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PloS One 2024This systematic review and meta-analysis aimed to evaluate the expression levels of various T helper (Th) cell-secreted cytokines in recurrent aphthous stomatitis (RAS).... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis aimed to evaluate the expression levels of various T helper (Th) cell-secreted cytokines in recurrent aphthous stomatitis (RAS). Case-control studies comparing the serum or salivary levels of cytokines between RAS patients and healthy controls were searched in PubMed, EMBASE, Web of Science, and Google Scholar prior to September 30, 2023. Cytokines produced by Th1 (interleukin [IL]-1, IL-2, IL-8, IL-12, tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), and Th17 (IL-17A) cells were investigated. The standard mean difference (SMD) with 95% confidence interval (CI) was calculated to detect the difference. A total of 20 studies comprising 1070 RAS patients and 536 healthy controls were included. RAS patients had significantly higher salivary levels of IL-2 (SMD = 4.15, 95%CI 0.83-7.48), IL-5 (SMD = 0.53, 95%CI 0.05-1.00), IL-6 (SMD = 0.48, 95%CI 0.12-0.84), IL-12 (SMD = 0.94, 95%CI 0.18-1.71), and TNF-α (SMD = 1.31, 95%CI 0.44-2.18) compared to healthy controls. Serum levels of IL-6 (SMD = 0.48, 95%CI 0.30-0.66), TNF-α (SMD = 0.70, 95%CI 0.22-1.17), and IFN-γ (SMD = 0.72, 95%CI 0.17-1.28) were significantly increased, while serum IL-10 levels (SMD = -2.25, 95%CI -3.99 to -0.52) were reduced in RAS patients. Patients diagnosed with major RAS had markedly elevated serum IL-8 levels (SMD = 0.39, 95%CI 0.07-0.71) and a trend toward higher serum IL-6 levels (SMD = 0.51, 95%CI -0.02 to 1.04) than those with minor RAS. In conclusion, Th1/Th2-related cytokines, especially IL-2, IL-6, and TNF-α, are involved in the pathogenesis of RAS development and progression and are potential therapeutic targets for RAS.
Topics: Humans; Stomatitis, Aphthous; Cytokines; Case-Control Studies; Saliva; Th1 Cells
PubMed: 38861558
DOI: 10.1371/journal.pone.0305355 -
BMC Oral Health Aug 2023Recent investigations have highlighted autoimmune origins and abnormal immune responses; particularly those related to T cell-mediated immunity and elevated T lymphocyte...
BACKGROUND
Recent investigations have highlighted autoimmune origins and abnormal immune responses; particularly those related to T cell-mediated immunity and elevated T lymphocyte cells in the oral mucosa. Therefore, we investigated the relationship between recurrent aphthous stomatitis (RAS) and autoimmune thyroid diseases (ATDs) in an Iranian population.
METHODS
A cross-sectional study was performed on 102 patients diagnosed with ATD (cases) and 102 healthy patients (controls) who had been referred for the routine dental treatment. All participants were asked for the history of RAS and their age, gender, other systemic diseases, medications, and frequency of RAS in a year. Matching was performed based on the propensity scores for age and sex. In addition, the number of lesions in each recurrence in both groups was assessed and compared. The type of thyroid disease has been assessed for case participants and has been confirmed by the endocrinologist. The chi-square test, t-test, and Mann-Whitney U test were used to analyze the data using SPSS 18.
RESULTS
Patients with ATD had higher RAS than healthy controls (P = 0.040). ATD patients had 1.93 times more risk for RAS, and the frequency of RAS in a year was 3.15times higher in these patients (P = 0.011). Moreover, the frequency of RAS was higher in patients with hypothyroidism than in those with hyperthyroidism. However, there were no significant differences in the size and the number of lesions between the groups.
CONCLUSION
The risk and frequency of RAS were significantly higher in patients with ATDs. This would provide valuable insights into the underlying mechanisms and potential treatment strategies for both conditions.
Topics: Humans; Stomatitis, Aphthous; Autoimmunity; Cross-Sectional Studies; Iran; Hashimoto Disease
PubMed: 37649008
DOI: 10.1186/s12903-023-03326-y -
Journal of Dentistry (Shiraz, Iran) Sep 2023Recurrent aphthous stomatitis (RAS) has been identified as a common oral lesion with an unknown pathogenesis. Various studies have been conducted to show the important... (Review)
Review
Recurrent aphthous stomatitis (RAS) has been identified as a common oral lesion with an unknown pathogenesis. Various studies have been conducted to show the important role of two factors named epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) in RAS, but certain results have not been achieved. The present meta-analysis was conducted to evaluate the salivary levels of EGF and VEGF in patients with RAS. For this purpose, the related articles in the Web of Science, PubMed, Embase, ProQuest and Scopus databases until January 2022 were searched and their abstracts were studied. Google scholar and scientific information database were also searched for articles in Persian. The searches were completed by the medical subject heading terms considering "recurrent aphthous stomatitis" and "saliva" in combination with "EGF" or "VEGF" keywords. All case control studies that evaluated the salivary levels of EGF and VEGF in patients with RAS were included in this study. To evaluate statistical heterogeneity between the studies, Cochrane Q and I tests were adopted. The extracted data then were used in the analysis process based on comprehensive meta-analysis software. Originally, 619 articles were considered, of which 7 articles were selected. According to this meta-analysis, salivary EGF and VEGF levels were significantly lower in the active and remission period of RAS than in healthy individuals (Value< 0.05). In addition, salivary levels of these factors were significantly lower in the active stage of RAS than in the healing phase. This review study suggests that decreasing of salivary EGF and VEGF levels have significant role in the development of RAS.
PubMed: 37727361
DOI: 10.30476/dentjods.2022.94772.1809 -
Dentistry Journal Jan 2024The systematic review assessed the efficacy and safety of propolis for treating recurrent aphthous stomatitis (RAS). The review adopted the PICO framework to examine the... (Review)
Review
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.
PubMed: 38248221
DOI: 10.3390/dj12010013 -
Clinical and Experimental Rheumatology Oct 2023To describe the clinical phenotype and response to treatment of autoinflammatory disease (AID) patients with the TNFRSF1A-pR92Q variant compared to patients with tumour...
OBJECTIVES
To describe the clinical phenotype and response to treatment of autoinflammatory disease (AID) patients with the TNFRSF1A-pR92Q variant compared to patients with tumour necrosis factor receptor-associated periodic syndrome (TRAPS) due to pathogenic mutations in the same gene and patients diagnosed with other recurrent fever syndromes including periodic fever with aphthous stomatitis, pharyngitis, and adenitis (PFAPA) and syndrome of undefined recurrent fever (SURF).
METHODS
Clinical data from pR92Q variant associated AID, classical TRAPS, PFAPA and SURF patients were obtained from the Eurofever registry, an international, multicentre registry enabling retrospective collection of data on AID patients.
RESULTS
In this study, 361 patients were enrolled, including 77 pR92Q variant, 72 classical TRAPS, 152 PFAPA and 60 SURF patients. pR92Q carriers had an older age of disease onset than classical TRAPS and PFAPA patients. Compared to pR92Q variant patients, classical TRAPS patients had more relatives affected and were more likely to have migratory rash and AA-amyloidosis. Despite several differences in disease characteristics and symptoms between pR92Q variant and PFAPA patients, part of the pR92Q variant patients experienced PFAPA-like symptoms. pR92Q variant and SURF patients showed a comparable clinical phenotype. No major differences were observed in response to treatment between the four patient groups. Steroids were most often prescribed and effective in the majority of patients.
CONCLUSIONS
Patients with AID carrying the TNFRSF1A-pR92Q variant behave more like SURF patients and differ from patients diagnosed with classical TRAPS and PFAPA in clinical phenotype. Hence, they should no longer be diagnosed as having TRAPS and management should differ accordingly.
Topics: Humans; Retrospective Studies; Fever; Hereditary Autoinflammatory Diseases; Pharyngitis; Lymphadenitis; Stomatitis, Aphthous; Receptors, Tumor Necrosis Factor, Type I
PubMed: 37470237
DOI: 10.55563/clinexprheumatol/am4phc -
Drug Design, Development and Therapy 2024Ulcer disorders including the oral mucosa, large intestine, and stomach mucosa, cause significant global health burdens. Conventional treatments such as non-steroid... (Review)
Review
Ulcer disorders including the oral mucosa, large intestine, and stomach mucosa, cause significant global health burdens. Conventional treatments such as non-steroid anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), histamine H receptor antagonists (HRAs), and cytoprotective agents have drawbacks like mucosal injury, diminish gastric acid secretion, and interact with concurrent medications. Therefore, alternative therapeutic approaches are needed to tackle this health concern. Plants are rich in active metabolites in the bark, roots, leaves, fruits, and seeds, and have been utilized for medicinal purposes since ancient times. The use of herbal therapy is crucial, and regulations are necessary to ensure the quality of products, particularly in randomized studies, to assess their efficacy and safety in treating ulcer disorders. This study aims to explore the anti-ulcer activity of medicinal plants in treating peptic ulcer disease, ulcerative colitis, and aphthous ulcers. Articles were searched in Scopus and PubMed, and filtered for publication from 2013 to 2023, resulting in a total of 460 from Scopus and 239 from PubMed. The articles were further screened by title and abstract and resulted in 55 articles. Natural products, rich in active metabolites, were described to manage ulcer disease by protecting the mucosa, reducing ulcer effects, inhibiting pro-inflammatory factors, and reducing bacterial load, thus improving patients' quality of life. Natural extracts have proven effective in managing other health problems, including ulcers by reducing pain and decreasing lesions. This review provides an overview of preclinical and clinical studies on medicinal plants, focusing on their effectiveness in treating conditions like peptic ulcers, ulcerative colitis, and aphthous ulcers.
Topics: Humans; Ulcer; Colitis, Ulcerative; Stomatitis, Aphthous; Quality of Life; Peptic Ulcer; Anti-Ulcer Agents; Histamine H2 Antagonists; Proton Pump Inhibitors; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38318501
DOI: 10.2147/DDDT.S446949 -
BMC Oral Health Dec 2023We performed this systematic review and meta-analysis to synthesize all studies that reported the level of oxidative and antioxidative markers in recurrent aphthous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We performed this systematic review and meta-analysis to synthesize all studies that reported the level of oxidative and antioxidative markers in recurrent aphthous stomatitis (RAS) patients compared to controls.
METHODS
We registered our study in PROSPERO (CRD42023431310). PubMed, ProQuest, Scopus, EMBASE, Google Scholar, and Web of Science were searched to find relevant publications up to June 5, 2023. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. We included 30 articles after multiple stags of screening.
RESULTS
We found that erythrocyte superoxide dismutase and Glutathione peroxidase activity were significantly lower in patients with RAS compared to healthy controls (SMD = - 1.00, 95%CI = -1.79 to -0.21, p = 0.013, and SMD = - 1.90, 95%CI = -3.43 to -0.38, p = 0.01, Respectively). However, there was not any difference between patients with RAS and healthy controls in erythrocyte Catalase (SMD = - 0.71, 95%CI = -1.56-0.14, p = 0.10). The total antioxidant status (TAS) level, in serum was significantly lower in patients than healthy controls (SMD = - 0.98, 95%CI = -1.57 to -0.39, p = 0.001). In addition, RAS patients had higher levels of serum Malondialdehyde (MDA), Serum total oxidant status, and serum oxidative stress index than healthy controls (SMD = 2.11, 95%CI = 1.43-2.79, p < 0.001, SMD = 1.53, 95%CI = 0.34-2.72, p = 0.01, and SMD = 1.25, 95%CI = 0.25-2.25, p = 0.014, Respectively); However, salivary MDA and TAS, and serum uric acid, vitamin E and C, and reduced glutathione levels of patients with RAS were not different from that of healthy controls.
CONCLUSIONS
The relationship between oxidative stress and RAS is well established in this meta-analysis. Although the molecular processes underlying the etiology of this pathology remain unknown, evidence indicating oxidative stress has a significant role in the pathogenesis of RAS has been revealed.
Topics: Humans; Antioxidants; Uric Acid; Stomatitis, Aphthous; Oxidative Stress
PubMed: 38042793
DOI: 10.1186/s12903-023-03636-1 -
Dentistry Journal Apr 2024Vitamins play a vital role in human health, particularly in the development and maintenance of oral health in children. These nutrients are broadly categorized into... (Review)
Review
Vitamins play a vital role in human health, particularly in the development and maintenance of oral health in children. These nutrients are broadly categorized into fat-soluble and water-soluble types, crucial for children's well-being. The objective of this study is to investigate the impact of vitamin deficiencies on the oral health of children, focusing on how these deficiencies contribute to various oral health issues and determining the relationship between specific vitamin shortages and oral diseases. Findings indicate that shortages in vitamins A and D lead to enamel issues and a higher susceptibility to dental diseases, vitamin E assists in treating oral mucositis, and vitamin K is essential for blood clotting in dental surgeries. Deficits in B-complex and vitamin C result in enamel hypomineralization and soft tissue ailments, including aphthous stomatitis and gingival petechiae. Additionally, a lack of vitamin B7 compromises the immune response, increasing oral candidiasis risk. Therefore, vitamin deficiencies markedly affect children's oral health, highlighting the need for joint efforts between dental professionals and caregivers for effective pediatric care. Addressing vitamin deficiencies through supplementation and tailored dental care emphasizes the significance of nutritional health in children's overall and dental well-being, advocating for a collaborative approach to achieve optimal health outcomes.
PubMed: 38668021
DOI: 10.3390/dj12040109 -
Journal of Dental Sciences Jul 2023Recurrent aphthous stomatitis (RAS) is one of the most prevalent oral mucosa diseases with unknown etiology. Reduced glutathione (GSH) is a major intracellular...
BACKGROUND/PURPOSE
Recurrent aphthous stomatitis (RAS) is one of the most prevalent oral mucosa diseases with unknown etiology. Reduced glutathione (GSH) is a major intracellular non-protein physiological antioxidant, and it has been demonstrated that GSH deficiency may be related to cardiovascular, immune, and diabetes. The purpose of this investigation was to evaluate the potential roles of GSH, oxidized glutathione (GSSG), and glutathione reductase (GR) in the etiopathogenesis of minor recurrent aphthous stomatitis (MiRAS).
MATERIALS AND METHODS
The study comprised 87 patients with idiopathic MiRAS and 90 race-, age-, and gender-matched healthy individuals. The spectrophotometric method was used to determine serum GSH and GSSG concentrations as well as GR activity. The GSSG/GSH ratios were subsequently computed. For statistical evaluation, the independent sample t test, Pearson's chi-square test, Mann-Whitney U test, Kruskal-Wallis H test, and Binary logistic regression analysis were used.
RESULTS
The serum GSSG level, GR activity and GSSG/GSH ratio were statistically higher in MiRAS patients, whereas the concentration of serum GSH was significantly decreased. With the exception of GR, serum GSSG, GSH, and GSSG/GSH were all significantly associated with MiRAS. Serum GSSG can be regarded as a risk factor, whereas serum GSH and GSSG/GSH maybe considered as protective factors against the occurrence of MiRAS.
CONCLUSION
GSSG may be a potential danger factor to MiRAS and GSH may be a protective factor, while GR may not play an important role in the aetiopathogenesis of MiRAS.
PubMed: 37404670
DOI: 10.1016/j.jds.2022.11.016 -
Archives of Rheumatology Mar 2024This study aimed to extend the literature by analyzing immunoglobulin (Ig) A, IgE, IgG, IgG2, IgG3, and IgM antibody levels in periodic fever, aphthous stomatitis,...
OBJECTIVES
This study aimed to extend the literature by analyzing immunoglobulin (Ig) A, IgE, IgG, IgG2, IgG3, and IgM antibody levels in periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) patients.
PATIENTS AND METHODS
This study retrospectively analyzed the antibody test results of 20 pediatric patients (10 males, 10 females; mean age: 2.5±1.5 years; range, 0.5 to 5.4 years) with and without flare who were initially evaluated for a number of underlying diseases due to periodic fever/infectious symptoms but then diagnosed with PFAPA between January 2015 and December 2020. Antibody levels were determined by chemiluminescence microparticle immunoassay. The results were retrospectively compared with a group of healthy children after the PFAPA diagnosis was confirmed.
RESULTS
The chemiluminescence microparticle immunoassay revealed 35%, 65%, 20%, 86.6%, and 55% of PFAPA cases with low serum levels of IgA, IgG, IgG2, IgG3, and IgM respectively, while 56.2% had high IgE levels. Moreover, low serum levels of at least two antibody classes or subclasses were reported in 80% of the PFAPA children. While cases with low IgG serum levels were with the highest incidence rates among the low IgG3 PFAPA patient population, both high IgE and low IgM cases were common in the rest of the patients.
CONCLUSION
Our results suggest an association between PFAPA and low serum antibody levels, particularly of IgG3. Future studies are needed to confirm our conclusion.
PubMed: 38774691
DOI: 10.46497/ArchRheumatol.2023.9988