Salivary and serum biomarkers to evaluate psychological disorders in burning mouth syndrome: A systematic review and meta-analysis.

BACKGROUND: Burning mouth syndrome is a chronic pain syndrome mainly characterized by an intensive burning sensation of tongue. Previous studies have suggested that saliva/serum biomarkers in burning mouth syndrome might be associated with psychological disorders. The aim of systematic review was to observe whether the biomarkers in serum/saliva could be an alternative method to evaluate the psychological disorders in patients with burning mouth syndrome. MATERIALS AND METHODS: The PubMed, Embase, and Cochrane Library databases were searched for papers published up to March 15, 2023. Risk of bias was measured by using the Newcastle-Ottawa Scale. RevMan was used for meta-analysis. RESULTS: A total of 467 articles were screened, which of 12 studies were included. These studies collected 43 different biomarkers in saliva and 35 in serum. Of these biomarkers, only three (cortisol, α-amylase, and IL-6) were analyzed in two or more studies. Only salivary cortisol levels were significantly higher in the patient group compared to the controls (Mean Difference = 1.39; 95% CI [0.80-1.97]; p < 0.001). Moreover, cortisol might be relevant to psychological scores, especially anxiety. CONCLUSION: Different papers have investigated salivary and serum biomarkers in burning mouth syndrome patients with controversial results. This meta-analysis showed that cortisol levels in saliva may be a potential biomarker to assess the psychological disorders in burning mouth syndrome patients.

Oral dysaesthesia: a special focus on aetiopathogenesis, clinical diagnostics and treatment modalities.

Oral dysaesthesia is a condition characterised by persistent alteration to oral sensation, perceived by the patient to be abnormal and/or unpleasant, in the absence of any mucosal pathology. The condition can be difficult to detect and diagnose. A possible peripheral or central neuropathic aetiology has been proposed. Burning mouth syndrome (BMS) is the most common idiopathic oral dysesthesia in which long-term suffering is often reported by patients. Recent efforts from professional organisations and study groups have provided a consensus on BMS disease definition and diagnostic criteria. Large-scale epidemiological studies are required to provide an accurate estimate for prevalence and incidence of the condition. Meticulous diagnostic investigations which may require interdisciplinary teamwork are often warranted to reach an accurate diagnosis. A combination of interventional modalities, with a holistic approach, is key for successful management and improvement in patients' quality of life.

Use of oral devices in the management of oral dysesthesia: case reports and literature review.

Oral dysesthesia (OD) is a diagnosis of exclusion that manifests as an unpleasant and abnormal sensation of the oral mucosa without any noticeable oral lesions. Burning sensation is one of the manifestations of OD which may advocate for similar pharmacotherapeutic options to burning mouth syndrome (BMS), resulting in possible adverse events. The aim of these case reports was to illustrate the significance and rationale for the use of oral devices as a mechanical/physical barrier and a safe approach in the management of OD, without experiencing any antagonistic effects from pharmacotherapeutic agents. Two patients with spontaneous and evoked (following dental procedures) OD symptoms in the right posterior mandibular quadrant and anterior hard palatal areas were evaluated. Additionally, their OD symptoms were associated with hyposalivation and taste changes. A thorough history and complete head and neck examination, with the exclusion of oral lesions and systemic conditions, were performed. These patients were previously prescribed topical clonazepam rinses. An in-office trial, with application of orthodontic wax to the affected area, was performed as a preliminary test in order to justify the fabrication of an oral device for possible symptomatic relief. Conclusion: The case reports demonstrated significant improvement of OD symptoms and amelioration of pain following fabrication of oral devices in two patients with no undesirable effects from pharmacotherapy. Additionally, the oral devices aided as a mechanical/physical barrier, potentially exerting a placebo effect while facilitating an improved quality of life. Furthermore, the cost-effectiveness and ease of fabricating the oral device has been advantageous over other systemic medications. This encourages the need for a detailed prospective study.

A Case Report of Burning Mouth Syndrome with Dry Mouth Managed by Kampo Medicine.

The patient was a 56-year-old woman who complained of chronic pain involving her tongue. We diagnosed her with burning mouth syndrome (BMS) based on exclusion of any local factors or systemic conditions. The patient not only had tongue pain but also had other signs and symptoms like scalloped tongue, dry mouth, and headache. To manage these additional issues, we used Goreisan, an herbal Kampo medicine, as a complementary alternative medicine (CAM) approach along with cognitive behavioral therapy (CBT). The patient's BMS was successfully managed with the combination of CAM and CBT, which may suggest that the pathophysiology for BMS might be nociplastic pain rather than purely nociceptive or neuropathic.

Therapeutic effects of clonazepam in patients with burning mouth syndrome and various symptoms or psychological conditions.

Burning mouth syndrome (BMS) is frequently accompanied by dysgeusia and xerostomia. Clonazepam has been widely prescribed and is effective, but it is unclear whether clonazepam also affects the symptoms that accompany BMS, or whether such symptoms affect treatment outcomes. Here, we investigated the therapeutic outcomes in BMS patients with various symptoms or comorbidities. We retrospectively reviewed 41 patients diagnosed with BMS between June 2010 and June 2021 at a single institution. Patients were instructed to take clonazepam for 6 weeks. Before the first dose, burning pain intensity was measured using a visual analog scale (VAS); the unstimulated salivary flow rate (USFR), psychologic characteristics, site(s) of pain, and any taste disturbance were evaluated. Burning pain intensity was measured again after 6 weeks. Thirty-one of the 41 patents (75.7%) exhibited a depressed mood, whereas more than 67.8% of the patients exhibited anxiety. Subjective xerostomia was reported by ten patients (24.3%). The mean salivary flow rate was 0.69 mL/min and hyposalivation (an unstimulated salivary flow rate ≤ 0.5 mL/min) was apparent in ten patients (24.3%). Dysgeusia was present in 20 patients (48.7%); a bitter taste (n = 15, 75%) was reported by the largest proportion of patients. Patients who reported a bitter taste responded best in terms of burning pain reduction after 6 weeks (n = 4, 26.6%). Overall, 32 patients (78%) reported decreased oral burning pain after clonazepam (mean VAS score changed from 6.56 to 5.34) use. Patients who reported taste disturbances exhibited a significantly greater decrease in burning pain, compared with other patients (mean VAS score changed from 6.41 to 4.58) (p = 0.02). Clonazepam significantly improved burning pain in BMS patients who had taste disturbances.

Evaluation of peripheral nerve fibers and mast cells in burning mouth syndrome.

Emerging evidence has revealed a cross-talk in the etiopathogenesis of burning mouth syndrome (BMS) related to peripheral nerve fibers (NF) and neuropeptides secreted by mast cells. Here, we investigated the S-100+ density and PGP 9.5+ integrity of peripheral NF and the tryptase+ mast cell density in the oral mucosa of BMS patients and healthy individuals. A total of 23 oral mucosa specimens (12 BMS and 11 controls) were evaluated. The clinical diagnosis of BMS was based on a careful examination, excluding other local and systemic causes. Samples were taken from an incisional biopsy of the tongue mucosa of individuals with symptomatic BMS, while the margins of the non-neoplastic tongue biopsy served as controls of healthy individuals. Immunohistochemistry was performed to determine the density/mm2 of S-100+, PGP 9.5+ peripheral NF, and tryptase+ mast cells. Similar densities of S-100+, PGP 9.5+ peripheral NF, and tryptase+ mast cells were found in cases of BMS, with a median value of 3.70, 0.70, and 29.24/mm2, respectively, and in the control group, with a median value of 2.60, 0.80, and 26.01/mm2, respectively (p > 0.05). Moreover, the relationship between S100+ and PGP 9.5+ peripheral NF was the same in both groups (p = 0.70). This study demonstrated that there were no alterations in the density and integrity of peripheral NF in the tongue of symptomatic BMS patients. However, the sensitization of peripheral NF in this disease may not depend on mast cell density.

Burning mouth syndrome and pelvodynia: A literature review.

Burning mouth syndrome (BMS) and pelvodynia are chronic pain still poorly understood and the links between them are all the more so. Health professionals therefore have few resources to understand, diagnose and treat these pains. They may consider and treat these ailments individually, which does not represent optimal care management for the patient and leads to overmedication. This article aims to highlight their contiguity from epidemiological, etiological, diagnostic, and therapeutic perspectives. This study was based on articles which were found using databases such as PubMed and Web of Science. No exclusion criteria were used. Fourteen studies were reviewed. This present work shows that the clinical presentations of these syndromes are similar, as exemplified by their strong association with anxiety and depression. The neurophysiological mechanisms involved in these conditions are similar to those in patients. The diagnosis is essentially based on visual examination and an elimination of all other possible causes. In addition, this work promotes the fact that a common therapy can be implemented when BMS and pelvodynia co-occur. However, the literature on the subject is still very limited. This can be deepened by exploring all the effective treatments in BMS and vulvodynia for penoscrotodynia. Finally, for all these pains, there is a therapeutic order to respect starting with a psychological approach, then topical treatments, systemic therapy and surgical. This therapeutic gradient assists practitioner in their patient's pain management. This article also allows health care providers to quickly find an effective systemic treatment for a patient with both BMS and pelvodynia.

Low-dose naltrexone for treatment of burning mouth syndrome.

OBJECTIVE: The International Classification of Disease defines burning mouth syndrome (BMS) as a chronic intraoral burning sensation, with no identifiable local or systemic cause. Since current management is often unsatisfactory, the aim of this report is to describe a new treatment modality (i.e., low-dose naltrexone [LDN]). STUDY DESIGN: A 62-year-old woman presented with the complaint of burning on the tongue of 3 years' duration. Existing comorbidities were fibromyalgia, irritable bowel syndrome, headache, and interstitial cystitis. Her reported pain intensity ranged from 2/10 (morning) to 8/10 (evening) on a numeric rating scale. With the diagnosis of BMS and hyposalivation, and in light of her current clonazepam use and fibromyalgia, a dry mouth protocol and LDN (3 mg) were prescribed. RESULTS: After 1 month, her pain intensity decreased by 50%, with no pain upon awakening. After 2 months, the widespread pain associated with her chronic morbidities also reduced by 50%, and her headache disappeared. After adjusting LDN dose to 4.5 mg, the patient was stable at 6 months, with 50% reduction of widespread pain and 2/10 BMS pain, and no reported side effects. CONCLUSIONS: These preliminary results suggest that LDN may be a feasible and effective treatment for BMS, especially in patients' refractory to traditional treatment.

Innovative histological and histochemical characterization of tongue biopsies from patients with burning mouth syndrome.

OBJECTIVES: The present pilot study aims to perform an innovative histological and histochemical characterization of samples from patients with burning mouth syndrome (BMS) to correlate these findings with the clinical scenario. METHODS: To carry out this objective, the study samples were stained with the hematoxylin-eosin stain and later, an histochemical study was carried out to determine the composition of the extracellular matrix (ECM) using the stains of Alcian Blue, Picrosirius, Reticulin from Gomori and Verhoeff. RESULTS: The results of this study revealed histological patterns compatible with cellular hypertrophy in different layers of the epithelium as well as a greater keratinization in BMS cases. On the other hand, a lower amount of proteoglycans and a greater amount of collagen fibers were observed compared to the control. In addition, older patients had fewer reticular fibers and younger patients had fewer elastic fibers compared to the control. CONCLUSIONS: In conclusion, the present study shows the existence of a correlation between the histological patterns, age and symptoms of patients with BMS. Therefore, it is necessary to develop synergistic studies in order to assess and implement new classification systems that could improve the therapeutic approach of patients with BMS.

Burning Mouth Syndrome.

Burning mouth syndrome (BMS) is a rare chronic neuropathic pain condition characterized by recurring burning pain or dysesthesia in the absence of any local or systemic causes of symptoms. The exact pathophysiology of BMS is unknown, but recent research suggests a medley of neuropathic, endocrinological, and psychosocial elements. This article presents a case history and reviews the epidemiology, diagnostic criteria, clinical features, diagnostic investigations, pathophysiology, and management of BMS.

[My tongue is burning!-Glossodynia/orofacial pain disorder]. / Meine Zunge brennt! ­ Glossodynie/orofaziales Schmerzsyndrom.

Glossodynia or orofacial pain disorder is known as burning mouth syndrome. It is a therapeutic challenge. Its etiology is not well defined. Recent studies show not only a correlation with neuropathic changes, but there are also indications of comorbidities such as depression, anxiety, and carcinophobia. These can also manifest as a reaction to the disease and are not necessarily considered causative. Burning mouth syndrome poses a diagnostic challenge since its differential diagnosis is broad. With regard to dermatological aspects, lichen planus mucosae, oral leucoplakia, pemphigus vulgaris, and aphthous mouth ulcers should be considered. Diabetes, anemia, vitamin deficiency, and endocrinological influences should be considered regarding the predominance of elderly and female patients. Meta-analyses of treatment studies usually show a low level of evidence of the randomized, controlled trials. According to the literature mainly psychotherapy and antidepressants are proposed for therapy. Alpha lipoic acid as a dietary supplement shows short-term improvement and low-level laser therapy might have some benefit.

Salivary characteristics in burning mouth syndrome: a systematic review.

INTRODUCTION: Compare through case-control studies, the salivary characteristics of patients with and without BMS. EVIDENCE ACQUISITION: Searches in Embase, PubMed, Web of Science, Scopus, Cochrane, and BIREME were conducted for the identification of case-controls studies reported. EVIDENCE SYNTHESIS: Thirty-three studies were included, of which 26 articles evaluated OSB, 17 SRF, and 7 SE. Nineteen organic biomarkers showed higher levels in BMS patients, the two most indicated being α-amylase and cortisol. Ten organic biomarkers, including Tumor Necrosis Factor-alpha (TNF-α) and IL-6, showed lower levels in BMS patients. Regarding salivary flow rate (SFR), five articles indicated that BMS patients have less unstimulated SFR (uSRF)Two articles indicate that stimulated SFR (sSRF) is lower in BMS patients nevertheless, but eight did not show differences. Sialochemical analysis revealed that sodium (Na), chloride (Cl), potassium (K), sodium (Na), and calcium (Ca), showed higher levels in BMS patients according to three studies, but two studies did not establish any differences. Two study established that BMS patients have lower Mg salivary levels. CONCLUSIONS: Qualitative salivary characteristics suggest that BMS has neuropathic, inflammatory, emotional, immune, and hormonal involvements. BMS can be associated with changes in salivary biomarkers of inflammation and oxidative stress, is related to anxiety and degree of pain.

Thermography as a Non-Ionizing Quantitative Tool for Diagnosing Burning Mouth Syndrome: Case-Control Study.

OBJECTIVES: Thermography is an imaging technique based on the acquisition and analysis of thermal data. The present study evaluates the use of tongue infrared thermography (IRT) as a tool for the diagnosis of burning mouth syndrome (BMS). MATERIAL AND METHODS: An IRT study was carried out in patients diagnosed with BMS according to the criteria of the International Association for the Study of Pain (n = 32) and in healthy controls (n = 35). Burning sensations, dry mouth and taste disturbances were assessed, and three temperature values were recorded for each tongue surface (dorsal, right lateral, left lateral and tip), along with body temperature and environmental temperature. RESULTS: A statistically significant difference was recorded in the temperature of the dorsal surface of the tongue between the BMS group and the controls (p = 0.01). The area under the curve (AUC) was 0.731 (95% CI: 0.402-0.657; p = 0.003). The sensitivity and specificity obtained was 62% and 77%, respectively. CONCLUSIONS: Infrared thermography appears to be useful as a complementary tool for the diagnosis of BMS, though further studies are needed in this field.

Comparison of Clonazepam and Tongue Protector in the Treatment of Burning Mouth Syndrome.

BACKGROUND: BMS is a chronic pain syndrome affecting the oral mucosa. It consists of experiencing a burning or dysesthetic sensation. BMS prevalence varies, with up to 15% among women. An effective treatment is still unattainable. MATERIAL AND METHODS: A total of 60 patients with BMS qualified for a randomised trial, divided in two groups: the clonazepam-treated and tongue protector group. Treatment was provided for 4 weeks in both groups. In the former, the oral dosage of clonazepam 0.5 mg; in the latter, a tongue protector was used. Clinical oral examination was performed, and the presence of taste disorder and pain intensity, on the visual analogues scale, were recorded. Psychological domains were explored with the Beck depression inventory (depression), Athens insomnia scale (insomnia), Eyesenck personality questionnaire-revised (personality traits), and WHO quality of life questionnaire (quality of life). RESULTS: Complete recovery was observed in three patients after clonazepam and one patient after tongue guard treatment. A greater improvement in the VAS scores, from baseline to the control values, was demonstrated in the clonazepam group, and it was statistically significant. In women, the level of depression significantly correlated with all domains of quality of life. CONCLUSIONS: BMS is an ongoing multi-specialist challenge. The development of new pathophysiological concepts of BMS offers hope for more effective treatment. Considering the influence of BMS on the quality of life and mental disorders in most patients, further research on the possibilities of therapy seems to be very important.

Phantosmia and psychogenic non-epileptic seizures in a patient with burning mouth syndrome suffering from severe depression.

Burning mouth syndrome (BMS) is a rare but serious medical condition with important psychiatric comorbidity and specific psychological correlates. Psychopathology related with BMS represents a real challenge for clinical decision-making. In this case, depression is the leading psychiatric diagnosis associated with patient's BMS somatic pain and is driven by anxiety and a dissociative functioning. Facing a complex psychosomatic symptomatology, we offer new clinical perspectives for the screening of psychological traits of BMS. Moreover, we highlight the need to foster interdisciplinarity to improve differential diagnosis and defining an optimal care path. This case report stimulates a reflection on management challenges for the consultation-liaison psychiatry and shows the importance of a person-centred approach when communicating the diagnosis.

Burning Mouth Syndrome Etiology: A Narrative Review.

Burning mouth syndrome (BMS) is defined as "idiopathic orofacial pain with intraoral burning or dysesthesia recurring daily for more than 2 hours per day and more than 3 months, without any identifiable causative lesions, with or without somatosensory changes" in International Classification of Orofacial Pain, 2020. Worldwide prevalence of BMS was estimated to be 1.73% in population-based studies, while female and elderly are at higher risk of BMS. The aim of this narrative review is to clarify the main etiopathogenetic factors of BMS investigated so far in the scientific literature. There is growing evidence of an important role of peripheral neuropathology in BMS, supported by immunohistochemical studies which have demonstrated a significant loss of epithelial and subepithelial nerve fibers. Other possible etiopathogenetic factors emerging from literature are laryngopharyngeal reflux and hormonal and salivary changes related to aging and menopause. Finally, the role of the oral microbiota in BMS has not yet been thoroughly investigated. Further studies are necessary to investigate the probably multifactorial etiopathogenesis of primary BMS, a pathology which has a serious impact on the quality of life of our patients, a disease we find ourselves treating without the adequate therapy and the necessary knowledge.