and duration of symptoms as well as associated medical conditions, medications, history of oral prosthesis, and comorbidities. Elements of the history that support the diagnosis include bilateral mouth burning/pain, history of chronic anxiety, perimenopausal females, pain deep in the oral mucosa, whether symptoms are alleviated or aggravated by eating/drinking/hot/cold, mood disorders, xerostomia, and dysgeusia. The absence of these factors does not exclude burning mouth syndrome. True burning mouth syndrome is an idiopathic condition and not associated with oral lesions. However, the physical examination should focus on the tongue and oral mucosa which may have lesions. Pain is often occurring for greater than 6 months. Lastly, malignancy should be ruled out before diagnosis.[9]

Evaluation

Burning mouth syndrome is a diagnosis of exclusion, so laboratory evaluation should focus on ruling out other causes of oral pain and associated conditions. This includes CBC with differential, serum folate, serum B12, ferritin, comprehensive metabolic panel, urinalysis, thyroid-stimulating hormone and free T4, thyroid binding globulin, antithyroglobulin abs, antithyroperoxidase abs, ESR, SSA abs, SSB abs, Ro abs, SS-La abs, antinuclear antibody, rheumatoid factor, anti-citrullinated abs, sialochemistry, luteinizing hormone, follicle stimulating hormone, and hemoglobin A1c. Imaging is not useful for idiopathic burning mouth syndrome but may identify underlying etiology. CT head, maxillofacial may find underlying etiology. MRI brain, C-spine may identify mass lesions, abscess, underlying multiple sclerosis, or prompt further workup for other systemic pathology. Ultrasound evaluation of the thyroid may reveal the underlying mass, multinodular goiter, or other concerning thyroid pathology. Other workup to consider includes blood and fungal cultures, biopsy of oral mucosa, lumbar puncture with gel electrophoresis, allergy testing, sialometry, Schirmer test, and laryngoscopy or endoscopy.

Treatment / Management

Treatment is focused on the underlying and associated conditions as well as symptomatic management. Medications include oral or topical clonazepam, viscous lidocaine, SSRIs, alpha-lipoic acid, hormone replacement therapy, oral or topical capsaicin, tricyclic antidepressants, olanzapine, and topiramate. Patients are instructed to avoid medications that may provoke symptoms and medications to treat underlying disorders. Other therapies include acupuncture, cognitive behavioral therapy, and near-infrared irradiation of the stellate ganglion to inhibit sympathetic discharge as well as improving blood flow to the tongue has been investigated.

Differential Diagnosis

Burning mouth syndrome may be primarily idiopathic with no known underlying pathology or may be secondary to the underlying condition. Differential includes herpes simplex virus infection, oral candidiasis, HIV, medications, GERD, scleroderma, Sjogren syndrome, neuropathy, diabetes, Vitamin deficiency, multiple sclerosis, fibromyalgia, anemia, dehydration, anxiety, anticholinergic effects, stomatitis, pemphigus, malignancy, hyperplasia, areca nut extract exposure, infections of teeth and gums, ciguatera, leukoplakia, and chronic tobacco use.

Prognosis

Prognosis is variable and based on underlying mechanism and comorbidity. While some cases are transient and resolve with symptomatic treatment and time, symptoms can persist for months to years or never resolve. The disease is not progressive or known to cause death.

Enhancing Healthcare Team Outcomes

The diagnosis and management of burning mouth syndrome is very difficult and best done with a multidisciplinary team that includes a dentist, psychiatrist, ENT surgeon, an emergency department physician, psychiatric nurse, and a pharmacist. The cause of the disorder remains unknown and the treatment remains empirical. Treatment is focused on the underlying and associated conditions as well as symptomatic management. Medications include oral or topical clonazepam, viscous lidocaine, SSRIs, alpha-lipoic acid, hormone replacement therapy, oral or topical capsaicin, tricyclic antidepressants, olanzapine, and topiramate. Patients are instructed to avoid medications that may provoke symptoms and medications to treat underlying disorders. Other therapies include acupuncture, cognitive behavioral therapy, and near-infrared irradiation of the stellate ganglion to inhibit sympathetic discharge as well as improving blood flow to the tongue has been investigated. 

The overall prognosis for patients with BMS is guarded. Some patients improve without treatment and others lead a poor quality of life with no relief from symptoms.[10][11] (Level V)


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Burning Mouth Syndrome - Questions

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A 53 year old female has had a several year history of persistent burning sensation of her tongue and mouth. It has affected her sense of taste. The patient has been on fluoxetine for depression for almost 20 years but has no other significant past medical history. Exams by otolaryngologists and dentists have been normal. She does have dry eyes and has scheduled an appointment with an ophthalmologist. Select the most likely diagnosis.



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Which of the following is true regarding patients diagnosed with burning mouth syndrome?



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A 51-year-old female presents to the emergency department complaining of the gradual onset of a burning sensation in her buccal mucosa bilaterally. She has a stated history of hypertension, anxiety, and mild depression with no previous psychiatric admissions. What workup will confirm a diagnosis of burning mouth syndrome?



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A 49-year-old female with a past medical history pertinent for hypertension, asthma, anxiety, and depression presents complaining of a burning sensation in her mouth. She does not experience the sensation upon waking, it is most intense during the day, and it improves at night. She has no evidence of ulceration or infection and is diagnosed with burning mouth syndrome. This syndrome is classified based on comorbidities and timing of symptoms. This patient most closely fits which type of burning mouth syndrome?



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A 48-year-old female with a history of type 2 diabetes mellitus, hypertension, anxiety, depression, fibromyalgia, and 18 months of using an orthodontic prosthesis as a teenager presents complaining of burning oral pain that worsens throughout the day. She denies oral ulceration and states that symptoms have occurred on and off for 6 months. She has been evaluated by her primary care provider and her dentist. Treatment with acyclovir and viscous lidocaine has been unsuccessful. A workup for an autoimmune disorder is negative. What is the most likely diagnosis?



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Which of the following oral conditions has an association with chronic anxiety?



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Burning Mouth Syndrome - References

References

Understanding of Burning Mouth Syndrome Based on Psychological Aspects., Kim MJ,Kho HS,, The Chinese journal of dental research : the official journal of the Scientific Section of the Chinese Stomatological Association (CSA), 2018     [PubMed]
Taiminen T,Kuusalo L,Lehtinen L,Forssell H,Hagelberg N,Tenovuo O,Luutonen S,Pertovaara A,J��skel�inen S, Psychiatric (axis I) and personality (axis II) disorders in patients with burning mouth syndrome or atypical facial pain. Scandinavian journal of pain. 2011 Oct 1     [PubMed]
Ritchie A,Kramer JM, Recent Advances in the Etiology and Treatment of Burning Mouth Syndrome. Journal of dental research. 2018 Jun 1     [PubMed]
Alnazzawi A, Effect of Fixed Metallic Oral Appliances on Oral Health. Journal of International Society of Preventive     [PubMed]
Kelava N,Lugovi?-Mihi? L,Duvanci? T,Romi? R,Situm M, Oral allergy syndrome--the need of a multidisciplinary approach. Acta clinica Croatica. 2014 Jun     [PubMed]
Gurvits GE,Tan A, Burning mouth syndrome. World journal of gastroenterology. 2013 Feb 7     [PubMed]
Shinoda M,Noma N, [Pathophysiology and treatment of orofacial pain.] Clinical calcium. 2017     [PubMed]
Acharya S,Hägglin C,Jontell M,Wenneberg B,Ekström J,Carlén A, Saliva on the oral mucosa and whole saliva in women diagnosed with burning mouth syndrome. Oral diseases. 2018 Jun 19     [PubMed]
Steele JC, The practical evaluation and management of patients with symptoms of a sore burning mouth. Clinics in dermatology. 2016 Jul-Aug     [PubMed]
Ariyawardana A,Chmieliauskaite M,Farag AM,Albuquerque R,Forssell H,Nasri-Heir C,Klasser GD,Sardella A,Mignogna MD,Ingram M,Carlson CR,Miller CS, World Workshop on Oral Medicine VII: Burning Mouth Syndrome: A Systematic Review of Disease Definitions and Diagnostic Criteria Utilized in Randomized Clinical Trials. Oral diseases. 2019 Feb 20;     [PubMed]
Kim Y,Yoo T,Han P,Liu Y,Inman JC, A pragmatic evidence-based clinical management algorithm for burning mouth syndrome. Journal of clinical and experimental dentistry. 2018 Apr;     [PubMed]

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