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.

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.

Oral microbiota dysbiosis accelerates the development and onset of mucositis and oral ulcers.

With the rapid development of metagenomic high-throughput sequencing technology, more and more oral mucosal diseases have been proven to be associated with oral microbiota shifts or dysbiosis. The commensal oral microbiota can greatly influence the colonization and resistance of pathogenic microorganisms and induce primary immunity. Once dysbiosis occurs, it can lead to damage to oral mucosal epithelial defense, thus accelerating the pathological process. As common oral mucosal diseases, oral mucositis and ulcers seriously affect patients' prognosis and quality of life. However, from the microbiota perspective, the etiologies, specific alterations of oral flora, pathogenic changes, and therapy for microbiota are still lacking in a comprehensive overview. This review makes a retrospective summary of the above problems, dialectically based on oral microecology, to provide a new perspective on oral mucosal lesions management and aims at improving patients' quality of life.

Association of Serotonin Transporter Gene Polymorphism with Recurrent Aphthous Stomatitis.

BACKGROUND: Recurrent Aphthous Stomatitis (RAS) is one of the most common diseases of the oral cavity all over the world (5-66%). RAS has a multifactorial etiology, while psychological factors such as stress and anger play a role in its manifestation. The serotonergic mechanisms particularly the serotonin-transporter gene (5-HTT) may affect the risk of psychological alterations and stress response. The aim of the present study was to evaluate the polymorphism of the promoter region of 5-HTT (5-HTTLPR) in the patients with RAS, compared to that in the control subjects. METHODS: In this case-control study, 100 patients with RAS and 100 healthy subjects were enrolled. PCR was performed on DNA of the samples, using a pair of primers capable of distinguishing S/L alleles and replicating 5-HTTLPR. RESULTS: No statistically significant difference existed between LL and LS genotype frequencies in the case and control groups. However, SS genotype frequency was significantly higher in the case group, as compared to the control group (p=0.001). CONCLUSION: The conclusion of the present study demonstrated that S allele could approximately double the risk of RAS.

"Ozone" - the new NEMESIS of canker sore.

BACKGROUND: Recurrent aphthous ulceration or recurrent aphthous stomatitis is one of the most debilitating and painful oral mucosal disease. This disease entity has no specific cause to occur and no proper laboratory procedures are present to elicit the diagnosis. The treatment options are largely palliative and aimed at reducing symptoms thereby improving patient's oral condition. In the present study the subjects witnessed alleviation of clinical symptoms related to the aphthous ulceration. AIMS AND OBJECTIVES: The aim of the study was to explore the effectiveness of ozonated oil in the treatment of recurrent aphthous ulcer and to compare with sessame oil in order to analyse the effectiveness between the two topical oil medications. MATERIALS AND METHODS: A single-blinded placebo-controlled trial comprising of 30 subjects with recurrent aphthous ulcers were divided into Group 1, Group 2 and Group 3 with 10 subjects in each group was performed. Patients in Group 1 received ozonated oil, Group 2 received sesame oil and Group 3 received placebo. Treatment response was assessed by measures of pain reduction, ulcer duration on 2(nd), 4(th) and 6(th) day. Data were analyzed using Wilcokson signed rank test and Friedman test. RESULTS: Participants treated with ozonated oil showed significant reduction in ulcer size, erythema and also alleviated the ulcer pain on 4(th) day of evaluation when compared to sesame oil and placebo group. On 6(th) day subjects treated with ozonated oil and sesame oil showed significant reduction in ulcer size and erythema. No significant difference was observed in placebo group when compared with other two groups on subsequent 2(nd), 4(th) and 6(th) day of evaluation. CONCLUSION: Ozonated oil and sessame oil, both showed similar effectiveness in relieving the ulcer pain. Ozone with its wide variety of inherent properties has proven to be choice of treatment in completely relieving the ulcer pain and ulcer size when compared with that of its counter medication (i.e. sesame oil).Therefore the results obtained in the present study forecast ozone to be used as a novel treatment approach in recurrent aphthous ulcers.

Clinical study to know the efficacy of Amlexanox 5% with other topical Antiseptic, Analgesic and Anesthetic agents in treating minor RAS.

BACKGROUND: To evaluate the efficacy of topical antiinflammatory agent (amlexanox 5%), along with topical antiseptic, analgesic, and anesthetic agent (benzalkonium chloride 0.01%, choline salicylate 8.7% and lidocaine hydrochloride 2%), in promoting ulcer healing, decreasing ulcer size, erythema, pain and recurrence in minor RAS. MATERIALS & METHODS: A randomized control trial was conducted on 100 patients of RAS who fulfilled the inclusion criteria. The number, size, erythema and pain with the ulcer were recorded. Visual analogue scale (VAS) and erythema scale were used to record pain and erythema. 50 patients comprising the study group received anti inflammatory paste (amlexanox 5%) applied four times daily and the control group of 50 patients received topical antiseptic, analgesic, and anesthetic agent (benzalkonium chloride 0.01%, choline salicylate 8.7% and lidocaine hydrochloride 2%) paste, patients were evaluated after 3rd, 6th, 9th and on 30th, 60th day for recurrence. RESULTS: The study group had reduction in ulcer number, size; erythema, pain and frequency of ulcers during follow up. The healing period and recurrence of ulceration reduced in both the groups but the study group had significant reduction in 30th and 60th day follow up for recurrence of ulcers. CONCLUSION: Amlexanox 5% can reduce the frequency, duration and symptoms associated with the aphthous ulcers with no sideeffects attributed to the drug. How to cite the article: Darshan DD, Kumar CN, Kumar AD, Manikantan NS, Balakrishnan D, Uthkal MP. Clinical study to know the efficacy of Amlexanox 5% with other topical Antiseptic, Analgesic and Anesthetic agents in treating minor RAS. J Int Oral Health 2014;6(1);5-11.

STUDY OF “AKHIZUNBER” SOLUTION FOR THE TREATMENT OF INFLAMMATORY ORAL STOMATITIS / Шинэ санаа Шинэ нээлт

@#ABSTRACT. Recurrent aphthous stomatitis, or RAS, is common oral disorder of uncertain etiopathogenesis for which only symptomatic therapy is available. This article reviews the current clinical features of RAS among study patients and the result of therapeutic effects of the herbal preparation Akhizunber. Over the past four years we have treated 61 RAS patients with different clinical forms by herbal preparation Akhizunber or Alumekatin. The distribution of clinical forms RAS RAS among study patients were minor aphthae -75.4%, major aphthae -16.4% and herpetiform ulcers -8.2% respectively. The healing time of treated Akhizunber was in minor aphthae -9.28±4.82 days, major aphthae -14 days and herpetiform ulcers -12 days. Of the total study participants, the patients treated by Akhizunber reported a rapid and complete recovery from RAS during treatment compared with treated patients by Alumekatin. Treatment with herbal preparation Akhizunber can be effective for patients suffering from RAS in any clinic form, regardless of their ulcer number and size.

Recurrent aphthous stomatitis / Шинэ санаа Шинэ нээлт

@#Aphthae are common oral lesions that affect approximately 10% to 20% of the population. Recurrent Aphthous Ulcers (RAU) are usually classified into three different types: minor, major and herptiform RAU. The etiology of aphthous stomatitis is unknown but according to increasing evidence, its development has an immunogenic process that causes the ulceration of the involved oral mucosa. Similar-appearing lesions may arise in following systemic disorders: 1. Behcet’s disease 2. Sweet’s syndrome 3. Cyclic neutropenia 4. Benign familial neutropenia 5. MAGIC syndrome 6. A periodic syndrome with fever and pharyngitis 7. Various nutritional deficiencies with or without underlying gastrointestinal disorders Several studies from the UK, United States, and Spain have demonstrated that hematinic deficiency (iron, folic acid, or vitamin B12) are twice as common in RAS patients than incontrols. Case report: A 10 year old male patient presented a 3-year history of episodes of multiple minor recurrent Ulcers, this year major aphthae on the anterior ventral surface of the soft palate. Patient had difficulty in eating and in speech. Clinical examination revealed multiple symptomatic ulcers with a perilesional erythematous halo covered with a pseudomembrane. The size of major aphthae was than 20 mm in diameter. The ulcers were not associated with any type of discharge. The ulcers were tender on palpation. The medical history and the family history were non-contributory. A clinical diagnosis of major aphthous ulcers was made on the basis of the history and the clinical examinations. The patient was subjected to a therapeutic regimen consisting of daily topical application of Prednizoloni 0.05%, topical lidoksor and systemic vitamin and Cefatoxime Natrii, Immunomodulators Biferon, Amphotericin B. Recurrent aphthous stomatitis (RAS) or recurrent aphthous ulcers (RAU) remains a common oral mucosal disorder in most communities of the world. Proper systemic evaluation is important before prescribing the medication.

Utility of dermatoglyphics as a non-invasive diagnostic tool inrecurrent aphthous stomatitis / Utilidade da dermatoglifia como ferramenta diagnóstica não invasivapara estomatite aftosa recorrente

Introduction: Dermatoglyphics is an advancing branch of medical science in which the dermal ridge patterns are studied and used in prediction of genetic disorders. Objective: To assess the usefulness of dermatoglyphics, as a non-invasive early predicator in RAS, since genetics plays a role in both. Materials and methods: This case control study comprised of 40 patients with recurrent aphthous stomatitis compared to 30 control subjects of similar age and sex. All subjects were investigated for their dermatoglyphic patterns of both hands, which were obtained by smearing the ink uniformly over the palm and fingers and pressing the hands firmly against the good quality paper. Qualitative analysis of prints was done for arches, loops and whorls and quantitative analysis included Total Finger Ridge Count (TFRC) and atd angle. Fisher’s Exact Tests were used to evaluate the significance between recurrent aphthous stomatitis and the dermatoglyphic features. Results: Among various dermatoglyphic parameters analyzed, recurrent aphthous stomatitis patients showed 9% arches, 62% loops and 29% whorls as the finger ridge configuration. In comparing the results between the two groups, the frequency of arches was observed more in study group while composite whorl and the nar pattern were more frequent in control group, the results were statistically significant (p < 0.05). In addition to this, study group patients demonstrated higher frequency of total finger ridge count, and control group showed higher frequency for atd angle on both hands, statistically significant difference is observed (p < 0.05). Conclusion: The study found significant correlation between palmar dermatoglyphics and recurrent aphthous stomatitis, suggesting that genetics is one of the host risk factor associated with the latter, and could aid in early detection of the disease.

Introdução: Dermatoglifia é um avançado ramo da ciência médica em que os padrões de cristas dérmicas são estudados e utilizados para predizer distúrbios genéticos. Objetivo: Avaliar a utilidade da dermatoglifia, como método de diagnóstico não invasivo para a estomatite aftosa recorrente, uma vez que a genética desempenha um papel em ambos. Materiais e métodos: Estudo caso-controle composto por 40 pacientes com estomatite aftosa recorrente comparados a 30 controles de mesma idade e sexo. Todos os sujeitos foram avaliados quanto a seus padrões dermatóglifos de ambas as mãos. Os padrões dermatóglifos foram obtidos espalhando uniformemente uma tinta sobre a palma da mão e os dedos e pressionada firmemente contra um papel de boa qualidade. A análise qualitativa das impressões foi feita por arcos, laços e espirais e a análise quantitativa pela contagem total da polpa do dedo (TFRC) e ângulo atd. Teste de Fischer foi utilizado para avaliar a significância entre estomatites recorrentes e características dermatoglíficas. Resultados: Entre os vários parâmetros dermatoglíficos analisados, os pacientes com estomatite aftosa recorrente mostraram 9% de arcos, 62% de laços e 29% de espirais na configuração da polpa digital. Ao comparar os resultados entre os dois grupos, a frequência de arcos foi mais observada no grupo de estudo, enquanto verticilos e padrão tênar foram mais frequentes no grupo controle, com resultados estatisticamente significativos (p < 0,05). Além disso, os pacientes do grupo de estudo demonstraram maior frequência de contagem total da polpa digital e o grupo controle apresentou maior frequência para o ângulo atd em ambas as mãos, com diferenças estatisticamente significativas (p < 0,05). Conclusão: O estudo encontrou correlação significativa entre a dermatoglifia palmar e estomatites recorrentes, sugerindo que a genética é um dos fatores de risco de hospedeiro associado com estomatite aftosa recorrente, e poderia ajudar na detecção precoce da doença.

Expresión de moléculas de adhesión y subpoblaciones linfocitarias en lesiones de pacientes con Estomatitis Aftosa Recurrente

Introducción: La Estomatitis Aftosa Recurrente (EAR) es una condición muy común, caracterizada por la recurrencia de úlceras en la mucosa bucal no queratinizada. Actualmente las investigaciones dirigidas a determinar la etiología de la EAR, se enfocan hacia el componente inmunológico, la evidencia más relevante indica que los individuos afectados, presentan alteración de la respuesta inmunológica mediada por células. Adicionalmente, existe atención en destacar la importancia y participación de las moléculas de adhesión en el reclutamiento del infiltrado inflamatorio en esta condición. Objetivo: Determinar la expresión de las moléculas de adhesión ICAM-1, VCAM-1 y las subpoblaciones de linfocitos T CD4+ y CD8+, en lesiones de pacientes con EAR. Material y Método: Se incluyeron 19 pacientes de los cuales 15 presentaban EAR Menor y 4 tenían EAR Mayor. El grupo control incluyó muestras de encía de 10 pacientes sin historia de EAR. A los pacientes les fue realizada una biopsia de la lesión que fue procesada por inmunohistoquímica. Resultados y Conclusión: Se observó un marcado aumento en las subpoblaciones de linfocitos, especialmente de los CD8+, lo que sugiere la implicación de los linfocitos T, y de una respuesta inmune mediada por células activadas, en la patogénesis de esta entidad. La expresión de las moléculas de adhesión de los pacientes con EAR, fue mayor en comparación con el grupo control, siendo estas diferencias estadísticamente significativas. Con respecto a ICAM-1, se observó un fuerte marcaje en el corion-infiltrado seguido del corion-endotelio y epitelio, mientras que en relación a VCAM-1 fue similar en corion-infiltrado y corion-epitelio. Estos resultados implicarían a las moléculas de adhesión jugando un papel importante en las interacciones celulares y en el reclutamiento del infiltrado celular inflamatorio, pudiéndose convertir en blanco para el daño citotóxico y contribuyendo de esta forma, a la ruptura del tejido que ocurre en los sitios de ulceración.

Recurrent aphthous stomatitis (RAS) is the most common oral mucosal disease characterized by aphthous ulcerations in the oral mucosal. Actually the investigations have been directed to determine the etiology of the RAS with special attention to the cellular immune response. Aditionally, is very important to determine the rol of the adhesion molecules in this condition. The purpose of this work was to determine the of the adhesion molecules expression, ICAm-1, VCAM-1, CD4 and CD8 cell count in patients with RAS. We evaluated 19 patients, 15 with RAS minor and 4 with major RAS. The control group included oral health tissue of subjects without RAS. We observed a higher level of CD8 cell count that suggest the implication of T cells and cellular immune response in the pathogenesis of this entity. The adhesion molecules expression was higher than in the control group. These results suggest that the adhesion molecules may play an important role in the cell interactions that we observed in this entity.