White matter hyperintensities in Burning Mouth Syndrome assessed according to the Age-Related White Matter Changes scale.

Background: White matter hyperintensities (WMHs) of the brain are observed in normal aging, in various subtypes of dementia and in chronic pain, playing a crucial role in pain processing. The aim of the study has been to assess the WMHs in Burning Mouth Syndrome (BMS) patients by means of the Age-Related White Matter Changes scale (ARWMCs) and to analyze their predictors. Methods: One hundred BMS patients were prospectively recruited and underwent magnetic resonance imaging (MRI) of the brain. Their ARWMCs scores were compared with those of an equal number of healthy subjects matched for age and sex. Intensity and quality of pain, psychological profile, and blood biomarkers of BMS patients were further investigated to find potential predictors of WMHs. Specifically, the Numeric Rating Scale (NRS), Short-Form McGill Pain Questionnaire (SF-MPQ), Hamilton rating scale for Depression and Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) were administered. Results: The BMS patients presented statistically significant higher scores on the ARWMCs compared to the controls, especially in the right frontal, left frontal, right parietal-occipital, left parietal-occipital, right temporal and left temporal lobes (p-values: <0.001, <0.001, 0.005, 0.002, 0.009, 0.002, and <0.001, respectively). Age, a lower educational level, unemployment, essential hypertension, and hypercholesterolemia were correlated to a higher total score on the ARWMCs (p-values: <0.001, 0.016, 0.014, 0.001, and 0.039, respectively). No correlation was found with the blood biomarkers, NRS, SF-MPQ, HAM-A, HAM-D, PSQI, and ESS. Conclusion: Patients with BMS showed a higher frequency of WMHs of the brain as suggested by the higher ARWCs scores compared with the normal aging of the healthy subjects. These findings could have a role in the pathophysiology of the disease and potentially affect and enhance pain perception.

Clinical validation of 13-gene DNA methylation analysis in oral brushing samples for detection of oral carcinoma: Italian multicenter study.

BACKGROUND: The aim of this Italian multicenter study was to evaluate the diagnostic performance of a minimally invasive method for the detection of oral squamous cell carcinoma (OSCC) based on 13-gene DNA methylation analysis in oral brushing samples. METHODS: Oral brushing specimens were collected in 11 oral medicine centers across Italy. Twenty brushing specimens were collected by each center, 10 from patients with OSCC, and 10 from healthy volunteers. DNA methylation analysis was performed in blindness, and each sample was determined as positive or negative based on a predefined cutoff value. RESULTS: DNA amplification failed in 4 of 220 (1.8%) samples. Of the specimens derived from patients with OSCC, 93.6% (103/110) were detected as positive, and 84.9% (90/106) of the samples from healthy volunteers were negative. CONCLUSION: These data confirmed the diagnostic performance of our novel procedure in a large cohort of brushing specimens collected from 11 different centers and analyzed in blindness.

The health-related quality of life and psychological profile in patients with oropharyngeal Pemphigus Vulgaris in complete clinical remission: A case-control study.

BACKGROUND: Pemphigus Vulgaris (PV) is a severe autoimmune blistering disease which may affect the patient's health-related quality of life (HR-QoL) and mood even during quiescent disease activity. We sought to evaluate HR-QoL, quality of sleep (QoS), anxiety and depression in oropharyngeal PV patients (OPV) in complete clinical remission on or off therapy (CCR-on, CCR-off). METHODS: Thirty OPV patients and 30 healthy controls were enrolled. The Short Form 36 Health Survey Questionnaire (SF-36), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) were administered. Descriptive statistics, including the Mann-Whitney U test and hierarchical multiple linear regression analysis, were used. RESULTS: The OPV patients had statistically lower scores in the majority of items of the SF-36 and higher scores in the PSQI, HAM-A and HAM-D than the healthy controls (P < .004; P < .001; and P < .001 respectively). Nine (30%) of the OPV patients were poor sleepers (PSQI > 5) with higher scores in the SF-36, HAM-A and HAM-D compared with the good sleepers (PSQI < 5). No statistically significant difference was detected in the OPV group when comparing patients in CCR-on and CCR-off, or in consideration of the cumulative time of the disease duration. CONCLUSIONS: HR-QoL of OPV patients can be impaired even over periods of relatively well-being, therefore, clinicians should monitor periodically their HR-QoL, QoS and psychological profile in order to guide treatments also toward improving their HR-QoL.

Medication-Related Osteonecrosis of Jaws (MRONJ) Prevention and Diagnosis: Italian Consensus Update 2020.

The Medication-Related Osteonecrosis of Jaws (MRONJ) diagnosis process and its prevention play a role of great and rising importance, not only on the Quality of Life (QoL) of patients, but also on the decision-making process by the majority of dentists and oral surgeons involved in MRONJ prevention (primary and secondary). The present paper reports the update of the conclusions from the Consensus Conference-held at the Symposium of the Italian Society of Oral Pathology and Medicine (SIPMO) (20 October 2018, Ancona, Italy)-after the newest recommendations (2020) on MRONJ were published by two scientific societies (Italian Societies of Maxillofacial Surgery and Oral Pathology and Medicine, SICMF and SIPMO), written on the inputs of the experts of the Italian Allied Committee on ONJ (IAC-ONJ). The conference focused on the topic of MRONJ, and in particular on the common practices at risk of inappropriateness in MRONJ diagnosis and therapy, as well as on MRONJ prevention and the dental management of patients at risk of MRONJ. It is a matter of cancer and osteometabolic patients that are at risk since being exposed to several drugs with antiresorptive (i.e., bisphosphonates and denosumab) or, more recently, antiangiogenic activities. At the same time, the Conference traced for dentists and oral surgeons some easy applicable indications and procedures to reduce MRONJ onset risk and to diagnose it early. Continuous updating on these issues, so important for the patient community, is recommended.

Global research trends in complex oral sensitivity disorder: A systematic bibliometric analysis of the framework.

OBJECTIVES: A systematic bibliometric analysis was performed to investigate trends in complex oral sensitivity disorder (COSD) research worldwide and compare the contributions of different countries/institutions, scientific journals, authors, keywords, and citations. METHODS: Web of Science database from 1985 to 2018 was systematically searched to identify all relevant articles using the MeSH terms "complex oral sensitivity disorder" and all synonyms used in the literature. We included original articles, review articles, letters to the editor, and book chapters in the English language and in 27 different ISI categories of medical sciences. Several bibliometric indicators were used. RESULTS: We identified 10 633 articles, of which only 3349 were eligible with only 443 being included for quantitative analyses. The annual percentage growth rate for article publication was 9.16 fractionalized articles with the most productive countries (reported only in 428 out of 443 articles) being Italy (n = 66, 15.42%) followed by USA (n = 61, 14.25%) and with Italy achieving the greatest number of citations (n = 1415). Similarly, the most productive institution for article publication was the University of Turku, Finland, with 39 (8.8%) published articles. Among the top 20 departments, 15 were affiliated with dental institutions. The most productive source was "Journal of Oral Pathology and Medicine" with 38 (8.58%) articles, whereas the most productive author was "Lopez-Jornet P" with 19 articles (6.52 fractionalized articles). CONCLUSIONS: There is an increasing trend for publications on COSD. Collaboration among different countries must improve in order to implement research on this disorder, which seems to be mainly a condition for the dental discipline.

Global research trends in complex oral sensitivity disorder: A systematic bibliometric analysis of the structures of knowledge.

OBJECTIVES: A systematic bibliometric analysis of the structure of knowledge was performed to investigate the co-word analysis, the co-citation analysis, and the social network analysis regarding complex oral sensitivity disorder (COSD). METHODS: Web of Science database from 1985 to 2018 was systematically searched to identify all relevant articles using the MeSH terms "complex oral sensitivity disorder" and all synonyms used in the literature. We included original articles, review articles, letters to the editor, and book chapters in the English language and in 27 different ISI categories of medical sciences. Several bibliometric indicators were used. RESULTS: The co-word analysis identified 741 KeyWords Plus (KWP) grouped into 4 different clusters. The terms "pain," "management," "prevalence," and "efficacy" reached the highest centrality, whereas the top 10 KWP had a frequency of 7%-29% in 443 articles. Over a period of 32 years, a complex thematic evolution occurred, going from 2 to 6 different themes, and the KWP migration rate from one cluster to another ranged from 11% to 100%. The co-citation network analysis based on the complete reference list (5932 references) of 443 articles identified only 2 clusters for journals, authors, and articles. The most prominent co-cited journal was "Oral Surgery Oral Medicine Oral Pathology" (centrality: 171.75), the most co-cited author was "Grushka M" (centrality: 330.95), and the most co-cited article was "Grushka M. Oral Surg Oral Med Oral Pathol (1987) 63:30-36" (centrality: 269.79). On the other hand, the direct citation network revealed that "Scala A et al, 2003" reached both the highest global citation score (GCS = 231) and local citation score (LCS = 161). Lastly, the social network analysis revealed an isolated collaboration among groups of authors, or countries or institutions. The worldwide collaboration analysis indicated that United States-Israel and United Kingdom-Italy were the most collaborative countries. CONCLUSIONS: The structure of knowledge of publications on COSD revealed that research in this field has been dominated by few core topics and a limited collaboration among authors and institutions from different countries. More multicenter studies on COSD are warranted in the near future when launching new projects.

Autoimmune mucocutaneous blistering diseases in the south of Italy: a 25-year retrospective study on 169 patients.

BACKGROUND: Autoimmune mucocutaneous blistering diseases (AMBDs) represent a heterogeneous group of organ-specific and potentially life-threatening diseases. We sought to determine the relationship between clinical remission and therapeutic regimens with clinical type and phenotype of AMBDs, as well as clinical outcomes achieved based on different therapeutic regimens. METHODS: A retrospective single-center study on 169 AMBDs patients, including pemphigus vulgaris (PV), mucous membrane pemphigoid (MMP), paraneoplastic autoimmune multiorgan syndrome (PAMS), and lichen planus pemphigoides (LPP), was performed from 1994 to 2019 in an oral medicine tertiary center, where we collected sociodemographic data, clinical type and phenotype, prescribed therapies, and related outcomes. RESULTS: The mean age of AMBDs patients was 55.0 ± 16.4 years. They were followed for a mean of 8.4 ± 5.8 years. The majority of these patients (62.1%) were successfully managed with conventional immunosuppressive therapy (CIST) alone. However, 37.9% of patients required additional biological treatments, either because they were non-responders or developed severe side effects from CIST, or because of the rapid and severe progression of the disease. Overall, complete clinical remission was achieved in 92.3% of patients. A statistically significant difference was noted between the frequency distribution of AMBDs patients among different therapeutic regimens (P = .002), of different clinical phenotype and type of AMBDs patients and clinical remission (P = .012 and P = .005, respectively). No difference was reported regarding clinical outcomes and different therapeutic regimens. CONCLUSIONS: AMBDs' management may be challenging, nonetheless CIST and biologic regimens introduced, when needed as reliable alternatives to CIST, result in a very high percentage of CCR.

The use of rituximab as an adjuvant in the treatment of oral pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris patients with exclusive oral involvement (OPV) treated with conventional immunosuppressive therapy may be non-responders or experience severe side effects and/or relapses. In such cases, rituximab could be used as an adjuvant in recalcitrant OPV patients. METHODS: A retrospective single-center study on patients with oral pemphigus vulgaris treated with RTX at a dose of 375 mg/m2 was performed, evaluating the complete clinical and immunological remission, side effects of RTX, and possible correlation between anti-desmoglein (Dsg) 3 antibodies and clinical remission. RESULTS: We treated 10 OPV patients, of which 60% had a moderate and 40% mild disease severity before therapy with RTX. Complete clinical remission (CCR) was achieved in 100% of OPV patients, of which 20% developed side effects and 20% experienced a relapse in a mean time of 15.2 ± 10.2 weeks. The mean time for CCR was achieved in 19.8 ± 10.3 weeks, whereas the duration of the CCR consisted in 37.4 ± 33.5 weeks. OPV patients underwent a mean follow-up of 57.2 ± 37.7 weeks. In all patients, the mean of pemphigus disease area index (PDAI) decreased from 20.3 ± 14.1 to 0.4 ± 0.0, whereas the mean Dsg3 value dropped from 157.1 ± 40.6 to 67.0 ± 26.6 after therapy with RTX. However, no correlation was found between PDAI and anti-Dsg3 antibodies before and after therapy with RTX (P > .05). CONCLUSIONS: RTX represents a valid and safe alternative as an adjuvant in OPV patients with low rate of relapses and side effects.

World Workshop in Oral Medicine VII: Reporting of IMMPACT-recommended outcome domains in randomized controlled trials of burning mouth syndrome: A systematic review.

OBJECTIVES: To determine the frequency of use of the core outcome domains published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) in burning mouth syndrome (BMS) randomized controlled trials (RCTs). METHODS: This systematic review, conducted as part of the World Workshop on Oral Medicine VII (WWOM VII), was performed by searching the literature for studies published in PubMed, Web of Science, PsycINFO, Cochrane Database/Cochrane Central, and Google Scholar from January 1994 (when the first BMS definition came out) through October 2017. RESULTS: A total of 36 RCTs (n = 2,175 study participants) were included and analyzed. The overall reporting of the IMMPACT core and supplemental outcome domains was low even after the publication of the IMMPACT consensus papers in 2003 and 2005 (mean before IMMPACT consensus publication = 2.6 out of 6; mean after IMMPACT publication = 3.8 out of 6). Use of validated assessment tools recommended by the IMMPACT consensus was scarce (1.9 out of 6). None of the RCTs reviewed cited the IMMPACT consensus papers. CONCLUSIONS: The underreporting of IMMPACT outcome domains in BMS RCTs is significant. Raising awareness regarding the existence of standardized outcome domains in chronic pain research is essential to ensure more accurate, comparable, and consistent interpretation of RCT findings that can be clinically translatable.

The usefulness of YouTube™ videos as a source of information on burning mouth syndrome.

OBJECTIVES: The aim of this review was to investigate quality assessment and quantitative information on burning mouth syndrome (BMS) on YouTube™ videos. METHODS: An electronic search of YouTube™ videos on BMS was performed using subject headings, keywords and synonyms of BMS. For each video, quality information, via the quality assessment score (QAS) and quantitative information, such as the total number of results per term searched, date of upload, clip length, view count, source category (professional, personal, educational, mixed), number of likes and dislikes and YouTube™ category were evaluated. RESULTS: The search identified 3768 videos of which only 114 were included in our analysis: the quality of videos was very poor (mean ± standard deviation = 1.76 ± 1.64). The most representative categories were "educational" with 53 (46.5%) videos scoring between 0 and 4 and "mixed" with 24 (21.1%) videos scoring between 0 and 2. Significant differences were found among all four categories in relation to length in seconds (P < 0.001), number of views (P = 0.006) and interaction index (P = 0.001), as well as between "professional" and the other categories and between "educational" and "personal" in relation to length in seconds (P < 0.001), between "educational" and "personal" (P < 0.001) and "personal" and "mixed" category in relation to interaction index (P = 0.003) and between "professional" and "personal" in relation to views per day (P = 0.015). CONCLUSIONS: A large number of videos regarding BMS have published on YouTube™, with a wide range of distribution regarding their length and views. Unfortunately, they presented unreliable information which is most often scientifically inaccurate. Health care institutions and professionals should be more actively involved in improving high-quality e-information about BMS on YouTube™.

Escalating dose of adalimumab as monotherapy to treat unusual giant and refractory oral-pharyngeal ulcerations in Crohn's disease.

Crohn's disease (CD) is a chronic, autoimmune inflammatory disease which may affect the entire gastrointestinal tract, from the oral cavity to the anus. Oral-pharyngeal ulcerations may be significant and persistent in patients with established CD, and the use of TNF-α inhibitor has demonstrated to be useful. We report a unique case of an unusual manifestation of oral CD characterized only by multiple, giant, long-lasting, relapsing ulcerations successfully treated with an escalating dose of Adalimumab at 40 mg weekly as a monotherapy.

Necrotizing sialometaplasia can hide the presence of salivary gland tumors: A case series.

OBJECTIVE: Necrotizing sialometaplasia (NS) is an uncommon benign process which affects minor and, more rarely, major salivary glands. While self-limiting, the condition might be clinically and histologically mistaken for malignancy. Furthermore, NS may accompany neoplasms. The aim of this paper was to report a series of Italian patients affected by NS associated with an unusual high presence of neoplasms of minor and major salivary glands. STUDY DESIGN: Clinical and histological features of twelve patients with NS were retrospectively evaluated. RESULTS: Eight patients presented NS of the minor salivary glands of the palate, and two of them had associated neoplasms (pleomorphic adenoma and adenoid cystic carcinoma) at the same site. Four patients had NS of the parotid gland associated with a history of fine-needle aspiration biopsy performed to diagnose parotid neoplasms. These were epithelial-myoepithelial carcinoma, adenoid cystic carcinoma, Warthin's tumor, and oncocytoma, respectively. CONCLUSION: Tumors of minor and major salivary glands might be associated with NS more frequently than previously reported. While NS of the parotid is generally the result of invasive diagnostic procedure and is detected after the excision of the tumor, NS of the minor salivary glands may obscure an underlying neoplasm, resulting in delays in referral or treatment.

World Workshop on Oral Medicine VII: Burning mouth syndrome: A systematic review of disease definitions and diagnostic criteria utilized in randomized clinical trials.

OBJECTIVE: To conduct a systematic review analyzing disease definitions and diagnostic criteria used in randomized controlled trials (RCTs) involving burning mouth syndrome (BMS). METHODS: A systematic search conducted in PubMed, Web of Science, PsycINFO, Cochrane Database/Cochrane Central, and Google Scholar that included RCTs on BMS published between 1994 and 2017 was performed. RESULTS: Considerable variability in BMS disease definitions and diagnostic criteria used created substantial heterogeneity in the selection of participants and weakened the rigor of the 36 RCTs identified. The analyzed RCTs routinely under-reported the methods used to rule in or out study participants and the number of individuals excluded from BMS RCTs. CONCLUSIONS: Our findings indicate that a large proportion of participants enrolled in these studies may have had an underlying condition that could have explained their BMS symptoms. Thus, outcomes of therapeutic interventions from these BMS RCTs should be interpreted with caution due to heterogeneous disease definitions and diagnostic criteria. In order to improve the quality of clinical trials, future research should focus on establishing consensus for a single definition of BMS that includes specific inclusion and exclusion criteria that should be used to select study participants for clinical trials.

Psychological profiles in patients with symptomatic reticular forms of oral lichen planus: A prospective cohort study.

OBJECTIVES: To analyze intra, extra-oral symptoms and psychological profiles in symptomatic patients with reticular (R) forms of oral lichen planus (OLP). MATERIALS AND METHODS: Thirty symptomatic R-OLP (sR-OLP) patients were compared with an equal number of non-symptomatic R-OLP (nsR-OLP) patients, burning mouth syndrome (BMS) patients, and healthy subjects (HS). The Numeric Rating Scale (NRS), the Total Pain Rating Index (T-PRI), and the Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) were administered. Descriptive statistics, the non-parametric ANOVA procedure by Kruskal-Wallis, the exact Fisher test, and the multiple comparison test by the Mann-Whitney U test were performed. RESULTS: The median and IQR of the HAM-D and HAM-A were 16.0 (11.7-24.0) and 17.5 (13.7-27.2) for the BMS, 13.5 (12.0-15.0) and 15.5 (10.7-18.0) for the sR-OLP patients, 2.0 (2.0-3.2) and 2.0 (2.0-4.0) for the nsR-OLP patients, and 3.0 (2.0-4.0) and 3.0 (2.0-4.0) for the HS, respectively. The median and IQR of the NRS and T-PRI were 9.0 (7.7-10.0) and 11.0 (9.0-12.2) for the BMS and 9.0 (7.7-10.0) and 11.5 (7.0-13.0) for the sR-OLP patients, respectively. Comparison analysis between the BMS and sR-OLP patients revealed a non-significant difference between the medians of the psychological profile and pain in the two groups (P-value>.05). CONCLUSIONS: The oral complaints are correlated with anxious and depressive symptoms in sR-OLP patients. Mood disorders could modulate the pain perception or that patients could develop two different associated oral diseases, OLP and BMS.

Oral lichen planus in childhood: a case series.

BACKGROUND: Although the exact incidence of pediatric oral lichen planus (OLP) is unknown, the oral mucosa seems to be less commonly involved, and the clinical presentation is often atypical. The aim of the study is to present a case series of OLP in childhood. METHODS: From our database, we retrospectively selected and analyzed the clinical data of OLP patients under the age of 18 where the diagnosis had been confirmed by histopathological analysis. RESULTS: The case series from our database shows eight patients, four males and four females. The mean (±SD) age at the time of diagnosis of the disease was 13.5 (±2.73) years, ranging in age from 9 to 17. Clinically, a reticular pattern was present in six patients (75%), and the tongue was the most commonly involved oral site (six cases, 75%). We also report the first case of OLP in a 9-year-old girl affected by autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. CONCLUSIONS: We report the largest case series of pediatric OLP published in literature thus far. Differences in the disease between adults and pediatric patients have been detected, but further investigation and a larger case series are needed to establish any detailed differences in clinical outcomes.

Antimicrobial activity and regulation of CXCL9 and CXCL10 in oral keratinocytes.

Chemokine (C-X-C motif) ligand (CXCL)9 and CXCL10 are dysregulated in oral inflammatory conditions, and it is not known if these chemokines target microorganisms that form oral biofilm. The aim of this study was to investigate the antimicrobial activity of CXCL9 and CXCL10 on oral microflora and their expression profiles in oral keratinocytes following exposure to inflammatory and infectious stimuli. Streptococcus sanguinis was used as a model and Escherichia coli as a positive control. The antimicrobial effect of CXCL9/CXCL10 was tested using a radial diffusion assay. mRNA transcripts were isolated from lipopolysaccharide (LPS)-treated and untreated (control) oral keratinocyte cell lines at 2-, 4-, 6-, and 8-h time-points of culture. The CXCL9/10 expression profile in the presence or absence of interferon-γ (IFN-γ) was assessed using semiquantitative PCR. Although both chemokines demonstrated antimicrobial activity, CXCL9 was the most effective chemokine against both S. sanguinis and E coli. mRNA for CXCL10 was expressed in control cells and its production was enhanced at all time-points following stimulation with LPS. Conversely, CXCL9 mRNA was not expressed in control or LPS-stimulated cells. Finally, stimulation with IFN-γ enhanced basal expression of both CXCL9 and CXCL10 in oral keratinocytes. Chemokines derived from oral epithelium, particularly CXCL9, demonstrate antimicrobial properties. Bacterial and inflammatory-stimulated up-regulation of CXCL9/10 could represent a key element in oral bacterial colonization homeostasis and host-defense mechanisms.