Burning mouth syndrome. Difficulties in diagnosis
DOI: 10.32364/2587-6821-2020-4-9-560-565
E.V. Parkhomenko1, K.V. Lunev1, E.A. Sorokina2
1Altai State Medical University, Barnaul, Russian Federation
2Regional Clinical Hospital, Barnaul, Russian Federation
The article presents data on the prevalence, classification, diagnosis, and treatment of burning mouth syndrome (BMS). Given the variety of etiological factors, special attention is paid to the differential diagnosis of idiopathic (primary) and secondary BMS. The article also examines topical and systemic causes of burning tongue, which should be excluded when examining patients with complaints specifically attributed to BMS. The information presented in the article allows physicians of various specialties to make an individual plan of diagnostic measures for each patient, taking into account the comorbid background and anamnestic data. The main cause of treatment difficulties in BMS is a complex, not fully investigated etiopathogenesis. Due to the fact that the multifactorial nature of this disorder is most likely to involve topical, systemic and psychogenic causes, a multidisciplinary method involving physicians of various specialties (neurologist, dentist, therapist, psychi atrist) is optimal in the patient management with BMS.
Keywords: burning mouth syndrome, burning tongue, differential diagnosis, neuropathic pain, treatment.
For citation: Parkhomenko E.V., Lunev K.V., Sorokina E.A. Burning mouth syndrome. Difficulties in diagnosis. Russian Medical Inquiry. 2020;4(9):560–565. DOI: 10.32364/2587-6821-2020-4-9-560-565.
Background
Burning mouth syndrome (BMS) which is considered a poorly curable disease is a controversial condition in terms of pathogenesis. The symptom triad of BMS includes a burning tongue sensation, dry mouth, and taste changes without an obvious cause. These patients describe their unpleasant feelings as “burning”, “tingling”, “itching”, “numbness”, or “shivering”. In more than a half of patients, complaints of burning are associated with a painful sensation of the tongue of various severity. The symptoms are usually bilateral and affect the anterior ⅔ of the tongue and its lateral surfaces, lips, gums, and buccal mucosa. The most common site of burning sensation is the tip of the tongue. More than 70% of patients experience taste changes, a bitter or metallic taste. About ⅔ of patients complain of a dry mouth sensation.
These patients can seek treatment from any specialist. Rare diagnosis of BMS is accounted for by its low prevalence and little awareness on this disease. According to some international studies, diagnostic search sometimes takes 7 years [1].
BMS is defined as an intraoral burning or dysesthesic sensation, recurring daily for more than 2 hours per day over more than 3 months, without clinically evident causative lesions [2]. Other terms used for BMS are glossodynia, oral dysesthesia, glossopyrosis, stomatopyrosis, and stomatodynia.
BMS is more common in elderly patients (mean age of onset is ~ 60 years) being rare in patients younger than 40 years [3]. According to international studies, the prevalence of BMS ranges from 0.6% to 15% [4, 5]. This condition is diagnosed predominantly in peri- and postmenopausal women (female to male ratio is 7:1) [6].
The 3rd edition of the International Classification of Headache Disorders (ICHD-3, 2018) includes BMS into chapter 13 “Painful lesions of the cranial nerves and other facial pain” (13.11 Burning mouth syndrome).
According to the ICHD-3, the diagnostic criteria of BMS are as follows [2]:
A. Oral pain fulfilling criteria B and C.
B. Recurring daily for >2 hours/day for >3 months.
C. Pain has both of the following characteristics:
1) burning quality;
2) felt superficially in the oral mucosa.
D. Oral mucosa is of normal appearance and clinical examination including sensory testing is normal.
E. Not better accounted for by another ICHD-3 diagnosis.
The International Classification of Orofacial Pain (ICOP Version 1.0 beta 2020) includes BMS into chapter 6 “Idiopathic orofacial pain”. The diagnostic criteria are almost similar to those described in the ICHD-3. However, ICOP categorizes two additional variants, i.e., with or without somatosensory changes [7].
In the ICHD-3 and ICOP Version 1.0 beta 2020, a term “BMS” is applied for idiopathic conditions without an obvious cause. Since numerous local and systemic disorders as well as medications can provoke similar symptoms, “secondary” or “symptomatic” are more suitable terms. However, these classifications do not include these definitions [8]. Therefore, determining the exact position of BMS among facial pains and the use of diagnostic criteria in clinical practice will improve our understanding of BMS and provide adequate medical care.
Causes of BMS
Determining the etiology of this disorder is challenging since BMS symptoms can be secondary or idiopathic. The triggers of the pathological process involving oral mucosa can be both local (e.g., infections, allergies, malignancies etc.) and systemic [3].
Local factors
A careful examination of the oral cavity and tongue in patients with burning tongue complaints allows for suggesting the local cause of this symptom. Local factors include physical, chemical, and biological ones (e.g., some fungi, bacteria, viruses). Fungal (Candida albicans), bacterial (Enterobacter, Klebsiella, Fusobacterium, Staphylococcus aureus), and viral (Herpes) infections of the oral cavity are accompanied by burning tongue sensation [9]. The pathogenesis of BMS in patients with fungal infections is probably accounted for by the atrophy, erythema, and ulceration of the oral mucosa which can result in burning pain [10, 11].
Geographic tongue (also known as benign migrating glossitis) is a chronic recurrent inflammatory dystrophic disorder of tongue mucosa. The etiology of this condition is currently unknown. In most patients, benign migrating glossitis is asymptomatic and diagnosed accidentally. However, some patients complain of discomfort and burning tongue [12]. V. Ching et al. [13] suggest that geographic tongue in men is a predictor of BMS.
Among the local causes of BMS, contact allergy to food, cosmetics, and dental materials should be excluded. The allergy to dental materials can provoke allergic glossitis or stomatitis [14]. Difficulties in identifying these allergens prevent the early diagnosis of BMS related to contact glossitis.
The discrepancy between the borders of a removable partial denture to the borders of a prosthetic bed and, therefore, persistent traumatization of mucosae are a common cause of pain and burning mouth [15].
Oral parafunctional habits which result in the traumatization of the tongue and oral mucosa induce and maintain BMS. Among them are chronic biting of the oral mucosa (cheeks, lips, tongue), finger sucking, biting hard objects (pencils, pens etc.). Similar mechanism of BMS pathogenesis is seen in myofascial pain of the jaw muscles, bruxism, and temporomandibular joint dysfunction (TMD). Notably, anxiety disorder is accompanied by the above-mentioned motor reactions. Although currently there are no strong evidence that oral parafunctional habits can cause BMS, they should be considered when collecting medical history [16]. Examination can identify worn teeth, damaged tongue and/or mucosae. Tests for TMD can be performed as well.
Galvanosis of the oral cavity resulting from the differences in the electrochemical potential of dissimilar metals used for prosthetics still occurs in clinical practice as the cause of BMS [17].
General causes
Menopause
The prevalence of BMS is the highest in postmenopausal women [18]. In women, ocular, oral, and vaginal dryness are known to increase with age, and the rate of these symptoms after age 65 is 30% [19]. Dry and burning mouth is observed in many menopausal women in addition to other climacteric symptoms (i.e., vasomotor, psychological, urogenital, sexual, metabolic, cardiovascular, musculoskeletal). Specific mechanisms linking menopausal hormonal changes and oral discomfort are still unclear. The similarity of the histology of the oral and vaginal mucosa may partially account for the combination of these symptoms. The presence of estrogen receptors in female oral mucosa and salivary glands is an example of this similarity [20]. The composition of the saliva of menopausal women presumably depends on the level of estrogens [21, 22]. Moreover, hormone replacement therapy fails to control the symptoms of oral discomfort for satisfaction [18].
Iron and vitamin deficiency
Several studies suggest the impact of vitamin and mineral deficiency on BMS pathogenesis. Retrospective analysis of biochemical and laboratory tests has demonstrated that the deficiencies of B vitamins, zinc, folic acid, iron, and vitamin В are the most common deficits [23].
Other studies report on the significant reduction in the levels of hemoglobin, serum iron, and vitamin B12 in patients with BMS which are commonly associated with high blood levels of homocysteine and the presence of anti-gastric parietal cell antibodies. These antibodies destroy parietal cells which results in hypochlorhydria, the reduction in the level of intrinsic factor, impaired absorption, and vitamin B12 deficiency which is characterized by the complex lesion of the nervous system, gastrointestinal (GI) tract, and hematopoiesis [24]. In addition, low gastric secretion of hydrochloric acid (resulting from the intake of antacids, H2 blockers, or proton pomp inhibitors) in patients with GI disorders induces hypochlorhydria and, therefore, anemia [25]. Currently, there is no consensus on the importance of nutrition, anemia, and B vitamin deficiency in the development of BMS. Nevertheless, the coexistence of BMS and B vitamin deficiency requires specific screening tests and careful history taking (strict diet, vegetarianism) to exclude malnutrition, anemia, and conditions which result in the impaired intake or metabolism of vitamins.
Diabetes
A common coexistence of BMS and diabetes can be accounted for by oral opportunistic infections and salivary gland hypofunction which are considered frequent complications of uncontrolled diabetes [26].
Hypothyroidism
Some authors report on a potential etiopathologic association between hypothyroidism and BMS, decreased taste sensitivity, and bitter taste. It was demonstrated that thyroid hormones are involved in the maturation and specialization of the taste receptors of the tongue [27]. It was suggested that hypothyroidism affects the fungiform papillae of the tongue and results in taste and trigeminal somatosensory sensitivity changes [28]. Z. Talattof et al. [29] have demonstrated that in patients with autoimmune thyroiditis, the levels of thyroid-stimulating hormone (TSH), thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies, and free T3 correlate with BMS severity. Meanwhile, the level of free T4 is associated only with the presence of BMS but not its severity [29].
Gastroesophageal reflux disease
The manifestations of gastroesophageal reflux disease (GERD) include not only esophageal symptoms (e.g., heartburn, burping, dysphagia, odynophagia, non-cardiac chest pain etc.) but also extraesophageal (in particular, dental) signs (e.g., caries, dental erosions, halitosis, and, occasionally, aphthous stomatitis) [30]. According to various authors, the rate of oral lesions in GERD ranges from 5% to 69.4% [30, 31]. Diagnosing the dental manifestations of GERD can be challenging due to minor early clinical signs, polymorphic clinical presentation, and the potential effects of other factors which may result in similar lesions of oral tissues. Burning sensation affecting the tongue root and occurring at night (when gastric content refluxed up into the oral cavity) is likely to be accounted for by GERD.
Autoimmune diseases
Xerostomia and burning tongue sensation are typical manifestations of autoimmune diseases. In idiopathic Sjögren’s syndrome and Sjögren’s syndrome in connective tissue disorders (e.g., rheumatoid arthritis, systemic lupus erythematosus, systemic scleroderma, autoimmune liver disorders etc.), some patients experience dry mouth symptoms with or without burning tongue sensation long before the diagnosis [32, 33]. Notably, Sjögren’s syndrome occurs predominantly in menopausal women [34]. Additionally, patients with autoimmune diseases receiving steroids or immunosuppressants may develop oral candidiasis which provokes both BMS and dysgeusia [35].
Medications
Complaints of burning tongue sensation may occur in patients receiving ACE inhibitors (i.e., enalapril, captopril, lisinopril etc.) [36]. BMS can be associated with the intake of drugs affecting the renin-angiotensin system [37]. Patients receiving topiramate or acetazolamide may complain of the sensation of goosebumps on the palms, foots, face, and tongue. Some medications (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors, neuroleptics, antihistamines, diuretics, beta blockers etc.) affect the secretion of saliva and provoke xerostomia [38]. Dry mouth severity sometimes depends on drug dose and improves after dose reduction or drug withdrawal.
Psychic disorders
Anxiety, depression, hypochondria, and cancerophobia are the most common psychic disorders in patients with BMS. However, their role in BMS pathogenesis remains elusive [39]. BMS leaves uncertainty for the patients until the diagnosis, as a result, most patients develop anxiety and awfulizing [40]. Age is an important factor favoring cancerophobia since the onset of BMS usually occurs after 60 years. This period is associated with the increased awareness on cancer.
Therefore, a diagnostic algorithm for BMS should include:
complaints and history taking, a detailed information on the localization, duration, and severity of burning sensation as well as the factors worsening (spicy or hot food, speaking, stress, fatigue) or improving (eating, chewing gum, candies) burning sensation; it is important to identify bruxism, oral parafunctional habits, prosthesis, comorbidities, or taking medications;
· examination of the oral cavity and tongue, palpation of mastication muscles and temporomandibular joint, assessment of jaw mobility, three finger test;
· complete blood count;
· blood biochemistry (fasting glucose, glycated hemoglobin, serum iron, ferritin, vitamin B12);
· measurements of TSH and T4 levels;
· detection of antinuclear antibodies, rheumatoid factor, LE cells;
· microscopy/culturing of tongue swab;
· consulting medical specialists across other disciplines and additional tests (thyroid ultrasound, esophagogastroduodenoscopy etc.) as needed.
Differential diagnosis of BMS requires interdisciplinary collaboration of neurologists, dentists, therapists, gynecologists, rheumatologists, and psychiatrists. An idiopathic (primary) BMS should be considered only when any potential local and systemic causes were excluded.
Pathogenesis and treatment approaches to BMS
Pathophysiological mechanisms underlying idiopathic BMS are still understudied. BMS is expected to be multifactorial. The studies involving blink reflex, quantitative sensory testing, and functional brain imaging confirmed the neuropathic origin of BMS and the involvement of the different levels of somatosensory system [41]. Neurotrophic factors and neuroprotective steroids may have a crucial role in the mechanisms related to the atrophy of small nerve fibers. The denervation of the chorda tympani innervating fungiform papillae results in the collateral innervation via the trigeminal nerve which leads to dysgeusia and burning pain. Central mechanisms of BMS involve the depletion of neuroprotective steroids affecting pain system and mood [42]. Changes in the dopaminergic system are one of the potential pathogenic mechanisms. The nigrostriatal system is known to be involved in the modulation of central pain [43]. Altered ratio of D1 and D2 dopamine receptors was revealed in BMS patients thus indicating the reduction in the level of endogenous dopamine [44]. Despite the involvement of the dopaminergic system in the pathophysiological mechanisms of pain and BMS, J.Y. Kim [45] failed to demonstrate higher prevalence of Parkinson’s disease among BMS patients.
In secondary BMS, pain relief is mainly accounted for by the treatment of the primary disease which resulted in BMS. Meanwhile, the diagnosis and treatment of idiopathic BMS (as many other diseases associated with facial and oral pain) are still challenging [46, 47].
The difficulties with treatment selection for the primary BMS are currently accounted for by poorly studied pathogenesis and scarce information on the medical treatment. Almost all approaches and medications provide symptomatic relief. Meanwhile, unapproved use of drugs for BMS requires a particular responsibility and clinical competence [48].
Published data suggest that clonazepam, gabapentin, amitriptyline, selective serotonin reuptake inhibitors, and tioctic acid are effective in the treatment of BMS. The combination of pharmacotherapy and psychotherapy (including cognitive behavioral therapy) is also useful [46].
Conclusions
Burning mouth syndrome is an understudied condition characterized by a complex etiopathogenesis and heterogeneous clinical presentation evolving throughout the disease and depending on local, systemic, and psychogenic factors and comorbidities. The diagnosis and treatment of BMS are very challenging even for experienced clinicians. Multidisciplinary management approach involving neurologists, dentists, therapists, psychiatrists, and other specialists is the most reasonable strategy allowing for the selection of optimal and effective therapy to improve the quality of life of these patients.
About the authors:
Ekaterina V. Parkhomenko — Cand. of Sci. (Med.), Associate Professor of the Department of Neurology and Neurosurgery with an Institute of Continuing Professional Education course, Altai State Medical University: 40, Lenina prospect, Barnaul, 656038, Russian Federation; ORCID iD 0000-0003-0489-9845.
Konstantin V. Lunev — postgraduate student of the Department of Neurology and Neurosurgery with an Institute of Continuing Professional Education course, neurologist, Altai State Medical University: 40, Lenina prospect, Barnaul, 656038, Russian Federation; ORCID iD 0000-0002-1875-3890.
Ekaterina A. Sorokina — neurologist, Regional Clinical Hospital: 1, Lyapidevskogo str., Barnaul, 656024, Russian Federation; ORCID iD 0000-0001-9495-9500.
Contact information: Ekaterina V. Parkhomenko, e-mail: parekva@mail.ru. Financial Disclosure: no authors have a financial or property interest in any material or method mentioned. There is no conflict of interests. Received 21.09.2020, revised 05.10.2020, accepted 19.10.2020.
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