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.

Usefulness of pepsin saliva measurement for the detection of primary burning mouth syndrome related to reflux.

OBJECTIVES: To study the diagnostic value of salivary pepsin tests for detecting laryngopharyngeal reflux (LPR) in patients with primary burning mouth syndrome (BMS). METHODS: Patients with BMS and asymptomatic individuals were consecutively recruited from September 2018 to June 2023. Patients underwent hypopharyngeal-esophageal impedance pH-monitoring (HEMII-pH) and saliva collections to measure pepsin. Stomatology evaluation was carried out to exclude other causes of BMS. Oral, pharyngeal and laryngeal signs and symptoms were evaluated with Reflux Sign Assessment (RSA) and Reflux Symptom Score (RSS). Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of pepsin test were calculated considering the highest values of pepsin tests at ≥ 16, ≥ 36, and ≥ 100 ng/mL cutoffs. Receiver operating characteristic curve (ROC) was evaluated. RESULTS: Forty-nine patients with both BMS and LPR at the HEMII-pH and 21 asymptomatic individuals were recruited. Pepsin test was 83.7%, 79.6%, and 71.4% sensitive at cutoffs ≥ 16, ≥ 36, and ≥ 100 ng/mL, respectively. The ROC analysis reported that a threshold of ≥ 21.5 ng/mL was associated with sensitivity, specificity, PPV and NPV of 81.6%, 81.0%, 90.1% and 65.4%, respectively. The severity score of burning mouth symptom was significantly associated with the saliva pepsin concentration (rs = 0.263; p = 0.029) and the oral RSA (rs = 0.474; p = 0.007). CONCLUSION: Pepsin test is a valuable diagnostic approach for detecting LPR in patients with BMS. Patients with high level of saliva pepsin reported more severe burning mouth symptoms. Future studies are needed to confirm the role of LPR in the primary BMS.

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 disorder and Parkinson's disease: A scoping review of the literature.

BACKGROUND: Burning mouth disorder (BMD) is a complex medical condition characterized by a burning sensation in the mouth of fluctuating intensity. BMD is considered a diagnosis of exclusion, as oral burning can occur secondary to local or systemic conditions. Parkinson's disease (PD) is one such condition. OBJECTIVE: To provide a scoping review of the literature by assessing all articles written in English that investigated the relationship between BMD and PD. MATERIALS AND METHODS: Various databases (PubMed, Ovid, Web of Science, Science Direct and Scopus) and a search platform (EBSCOhost) were searched following similar investigative approaches. Duplicates were removed and reference lists of original studies were scrutinized for additional articles. Any decision about the inclusion/exclusion in the review was by consensus among the co-authors. RESULTS: Twenty-five original articles and one supplemental article were included in the final review, of which 13 met the inclusion criteria. These were further divided into five categories based on the study design/article, which included Prevalence studies (n = 6), Letter to the editor (n = 1), Incidence study (n = 1), Case reports (n = 2) and Experimental studies (n = 3). Strongest data was provided by epidemiological studies, which suggest BMD and PD are poorly associated. CONCLUSIONS: A scoping review of the existing literature does not suggest that PD patients are any more at risk of developing BMD compared to the general population. While there may be a link through the dopaminergic system as determined by imaging studies, it is unlikely that the pathogenesis of PD disease shares significant commonality with BMD.

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.

Role of thyroid hormones in burning mouth syndrome. Systematic review

Background: Burning mouth syndrome is an idiopathic condition characterized by burning pain in a normal-appearing oral mucosa lasting at least four to six months. In the case of secondary burning mouth syndrome is associated with local or systemic factors (such as thyroid disorders) that can cause these symptoms. The aim of this review was to study the relationship between thyroid disorders and burning mouth syndrome.Material and methods: The present study followed the PRISMA guidelines. An electronic search strategy was developed for PubMed/Medline, Scopus and Cochrane. The following combination of keywords and Boolean operators were used: Thyroid AND burning mouth; Thyroid AND burning mouth syndrome; Hypothyroidism AND burning mouth; Hypothyroidism AND burning mouth syndrome; Hyperthyroidism AND burning mouth; Hyperthyroidism AND burning mouth syndrome. The results were processed by existing free software in https://www.graphpad.com/. To evaluate the association of the categorical variables we used the Fisher test at a level of significance of p-value ≤ 0,05. As a primary summary measure the Odds Ratio (OR) has been used. To analyze the risk of bias the guidelines of the GRADE guide were used and the grade of evidence was analyzed by the guide of Joanna Briggs Institute: Levels of Evidence and Grades of Recommendations.Results: After applying the inclusion and exclusion criteria, 5 studies were selected for review. The Chi-square was 10.92 and the Odds Ratio was 3.31 with respect to TSH values with p <0.0001 (Fisher's test). The population of patients with TSH alterations is increased in 80.49% and decreased in 19.51%.Conclusions: It can be concluded that thyroid hormone abnormalities are a factor in secondary burning mouth syndrome; specially in patients with hypothyroidism. (AU)

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.

Role of thyroid hormones in burning mouth syndrome. Systematic review.

BACKGROUND: Burning mouth syndrome is an idiopathic condition characterized by burning pain in a normal-appearing oral mucosa lasting at least four to six months. In the case of secondary burning mouth syndrome is associated with local or systemic factors (such as thyroid disorders) that can cause these symptoms. The aim of this review was to study the relationship between thyroid disorders and burning mouth syndrome. MATERIAL AND METHODS: The present study followed the PRISMA guidelines. An electronic search strategy was developed for PubMed/Medline, Scopus and Cochrane. The following combination of keywords and Boolean operators were used: Thyroid AND burning mouth; Thyroid AND burning mouth syndrome; Hypothyroidism AND burning mouth; Hypothyroidism AND burning mouth syndrome; Hyperthyroidism AND burning mouth; Hyperthyroidism AND burning mouth syndrome. The results were processed by existing free software in https://www.graphpad.com/. To evaluate the association of the categorical variables we used the Fisher test at a level of significance of p-value ≤ 0,05. As a primary summary measure the Odds Ratio (OR) has been used. To analyze the risk of bias the guidelines of the GRADE guide were used and the grade of evidence was analyzed by the guide of Joanna Briggs Institute: Levels of Evidence and Grades of Recommendations. RESULTS: After applying the inclusion and exclusion criteria, 5 studies were selected for review. The Chi-square was 10.92 and the Odds Ratio was 3.31 with respect to TSH values with p <0.0001 (Fisher's test). The population of patients with TSH alterations is increased in 80.49% and decreased in 19.51%. CONCLUSIONS: It can be concluded that thyroid hormone abnormalities are a factor in secondary burning mouth syndrome; specially in patients with hypothyroidism.

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.

Burning mouth syndrome and Reflux Disease: relationship and clinical implications.

BACKGROUND AND AIM: An association between reflux and burning mouth syndrome (BMS) has been proposed. Aims of this study were: 1) to investigate the frequency of BMS in a sample of GERD patients; 2) to measure G17, in a sample of BMS patients; 3) to assess the efficacy of different therapeutical schedules for GERD in BMS patients. METHODS: We divided the study in 3 main steps. In step one, we analyzed 500 consecutive GERD patients' type and frequency of extraesophageal manifestations including BMS. In step two, we collected 124 consecutive BMS patients' symptoms and  G17.  In step three, we evaluate the efficacy of 3 different drugs on BMS. RESULTS: In step one, 204 patients complained heartburn; 31 globus pharyngeus; 52 chronic cough; 54 pharyngitis; 31 postnasal drip; 56 burning mouth symptoms; 34 noncardiac chest pain; 17 asthma and 21 sleep apnea. In step two, 29 patients had G17 ≤ 1 pg/L; 64 patients between 1 and 3; and 31 patients ≥ 3. In step three, 49 patients reported slight benefit with PPI, 75 no benefit. 61 patients reported slight benefit with sodium alginate and sodium bicarbonate, 63 no benefit. 23 reported an almost complete remission with HYCHSA, 26 slight benefit, 33 no benefit. CONCLUSIONS: Prevalence of BMS in GERD patients was similar to that reported for chronic chough and pharyngitis. Low levels of G17 were found in the majority of BMS patients. Finally, we observed a greater benefit from barrier drugs therapy than from PPI therapy in BMS patients. (www.actabiomedica.it).

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.

Glossodynia, burning mouth syndrome, and COVID-19.

PURPOSE: To evaluate whether the prevalence of glossodynia increased among patients affected by COVID-19 compared to other hospital populations. METHODS: The i2b2 patient registry platform at the University of Florida Health Center was used to generate a count of patients using the international classification of diseases (ICD)-10 diagnosis codes from October 2015 to June 2021. Logistic regression of the aggregates was used for analysis. RESULTS: Of the patients with both glossodynia and COVID-19, 60% were females, 32% were African American, 64% were white, and 100% were adults. There were 72% females, 19% African Americans, 72% whites, and 93% adults with glossodynia only. For COVID-19 patients, 57% were females, 23% were African American, 56% whites, and 90% were adults. The odds ratio (OR) for glossodynia in the COVID-19 patients was significant (OR = 2.9; 95% CI, 1.94-4.32; P < 0.0001). CLINICAL SIGNIFICANCE: Glossodynia is significantly more common in COVID-19 patients and should be considered in the differential diagnoses among the oral complications of this infection.

Síndrome de la boca ardiente: revisión de la literatura / Burning mouth syndrome: literature review

Resumen El síndrome de la boca ardiente (SBA) es una condición de dolor crónico en la cavidad oral, que se presenta mayoritariamente en mujeres de edad media. Diversas causas locales y sistémicas pueden producirlo en forma secundaria, o bien, puede representar un cuadro primario, sin etiología específica identificable. Su etiopatogenia y evolución clínica es poco comprendida. Las opciones terapéuticas son variadas y en general es necesario un tratamiento multidisciplinario. A continuación, se presenta una revisión de la literatura respecto a esta patología para difusión en nuestro medio.

Abstract Burning mouth syndrome (BMS) is a chronic pain condition of the oral cavity, which occurs more frequently in middle-aged women. It can be secondary to different local and systemic causes, or represent a primary condition, with no specific identifiable etiology. Its etiopathogenesis and clinical evolution are poorly understood. Therapeutic options are multiple and a multidisciplinary treatment is necessary. We present a review of the literature regarding BMS, to provide information relevant to our area of expertise.

Burning Mouth Syndrome: An Overview and Future Perspectives.

Burning Mouth Syndrome (BMS) is a complex chronic neuropathic orofacial pain disorder characterized by a generalized or localized intraoral burning, dysesthetic sensation or pain of the oral mucosa, recurring daily for more than 2 h per day for more than 3 months, without any evidence of specific mucosal lesions and/or laboratory findings [...].

Recent advances in the understanding of the aetiology and therapeutic strategies in burning mouth syndrome: Focus on the actions of cannabinoids.

Burning mouth syndrome (BMS) is a neuropathic pain disorder associated with a burning sensation on oral mucosal surfaces with frequently reported xerostomia, dysgeusia and tingling or paraesthetic sensations. However, patients present no clinically evident causative lesions. The poor classification of the disorder has resulted in a diagnostic challenge, particularly for the clinician/dentist evaluating these individuals. Major research developments have been made in the BMS field in recent years to address this concern, principally in terms of the pathophysiological mechanisms underlying the disorder, in addition to therapeutic advancements. For the purpose of this review, an update on the pathophysiological mechanisms will be discussed from a neuropathic, immunological, hormonal and psychological perspective. This review will also focus on the many therapeutic strategies that have been explored for BMS, including antidepressants/antipsychotics, non-steroidal anti-inflammatories, hormone replacement therapies, phytotherapeutic compounds and non-pharmacological interventions, overall highlighting the lack of controlled clinical studies to support the effectiveness of such therapeutic avenues. Particular focus is given to the cannabinoid system and the potential of cannabis-based therapeutics in managing BMS patients.

Burning mouth syndrome: a review of therapeutic approach.

Burning mouth syndrome (BMS) is described by an intense burning sensation of the tongue or other oral areas without a clear etiopathology. The diagnosis of BMS is challenging due to variations of manifestations. The management of BMS is complicated due to the complex etiology of the disease. Many medications and treatment methods have been recommended for BMS management, but no one confirmed as the standard method. In this study, the therapeutic approaches of BMS were evaluated. The data of the article was obtained from PubMed/MEDLINE, Cochrane Library, and Web of Science. The following terms including "burning mouth syndrome", "therapy", and "treatment" were used for search in the databases. A wide range of articles about the therapeutic approach of BMS was searched and reviewed. Pharmacological and non-pharmacological approaches have been used for BMS management. Pharmacological treatments are including Capsaicin, Clonazepam, Low-dose aripiprazole, Alpha-lipoic acid, Duloxetine, Amitriptyline, Gabapentin, and Pregabalin, and ultra-micronized palmitoylethanolamide. Non-pharmacological therapies for BMS are cognitive therapy, Electroconvulsive therapy, Laser therapy, Acupuncture and auriculotherapy, Transcranial Magnetic Stimulation (rTMS), Salivary Mechanical Stimulation, and Botulinum Toxin. A detailed assessment of the etiology and pathophysiology of BMS, and having information about novel therapeutic interventions are essential for the management of BMS.

Clinical characterization of gingival type of burning mouth syndrome: a cross-sectional study / Caracterización clínica del síndrome de boca ardiente de tipo gingival: un estudio transversal

Background: The aim of this study is to investigate the prevalence of localized intraoral neuropathic pain in acluster of patients who reported the involvement of gingival site as only clinical manifestation of dysesthesia,analysing type and distribution of symptoms.Material and Methods: Burning mouth syndrome (BMS) patients were enrolled in the study. Patients werescreened through laboratory test and a conventional oral examination with periodontal chart. A questionnaire tocollect data on symptoms, oral site involved, quality of sleep, anxiety was submitted to all the patients.Results: A total of 236 patients were recruited. Seventy-six patients (32.2%) presented generalized type, whereas160 (67.8%) had localized type. In the localized BMS group, the gingiva was involved in 70 patients and in 33 ofthese it was the only site involved. In the gingival subgroup, 35 patients reported burning, 29 pain and 24 xero-stomia.Conclusions: To best our knowledge, this study is the first that analyses gingival involvement as the only site inBMS and it could encourage further investigations to understand the etiopathogenesis of gingival BMS.(AU)