Effectiveness of low-level laser therapy in reducing pain score and healing time of recurrent aphthous stomatitis: a systematic review and meta-analysis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common chronic inflammatory oral disease that negatively impacts the quality of life. Current therapies aim to reduce pain and healing process yet challenges such as rapid loss due to salivary flushing in topical drugs and adverse effects due to prolonged use of systemic medications require further notice. Low-level laser therapy is reported with immediate pain relief and faster healing thus preserving the potential for optimal treatment modalities. This review critically analyses and summarizes the effectiveness of LLLT in reducing pain scores and healing time of RAS. METHODS: A systematic search was conducted in ScienceDirect, PubMed, and Scopus using keywords of low-level laser therapy, photo-biomodulation therapy, and recurrent aphthous stomatitis. RCTs between 1967 to June 2022, presenting characteristics of the laser and reporting pain score and/or healing time of RAS after irradiation were included. Animal studies and recurrent aphthous ulcers with a history of systemic conditions were excluded. Studies were critically appraised using the RoB 2 tool. A meta-analysis was performed using inverse variance random effects. RESULTS: Fourteen trials with a total of 664 patients were included. Reduced pain was reported in 13 studies, while shortened healing time was presented in 4. The pooling of two studies after CO2 irradiation demonstrated faster healing time compared to placebo (MD - 3.72; 95% CI - 4.18, - 3.25). CONCLUSION: Pain score and healing time of RAS were reduced after irradiation with LLLT. RoB resulted in "some concerns" urging well-designed RCTs with larger samples to further assess each laser application for comparison. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022355737.

Treatment of Aphthous Ulcers with Photodynamic Therapy: A Randomized Controlled Clinical Study.

BACKGROUND: This study aims to assess whether photodynamic therapy (PDT) offers a clinically effective alternative for treating oral aphthous ulcers, contributing to the ongoing quest for methods to expedite their treatment process amidst the limited understanding of their etiology. MATERIALS AND METHOD: The study involved thirty volunteers with aphthous ulcers, split equally between a control group and a PDT group. Patients in the PDT group received laser treatment using Indocyanine green upon admission, while the control group received no intervention. Lesion diameter was measured at presentation and on the 3rd, 5th, and 7th days for all patients, with wound healing assessed on the 7th day. Additionally, pain levels were evaluated using the Visual Analog Scale (VAS) preoperatively and on the 1st, 3rd, 5th, and 7th days for the PDT group, and on the corresponding days for the control group. RESULTS: Lesion diameters in the PDT group showed a significant reduction over time (p=0.001), particularly from preoperative to final measurements. The control group also exhibited a decrease, albeit slower (p=0.001). The 7th-day healing scores favored the PDT group significantly (p=0.012). VAS scores in the PDT group decreased significantly over time (p=0.001), indicating pain reduction. A similar trend was observed in the control group, albeit slower. Between-group differences in healing data and pain data were statistically significant. CONCLUSION: PDT proves effective in reducing aphthous ulcer diameters and pain intensity, facilitating faster healing than the control group. These results advocate for PDT as a viable treatment option for aphthous lesions.

Impact of Photobiomodulation on IL1ß and TGFß-1 concentrations in patients with aphthous stomatitis.

Laser therapy has shown effectiveness in promoting wound healing by influencing various physiological factors such as blood flow, cytokines, histamine, nerve signals, lymphocyte function, tissue oxygenation, and cell growth. This study aims to evaluate the therapeutic efficacy of Photobiomodulation (PBM) treatment, by using diode laser, in modifying the levels of interleukin-1 beta (IL1ß) and transforming growth factor beta-1 (TGFß-1) in patients diagnosed with aphthous stomatitis. A before-after interventional design was conducted over 10 months with 20 subjects. Data on demographic details and serum concentrations of IL1ß and TGFß-1 were collected pre-treatment and on Days 3 and 7 post-treatments. The intervention involved a single session of four 30-second applications of a QuickLase dual-wavelength laser operating at 980 nm. Results show significant reductions in IL1ß and TGFß-1 levels after 7 days of treatment, indicating a time-dependent effect of PBM therapy on these inflammatory markers. The findings suggest that PBM therapy holds promise as an intervention for reducing inflammation associated with aphthous stomatitis.

Evaluation of the Effects of Punica granatum Flower Tablets on Pain and Healing of Minor Recurrent Aphthous Stomatitis: A Randomized Clinical Trial.

OBJECTIVES: The purpose of this study was to determine the therapeutic effect of the Punica granatum (PG) flower on recurrent aphthous stomatitis in comparison with corticosteroid therapy. MATERIALS AND METHODS: This cross-over randomized clinical trial was conducted on the patients who had been referred to Shiraz Dental School for their RAS in 2021. All the participants used both P. granatum flower tablets and Triadent a month apart for wash-out time and all compared themselves. In the experimental group, 30 patients received pomegranate flower tablets, three tablets daily, for 6 days. In the control group, oral paste Triadent has been prescribed three times a day for 6 days. The visual analog scale (VAS) and the size of RAS were evaluated on Days 0-6. Data were analyzed by SPSS version 21. The Wilcoxon test was used. RESULTS: The mean age of participants was 27.8 ± 14.77 years old. In this study, 15 patients (50%) were men and 15 patients (50%) were women. The mean value of VAS after using prescribed treatment in both evaluated groups on all days was significantly different such that the VAS values were lower for PG flower tablets than Triadent (p value < 0.05). The size of oral lesions in participants who used PG flower tablets was significantly less than those who used Triadent on all evaluation days (p value < 0.05) except on Day 1 (p value = 0.29). The descending slope of VAS from Days 1 to 6 for both Triadent and PG flower tablet users was significant and noticeable. (p value < 0.05). CONCLUSION: According to the result of this study, both P. granatum flower tablet and Triadent are useful in reducing the size, period of healing, and VAS of patients with RAS, but the PG flower tablet is more effective.

A bibliometric study on research trends and hotspots of recurrent aphthous stomatitis.

Background/purpose: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease. Despite a variety of scientific articles have been available till date, merely a few scientometric analyses have been systematically carried out in this field. The objective of this study was to recognize the hotspots and research trends related to RAS via bibliometric approach. Materials and methods: The Elsevier's Scopus database was searched to retrieve qualified literature through an advanced search strategy on 9 Feb 2023. The basic information was collected as following: article type, publication year, journals, impact factor, the count of citations, citation density, keywords, authors, contributing institutions and country. Results: A list of 986 publications were identified from 1933 to 2022, and the number of citations for each paper varied from 0 to 283. A steady increasing trend in the number of documents could be observed each decade with the summit in 2010s. Controlled study (n = 334) and major clinical study (n = 192) were the most common types of study design. Scully C (n = 26) was identified as the most productive author. United States (n = 166) and Turkey (n = 101) top the list of dedicating countries. Conclusion: This report would offer profound insight into the current status of RAS research and serve as a reference source for anyone planning to enhance the quality of future work.

Depression, Anxiety, Stress, and Pain Severity in Patients With Recurrent Aphthous Stomatitis: A Cross-Sectional Study.

Background Recurrent aphthous stomatitis (RAS) is a chronic oral ulcerative condition with an elusive etiology that is associated with excruciating pain. Psychological factors have been suspected as a possible risk factor in its onset and development. Depression, anxiety, and stress play pivotal roles in how people experience pain. Hence, we aimed to explore the relationship between depression, anxiety, stress, and the severity of pain perceived due to recurrent ulcers in RAS patients. Materials and methods A cross-sectional comparative study was conducted on 248 patients, comprising 124 diagnosed with RAS and 124 healthy subjects without this oral condition. Patients from both of these groups were matched with regard to age and sex and recruited over a period of one year from a dental hospital in Bengaluru, India. Patients with any other oral lesions, painful oral conditions, or systemic and psychological illnesses were excluded. Depression, anxiety, and stress were assessed in these patients using the Depression Anxiety Stress Scale 21 (DASS-21). Utilizing a Visual Analog Scale, ulcer-related pain was assessed in patients with RAS. The data were analyzed using the chi-square test and Pearson's correlation test in IBM SPSS Statistics for Windows, Version 26.0 (released 2019, IBM Corp., Armonk, NY). Results The chi-square analysis showed that participants with RAS showed a statistically significant higher prevalence of extreme stress (n = 39, 31.5%), extreme anxiety (n = 82, 66.1%), and depression (n = 38, 30.6%) as opposed to those without this oral condition. A moderately positive correlation was observed in the Pearson's test between the severity of pain experienced and stress and anxiety (r = 0.65 and 0.60, respectively, p < 0.05), while a mild positive correlation was observed between the severity of pain and depression (r = 0.35, p < 0.05). Conclusion Depression, anxiety, and stress influenced the severity of pain in these lesions, dictating the need for a holistic approach that integrates psychological interventions in the management of such chronic oral conditions with psychological links.

Full-Thickness Macular Hole: An Exceptional Case Presentation in Behçet's Disease.

Behçet's disease (BD) is a vascular disorder affecting a variety of organ systems. It is an auto-immune disease with inflammatory vasculitis that is systemic in nature, the exact etiology of which is unknown. Obliterative vasculitis, recurrent aphthous ulcers, mucocutaneous manifestations, recurrent genital ulcerations, and intraocular inflammation, especially chronic relapsing uveitis, are the characteristic features of BD. The case report presents a unique manifestation of BD in a 20-year-old Pakistani male who presents with a one-year-old history of viral encephalitis, after which he developed a blurring of vision. On examination, he had recurrent aphthous ulcers, recurrent ulcerations of genitalia, and a history of lesions of the skin. After making the patient undergo a cascade of investigations for evaluating and assessing the various signs and symptoms, a diagnosis of BD with bilateral panuveitis and a full-thickness macular hole (FTMH) in the right eye was established. Immuno-suppressants, steroids, and azathioprine were used as treatment options, following which the state of remission was attained.

Efficacy and safety of total glucosides of paeony in the treatment of recurrent aphthous ulcers: a systematic review and meta-analysis.

Background: Recurrent aphthous ulcer (RAU) had high prevalence and lacked widely recognized treatment. Total glucosides of paeony (TGP) was used in the treatment of RAU in recent years. This study was to summarize the efficacy and safety of TGP in the treatment of RAU. Methods: We searched eight commonly used databases for relevant studies that published before 1 November 2023. Primary outcome was visual analogue scale (VAS). Secondary outcomes included overall response rate, significant response rate, ulcer healing time, interval, number of ulcers, and serum inflammatory factors. We conducted the meta-analysis, assessed risk of bias and the confidence of the evidence, by using Stata 15.0, Review Manager 5.4, and Gradepro. Results: Nine randomized controlled trials (RCTs) encompassing 883 patients with RAU were included in the final analysis. The VAS in the TGP group was lower than that in the control group (MD = -1.18, 95% CI = -1.58 to -0.78, p < 0.001, moderate-certainty evidence), subgroup analysis suggested longer (>8 weeks) medication and observation led to a more significant reduction in pain (p = 0.02). Moreover, TGP had higher overall response rate (RR = 1.18, 95% CI = 1.04 to 1.33, p = 0.008, very low-certainty evidence) and significant response rate (RR = 1.72, 95% CI = 1.38 to 2.14, p < 0.001, very low-certainty evidence), accelerated ulcer healing (MD = -1.79, 95% CI = -2.67 to -0.91, p < 0.001, low-certainty evidence), and extended intervals (MD = 23.60, 95% CI = 14.17 to 33.03, p < 0.001, very low-certainty evidence). The efficacy of TGP in reducing the number of ulcers showed no significant difference compared to the control group (MD = -1.66, 95% CI = -3.60 to 0.28, p = 0.09, low-certainty evidence). Moreover, TGP treatment was associated with a higher incidence of abdominal symptoms (RR = 3.27, 95% CI = 1.62 to 6.60, p < 0.001). Conclusion: TGP appears to hold promise as a widely-used clinical therapeutic option for treating RAU. Nevertheless, further rigorous studies of high quality are required to validate its effectiveness. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=471154, Identifier CRD42023471154.

SER recommendations on treatment of refractory Behçet's syndrome.

OBJECTIVE: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (BS) (difficult to treat, severe resistant, severe relapse) to conventional treatment. METHODS: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format (patient, intervention, comparison and outcome). Systematic reviews of the evidence were conducted, the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations Assessment, Development, and Evaluation (GRADE). After that, the multidisciplinary panel formulated the specific recommendations. RESULTS: 4 PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with BS with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. CONCLUSIONS: The treatment of most severe clinical manifestations of BS lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official Recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.

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.

The evaluation of depression and anxiety levels of mothers of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome and familial Mediterranean fever.

OBJECTIVE: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome and familial Mediterranean fever (FMF) are autoinflammatory disorders typically characterized by recurrent fever attacks. These recurrent fever attacks can lead to depression and anxiety in mothers of these patients. This study aimed to compare the depression and anxiety levels in mothers of PFAPA and FMF patients. METHODS: This study is a cross-sectional observational study. 48 mothers of children with FMF and 70 mothers of children with PFAPA participated in the study. Mothers in these two groups were compared in terms of anxiety and depression by using the validated Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). RESULTS: Depression and anxiety scores of mothers were found to be similar in FMF and PFAPA groups. Moderate or high level of anxiety was seen in 32% of mothers of patients with PFAPA and 27% of mothers of patients with FMF. 23% of mothers of patients with PFAPA were evaluated as having moderate or severe depression, and 18% of mothers of patients with FMF were evaluated as having moderate depression. There was no statistically significant difference between the duration, frequency of attacks, recurrent hospitalizations, sociodemographic characteristics, and inventory scores. CONCLUSION: Depression and anxiety scores of mothers with children diagnosed with FMF and PFAPA are similar. These two diseases affect families psychosocially at similar levels. It is important to provide psychosocial support to families.

Immediate pain alleviation in oral mucositis and other oral ulcerative diseases through photobiomodulation therapy: the preemptive treatment concept.

OBJECTIVE: Photobiomodulation therapy is recommended by multiple international societies for managing oral mucositis. These recommendations are based on extensive evidence. However, the search for an optimal photobiomodulation protocol continues. This mapping review focuses on a novel aspect of photobiomodulation therapy which is the immediate effect on pain levels associated with oral ulcerative conditions. DATA SOURCES: This literature review systematically compiles and evaluates the evidence about oral mucositis, alongside other oral ulcerative conditions, as the protocols that achieved pain relief for these oral conditions may have potential applicability to oral mucositis management. The scientific database used was PubMed. CONCLUSION: Whereas most of the randomized controlled trials about photobiomodulation therapy for oral mucositis and other ulcerative oral diseases reported delayed pain relief, certain photobiomodulation therapy protocols reported immediate pain relief. The results of this review highlight the concept of preemptive photobiomodulation therapy, in which photobiomodulation therapy is delivered early in the development of oral mucositis throughout the oncotherapy and may achieve immediate pain relief consistently in most of the patients and close to a negligible pain level. Photobiomodulation therapy, as a powerful nonpharmacologic tool for immediate pain relief, has a great beneficial value in patients suffering from oral mucositis and other painful oral ulcerative diseases such as recurrent aphthous stomatitis and chronic graft-versus-host disease.

Clinical Efficacy of Topical Kenacort and Aloe Vera Gel in Minor Aphthous Stomatitis: A Comparative Study.

Aim: The aim of the study is to compare the clinical efficacy of both the topical agents-aloe vera gel and Kenacort oral paste (0.1% triamcinolone acetonide) in patients with minor aphthous stomatitis. Materials and Methods: 60 patients were recruited for the study and were randomly divided into two groups-Group A (aloe vera gel group) and Group B (Kenacort oral paste group). The baseline parameters were taken and recorded on the day of the first visit which included ulcer size, pain, and burning sensation. Evaluation of reduction in ulcer size, pain, and burning sensation were made on day 3 and day 7. Results: The results of the present study revealed that both the study groups showed no significant difference in the size of ulcer at day 1, day 3, and day 7 when compared using independent t-test as P > 0.05 at all study intervals. Therefore, both the agents were found to be equally effective against reducing the size of ulcer, pain, and burning sensation. Conclusion: The present study findings demonstrate that topical application of the aloe vera gel was able to decrease the ulcer size, intensity of pain, and burning sensation, thereby accelerating the healing without any side effects. Thus, topical aloe vera could be safe and a better alternative to topical steroid for RAS.

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.

Pulmonary artery involvement in Behçet's disease: A challenging case and comprehensive management approach.

A 26-year-old male with Behçet's disease (BD) presented with recurrent oral and genital ulcers, bilateral pneumonia, and a left lower pulmonary artery aneurysm. Endovascular coil embolization was initially performed, followed by treatment with prednisone, colchicine, and azathioprine. Despite treatment, disease progression occurred, requiring additional embolization, intravenous pulse methylprednisolone, and cyclophosphamide. Ultimately, a combination of medical and endovascular interventions resolved the pulmonary arterial aneurysms. This case highlights BD's systemic inflammatory nature and vascular complications like pulmonary artery aneurysms. It emphasizes the importance of early detection and individualized, multidisciplinary care for such complications.

Recomendaciones SER sobre el tratamiento del síndrome de Behçet refractario / SER recommendations on treatment of refractory Behçet's syndrome

Objetivo: Elaborar recomendaciones multidisciplinares, basadas en la evidencia disponible y el consenso de expertos, para el manejo terapéutico de los pacientes con síndrome de Behçet refractario (difícil de tratar, resistente grave, recidivante grave) al tratamiento convencional. Métodos: Un panel de expertos identificó preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO –paciente, intervención, comparación, outcome o desenlace–. A continuación, se realizaron revisiones sistemáticas; la evaluación de la calidad de la evidencia se realizó siguiendo la metodología del grupo internacional de trabajo Grading of Recommendations, Assessment, Development, and Evaluation. Tras esto, el panel multidisciplinar formuló las recomendaciones. Resultados: Se seleccionaron 4 preguntas PICO relativas a la eficacia y seguridad de los tratamientos farmacológicos sistémicos en los pacientes con síndrome de Behçet con manifestaciones clínicas refractarias a terapia convencional, relacionadas con los fenotipos mucocutáneo y/o articular, vascular, neurológico-parenquimatoso y gastrointestinal. Se formularon un total de 7 recomendaciones estructuradas por pregunta, con base en la evidencia encontrada y el consenso de expertos. Conclusiones: El tratamiento de las manifestaciones clínicas más graves del síndrome de Behçet carece de evidencia científica sólida y no existen documentos de recomendaciones específicas para los pacientes con enfermedad refractaria a la terapia convencional. Con el fin de aportar una respuesta a esta necesidad, se presenta el primer documento de recomendaciones de la Sociedad Española de Reumatología específicas para el abordaje terapéutico de estos pacientes, que servirá de ayuda en la toma de decisiones clínica y la reducción de la variabilidad en la atención.(AU)

Objective: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (difficult to treat, severe resistant, severe relapse) to conventional treatment. Methods: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format –patient, intervention, comparison and outcome–. Systematic reviews of the evidence were conducted; the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations, Assessment, Development, and Evaluation. After that, the multidisciplinary panel formulated the specific recommendations. Results: Four PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with Behçet's syndrome with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. Conclusions: The treatment of most severe clinical manifestations of Behçet's syndrome lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.(AU)

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.

Combined treatment of dexamethasone mouthwash and low-level laser therapy in the management of aphthous-like ulcers caused by nonsteroidal anti-inflammatory drugs: A case report.

A case of major aphthous-like ulcer was described in a 50-year-old patient. The patient showed the main signs of aphthous stomatitis painful ulcer, 1-2 cm in diameter, located on the ventral of the tongue, buccal mucosa, and the palate. These ulcers persisted for more than 3 weeks. The patient's self-administration of a nonsteroidal anti-inflammatory drug (NSAID) was suggested as the leading cause of aphthous-like ulcers in this case. ulcers were treated with dexamethasone mouthwash and low-level laser therapy (LLLT).

COVID 19 vaccination as a trigger of acute genital ulcers in an immunocompromised adolescent-case study and literature review.

Acute genital ulcers can affect females of all ages. In children, they often appear as an emergency and remain a diagnostic challenge for pediatricians, gynecologists and dermatologists. Prompt diagnosis and identification of disease- related factors help to implement appropriate treatment. Firstly, it is crucial to properly compile the past medical history of the patient. Past infectious, autoimmune, malignant or traumatic conditions, as well as vaccinations may contribute to the occurrence of acute genital ulcers. Moreover, new infectious agents, such as severe acute respiratory syndrome coronavirus 2 and vaccinations against Coronavirus disease of 2019, may play a significant role in the development of atypical clinical symptoms. Here we present a case of a 12-year-old girl with acute genital ulcers. Additional symptoms accompanying the ulcer included: abdominal pain, nausea, vomiting, dysuria, vulvar pain and fever. Blood test showed leukocytosis, especially neutrophilia and monocytosis and increased levels of c-reactive protein and procalcitonin. Serological tests for the most common infections were negative. Moreover, the patient had a history of autoimmune diseases. She had periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome, and IgA vasculitis, also known as Henoch-Schönlein purpura in her past medical history. Additionally, she was vaccinated against SARS-CoV-2 shortly before the lesions appeared.

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.