Burning Mouth Syndrome

 Burning mouth syndrome is a condition that can be quite challenging to diagnose and treat. Patients commonly report a persistent burning sensation on one or more oral mucosal surfaces, yet understanding of this condition and evidence-based solutions remain scarce. Clinicians often find themselves at a loss when dealing with this particular condition.

This syndrome is defined as an intra-oral burning sensation without any discernible medical or dental cause. Diagnosis hinges on patients experiencing generalized or localized intraoral burning, impaired sensation, or pain of the oral mucosa that recurs daily for more than two hours per day for more than three months without any evidence of specific mucosal lesions or abnormal laboratory findings. Distinguishing this condition from oral mucosal burning caused by known factors is essential for effective treatment. 

Burning mouth syndrome affects women more than men and, most often, perimenopausal or postmenopausal women and is frequently associated with stressful life events, anxiety, and depressive disorders. It is unclear whether the poor quality of life associated with burning mouth syndrome is what precipitates the psychogenic symptoms or if a psychogenic disorder triggers the burning mouth syndrome.

Clinical presentation

Patients with burning mouth syndrome will typically experience spontaneous burning pain in the oral mucosa, particularly on the tongue, hard palate, and lips. It may be accompanied by subjective dryness, tingling/numbness, and abnormal taste. The burning sensation is usually moderate to severe in intensity, present on both sides, and occurs everyday. However, it is often minimal or non-existent during early mornings and mealtimes and typically doesn’t affect sleep.

Differential diagnoses

A diagnosis of burning mouth syndrome depends on excluding an organic cause for the complaints. Thus, there are several conditions that must be ruled out before a diagnosis can be made. These are discussed below: 

1. Local irritation is the most common cause of complaints similar to burning mouth syndrome. For example, irritation from an improperly-fitting dental prosthesis, rough dental restoration, contact hypersensitivity to dental materials, oral rinses, acidic foods, or smoking can cause generalized oral mucosal irritation.
2. Systemic conditions including diabetes, decreased levels of vitamins B1, B2, B12, folate, iron, and zinc, as well as abnormal thyroid function, autoimmune diseases, hormonal disturbances, and Parkinson's disease can cause mucosal burning or abnormal taste. 
3. Oral candidiasis, a fungal infection in the mouth caused by Candida albicans, also must be ruled out. This infection usually appears as white, red, or red-and-white mixed lesions in the mouth. However, there may be no visible changes in some cases, making it challenging to identify. To diagnose this condition, an oral swab is necessary. 
4. Adverse drug reactions can also cause symptoms similar to burning mouth syndrome. Paroxetine, a selective serotonin reuptake inhibitor used to treat depression, can cause ulcerations in the mouth. Angiotensin-converting enzyme inhibitors, like Lisinopril, used to lower blood pressure, can cause a burning sensation in the mouth. Nonsteroidal anti-inflammatory drugs (NSAIDs), beta-blockers, antihistamines, and some other drugs can cause what is known as lichenoid drug reactions inside the mouth that could mimic burning mouth syndrome.
5. Xerostomia (decreased salivary flow) and altered salivary quality can be caused by radiotherapy, chemotherapy, drugs that decrease salivary flow, and Sjogren's syndrome (an autoimmune disease that affects the salivary gland and lowers saliva production).
6. Oral mucosal conditions such as lichen planus, benign mucous membrane pemphigoid, pemphigus, and inflammatory disorders such as migratory glossitis, must also be ruled out.
7. Viral infections such as herpes simplex or shingles within the oral cavity can result in symptoms patients may interpret as burning. Although eruptions of vesicles are diagnostic of Herpes viruses, there can be a prodromal phase before the appearance of lesions which can involve burning sensations. 
8. Nerve damage secondary to chemotherapy, also called chemotherapy-associated neuropathy, can present as burning inside the mouth and must also be considered as the cause for these symptoms.

Healthcare providers must gather a comprehensive medical, dental, and illness history, conduct a thorough oral examination, and order necessary laboratory tests. If all possible causes of the symptoms are eliminated, or the patient does not respond to a typical treatment regimen, considering a diagnosis of burning mouth syndrome may be appropriate.

Causes 

The causes of burning mouth syndrome are still not fully understood. However, many theories exist to explain the possible causes of the condition. 

1. Nerve degeneration has been found in patients with burning mouth syndrome. This is especially true for the nerves responsible for sensing heat, cold, and taste.
2. Laryngopharyngeal reflux (LPR) and gastroesophageal reflux disease (GERD) have been suggested to play a role in the pathogenesis of burning mouth syndrome. The ascent of gastric fluids to the oral cavity, a common occurrence in both conditions, can irritate the mucosa and modify the local microbiota.
3. Psychological conditions. Burning mouth syndrome is frequently associated with stressful life events, anxiety, and depressive disorders. The cause-and-effect relationship between physiological and oral symptoms is not clear, as the psychic factors may either contribute to or result from the oral symptoms.
4. A decrease in neuroactive steroids, which are produced in the nervous system and regulate nerve excitability, is considered a potential factor. Anxiety or stress may lead to an abnormal decrease in the steroid hormones produced in the adrenal gland, affecting the production of neuroactive steroids in the skin, mucosa, and nervous system. Additionally, menopause and the corresponding decrease in sex hormones can exacerbate this process, leading to nerve fiber damage in the mouth.
5. Studies that analyzed the saliva composition of postmenopausal women with burning mouth symptoms observed a decrease in salivary proteins, such as salivary α-amylase, which could change digestion capacity. Additionally, they found that the amount of mucin, which has an antimicrobial and lubricant action, was also reduced. One study also noted increased nucleic acid in saliva, indicating a possible increased bacterial proliferation in the oral cavity.

Management

Given the poorly understood etiology of burning mouth syndrome, no standard management is currently available for this condition. Treatments are currently for symptomatic relief only, meaning they are not curative of the disease. 

1. Antidepressants have been found to reduce the intensity of neuropathic pain. Additionally, burning mouth syndrome is closely linked with generalized anxiety and depressive disorders, which makes antidepressants a logical choice for treatment.
2. Clonazepam, a benzodiazepine, can help reduce pain signals in the body. When applied topically to the oral mucosa, this medication is thought to decrease the firing of sensory nerves, and when given systemically, it has central sedative, anti-anxiety, and pain alleviating effects. Both topical and oral clonazepam have been reported to reduce the intensity of the pain of burning mouth syndrome.
3. Capsaicin, the hot component of chili peppers, interestingly offers relief by inducing reversible degeneration of sensory nerves in the mouth, thereby reducing pain sensations when applied topically.
4. Alpha lipoic acid, a potent antioxidant, can remove heavy metals from the body, thus reducing oxidative stress-induced inflammation and damage to the nerves in the mouth. Studies have shown that this compound can alleviate nerve pain and numbness/tingling. It can be used to treat burning mouth syndrome alone or in combination with other therapies.
5. Gabapentin, an antiseizure medication commonly used to treat neuropathic pain disorders, has been found to be effective in reducing pain associated with burning mouth syndrome. This medication works by inhibiting the release of certain neurotransmitters that are responsible for chronic pain.
6. Cognitive-behavioral therapy is a short-term psychological treatment that aims to correct dysfunctional emotional responses, such as pain, fear, helplessness, vulnerability, or exhaustion, by modifying thoughts and behaviors. This therapy has been shown to decrease the intensity of pain experienced in burning mouth syndrome in a significant number of patients and can be used alone or in combination with medications.

Conclusion

Burning mouth syndrome appears to be rooted in both physiological and psychological etiologies. Accurate diagnosis requires a meticulous exclusion of other systemic conditions and oral disorders. Despite the absence of a standardized treatment protocol, the available evidence points towards a multifaceted approach. Patient reassurance is crucial, and the integration of medication and psychological support may be necessary. In the absence of a definitive cure, the need for a holistic approach shines evermore.

Written by Dima Bader

Edited by Tiffany vanLieshout, PhD

References

1. Classification and diagnostic criteria for headache disorders, cranial neuralgias, and facial pain. Headache Classification Committee of the International Headache Society. Cephalalgia. 1988;8 Suppl 7:1-96.
2. International Classification of Orofacial Pain, 1st edition (ICOP). Cephalalgia. 2020;40(2):129-221. doi:10.1177/0333102419893823
3. Feller L, Fourie J, Bouckaert M, Khammissa RAG, Ballyram R, Lemmer J. Burning Mouth Syndrome: Aetiopathogenesis and Principles of Management. Pain Res Manag. 2017;2017:1926269. doi:10.1155/2017/1926269
4. Mock D, Chugh D. Burning mouth syndrome. Int J Oral Sci. 2010;2(1):1-4. doi:10.4248/IJOS10008
5. Russo M, Crafa P, Guglielmetti S, Franzoni L, Fiore W, Di Mario F. Burning Mouth Syndrome Etiology: A Narrative Review. J Gastrointestin Liver Dis. 2022;31(2):223-228. Published 2022 Jun 12. doi:10.15403/jgld-4245
6. Ismail SB, Kumar SK, Zain RB. Oral lichen planus and lichenoid reactions: etiopathogenesis, diagnosis, management and malignant transformation. J Oral Sci. 2007;49(2):89-106. doi:10.2334/josnusd.49.89
7. Lamey PJ, Lamb AB. Prospective study of aetiological factors in burning mouth syndrome. Br Med J (Clin Res Ed). 1988;296(6631):1243-1246. doi:10.1136/bmj.296.6631.1243
8. Yilmaz Z, Renton T, Yiangou Y, et al. Burning mouth syndrome as a trigeminal small fibre neuropathy: Increased heat and capsaicin receptor TRPV1 in nerve fibres correlates with pain score. J Clin Neurosci. 2007;14(9):864-871. doi:10.1016/j.jocn.2006.09.002
9. Lechien JR, De Vos N, Everard A, Saussez S. Laryngopharyngeal reflux: The microbiota theory. Med Hypotheses. 2021;146:110460. doi:10.1016/j.mehy.2020.110460
10. Woda A, Dao T, Gremeau-Richard C. Steroid dysregulation and stomatodynia (burning mouth syndrome). J Orofac Pain. 2009;23(3):202-210.
11. Zakrzewska JM. Critical commentary 1: steroid dysregulation and stomatodynia (burning mouth syndrome). J Orofac Pain. 2009;23(3):211-220.
12. Rodrigues LM, Alva TDM, da Silva Martinho H, Almeida JD. Analysis of saliva composition in patients with burning mouth syndrome (BMS) by FTIR spectroscopy. Vib Spectrosc. 2019;100:195–201. 
13. Cui Y, Xu H, Chen FM, et al. Efficacy evaluation of clonazepam for symptom remission in burning mouth syndrome: a meta-analysis. Oral Dis. 2016;22(6):503-511. doi:10.1111/odi.12422
14. Laklouk M, Baranidharan G. Profile of the capsaicin 8% patch for the management of neuropathic pain associated with postherpetic neuralgia: safety, efficacy, and patient acceptability. Patient Prefer Adherence. 2016;10:1913-1918. Published 2016 Sep 22. doi:10.2147/PPA.S76506
15. Komiyama O, Nishimura H, Makiyama Y, et al. Group cognitive-behavioral intervention for patients with burning mouth syndrome. J Oral Sci. 2013;55(1):17-22. doi:10.2334/josnusd.55.17