Effect of different treatments on recurrent aphthous stomatitis: laser versus medication.

Recurrent aphthous stomatitis (RAS) is a common disease with ulcers in oral cavity which may trigger chewing, speaking, and swallowing difficulties to patients. Treatment of RAS is primarily aimed at pain relief and the promotion of wound healing. However, few agents have been found to have definite effect in the management of RAS and most of the medicinal products may cause adverse reactions or other disadvantages, which makes their clinical usage questionable. The purpose of this randomized controlled clinical trial (RCT) was to assess the clinical effect of diode laser and traditional medication treatment on RAS. In this study, 56 patients were randomly assigned to two groups (n = 28). Laser group was treated using diode laser (810 nm, 1.0 W, CW, irradiation time 20 s for 3 applications) once daily for continuous 3 days. Medication group was treated with triamcinolone acetonide 0.1% three times a day until the lesion was healed. Spontaneous and functional pain level on the third day of treatment was significantly less in the laser group. Significant difference was observed with respect to healing time; however, the order of difference is small albeit of statistical significance. Diode laser with the chosen parameters had better effects on pain relief and no distinct advantage on wound healing comparing with medication. Trial registration number: ChiCTR2000030298; date of registration: 26 February 2020 (retrospectively registered).

Vestibular involvement of PFAPA syndrome.

OBJECTIVE: PFAPA syndrome is derived from the initials of the English words of the findings that make up the syndrome ("Periodic Fever", "Aphthous Stomatitis", "Pharyngitis", "Adenitis"). This study aims to evaluate the vestibular system in patients with PFAPA syndrome by the cVEMP test and to give a general review of PFAPA syndrome in light of current literature. METHODS: In this prospective study, 30 patients aged 4-6 who were diagnosed with PFAPA in a tertiary pediatrics clinic, between January 2016 and February 2020 and 30 children of the same age group who applied to a tertiary otorhinolaryngology clinic for other reasons and proven to have no hearing or vestibular problems were included and in addition to routine physical examination, electromyographic activity of the sternocleidomastoid muscle surface was measured. RESULTS: We found that the amplitude difference between cVEMP p1-n1 in patients with PFAPA syndrome in both ears decreased compared to the healthy control group. CONCLUSION: Our study proves there is a vestibular system involvement of PFAPA syndrome. This study is the first in the literature to search the relationship between PFAPA and the vestibular system.

Performance of recently proposed periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome criteria in a region endemic for familial Mediterranean fever.

The periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an auto-inflammatory condition characterized by recurrent episodes of fever accompanied by aphthosis, cervical adenitis, and pharyngitis. Diagnosis of PFAPA could be challenging due to clinic overlap with familial Mediterranean fever (FMF). An international consensus has been established recently, to define a new set of classification criteria for PFAPA syndrome. We aimed to evaluate the performance of recently proposed PFAPA criteria, to assess their utility in FMF regions. Patients diagnosed with PFAPA syndrome, FMF, and juvenile idiopathic arthritis (JIA) were included. Two investigators blindly evaluated all of patients for the newly proposed PFAPA criteria. A total of 542 patients (322 with PFAPA syndrome, 118 FMF and 102 JIA) were evaluated. Mean age of patients was 6.6 ± 2.81, 12.75 ± 3.9, and 12.42 ± 4.8 years for PFAPA, FMF, and JIA, respectively. We found quite high sensitivity (89.7%) but insufficient specificity of newly proposed PFAPA criteria (69.5%). When applied to control patients separately, specificity was found to be 61% and 79.4% for FMF and JIA patients, respectively. Positive predictive value was 81%, while negative predictive value was 82%. Recently proposed PFAPA criteria have satisfactory sensitivity, but its specificity is still under expectation. There is a need for a distinctive criterion between PFAPA syndrome and FMF, in FMF endemic regions, e.g., cryptic tonsillitis rapidly responsive to single dose of glucocorticoids. Further studies with higher patients' number in different regions are needed.

The influence of oral health and psycho-social well-being on clinical outcomes in Behçet's disease.

This study was designed to investigate the association of oral ulceration and oral health factors, together with psycho-social well-being in Behçet's disease (BD), and to clarify the importance of psycho-social support of patients in the overall management of BD. The study comprised of a cohort of 146 BD patients (mean age ± SD = 39.65 ± 13.20) and 20 recurrent aphthous stomatitis (RAS) patients (mean age ± SD = 42.32 ± 11.32). Oral ulcer severity score (OUSS), Behçet's disease current activities form (BDCAF), hospital anxiety and depression scale (HADS), and the work and social adjustment scale (WSAS) were investigated. Oral health risk factors were also included. The analysis of variance, regression, and factor analysis were used to scrutinise the data. Almost 73% of patients were at high caries risk in BD and RAS groups. Thirty-nine percent of BD and forty percent of RAS had a score of BPE3 (probing depth 3.5-5.5 mm). Regression analysis revealed that OUSS and WSAS had a positive impact to increase the BDCAF score in BD patients (ß = 0.395, P = 0.001; ß = 0.240, P = 0.019), respectively. Dental health, periodontal health, anxiety, depression, and WSAS variables had strong loadings by factor analysis based on gender and at the time of present and absent of oral ulceration. The main oral ulcer characteristics that had significant influences on the total of oral health quality of life by 68.6% were: size, duration, ulcer-free period, and pain. The results highlighted the significant influence of oral ulceration, patients' oral health, diet, and psycho-social well-being as multi-factorial causes on increasing disease activity in BD patients.

Recurrent aphthous stomatitis (RAS): a preliminary within-subject study of quality of life, oral health impacts and personality profiles.

BACKGROUND: RAS may affect quality of life and impacts oral health and daily activities; consequently, psychological factors, dental needs and patients' perceptions. Professionals should understand this relation to adequately manage oral ulcers. This study aimed at investigating the relationship between oral health impacts, oral health-related quality of life and psychological profiles in patients with recurrent aphthous stomatitis (RAS). METHODS: Fifty-three patients (30 men and 23 women, mean age: 31.1 ± 10.1 years) with RAS participated in this study. During ulcer episodes, participants completed Hospital Anxiety and Depression Scale (HAD), Neuroticism-Extraversion-Openness Five Factor Inventory (NEO-FFI), Oral Health Impact Profile (OHIP-14) and United Kingdom Oral Health-Related Quality of Life measure (OHQoL-UK) proformas. Patients completed OHIP-14 and OHQoL-UK again when they were ulcer-free. The statistically significance levels were set at P ≤ 0.05. RESULTS: During ulcer episodes, patients reported worse oral health impacts and an inferior quality of life in comparison with ulcer-free times (P < 0.0001). Higher OHIP scores were significantly associated with higher HAD depression (P = 0.036) and anxiety (P = 0.012) scores. NEO-FFI scores had no significant relations with OHIP and OHQoL-UK scores (P > 0.05). During ulcer-free periods, no relationships were detected between OHIP, OHQoL-UK, HAD and NEO-FFI scores (P > 0.05), except between OHQoL-UK and conscientiousness scores (P = 0.05). CONCLUSIONS: RAS increased the negative oral health impacts on patients and consequently lowered their quality of life. Stressful situations and conditions (including anxiety and depression), rather than inherent personality profiles and stable psychological traits, were related to oral health impacts and quality of life in patients with RAS.

Anamnestic findings from patients with recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is a common oral disorder with a prevalence varying between 5% and 66%. RAS appears in three forms; minor, major and herpetiform. The aetiology is unknown.The aim of this study was to evaluate associations between specific anamnestic information and different types of recurrent aphthous stomatitis (RAS). A group of 177 patients (mean age = 42.8 years; SD = 14.3; range 17-79 years) participated. Data were collected from a structured interview, consisting of 22 questions. Information about i) health status and medication, ii) predisposing factors, iii) RAS experience, iv) previous treatment methods and v) brand of toothpaste was collected. Sixty-eight per cent of the patients were healthy and 44% of the patients were not taking any medication. Forty-one per cent of the patients did not have any apprehension of the reason for their RAS, while stress (15.8%) was the most common apprehended aetiological factor. Sixty-two per cent had one to three minor ulcers at one time. Forty-eight per cent reported having had a major aphthous ulcer at least once.The most frequent symptom reported was pain (53.7%), followed by a smarting sensation (18.6%) and tenderness (4%). The most common treatment for RAS was Zendium™ toothpaste/mouthrinse (28%), followed by corticosteroids (25%). Fifty-four per cent of the patients experienced no relief from the treatment. When toothpaste habits were investigated, Zendium™ was used by 32% of the patients and toothpaste containing sodium-lauryl-sulfatase was used by 32%.There was no positive correlation between the use of Zendium™ toothpaste and the relief of symptoms or the size, number or frequency of the aphthous ulcers. Sixty-four per cent of the patients had never smoked, while 7% were smokers. No positive correlation was found when age, gender, allergy, medication and smoking were correlated to the frequency, number and size of the aphthous ulcers. In conclusion, we found that the aetiology behind RAS is still unclear and probably multifactorial. Standard treatment methods like Zendium™ should perhaps be questioned and this study did not find any support for smoking as a "protective" factor, i.e. having less likelihood of experiencing major problems from RAS.

Association of aphthous ulcers with self-reported symptoms of depression in a sample of smartphone users.

BACKGROUND: Our goal is to examine the association of recurrent aphthous stomatitis (RAS) with symptoms of depression using a smartphone-based questionnaire survey. METHODS: An electronic survey was administered through a smartphone app asking respondents about current depressive symptoms using the Quick Inventory of Depressive Symptoms (QIDS), and asking whether they had ever or recently experienced RAS. Multivariate logistic regression analysis was used to determine associations. RESULTS: A total of 478 individuals completed the survey, with 64% reporting a lifetime prevalence of RAS, and 21% experiencing an aphthous ulcer within the last month. RAS was significantly associated with increased sleep, decreased appetite, low energy, and feeling sluggish. RAS was not associated with overall depression severity as measured by total QIDS score, or with cardinal features of depression such as sadness, insomnia, impaired concentration, self-blame, thoughts of death, or anhedonia. Prevalence of RAS did not differ by age, sex, or smoking status, but was less likely in blacks and Asians compared with whites. CONCLUSIONS: RAS was a common phenomenon in this sample of mostly depressed individuals, and was associated with some neurovegetative symptoms of depression, but not depression severity.

Impacts of recurrent aphthous stomatitis on quality of life of 12- and 15-year-old Thai children.

PURPOSE: To assess the prevalence and characteristics of oral impacts attributed to recurrent aphthous stomatitis (RAS) in 12- and 15-year-olds Thais. METHODS: A national oral health survey was conducted. Child-OIDP and OIDP indices were used to collect oral impacts in 1,100 12- and 871 15 year olds. RESULTS: RAS-related impacts were reported in 24.7% of 12 and 36.2% of 15 year olds. Girls were more likely than boys to report RAS-related impacts. Among all perceived causes of oral impacts, RAS ranked second for 12 and first for 15 year olds. Among 12 and 15 years olds, 79.8 and 86.8% respectively had impacts on eating, 81.0 and 84.4% on cleaning teeth and 51.7 and 60.3% on emotional stability. For individual children, impacts affected between 1-6 daily performances. Impacts were of 'little' and 'moderate' intensity for 12 and 15 year olds, respectively. RAS-related impacts occurred mostly in combination with impacts from other oral conditions. Combined with other oral conditions, the impacts were worse, in terms of score, intensity and extent, than when RAS occurred alone. CONCLUSIONS: RAS-related impacts were common in 12- and 15-year-old Thai children and mostly affected eating, cleaning teeth and emotional stability. RAS tended to occur with other conditions leading to more severe, more extensive impacts on quality of life.

Symptomatic changes of oral mucosa during normal hormonal turnover in healthy young menstruating women.

INTRODUCTION: Changes in hormonal levels, such as those that occur during puberty, pregnancy, menstruation and menopause, have varying effects on oral cavity. Many researchers have proposed a direct link between changing hormonal status and oral health among females. OBJECTIVES: To study the various symptoms and clinical manifestations of oral cavity during normal course of menstrual cycle in healthy women. METHOD: Our study comprised of forty healthy young women volunteers with normal menstrual cycle of 28 to 30 days. A proper menstrual history was recorded from the study subjects. The entire cycle was divided into four phases comprising of bleeding, proliferative, ovulation and secretory. All the study subjects had a menstrual cycle of 28 to 30 days. Thorough recording of oral discomforts during various phases of the cycle was done during the study period. RESULTS: 30% of study subjects complained of aphthous ulcers, 5% had herpes labialis, 25% of them complained of depression, 8% showed gingival bleeding. CONCLUSION: Complaints, like oral ulcerations, mood variations, recurrent herpetic lesions, gingival bleeding in females during normal menstrual period, are attributed to the role of female sex hormones. CLINICAL SIGNIFICANCE: Lesions, like oral ulcers, recurrent herpetic lesions and increased gingival bleeding, seen in females during normal menstrual periods, could be related to hormonal turnover and therefore treated accordingly.

Periodic Fever syndromes.

The periodic syndromes represent a heterogeneous group of disorders that can be very difficult for practicing physicians to diagnosis and treat. This article presents an orderly approach to hyperimmunoglobulin D syndrome; tumor necrosis factor receptor-1 periodic syndrome; familial Mediterranean fever; periodic fever with aphthous stomatitis, pharyngitis, and adenitis syndrome; and cryopyrin-associated periodic syndromes by highlighting the disease presentation, diagnosis, pathogenesis, and treatment. Recent advances are also discussed.

Consensus treatment plans for periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA): a framework to evaluate treatment responses from the childhood arthritis and rheumatology research alliance (CARRA) PFAPA work group.

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. There is considerable heterogeneity in management strategies and a lack of evidence-based treatment guidelines. Consensus treatment plans (CTPs) are standardized treatment regimens that are derived based upon best available evidence and current treatment practices that are a way to enable comparative effectiveness studies to identify optimal therapy and are less costly to execute than randomized, double blind placebo controlled trials. The purpose of this project was to develop CTPs and response criteria for PFAPA. METHODS: The CARRA PFAPA Working Group is composed of pediatric rheumatologists, infectious disease specialists, allergists/immunologists and otolaryngologists. An extensive literature review was conducted followed by a survey to assess physician practice patterns. This was followed by virtual and in-person meetings between 2014 and 2018. Nominal group technique (NGT) was employed to develop CTPs, as well as inclusion criteria for entry into future treatment studies, and response criteria. Consensus required 80% agreement. RESULTS: The PFAPA working group developed CTPs resulting in 4 different treatment arms: 1. Antipyretic, 2. Abortive (corticosteroids), 3. Prophylaxis (colchicine or cimetidine) and 4. Surgical (tonsillectomy). Consensus was obtained among CARRA members for those defining patient characteristics who qualify for participation in the CTP PFAPA study. CONCLUSION: The goal is for the CTPs developed by our group to lead to future comparative effectiveness studies that will generate evidence-driven therapeutic guidelines for this periodic inflammatory disease.

Common benign and malignant oral mucosal disease.

BACKGROUND: Mucosal diseases of the oral cavity are relatively common, and patients often seek initial assessment from their general practitioner. OBJECTIVE: The aim of this article is to provide an overview of common oral mucosal diseases to help with formulating a differential diagnosis and stratifying the urgency of referral. DISCUSSION: Pathological mucosal conditions of the oral cavity and jaws commonly present as a mucosal ulcer or a white, red or pigmented lesion. In this review, the authors outline the most common conditions organised according to their clinical presentation and describe their typical appearance and management.

A composite index for determining the impact of oral ulcer activity in Behcet's disease and recurrent aphthous stomatitis.

BACKGROUND: Although number, frequency and healing time of oral ulcers and pain are generally used for clinical practice and studies in Behcet's disease (BD) and recurrent aphthous stomatitis (RAS), no standardized activity index is currently present to monitor clinical manifestations associated with oral ulcers. The aim of this study was to develop a standardized composite index (CI) to assess oral ulcer activity in BD and RAS. METHODS: In this cross-sectional study, 121 patients with BD and 45 patients with RAS were included. Sixty-five percentage of BD and 68.9% of RAS patients were in active stage during the previous 3 months. The developed CI included the presence of oral ulcers, ulcer-related pain and functional status and was evaluated in patients with both active and inactive disease for content validity. RESULTS: Composite index score was observed to be higher in active patients with RAS (6.94 + or - 2.19) compared with active BD patients (6.01 + or - 2.04) (P = 0.04). The number of oral ulcers and healing time of oral ulcers were significantly higher in RAS compared with BD (P = 0.018, P = 0.001 respectively). CI score correlated with the number of oral ulcers in both BD and RAS (P = 0.000, P = 0.002 respectively). CI score was '0' for inactive patients without oral ulcer in BD and RAS. CONCLUSIONS: The presented CI as an oral ulcer activity index seems to be a reliable and suitable tool for evaluating the clinical impact and disease-specific problems in BD and RAS.

Abortive aphthous-like oral lesions: an underreported initial presentation of pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) usually presents as non-healing, painful oral erosions, but transient or aphtha-like lesions are not exceptional at the very beginning of the disease leading to the common misdiagnosis of recurrent aphthous stomatitis (RAS). We designed this cross-sectional, questionnaire-based study to evaluate this underreported yet important presentation of PV. MATERIAL AND METHODS: One hundred and eighty-five consecutive PV patients were interviewed and a questionnaire, comprising items related to the natural history of oral lesions, was filled in for each. Fourteen patients who had taken steroids (topical or systemic) before their final diagnosis were excluded. RESULTS: Twenty-three per cent of patients gave a history of transient aphthous-like lesions; 95% of them were misdiagnosed as aphthae. These lesions were especially reported by patients aged 40 years or older (P < 0.047). CONCLUSION: PV should be kept in mind as a rare differential diagnosis of transient oral ulcerations. We recommend careful observation of these patients and performing indirect immunofluorescence or desmoglein ELISA and even biopsy in atypical cases, to rule out PV especially in older patients and predisposed ethic groups. To find out the differential aspects of RAS and aphthous-like PV, a cohort study on RAS patients is suggested.

Relieving pain in minor aphthous stomatitis by a single session of non-thermal carbon dioxide laser irradiation.

This randomized controlled clinical trial was designed to evaluate the efficacy of single-session, non-thermal, carbon dioxide (CO(2)) laser irradiation in relieving the pain of minor recurrent aphthous stomatitis (miRAS) as a prototype of painful oral ulcers. Fifteen patients, each with two discrete aphthous ulcers, were included. One of the ulcers was randomly allocated to be treated with CO(2) laser (1 W of power in de-focused continuous mode) and the other one served as a placebo. Before laser irradiation, a layer of transparent, non-anesthetic gel was placed on both the laser lesions and the placebo lesions. The patients were requested to grade their pain on a visual analog scale up to 96 h post-operatively. The reduction in pain scores was significantly greater in the laser group than in the placebo group. The procedure itself was not painful, so anesthesia was not required. Powermetry revealed the CO(2) laser power to be 2-5 mW after passing through the gel, which caused no significant temperature rise or any visual effect of damage to the oral mucosa. Our results showed that a low-intensity, non-thermal, single-session of CO(2) laser irradiation reduced pain in miRAS immediately and dramatically, with no visible side effects.

Rapid cell senescence and apoptosis in lymphocytes and granulocytes and absence of GM-CSF receptor in congenital dysgranulopoietic neutropenia.

A girl with congenital dysgranulopoietic neutropenia (CDN) and her non-neutropenic mother with aphthae (A) were investigated. Apoptosis in lymphocytes and granulocytes of both patients (mother A+) were documented by high annexin and electron microscopic morphology. CD11b/CD18 of the daughter's granulocytes ranged between low to normal while that of the mother changed between very low to high levels through A(-) to A(+) periods. In both patients, CD11b/CD18 on lymphocytes were high; GM-CSF receptor was negative; CD4-/CD8- lymphocytes were high and the leukocytes which showed abnormal cell cycle were stained by senescence associated beta-galactosidase. We think that increased apoptosis and rapid cell senescence of leukocytes underlies the pathophysiology of CDN.

Recurrent aphthous stomatitis may be initiated by traumatic epithelial implantation and sustained by localized pathergic status.

Recurrent aphthous stomatitis (RAS) is the most common oral mucosal disease. The pathogenesis of RAS has been debated long and various etiological predisposing factors have been suggested. Nonetheless, these proposals do not explain development of aphtous ulcerations and the underlying mechanisms remain to be uncovered through more definitive cellular and molecular approaches. Soft tissues of oral cavity are subject to traumatic injuries owing to various functional activities demanding interactions of soft and hard tissues. These injuries may lead to implantation of epithelial cells at the sites of injury. Following implantation of keratinocytes, a mild sustained immunologic reaction to these cells may be expected which is characteristic of aphthous ulcerations. Subsequently, these localized sites of implantation may remain in a pathergic status. Thereafter, these sites exhibit higher vulnerability to recurrence of aphthous ulcerations when affected by environmental stimuli.

Plasma rich in growth factors as a potential therapeutic candidate for treatment of recurrent aphthous stomatitis.

Despite high prevalence of recurrent aphthous stomatitis (RAS), the treatment is mainly symptomatic. Considering epithelial implantation etiology of RAS, a novel therapeutic approach was presented. Plasma rich in growth factors (PRGF) contains various active ingredients including but not limited to transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), and fibrin products. PDGF accelerated the healing of ulcers. Moreover, it enhances epithelial-mesenchymal transition and hence aids in elimination of epithelial nests within underlying connective tissue. In addition, it modulated extracellular matrix and contributes to restoration of original tissue structure and function. Anti-inflammatory properties of PRGF in combination with the aforementioned scenario may prove useful both for resolution of acute periods of RAS as well as prevention of recurrent periods of the disease.

Oral and vulvar changes in pregnancy.

The endocrinologic, immunological, and vascular changes that occur during pregnancy are far-reaching. These systemic factors produce profound local impact on the physiology and pathology of the oral cavity, vagina, and vulva. Physiological changes can be expected and tolerable or of such severity that they are viewed as pathological. Existing disease can be exacerbated and dermatoses specific to pregnancy can erupt. Each of these conditions can pose potentially challenging treatment considerations.