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.

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.

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.

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.

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.

Anatomically Coiled Internal Carotid Artery Resulting in Severe Dysphagia and Burning Mouth Syndrome.

This is a report of a 65-year-old female presenting with symptoms of dysphagia due to a coiled left internal carotid artery, treated with resection and primary repair. Dysphagia lusoria is more commonly caused by aortic arch anomalies, aberrant subclavian or common carotid arteries. Internal carotid tortuosity as a cause of severe dysphagia and burning mouth syndrome is highly unusual. A literature review examines the etiology, natural history, and treatment options.

Clinical characterization of gingival type of burning mouth syndrome: a cross-sectional study.

BACKGROUND: The aim of this study is to investigate the prevalence of localized intraoral neuropathic pain in a cluster 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 were screened through laboratory test and a conventional oral examination with periodontal chart. A questionnaire to collect 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, whereas 160 (67.8%) had localized type. In the localized BMS group, the gingiva was involved in 70 patients and in 33 of these it was the only site involved. In the gingival subgroup, 35 patients reported burning, 29 pain and 24 xerostomia. CONCLUSIONS: To best our knowledge, this study is the first that analyses gingival involvement as the only site in BMS and it could encourage further investigations to understand the etiopathogenesis of gingival BMS.

Effect of antidepressant treatment on plasma levels of neuroinflammation-associated molecules in patients with somatic symptom disorder with predominant pain around the orofacial region.

OBJECTIVE: Burning mouth syndrome (BMS) and atypical odontalgia (AO) are examples of somatic symptom disorders with predominant pain around the orofacial region. Neuroinflammation is thought to play a role in the mechanisms, but few studies have been conducted. We aimed to better understand the role of neuroinflammation in the pathophysiology and treatment of BMS/AO. METHODS: Plasma levels of 28 neuroinflammation-related molecules were determined in 44 controls and 48 BMS/AO patients both pretreatment and 12-week post-treatment with duloxetine. RESULTS: Baseline plasma levels of interleukin (IL)-1ß (p < .0001), IL-1 receptor antagonist (p < .001), IL-6 (p < .0001), macrophage inflammatory protein-1ß (p < .0001), and platelet-derived growth factor-bb (.04) were significantly higher in patients than in controls. Plasma levels of granulocyte macrophage colony stimulating factor were significantly higher in patients than in controls (p < .001) and decreased with treatment (.009). Plasma levels of eotaxin, monocyte chemoattractant protein-1, and vascular endothelial growth factor decreased significantly with treatment (p < .001, .022, and .029, respectively). CONCLUSIONS: Inflammatory mechanisms may be involved in the pathophysiology and/or treatment response of somatic symptom disorders with predominant pain around the orofacial region.

History of burning mouth syndrome (1800-1950): A review.

This medical history historic literature review aims at understanding the evolution of the medical existence of burning mouth syndrome (BMS) over times. Three historic research tools were used (Medic@, IndexCat, Gallica) with several keywords, exploring the years 1800-1950. One hundred and fifty documents were obtained dating from 1803 to 1937, including 55 reviews, 44 original articles, 40 quotations, and 11 medical dictionaries. A total of 199 cases of BMS were reported which allowed for a narrative review of the early history of BMS (1800-1950). This review spans from the description of the first clinical cases by several authors in Europe to the creation of the syndrome by the French Academy of Medicine, its intellectual sponsorship by the emerging discipline of neuropsychiatry, to its subsequent evolution until the conceptual shift of the American authors. A better knowledge of the evolution of the nosology of BMS throughout history should bring a better understanding of current approaches for treating such an affection.

Burning mouth syndrome: a review of etiology, diagnosis, and management.

Burning mouth syndrome (BMS) is a chronic condition characterized by a burning sensation of the oral cavity and is often associated with taste disturbances and xerostomia. It primarily affects menopausal or postmenopausal women. Idiopathic or primary BMS can occur spontaneously and without any identifiable precipitating factors. When BMS is associated with systemic factors, it is defined as secondary BMS. While the exact etiology of BMS is still unknown, the condition appears to be multifactorial, and numerous local, systemic, and psychological factors have been associated with it. Primary BMS is a diagnosis of exclusion and can only be reached after all potential causes of secondary burning pain have been eliminated. Management strategies include reassurance of the patient as well as pharmacologic agents such as clonazepam, supplements such as α-lipoic acid, and psychological therapy.

Plasma N-acylethanolamine and endocannabinoid levels in burning mouth syndrome: Potential role in disease pathogenesis.

OBJECTIVE: The objective was to measure endocannabinoid (eCB) ligands and non-cannabinoid N-acylethanolamine (NAE) molecules in plasma from individuals with burning mouth syndrome (BMS) and to determine whether plasma eCB/NAE levels correlated with pain, inflammation and depressive symptomatology in this cohort. STUDY DESIGN: Plasma content of the eCBs, anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG), and the NAE molecules, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were assessed in healthy subjects (n = 8) and in a cohort of newly diagnosed BMS patients (n = 9) using liquid chromatography-tandem mass spectrometry. Plasma eCBs and NAE profiles were correlated with self-rated oral cavity pain intensities, depressive symptomatology and plasma IL-8 levels. RESULTS: Plasma levels of PEA, but not OEA, AEA or 2-AG, were significantly elevated in patients with BMS, when compared to plasma from healthy individuals. Plasma PEA, OEA and AEA levels correlated with depressive symptomatology. CONCLUSIONS: This is the first evidence to indicate that circulating eCB/NAE levels are altered in BMS.

Geriatric oral and maxillofacial dysfunctions in the context of geriatric syndrome.

OBJECTIVES: To propose the application of the concept of geriatric syndrome for common geriatric oral and maxillofacial dysfunctions and to suggest the necessity of developing effective evaluation methods for oral and maxillofacial frailty. DESIGN: The concepts of frailty and geriatric syndrome based on multi-morbidity and polypharmacy were applied to five common geriatric oral medicinal dysfunctional problems: salivary gland hypofunction (dry mouth), chronic oral mucosal pain disorders (burning mouth symptoms), taste disorders (taste disturbances), swallowing disorders (dysphagia), and oral and maxillofacial movement disorders (oromandibular dyskinesia and dystonia). RESULTS: Each of the dysfunctions is caused by various kinds of diseases and/or conditions and medications, thus the concept of geriatric syndrome could be applied. These dysfunctions, suggested as components of oral and maxillofacial geriatric syndrome, are associated and interacted with each other in a complexity of vicious cycle. The resulting functional impairments caused by this syndrome can cause oral and maxillofacial frailty. CONCLUSIONS: Geriatric oral and maxillofacial dysfunctions could be better appreciated in the context of geriatric syndrome. The development of effective methods for evaluating the severity of these dysfunctions and the resulting frailty is essential.

Clinical characterization and treatment outcome of patients with burning mouth syndrome.

Burning mouth syndrome (BMS) is a complex condition that affects the oral cavity, and data regarding effective treatment are limited. The purpose of this study was to explore the demographic and clinical information along with treatment outcomes for patients with BMS treated in a large referral center. Clinical records of the Oral Medicine Clinic at the University of Florida College of Dentistry were retrospectively searched for patients diagnosed between 2009 and 2014. Clinical data and treatment effectiveness were recorded. The records of 64 patients were included in this study. Women represented the majority of patients (81.2%), and the average age of all patients was 65 years. The most common systemic diseases were hypertension (59.4%), psycho-logical disorders (51.6%), and gastroesophageal reflux disease (50.0%). The majority of patients were taking 5 or more medications (70.3%). Treatment frequency and efficacy were as follows: a-lipoic acid, 47.5% frequency (57 prescribed treatments of 120 total treatments) and lasting improvement reported with 45.6% of prescribed treatments; clonazepam, 17.5% frequency (21/120) and improvement reported with 33.0% of prescribed treatments; oral disintegrating clonazepam, 15.8% frequency (19/120) and improvement reported with 52.6% of prescribed treatments; and topical vitamin E, 5.0% frequency (6/120) and improvement reported with 33.0% of prescribed treatments. Chi-square analysis indicated that a significantly better response to treatment was reported by women (P = 0.010) and patients who reported involvement limited to the tongue rather than multifocal oral involvement (P = 0.040); however, the significant relationships did not persist when the variables were evaluated together using logistic regression analysis. No other clinical or demographic features showed significant differences in response to treatment. Although treatment effectiveness in this study was variable and limited for some regimens due to infrequent usage, many of the patients reported alleviation of symptoms.

An overview of burning mouth syndrome for the dermatologist.

Burning mouth syndrome is characterized by an idiopathic burning pain affecting the oral mucosa, with no clinically apparent changes. It can present to a variety of health professionals including dermatologists. This article summarizes the important aspects of the condition, including theories of pathogenesis, diagnosis and management.

Peripheral nervous system involvement in primary burning mouth syndrome--results of a pilot study.

OBJECTIVE: The pathophysiology of primary burning mouth syndrome (BMS) has remained enigmatic, but recent studies suggest pathology within the nervous system at multiple levels. This study aimed to investigate in detail the contribution of either focal or generalized alterations within the peripheral nervous system (PNS) in the etiopathogenesis of BMS. SUBJECTS AND METHODS: Intraepithelial nerve fiber density (IENFD) of tongue mucosa was assessed in 10 carefully characterized BMS, and the results were compared to 19 age- and gender-matched cadaver controls, 6 with lifetime diabetes. Extensive neurophysiologic and psychophysical examinations of the trigeminal system and distal extremities were performed to profile PNS function in BMS. RESULTS: Patients with BMS had significantly fewer intraepithelial nerve fibers (0,27, s.e. 0,18 mm(-1); P = 0.0253) than non-diabetic controls (0,92, s.e. 0,15 mm(-1)). In the subepithelial space, the amount of nerve fibers did not differ between the groups. The majority (9/10) of patients with BMS showed neurophysiologic or psychophysical signs of a more generalized PNS dysfunction. CONCLUSIONS: Our results in neurophysiologically optimally characterized BMS patients confirm that pure focal small fiber neuropathy of the oral mucosa has a role in the pathophysiology of primary BMS. Furthermore, BMS may be related to a more generalized, yet subclinical peripheral neuropathy.

Burning Tongue as Initial Presentation of Celiac Disease in an Elderly Woman: A Case Report.

There are few reports in the literature where celiac disease presents with tongue manifestations, although atypical presentations of celiac disease are not uncommon. This case report highlights an atypical presentation of celiac disease in an elderly female. Our patient presented to clinic with complaints of a burning tongue for the past two years as well as occasional loose stools and fatigue. Work-up revealed iron deficiency anemia, zinc deficiency and an abnormal celiac panel. Complete symptom improvement was noted by 10 weeks into the initiation of a gluten free diet. Celiac disease can present at any age and should be considered as a differential in findings of malabsorption and gastrointestinal symptoms.

Burning Mouth Syndrome: A Review of the Etiopathologic Factors and Management.

Burning mouth syndrome (BMS) is characterized by pain in the mouth with or with no inflammatory signs and no specific lesions. Synonyms found in literature include glossodynia, oral dysesthesia, glossopyrosis, glossalgia, stomatopyrosis, and stomatodynia. Burning mouth syndrome generally presents as a triad: Mouth pain, alteration in taste, and altered salivation, in the absence of visible mucosal lesions in the mouth. The syndrome generally manifests spontaneously, and the discomfort is typically of a continuous nature but increases in intensity during evening and at night. The etiopathogenesis seems to be complex and in a large number of patients probably involves interactions among local, systemic, and/or psychogenic factors. The differential diagnosis requires the exclusion of oral mucosal lesions or blood test alterations that can produce burning mouth sensation. Management is always based on the etiological agents involved. If burning persists after local or systemic conditions are treated, then treatment is aimed at controlling neuropathic symptoms. Treatment of BMS is still unsatisfactory, and there is no definitive cure. As a result, a multidisciplinary approach is required to bring the condition under better control. The aim of this review was to discuss several aspects of BMS, update current knowledge, and provide guidelines for patient management.

Pain Part 8: Burning Mouth Syndrome.

Burning mouth syndrome (BMS) is a rare but impactful condition affecting mainly post-menopausal women resulting in constant pain and significant difficulty with eating, drinking and daily function. The aetiology of BMS remains an enigma. Recent evidence suggests it likely to be neuropathic in origin, the cause of which remains unknown. There is no cure for this condition and the unfortunate patients remain managed on a variety of neuropathic pain medication, salivary substitutes and other non-medical interventions that help the patient 'get through the day'. Some simple strategies can assist both clinician and patient to manage this debilitating condition. CPD/Clinical Relevance: The dental team will recognize patients presenting with burning mouth syndrome. They are difficult patients to manage and are often referred to secondary care and, ultimately, depend on their general medical practitioners for pain management.

Burning mouth syndrome: Evaluation of clinical and laboratory findings.

BACKGROUND AND PURPOSE: Burning mouth syndrome is a chronic and persistent painful condition characterized by burning sensation in the oral mucosa. We investigated the etiological factors of patients presented with the history of burning in the mouth who admitted our outpatient clinics over the 8-years period and who had no underlying identifiable local factors. We also tried to determine their demographic and clinical characteristics. Our aim was to investigate the association between burning mouth and psychiatric disorders such as depression and anxiety, chronic diseases like diabetes mellitus (DM) and other laboratory studies in patients complaining of solely burning in the mouth. METHODS: The study included patients with the history of burning in mouth who presented in our outpatient clinic between 2005 and 2012. They were evaluated by a neurologist, a psychiatrist, an internist, and a dentist. Complete blood counts, biochemical analysis and cranial magnetic resonance imaging (MRI) were performed for all patients. RESULTS: A total of 26 (22 (84%) females, 4 (15%) males; mean age 55.9 years) patients were enrolled in this study. Five (19.2%) of the patients had depression, 2 (7.7%) had anxiety disorder, 2 (7.7%) had diabetes mellitus, 8 (30%) had B12 vitamin deficiency, 3 (11.5%) had decreased ferritin levels in blood, and 1 (3.8%) had folic acid deficiency. Cranial MRI of all patients were normal. Nine patients (34.6%) had no etiological causes. CONCLUSION: A multidisciplinary approach in the management of burning mouth and establishment of common criteria for the diagnosis would provide insight into the underlying pathophysiological mechanism.