Major Recurrent Aphthous Stomatitis Research Articles

Assessment of Quality of Life in Patients with Chronic Oral Mucosal Diseases Using the Indonesian Version of the Chronic Oral Mucosal Disease Questionnaire-15 (COMDQ-15).

Chronic oral mucosal diseases (COMDs) can significantly impair the quality of life (QoL) of affected individuals. Monitoring the overall disease's impact and the efficacy of treatments requires the use of the Chronic Oral Mucosal Diseases Questionnaire-15 (COMDQ-15) as a standardized instrument for measuring QoL in these patients. This study aimed to assess QoL in patients with COMDs using an Indonesian version of the COMDQ-15. Seventy patients diagnosed with recurrent aphthous stomatitis (RAS), oral lichen planus, autoimmune blistering diseases (ABD), and cheilitis were included. Levels of QoL among different groups of disease were compared. Various potential factors influencing QoL were evaluated. Bivariate analysis was performed to identify factors associated with overall and specific aspects of QoL. The mean total COMDQ-15 score was 20.83 ± 10.07. The highest scores were in the physical discomfort domain (8.76 ± 4.65), while the lowest was in the medication and treatment domain (2.13 ± 1.99). Physical discomfort was significantly associated with gender, major RAS, and cheilitis. Social and emotional aspects were significantly associated with age and ABD, while patient support was linked to employment status, RAS types, and cheilitis. The Indonesian version of the COMDQ-15 is a valid and reliable tool for assessing QoL in patients with COMDs.

Evaluation of cytokine expressions in patients with recurrent aphthous stomatitis: A systematic review and 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.

Management of major recurrent aphthous ulcers with 5% amlexanox oral paste and rebamipide tablets- A case report with a brief literature review

Recurrent aphthous stomatitis (RAS) is a common chronic inflammatory oral mucosal disorder marked by the presence of painful, recurring ulcers, occurring either as solitary lesions or in multiple clusters. While the clinical features of this condition are easily recognizable, the precise etiology remains obscure. The disorder manifests in three forms, of which minor RAS are the commonest and heal within 10-14 days. Major RAS presents as larger, painful chronic ulcerations and heals with scarring in 6-8 weeks. A comprehensive medical history and a thorough systemic examination can aid the physician in determining whether the condition is idiopathic or linked to a underlying systemic disorder. The management of oral aphthous ulcers poses a significant challenge and there is no established and defined therapeutic regimen available for RAS. We present a case of major RAS in a 37-year-old patient who was unresponsive to topical and systemic steroid therapy. 5% Amlexenox paste and rebamipide tablets were used in the present case. The patient showed favourable healing within a week therapy with no recurrences during the 6-month follow up.

ULCERS AND GINGIVAL HEMORRHAGE AS SIGNS OF MEDULLARY APLASIA: CASE REPORT

Medullary aplasia (MA) is a hematological disorder, characterized by a failure to produce numbers of blood cells by the hematopoietic precursor cells in the bone marrow. It is reported a case of a female patient, 33-year-old, white-skinned, who presented non-infiltrative painful ulcers, reddish and spots of gingival hemorrhage. Clinical diagnostic hypotheses were major recurrent aphthous stomatitis or herpes simplex and blood dyscrasia. A blood test was requested and revealed low levels of red blood cells, leukocytes, and platelets. The patient was referred to the hematologist, who made the diagnosis of MA with idiopathic etiology. The patient died soon after bone marrow transplantation due to lung infection. This case illustrates the importance of a dental physician in the diagnosis and investigation of hematological conditions, since, despite being rare diseases, these can be initially diagnosed in the dental office. Medullary aplasia (MA) is a hematological disorder, characterized by a failure to produce numbers of blood cells by the hematopoietic precursor cells in the bone marrow. It is reported a case of a female patient, 33-year-old, white-skinned, who presented non-infiltrative painful ulcers, reddish and spots of gingival hemorrhage. Clinical diagnostic hypotheses were major recurrent aphthous stomatitis or herpes simplex and blood dyscrasia. A blood test was requested and revealed low levels of red blood cells, leukocytes, and platelets. The patient was referred to the hematologist, who made the diagnosis of MA with idiopathic etiology. The patient died soon after bone marrow transplantation due to lung infection. This case illustrates the importance of a dental physician in the diagnosis and investigation of hematological conditions, since, despite being rare diseases, these can be initially diagnosed in the dental office.

Effect of Lozenges Containing Lactobacillus reuteri on the Severity of Recurrent Aphthous Ulcers: a Pilot Study.

To investigate the effect of a probiotic supplement on the severity of aphthous lesions in patients with recurrent aphthous stomatitis (RAS) over a 3-month period. A second endpoint was to study the effect on pain related to the lesions. The study employed a double-blind randomized, placebo-controlled design with two parallel arms. Twenty patients with minor and major RAS were consecutively enrolled and randomly assigned to the test or the control group. The intervention consisted of lozenges containing two strains of Lactobacillus reuteri taken twice daily for 90days. Ulcer Severity Score (USS) consisting of six lesion characteristics (number, size, duration, ulcer-free period, site, and pain) was calculated at baseline and after the intervention. Oral pain related to the lesions was estimated by the patients with a Visual Analogue Pain Scale. An improvement of the USS, as well as oral pain, was evident in both groups after 90days but the reduction was only statistically significant (p < 0.05) compared with baseline in the test group. There were no significant differences between the groups, neither at baseline nor at follow-up. No side effects were recorded. Daily supplements with L. reuteri reduced the severity of aphthous lesions over a 90-day period but the improvement was not significantly better than placebo. The results encourage further research and provide a basis for power calculations of larger and extended studies. ClinicalTrials.gov Identifier: NCT02976922.

Gastric parietal cell and thyroid autoantibodies in recurrent aphthous stomatitis patients with concomitant oral lichen planus.

Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) have not yet been reported in recurrent aphthous stomatitis (RAS) patients with concomitant oral lichen planus (OLP/RAS patients). This study mainly assessed the frequencies of serum GPCA, TGA, and TMA (GPCA/TGA/TMA) positivities in 44 OLP/RAS patients. The frequencies of serum GPCA/TGA/TMA positivities in 44 OLP/RAS patients, OLP/RAS patients of four different subgroups, 520 RAS patients, and 352 healthy control subjects were calculated and compared. We found that 20.5%, 27.3%, and 31.8% of 44 OLP/RAS patients, 75.0%, 100.0%, and 100.0% of 4 OLP/major-typed RAS (OLP/major RAS) patients, 15.0%, 20.0%, and 25.0% of 40 OLP/minor-typed RAS (OLP/minor RAS) patients, 45.5%, 72.7%, and 54.5% of 11 atrophic glossitis-positive OLP/RAS (AG+OLP/RAS) patients, and 12.1%, 12.1%, and 24.2% of 33 AG-negative OLP/RAS (AG־OLP/RAS) patients had the presence of GPCA, TGA, and TMA in their sera, respectively. OLP/RAS patients and OLP/RAS patients of four different subgroups all had significantly higher frequencies of GPCA/TGA/TMA positivities than healthy control subjects. Moreover, OLP/RAS patients had a significantly higher frequency of TMA positivity than RAS patients, and OLP/major RAS and AG+OLP/RAS patients had significantly higher frequencies of GPCA/TGA/TMA positivities than RAS patients. Furthermore, OLP/major RAS patients had significantly higher frequencies of GPCA/TGA/TMA positivities than OLP/minor RAS patients. For OLP/RAS patients, the concomitant OLP may play a role in causing an increased frequency of TMA positivity, and major RAS and the concomitant AG are contributory factors causing the elevated frequencies of GPCA/TGA/TMA positivities.

The absence of an association between Interleukin 1β gene polymorphisms and recurrent aphthous stomatitis (RAS)

ObjectivesRecurrent aphthous stomatitis (RAS) is a chronic, ulcerative disease with a probable polygenic mode of inheritance and complex etiology with a strong immunological background. The aim of the present study was to determine the possible association between two single nucleotide polymorphisms (SNPs) of the IL-1β gene: IL-1β−511 T>C (rs16944) and IL-1β+3954C>T (rs1143634) and RAS susceptibility in a moderately large group of patients. DesignOne hundred and four patients with minor, major and herpetiform RAS and 75 healthy volunteers were genotyped at IL-1β−511 T>C (rs16944) and IL-1β+3954C>T (rs1143634) using the PCR-RFLP approach. The results were statistically analysed with chi-square test and test of difference between two rates of structure, with p<0.05 assumed to be a statistically significance level (Statistica 10, StatSoft®, Kraków, Poland). ResultsThere were no statistically significant differences in the genotype distribution for the IL-1β C[+3954]T polymorphism between the RAS and control groups. The frequency of IL-1β*T[-511]/*T[–511] homozygotes among the patients was significantly higher when compared to our study control (p<0.0347). The results after stratification into carriers and non-carriers of C and T alleles did not clearly indicate which SNP may be considered a risk factor for RAS. ConclusionsThe genetic association between the studied SNPs of the IL-1β gene and RAS remains controversial and requires further investigation.

Oxidative stress and recurrent aphthous stomatitis

This study analyzed the oxidative stress status in patients with recurrent aphthous stomatitis (RAS) in the presence and absence of active ulceration. Oxidative stress was analyzed in peripheral mononuclear cells of 28 RAS patients with active ulceration and 29 controls. A further blood sample was collected from nine subjects randomly selected from the 28 RAS cases, during the period in which the patients did not have active oral ulceration. The reduced glutathione (GSH), malondialdehyde (MDA), and oxidized glutathione (GSSG) levels were measured in these samples. The mean MDA and GSSG levels were significantly higher in patients with active RAS than in the controls, while GSH was lower in the RAS group (p < 0.01). There was a nonsignificant tendency toward higher MDA and GSSG levels in patients with major RAS compared with minor RAS. On comparing the serum findings in the nine RAS patients in the presence and absence of lesions, the presence of ulceration was associated with even higher MDA and GSSG levels and lower GSH concentrations (p < 0.05) CONCLUSIONS: Oxidative stress was detected in our RAS patients.

Cyclic Neutropenia Presenting as Recurrent Oral Ulcers and Periodontitis

Cyclic neutropenia (CN) is a rare congenital disease that can present with recurrent oral ulcers and periodontitis. CN can easily be misdiagnosed as major recurrent aphthous stomatitis (MaRAS) or aggressive periodontitis (AP) in dental clinics. We describe the case of an 8-year-old boy with CN, and compare the oral manifestations of CN with those of MaRAS and AP. An 8-year-old boy presented with a history of recurrent oral ulcers, periodontal destruction, pharyngitis and otitis media since the age of 3 months. Repeated, routine blood tests showed 1-week-long neutropenic periods that occurred at intervals of 2 weeks. A bone marrow cytology test during a neutropenic period demonstrated a decrease in granulocyte count. During a 2-year follow-up, his symptoms were well controlled by regular administration of granulocyte colony-stimulating factor and periodontal maintenance. Several clinical features help to differentiate CN from MaRAS and AP Early recognition of the systemic cause of oral symptoms is important.

Penatalaksanaan stomatitis aftosa rekuren mayor dengan infeksi sekunder Management of major recurrent aphtous stomatitis accompanied by secondary infection

Recurrent aphthous stomatitis (RAS)is an ulcerative condition that affects the oral mucosa without evidence ofunderlying disorder. It’s characterized by the appearance of recurring round, shallow ulcerations surrounded byinflammation that mainly involves the nonkeratinized mucosa. The classification of SAR are minor, major, andherpetiform types. Although rare, secondary infection may occur. Treatment is directed to avoid local traumaticprecipitants, lessen the pain and duration of ulceration by suppressing the local immune response, and preventsecondary infection. The objective of this paper is to discuss the treatment of RAS with secondary infection, a caseof 24-year-old man with multiple large ulcers that did not heal for almost 4 weeks. The ulcers were diagnosed asmajor RAS with secondary infection, and treated with metronidazole and ciprofloxacin, healed in 2 weeks withscars. Although secondary infection will delay healing, but with proper treatment, major RAS has good prognosis.

THE MOLECULAR ANALYSIS ON THE EXPRESSION OF ORAL MUCOSA PROTEIN ANOMALY IN RECURRENT APHTHOUS STOMATITIS (RAS)

The purpose of this study was to disclose one of the etiopathogenesis of recurrent aphthous stomatitis (RAS) at molecular level by analyzing the expression of protein anomaly in oral mucosa. This was a cross-sectional explorative and analytical observational study. Samples, who met inclusion and exclusion criteria, were taken from total population. Samples of protein swab were obtained from oral mucosa, serums were taken from 15 patients with major RAS, 20 patients with minor RAS and 15 were control. The characterization of protein anomaly expressed on the surface of oral mucosa epithelium was carried out using SDS-PAGE 12% and Westernblot methods. The result of oral mucosa protein anomaly expression analysis in patients with major RAS using SDS-PAGE 12% revealed five protein bands with molecular weights of 87, 65, 30, 25, and 20 kDa. In minor RAS cases with protein anomaly expression there were four patients with molecular weights of 87, 65, 25, and 20 kDa. The band disappearances by using Westernblot cases, of 30 kDa of major cases, 87 and 20 kDa of minor cases and 20 and 25 kDa of remission cases, indicated that those patients were not reacted with polyclonal antibodies of rabbit serum; therefore they had no role in the induction of RAS. In conclusion, the antigenic protein expressed in oral mucosa of major, minor, and remission RAS was predominantly 65 kDa molecular weight.

Practical aspects of management of recurrent aphthous stomatitis

Treatment of recurrent aphthous stomatitis (RAS) remains, to date, empirical and non-specific. The main goals of therapy are to minimize pain and functional disabilities as well as decrease inflammatory reactions and frequency of recurrences. Locally, symptomatically acting modalities are the standard treatment in simple cases of RAS. Examples include topical anaesthetics and analgesics, antiseptic and anti-phlogistic preparations, topical steroids as cream, paste or lotions, antacids like sucralfate, chemically stable tetracycline suspension, medicated toothpaste containing the enzymes amyloglucosidase and glucoseoxidase in addition to the well-known silver nitrate application. Dietary management supports the treatment. In more severe cases, topical therapies are again very useful in decreasing the healing time but fail to decrease the interval between attacks. Systemic immunomodulatory agents, like colchicine, pentoxifylline, prednisolone, dapsone, levamisol, thalidomide, azathioprine, methotrexate, cyclosporin A, interferon alpha and tumour necrosis factor (TNF) antagonists, are helpful in resistant cases of major RAS or aphthosis with systemic involvement.

Aids e estomatite aftóide recidivante

O estado de imunodeficiência em pacientes HIV positivos tem sido causa de episódios severos de Estomatite Aftóide Recidivante (EAR). OBJETIVO: Este estudo objetiva estabelecer evidências da relação entre o surgimento (ou agravamento) de EAR com o estado de imunossupressão causado pelo vírus HIV, por meio da contagem de células CD4+, CD8+ e da carga viral infectante. FORMA DE ESTUDO: estudo de série. MATERIAL E MÉTODO: Noventa e quatro pacientes HIV (1)-positivos (25 mulheres e 69 homens) com EAR foram acompanhados no ambulatório de Aids da Divisão de Clínica ORL do Hospital das Clínicas da FMUSP no período de janeiro de 1998 a dezembro de 2003. A idade dos pacientes variou de 19 a 63 anos (média = 35,3 anos). RESULTADO: Os pacientes com Aids e soropositivos apresentaram, respectivamente, oito aftas e duas aftas por surto. Da mesma maneira, os pacientes portadores de úlceras do tipo major apresentaram menor contagem de células CD8+, CD4+ e relação CD4+/CD8+ e maior valor médio da carga viral do que os pacientes portadores de aftas herpetiformes e minor. Entre os portadores de aftas minor e herpetiforme não houve diferença estatística. CONCLUSÕES O aparecimento das lesões, principalmente as do tipo major, está diretamente relacionado ao estado imunitário do paciente soropositivo, acarretando déficits nutricionais e piora na qualidade de vida. Desta forma, o diagnóstico e tratamento da EAR é um desafio que não deve ser desprezado.

AIDS and recurrent aphtous stomatitis

SummaryThe immunodeficiency state in HIV infected patients has been the cause of severe episodes of Recurrent Aphthous Stomatitis (RAS). Aim: Our study aims to establish correlation between the manifestations of RAS and the immunosuppression state caused by HIV infection, through counting of CD4+ cells, CD8+ cells, CD4+:CD8+ cells ratio and viral load. Study design: series study. Material and Method: Ninety-four HIV infected patients (25 women and 69 men) with RAS were evaluated in the ENT Department of the University of Sao Paulo-Medical School from January 1998 to December 2003. The age ranged between 19 and 63 years (mean = 35.3 years). The patients were divided in two groups: AIDS group and HIV infected group. Results: The patients with AIDS and HIV infection presented, respectively, eight ulcers and two ulcers by outbreaks. Similarly, patients with major RAS presented smaller counting of cells CD8+, CD4+ and CD4+/CD8+ cells, and higher mean value of viral load than the patients with herpetiform and minor RAS. Between patients with minor and herpetiform RAS there were no statistical differences. Conclusions: The emergence of the lesions, mainly in major RAS, is directly related to the immunological state of the HIV infected patient. These patients frequently present nutritional deficits and worsening in life style. Thus, diagnosis and treatment of RAS is a challenge that should not be neglected.

Management strategies for HIV-associated aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is the most common oral mucosal disorder found in men and women of all ages, races, and geographic regions. There are three forms of the lesions (minor, major, and herpetiform), with major aphthous ulcers causing significant pain and potential for scarring. In HIV-infected individuals, these ulcers occur more frequently, last longer, and produce more painful symptoms than in immunocompetent persons. In addition, they may be associated with similar ulcerations involving the esophagus, rectum, anus, and genitals. The diagnosis of HIV-induced RAS requires a careful history of the condition, and a thorough extra- and intra-oral examination. Oral mucosal biopsies are required for non-healing ulcers in order to exclude the possibility of deep fungal infections, viral infections, and neoplasms. The cause of the ulcers in HIV-positive persons has not been elucidated--local diseases, genetic, immunologic, and infectious factors all probably play a role. The goals of current treatments are to promote ulcer healing, to reduce ulcer duration and pain while maintaining nutritional intake, and to prevent or diminish the frequency of recurrence. Initial therapy for infrequent RAS recurrences includes over-the-counter topical protective and analgesic products. Initial therapy for frequent RAS outbreaks requires topical anesthetics, binding agents, and corticosteroids. Major RAS and non-healing minor or herpetiform RAS may require intralesional corticosteroids and systemic prednisone. Second-line immunomodulators for frequent and non-healing ulcers includes thalidomide and other immunomodulators.

Recurrent aphthous stomatitis in Behçet's disease: clinical features and correlation with systemic disease expression and severity.

Behçet's disease (BD) is a multisystem disease, in which recurrent aphthous stomatitis (RAS) is a universal finding. We studied the expression of RAS in patients with BD, and the correlation between major or minor RAS and systemic expression and severity of the disease. Thirty-five patients with BD were studied, of whom 13 (37%) had major, 21 (60%) had minor and one (3%) had herpetiform RAS. The frequency of major RAS was significantly higher compared with a control group of patients with idiopathic RAS (37% vs 9%, P < 0.05). The BD patients with major RAS had significantly more relapses of oral ulceration in a year, higher numbers of oral ulcers per relapse, and longer duration of aphthous episodes, compared with patients with minor RAS. Oral ulcers also appeared at a significantly younger age in patients with major than with minor RAS. However, the systemic expression of the disease, as well as the disease severity score, were similar in patients with major and minor RAS. The results of this study indicate that major RAS is common in patients with BD, and is associated with a more severe, repeated and prolonged oral disease. Nevertheless, the presence of major RAS in BD does not predict a more severe systemic illness.

Open preliminary clinical trial of clobetasol propionate ointment in adhesive paste for treatment of chronic oral vesiculoerosive diseases

Clobetasol propionate (Temovate), a novel high-potency topical corticosteroid, was used in open trial from 1987 to 1988 on 24 patients with persistent oral vesiculoerosive disease of at least 1 month's duration. Fourteen women and 10 men, ranging in age from 27 to 76 years (mean 48 years), participated. Nine patients had erosive lichen planus, one had benign mucous membrane pemphigoid, three had pemphigus vulgaris, seven had persistent major recurrent aphthous stomatitis, and four had chronic oral erythema multiforme. Fifteen patients had complete remission of signs and symptoms, seven had excellent response of signs and complete remission of symptoms, and two failed to respond. All other topical therapy was suspended before and during the study. All patients responded to two or three applications daily of medication. Side effects were minor and reversible, and included localized candidiasis (three patients), stomatopyrosis (two), and hypogeusia (one). Clobetasol propionate ointment in adhesive paste (Orabase) thus seems to be an effective topical steroid alternative to other less potent topical and systemic drugs for recalcitrant oral vesiculoerosive disease.