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.. 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. Burning mouth syndrome can be categorized into three categories based on the temporal distribution of symptoms, and suggested associated condition.
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. In addition, certain food allergies including peanuts, sorbic acid, chestnuts, and cinnamon have an association. 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. Other causes include the presence of orthodontic equipment, possible prescription drug adverse effects, increases in bradykinin as well as comorbid dermatologic conditions. Overall the disease comprises a spectrum of symptoms both in severity and temporal occurrence and may have multiple associations with the above conditions.
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%.
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.
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.
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.
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.
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 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.
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 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.