A Novel Therapeutic Approach of 980 nm Photobiomodulation Delivered with Flattop Beam Profile in Management of Recurrent Aphthous Stomatitis in Paediatrics and Adolescents-A Case Series with 3-Month Follow-Up.

Background/Objectives: Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal lesions and a very debilitating lesion, especially in paediatric and adolescent patients. The current pharmacotherapy offers a pain relief but not without side effects, and therefore photobiomodulation (PBM) can be an alternative therapy. To the authors' best knowledge, no published study has explored the efficacy of λ 980 nm laser PBM in the management of all RAS subtypes in paediatric and adolescent patients, and therefore, this prospective observational clinical study was conducted to bridge this gap by evaluating λ 980 nm laser PBM efficacy in symptomatic RAS management in paediatric and adolescent patients. The objectives were to evaluate (1) pain intensity alleviation; (2) wound healing rate; (3) wound size closure; (4) a complete resolution; (5) evidence of recurrence; and (6) patients' treatment satisfaction. Methods: The study's variables were assessed at the following timepoints: T0: pre-treatment; T1: immediately after first PBM session; T2: 5 hours (h) post first PBM session (via telephone call); T3: immediately after second PBM session (three days post first PBM session); T4: three-day follow-up (after complete PBM treatments); T5: two-week follow-up; and T6: three-month follow-up. The following PBM dosimetry and treatment protocols were employed: λ 980 nm; 300 mW; 60 s; 18 J; CW; flattop beam profile of 1 cm2 spot size; 18 J/cm2; and twice-a-week irradiation (72 h interval). Results: At T1, significant immediate pain intensity relief was reported. 33.33% recorded "4" and 66.67% reported "5" on the quantitative numeric pain intensity scale (NPIS), and this continued to improve significantly (83.33%) at T2. All the subjects reported "0" on the NPIS at T3, T4, T5 and T6. There was a significant reduction in the lesion surface area (>50% complete healing) at T3 compared to T0. Complete healing (100%) with no evidence of scarring and lesion recurrence observed at T4, T5 and T6. Very good patients' satisfaction was reported at all timepoints. Conclusions: This is the first report demonstrating λ980 nm efficacy in all RAS subtype management in paediatric and adolescent patients with a 3-month follow-up, whereby its PBM dosimetry and treatment protocols were effective from scientific and practical standpoints, and hence multicentre RCTs with large data are warranted to validate its reproducibility and to enrich the knowledge of PBM application in all RAS subtypes.

Natural and Synthetic Drugs Approached for the Treatment of Recurrent Aphthous Stomatitis Over the Last Decade.

Recurrent aphthous stomatitis (RAS) refers to a sore and frequently recurring inflammation of the oral tissues, distinguished by the presence of small ulcers that cause significant discomfort and cannot be attributed to any underlying disease. Different treatments have been used for RAS. This review aims to provide a comprehensive overview of the treatment options over the past decade for recurrent aphthous stomatitis (RAS), encompassing both natural and synthetic treatments. It will utilize clinical efficacy studies conducted in vivo and in vitro, along with a focus on the pharmaceutical approach through advancements in drug delivery development. We conducted a thorough literature search from 2013 to 2023 in prominent databases such as PubMed, Scopus, and Cochrane, utilizing appropriate keywords of recurrent aphthous stomatitis, and treatment. A total of 53 clinical trials with 3022 patients were included, with 35 using natural materials in their research and a total of 16 articles discussing RAS treatment using synthetic materials. All the clinical trials showed that natural and synthetic medicines seemed to benefit RAS patients by reducing pain score, ulcer size, and number of ulcers and shortening the healing duration.

Association of neutrophil defects with oral ulcers but undetermined role of neutrophils in recurrent aphthous stomatitis.

Objective: Recurrent oral ulcers and severe periodontal diseases in patients with quantitative or qualitative neutrophil defects highlight the important role of neutrophils in maintaining oral mucosal barrier homeostasis. Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease affecting up to 25% of the population, yet its etiopathogenesis remains unclear, and management is unsatisfactory. This review aims to gain insight into the pathogenesis of RAS. Design: This narrative review examines the characteristics of oral and blood neutrophils, the associations between neutrophil defects and the occurrence of oral ulcers, and the evidence for the involvement of neutrophils in RAS. To conduct the review, relevant literature was searched in PubMed and Google Scholar, which was then thoroughly reviewed and critically appraised. Results: Neutropenia, specifically a decrease in the number of oral neutrophils, impaired extravasation, and defective ROS production appear to be associated with oral ulcers, while defects in granule enzymes or NETosis are unlikely to have a link to oral ulcers. The review of the histopathology of RAS shows that neutrophils are concentrated in the denuded area but are latecomers to the scene and early leavers. However, the evidence for the involvement of neutrophils in the pathogenesis of RAS is inconsistent, leading to the proposal of two different scenarios involving either impaired or hyperactive neutrophils in the pathogenesis of RAS.

Hematological parameters in patients with recurrent Aphthous Stomatitis: a systematic review and meta-analysis.

OBJECTIVES: Recurrent Aphthous Stomatitis (RAS) known as recurrent aphthous ulcer is a common and painful ulcerations in oral cavity. It has been suggested that hematological parameters seems to be considered as an etiologic factor. So, this meta-analysis and systematic review was aimed to examine the relationship between RAS and hematological parameters. METHODS: Relevant studies were found using online international databases including Scopus, Science direct, Web of science (ISI), PubMed, and Google Scholar search engine between 2000 and October 2023. The quality of all papers was determined by NOS checklist. Heterogeneity between the results of primary studies was evaluated with I-square index and publication bias was performed by Egger's test and funnel plots. Also, sensitivity analysis was done to check the effect of each of the primary studies on the overall estimate. Also, the statistical analyses were done using Stata software Ver. 11. RESULTS: By combining the results of primary studies, the standardized mean difference (SMD) of vitamin B12, ferritin, folic acid, hemoglobin, iron and zinc indices with a 95% confidence interval (CI) between the case (patients with RAS) and control (Healthy) groups were estimated -0.52(-0.89, -0.14), -0.20(-0.51, 0.11), -0.42(-0.95, 0.11), -0.58(-0.90, -0.27), 0.01(-0.12, 0.15), -0.33(-0.81, 0.14) respectively. The patients with vitamin B12, ferritin, folic acid, and iron deficiencies and reduced hemoglobin (Hb) level reported 2.93(2.28, 3.78), 2.50(1.48, 4.22), 1.51(0.53, 4.29), 1.46(0.70, 3.03), and 2.14(1.38, 3.32), times more susceptible to develop RAS than healthy individuals. CONCLUSION: The results of the meta-analysis indicated that the SMD of vitamin B12 serum and Hb levels in the case group was 52%. Our result have also showed that the odds ratio of vitamin B12, ferritin deficiencies, and decreased Hb level in case group was 2.93, 2.50, and 2.14 times more than healthy group.

Optimization and preparation of a compound cod liver oil film former agent: an orthogonal design.

Background: Cod liver oil has anti-inflammatory properties and could help regulate recurrent aphthous stomatitis (RAS). An orthogonal experiment was used to evaluate and improve the dosage form of compound cod liver oil, which has replaced the previously used liniment preparation based on film method. Methods: An orthogonal experiment was adopted, and the appearance and film-forming time of the film coating agents were used as indicators. The optimal ratio in the preparation process for the compound cod liver oil film agent was then optimized. A method for determination of compound cod liver oil film was established using High-Performance Liquid Chromatography (HPLC). Results: The results indicate that the blank films prepared using 55 mg polyvinyl alcohol (PVA) (PVA low), 45 mg of PVA (PVA medium), and 10 mg glycerol had the optimal performance, which was defined as PVAa. The drug-carrying film prepared from 3 mL PVAa (i.e., film-forming material with the optimal proportion), 30 mg dexamethasone acetate, and 30 mg metronidazole had the optimal performance. The verified sample has a complete and smooth appearance, uniform thickness and color, and no evident bubbles, which meets the requirements for a film agent defined in the Chinese Pharmacopoeia, 2020 edition. HPLC was used to determine the major components: dexamethasone acetate, metronidazole, and dyclonine hydrochloride, and the optimal separation effect was obtained. The method has advantages of good specificity, good linear results, high recovery rate, and good repeatability. Conclusion: This study proposes an optimized compound cod liver oil film former agent and preparation method. The results indicate that the compound cod liver oil film former agent had good performance, reflecting the high feasibility of this research method. The detection method of compound cod liver oil film was established by HPLC. The method was feasible, and the validity and stability of the formulation and preparation technology were guaranteed. The role of the newly developed agent in patients with RAS should be investigated further.

α-Mangostin hydrogel film with chitosan alginate base for recurrent aphthous stomatitis (RAS) treatment: study protocol for double-blind randomized controlled trial.

Background: Recurrent Aphthous Stomatitis (RAS) is a common ulcerative disease of the oral mucosa which is characterized by pain, and recurrent lesions in the oral cavity. This condition is quite painful, causing difficulty in eating, speaking and swallowing. Topical medications have been used for this condition, but the obstacle in using topical medications is the difficulty of achieving drug effects due to saliva wash out. This problem can be overcome by film hydrogel formulation which can protect the ulcer and reduce the pain to some extent. α-mangostin is a xanthone isolated from the rind of the mangosteen fruit. One of the activities of α-mangostin is anti-inflammatory effects, which operate through the characteristic mechanism of inhibiting the inflammatory response. This protocol study aims to investigate the efficacy of an α-mangostin hydrogel film with a chitosan alginate base for recurrent aphthous stomatitis (RAS) in comparison with a placebo over a period of 7 days. Study design: This is a two-arm, double blinding, randomized controlled trial enrolling patients with RAS. The efficacy test of α-mangostin Hydrogel Film will be tested against the placebo. Patients with RAS will be allocated randomly into the two arms and the hydrogel film will be administered for 7 days. The diameter of ulcer and visual analog scale (VAS) score will be used as the primary efficacy endpoint. The outcome measure will be compared between the two arms at the baseline, day 3, day 5, and at the end of 7 days. Discussion: The purpose of this clinical research is to provide scientific evidence on the efficacy of α-mangostin hydrogel film with a chitosan alginate basis in treating recurrent aphthous stomatitis. The trial is expected to improve our capacity to scientifically confirm the anti-inflammatory effectiveness of α-mangostin compounds in a final formulation that is ready to use. Trial registration: NCT06039774 (14 September 2023).

Dynamic salivary cytokine profile of recurrent aphthous stomatitis patients in thalidomide maintenance treatment.

OBJECTIVE: To dynamically compare the longitudinal (time axis) and transverse (between groups) differences of the salivary cytokines during thalidomide maintenance treatment of recurrent aphthous stomatitis. METHODS: A randomized, controlled, clinical trial was performed. After the initial prednisone treatment, thalidomide (50 mg/d vs. 25 mg/d) was used as a maintenance drug for 4 or 8 weeks. The salivary IL-4, 5, 6, 10, TNF-α, and IFN-γ were dynamically detected with a cytometric bead array. RESULTS: Overall, the level of six elevated salivary cytokines after prednisone treatment was significantly downregulated, remained low during thalidomide maintenance, and rebounded at recurrence. The effect of 50 mg/d thalidomide on the salivary cytokines was not superior to 25 mg/d medication. The relapse-free period following drug withdrawal was the longest in the subgroup using 25 mg/d thalidomide for 8 weeks. The order of magnitude of IL-6 was the most obvious, and at week 8, only the level of IL-6 in the group (25 mg/d thalidomide for 8 weeks) continued to decline compared with the other groups. CONCLUSION: Thalidomide maintenance treatment can effectively sustain low levels of salivary IL-4, 5, 6, 10, TNF-α, and IFN-γ of recurrent aphthous stomatitis patients. IL-6 displayed a good correlation with the disease and is expected to become an index for diagnosis and follow-up. CLINICAL RELEVANCE: Low-dose long-term thalidomide maintenance treatment was supported for recurrent aphthous stomatitis. TRIAL REGISTRATION: Trial registration number of ChiCTR-IPR-16009759 at http://www.chictr.org/index.aspx .

Systemic and local effect of oxidative stress on recurrent aphthous stomatitis: systematic review.

Recurrent aphthous stomatitis (RAS) is a chronic and recurrent inflammatory disease of the mouth. It is characterised by the appearance of painful ulcers in the oral mucosa. RAS is believed to be a multifactorial disease with genetic predisposition, environmental factors and alterations in the immune system. Oxidative stress, caused by an imbalance between free radicals and the antioxidant system, also appears to be involved in the pathogenesis of RAS. Several risk factors, such as smoking, iron and vitamin deficiency and anxiety, may contribute to the development of the disease. Understanding the underlying mechanisms may help in the prevention and treatment of RAS. We searched PubMed, Scopus and Web of Science databases for articles on oxidative stress in patients with RAS from 2000 to 2023. Studies analysing oxidant and antioxidant levels in the blood and saliva of RAS patients and healthy controls were selected. Of 170 potentially eligible articles, 24 met the inclusion criteria: 11 studies on blood samples, 6 on salivary samples and 7 on both blood and salivary samples. Multiple oxidative and antioxidant markers were assessed in blood and saliva samples. Overall, statistically significant differences were found between RAS patients and healthy controls for most markers. In addition, increased oxidative DNA damage was observed in patients with RAS. Patients with RAS show elevated levels of oxidative stress compared to healthy controls, with a significant increase in oxidative markers and a significant decrease in antioxidant defences in saliva and blood samples.

Efficacy and Safety of Propolis for Treating Recurrent Aphthous Stomatitis (RAS): A Systematic Review and Meta-Analysis.

The systematic review assessed the efficacy and safety of propolis for treating recurrent aphthous stomatitis (RAS). The review adopted the PICO framework to examine the effects of topical and systemic propolis on RAS while also comparing it to established treatments, placebos, or no treatment. The main focus was on the healing time, pain levels, adverse effects, the likelihood of ulcer recurrence, and accompanying symptoms such as redness. The team included randomised controlled trials (RCTs) and quasi-randomised trials, excluding case reports and studies on oral ulcers other than RAS. In May 2022, the review team comprehensively searched nine databases and trial registries following the PRISMA guidelines. The protocol was registered in the PROSPERO database under the registration number CRD42022327123. Two review authors conducted a comprehensive and autonomous search for pertinent papers and extracted essential data. Where data permitted, the team utilised Review Manager 5 to conduct a random-effects meta-analysis, assessing the risk of bias and heterogeneity of the included studies. Where possible, the GRADE Pro programme was used to assess the certainty of the evidence for all the outcomes. This review included 10 RCTs, comprising 825 participants aged between 18 and 69 years. Seven studies evaluated the efficacy and safety of propolis when applied topically, all of which used different formulations, concentrations, and carriers. The remaining three studies assessed systemic administration in tablet form. The duration of investigations ranged from 5 days to 3 years. The review team classified two studies as having an overall 'high risk' of bias, while the remaining studies were categorised as having an overall 'uncertain risk'. The overall certainty of the evidence was 'very low'. The results indicate that topical and systemic propolis may decrease the duration of healing, alleviate pain, and reduce redness in patients with RAS compared to a placebo. However, the certainty of the evidence is very low. These may be due to the high risk of bias, substantial heterogeneity, and limited sample sizes in the included studies. For these reasons, the results of this review should be interpreted with caution. Nevertheless, the limited number of adverse effects observed suggests that propolis may have a favourable safety profile when used for a short period in treating RAS.

Cardiovascular diseases, risk factors, and ulcer relapse in older adults with aphthous stomatitis.

OBJECTIVES: To test the hypothesis that cardiovascular diseases and risk factors are associated with ulcer relapse in after-retirement patients with recurrent aphthous stomatitis. SUBJECTS AND METHODS: This retrospective cohort study analyzed the data of 40 minor recurrent aphthous stomatitis patients aged 55-75 years, admitted to Oral Medicine Clinic at one university hospital in China between 2016 and 2018. The diagnosis of minor recurrent aphthous stomatitis was made based on the history and manifestation of oral ulcers. The ulcer relapse was evaluated after a 5-week anti-inflammatory treatment, and the history of systemic diseases was collected. cardiovascular disease/metabolic risk referred to the presence of any cardiovascular diseases and metabolic cardiovascular disease risks. Associations among cardiovascular diseases, risk factors, and ulcer relapse were evaluated. RESULTS: The mean age of 40 patients with minor recurrent aphthous stomatitis was 62.4 years (SD 5.1), and 60% were women. The ulcer relapse rate was 37.5% (95% CI, 0.242-0.530). The proportion of cardiovascular disease/metabolic risk was higher in the relapse group than in the no-relapse group after 5-week anti-inflammatory treatment (Fisher's exact test, p = 0.041). CONCLUSIONS: According to this single-center experience, older patients with cardiovascular disease/metabolic risk may be more prone to oral ulcer recurrence. Nevertheless, larger prospective studies are needed to confirm our findings.

Serum level of vitamin D in patients with recurrent aphthous stomatitis: A systematic review and meta-analysis of case control studies.

OBJECTIVES: Recurrent aphthous stomatitis (RAS) is an ulcerative condition with unknown etiology. The effect of vitamin D in the etiology of RAS is still a matter of controversy. In this study, we aimed at review the available evidence on the role of vitamin D deficiency in RAS etiology. MATERIAL AND METHODS: PubMed, Cochrane Library for Systematic Reviews, ISI Web of Science, Scopus, and EmBase were systematically searched for evidence on RAS and vitamin D up to January 2020. Retrieved records were screened and assessed by two of the authors independently. Newcastle-Ottawa scale was used to assess the quality of individual studies. AMSTAR tool was used for assessing the quality of the study. RESULTS: Eight studies including 383 healthy control and 352 patients with RAS were eligible for the meta-analysis. Serum vitamin D levels were significantly lower in RAS patients. The weighted mean difference was -7.90 (95% CI: -11.96 to -3.85). CONCLUSIONS: The results highlighted the importance of vitamin D deficiency in the etiology of RAS. However, more studies are needed to reach a robust decision. The observed association between vitamin D and RAS is probably due to the effect of vitamin D on the immune system.

Elevated serum fibrinogen levels in Chinese patients with minor recurrent aphthous stomatitis: An observational study.

Fibrinogen is a protein that reflects systemic inflammation and regulates the immune response to disease. However, there is a scarcity of data on fibrinogen in recurrent aphthous stomatitis (RAS). We aimed to test the hypothesis that fibrinogen is involved in the aetiology of RAS. Between November 2016 and November 2018, we included 109 minor RAS patients and 29 age- and sex-matched controls in a single-center, observational study. Their clinical history and ulcer manifestations led to the diagnosis of minor RAS. The ulcer severity score (USS) was used to assess disease severity, and fibrinogen was also collected. We conducted three analyses: Analysis 1 (comparison of fibrinogen levels between patients and controls), Analysis 2 (comparison of fibrinogen levels between high and low USS patients) and Analysis 3 (comparison of fibrinogen levels between before and after anti-inflammatory treatment in patients). The fibrinogen levels in the 109 minor RAS patients were statistically higher than in the 29 controls (mean [SD], 2.6 [0.5] vs. 2.3 [0.3]; Student's t-test, p < 0.001). However, there were no significant differences in fibrinogen levels among the 43 patients with high USS and the 39 patients with low USS (mean [SD], 2.7 [0.5] vs. 2.6 [0.4]; Student's t-test, p = 0.278). Furthermore, fibrinogen levels were significantly higher before anti-inflammatory treatment in comparison to those after anti-inflammatory treatment in the 35 paired patients (mean [SD], 2.6 [0.4] vs. 2.5 [0.4]; Student's t-test, p = 0.026). Interestingly, fibrinogen levels were significantly higher in the 35 paired patients after anti-inflammatory treatment compared to the 29 control subjects (mean [SD], 2.5 [0.4] vs. 2.3 [0.3]; Student's t-test, p = 0.026]. Fibrinogen may play a role in the aetiology of RAS and may be a drug target for RAS treatment. Clinicians should be alert that high serum fibrinogen levels might be associated with the risk of RAS.

Dental implants for patients with oral mucosal diseases: A narrative review and clinical guidance.

Oral mucosal diseases are a group of conditions that affect the oral mucosa with variable severity and include recurrent aphthous stomatitis (RAS), oral lichen planus (OLP), pemphigus vulgaris (PV), mucous membrane pemphigoid (MMP), and systemic lupus erythematosus (SLE). These may manifest clinically as painful oral ulcerations, reticulations and/or erosions, with differences between each. Management protocols often include initial topical and/or systemic corticosteroid (CS) therapy to control the patient's acute symptoms, followed by CS-sparing agents for long-term maintenance therapy. Patients with oral mucosal diseases often require dental implants to replace missing teeth. However, data on potential complications and success rates for these cases is still lacking. Considering the steady increase in the incidence of immune-related systemic conditions in the general population globally, dentists are expected to have the needed knowledge and ability to safely place dental implants in this group of patients. Therefore, this review aims to discuss the underlying pathogeneses of common oral mucosal diseases, clinical presentations, best practice approaches, and recommendations for the placement of dental implants in patients with similar conditions.

Prevalence of Aphthous Stomatitis: A Cross-Sectional Epidemiological Study.

Introduction Recurrent aphthous stomatitis (RAS) is a common ulcer of idiopathic etiology but is recurrent, causing painful ulcers in the non-keratinized mucosa. The disease is commonly seen in people aged 10-40 years. The etiology of RAS has yet to be well established, but several risk factors that lead to the development of RAS have been proven in the literature. With an unknown etiology, developing a definitive cure and maintaining disease remission remains challenging. An epidemiological survey will shed some light on the disease's prevalence, which could provide insights into disease management. This study aimed to study the prevalence of aphthous stomatitis among the patients visiting the dental outpatient services of a dental college in South India. The objectives were to discover the different subtypes of aphthous stomatitis and the age predominance of the type of ulcer. Materials and methods The data was collected from the case records of Saveetha Dental College and Hospitals, Chennai, India, dated from June 2019 to June 2023. The age and gender of the patients with RAS were recorded. The details collected were systematically arranged in an Excel sheet (Microsoft Corporation, Redmond, Washington, United States) and further analyzed using IBM SPSS Statistics for Windows, Version 24.0 (Released 2016; IBM Corp., Armonk, New York, United States) and chi-square tests were run to check for statistical significance. Results A total of 1,44,056 patients visited the Dental OPD during the study period. Of these, 1115 patients had RAS. When the data was analyzed, there was a three-fold increase in the occurrence of RAS during the coronavirus disease 2019 (COVID-19) pandemic, which was statistically significant (p=0.043). The most commonly affected age group was 26-40 years. Among the clinical variants of RAS, it was found that 82.5% of RAS patients had a minor variant of aphthous stomatitis. Conclusion This study shows the prevalence of different types of aphthous stomatitis, wherein we noticed that the minor clinical variant was the most common, followed by the major variant. The lesions were more commonly seen in women. However, the age group most commonly affected was 26-40 years.

Otorhinolaryngological Manifestations and Esophageal Disorders in Celiac Disease: A Narrative Review.

Celiac disease (CeD) is a chronic gluten-sensitive immune-mediated enteropathy characterized by numerous intestinal and extra-intestinal signs and symptoms. Among extra-intestinal manifestations, otorhinolaryngological (ORL) complaints in CeD are relatively rare and their relation to CeD is frequently overlooked by physicians. Recent studies underlined that the prevalence of recurrent aphthous stomatitis, aphthous ulcers, geographic tongue, and xerostomia was significantly increased in CeD patients compared with healthy individuals. However, data about the other oral manifestations of CeD, such as atrophic glossitis, glossodynia, angular cheilitis, and salivary abnormalities, are scanty. Further ORL conditions associated with CeD include sensorineural hearing loss, nasal abnormalities, and obstructive sleep apnea. Moreover, several esophageal disorders such as gastroesophageal reflux disease and eosinophilic esophagitis have been associated with CeD. The pathophysiological link between both ORL and esophageal manifestations and CeD might be further investigated. In addition, also the role of gluten-free diet in improving these conditions is largely unclear. Certainly, otorhinolaryngologists can play an important role in identifying people with unrecognized CeD and may help prevent its long-term complications. The aim of this narrative review is to analyze the latest evidence on the association between CeD and ORL and esophageal manifestations.

The relationship between Helicobacter pylori infection and recurrent aphthous stomatitis: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was designed to provide new insights into the relationship between Helicobacter pylori (H. pylori) infection and recurrent aphthous stomatitis (RAS). MATERIALS AND METHODS: We included and evaluated studies on H. pylori infection and RAS from PubMed, EMBASE, Cochrane Library, and Web of Science databases published up to January 31, 2023. The characteristics of these studies were collected, and the quality was evaluated by Newcastle-Ottawa Scale (NOS). The random effects model was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI). To further explore the sources of heterogeneity, meta-regression analysis and subgroup analyses were performed. Funnel plot, Egger's test, and Begg's test were used to assess publication bias. RESULTS: In total, fifteen case-control studies with 1137 individuals (601 cases and 536 controls) were included. The H. pylori was found to be significantly associated with RAS (OR: 1.83 95% CI: 1.41-2.37, P = 0.001). In the subgroup analyses, studies that used PCR (OR: 2.03 95% CI: 1.31-3.15) or UBT (OR: 1.83 95% CI: 1.13-2.96) yielded a significant positive association, while a non-significant association (OR: 1.12 95% CI: 0.61-2.08) was found from studies that used ELISA method. Sensitivity analyses showed that the results were robust. No significant publication bias was found. CONCLUSIONS: The current evidence does not rule out an association between H. pylori and RAS. The effect of H. pylori on RAS varies in detection methods and sources of sample. Large samples, multiple clinical studies, and improved methods are still needed to determine the exact effect of H. pylori on RAS. CLINICAL SIGNIFICANCE: H. pylori infection may be a risk factor for the pathogenesis of RAS.

Hematological parameters, obesity, stress and oxidant - antioxidant indicators in patients with or without recurrent aphthous stomatitis: A case control study.

INTRODUCTION: Recurrent Aphthous Stomatitis (RAS) is a frequent chronic disease of the oral cavity that affects 5-25 % of the population with a plethora of predisposing factors. Despite its equivocal etiology, immune alterations, hematologic deficiencies and oxidative stress has been reported to be significant etiologic factors. Stress and obesity are other environmental factors that have been studied to understand associations with RAS. OBJECTIVES: This study investigated the association of stress, hematologic parameters, oxidative indices and other selected salivary factors in a case control study on RAS Methods: Twenty-two participants each in both case and control groups were recruited with saliva and serum samples collected from them after a self-administered Recent Life Changing Questionnaire (RLCQ). OHI-S and salivary flow rate (SFR) were calculated with selected hematologic parameters and oxidative indices such as Total oxidant (TOS) and anti-oxidant (TAS) levels and their ratio - Oxidative Stress Index (OSI). Anti-oxidative indices of Ferric-Reducing Antioxidant Power (FRAP) and Glutathione Peroxidase Activity (GsPHx) were also estimated. RESULTS: The RAS group had a significantly higher RLCQ scores at a median of 145 more than the control (57.5). There was no significant in their obesity indices, however there was a significant higher mean in the ESR (p< 0.0001) and Vit B12 (p = 0.0001); OHI-S was also significantly higher in the RAS group with a median of 1.65. Both the salivary and serum TOS were significantly higher in the RAS (10.0 ± 3.8, 15.4 ± 8.9) compared to the control group (7.92 ± 1.49, 9.56 ± 3.5). GsPHx activity was significantly higher in both the saliva and serum in the control group (0.08 ± 0.08, 0.19 ± 0.11) while nil significant difference was found in the FRAP activity. Regression showed most important variables to be the salivary GsPHx activity, followed by serum OSI and GsPHx activity. CONCLUSION: The oxidative indices of TOS, TAS and GsPHx can serve as significant biomarkers in detecting RAS. This further corroborates the role of immune dysregulation in the etiology and predisposition to RAS.

Coeliac disease and its implications on the oral health of children: A systematic review.

AIM: Apart from various typical gastrointestinal symptoms, coeliac disease may have its clinical manifestations in the oral cavity which is the entrance of the gastrointestinal tract. METHODS: A systematic review of literature was performed using the following databases: Medline, Scopus, EBSCOhost and Cochrane Library for Systematic Review. INCLUSION CRITERIA: observational or experimental original studies published in English with full text available between January 2000 and December 2022, regarding children and adolescents under the age of 20. Risk of bias was determined with the use of Risk Of Bias In Non-randomised Studies of Exposure. RESULTS: Thirty-four studies were included in the review. The analysis confirmed a higher prevalence of numerous oral manifestations in coeliac disease concerning both hard and soft tissues. Our study found the prevalence of dental enamel defects to be at the level of 17.9%-83.5% (P value <0.047) and recurrent aphthous stomatitis of 8.3%-69% (P value <0.039). CONCLUSION: Oral manifestations may precede gastrointestinal symptoms. Patients presenting such manifestations should be screened for coeliac disease. The cooperation of gastroenterologists and dentists could lead to an increased detectability of coeliac disease.

A Comparative Study of Dexamethasone Ointment along with Triamcinolone Acetonide in Treatment of Recurrent Aphthous Stomatitis.

Aim: To assess and compare the efficacy of dexamethasone ointment with triamcinolone acetonide, the gel form, in the treatment of minor recurrent aphthous stomatitis (RAS). Materials and Methods: This was a randomized clinical trial of 60 patients of either sex with clinically diagnosed RAS who were randomly divided into two groups-the dexamethasone ointment group (Group I) and the triamcinolone acetonide gel group (Group II). Patients were asked to apply the gel three times a day on each ulcer. Estimation of the efficacy of gel was done based on the time required for regression in pain, size, and number of ulcers. Results: The results showed there was a significant difference in size, pain, number, and duration of ulcers in Group I and Group II within 7 days. However, in both groups, no significant difference was noted in the treatment of RAS. Conclusion: Dexamethasone ointment was found to be efficient in this treatment and was safe as evaluated using clinical assessments.

Estomatitis aftosa recurrente / Recurrent aphthous stomatitis

La estomatitis aftosa recurrente (EAR) es la enfermedad clínica más frecuente de la mucosa oral. Su prevalencia en la población general varía entre el 5 y el 25%, siendo su pico de aparición en la segunda década de la vida. Hasta el momento, la etiopatogenia no está aclarada. En pacientes genéticamente predispuestos, el efecto de ciertos factores desencadenantes iniciaría la cascada de citocinas proinflamatorias dirigidas contra determinadas regiones de la mucosa oral. Las úlceras son redondas u ovaladas con márgenes eritematosos bien definidos y centro poco profundo ulcerado cubierto con una seudomembrana fibrinosa de color gris o amarillento. Pueden reaparecer a intervalos de pocos días y meses. Ante la aparición de aftas periódicas en la mucosa bucal, lo primero será realizar con correcto diagnóstico diferencial, descartar enfermedades sistémicas asociadas y valorar causas tratables antes de llegar al diagnóstico de EAR. En el momento actual no existe tratamiento curativo (AU)

Recurrent aphthous stomatitis (RAS) is the most common clinical disease of the oral mucosa. Its prevalence in the general population varies between 5 and 25%, with its peak appearance in the second decade of life. So far, the etiopathogenesis is not clear. In genetically predisposed patients, the effect of certain triggering factors would initiate the proinflammatory cytokine cascade directed against certain regions of the oral mucosa. Ulcers are round or oval with well-defined erythematous margins and a shallow ulcerated center covered with a gray or yellowish fibrinous pseudomembrane. The ulcers may reappear at intervals of a few days and months. Given the appearance of periodic thrush in the oral mucosa, the first thing to do is to make a correct differential diagnosis, rule out associated systemic diseases and assess treatable causes before reaching the diagnosis of RAS. At present, there is no curative treatment (AU)