OBJECTIVES:

Recurrent aphthous stomatitis (RAS) is a common ulcerative disease of the oral mucosa. Methylenetetrahydrofolate reductase (MTHFR) gene variants are associated with thrombophilia and vasculopathy that may result in oral ulceration. Oral ulcers are also the most common feature of Behcet's disease (BD). Association of MTHFR gene C677T mutation with BD has been reported in different populations. The aim of the present study was to investigate the possible association between MTHFR gene C677T mutation and RAS and evaluate if there was an association with clinical features in a relatively large cohort of Turkish patients.

MATERIALS AND METHODS:

The study included 188 patients affected by RAS and 200 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay for the MTHFR gene C677T mutation.

RESULTS:

The genotype and allele frequencies of C677T mutation showed statistically significant differences between RAS patients and controls (p = 0.002 and p = 0.0004, respectively). After stratifying RAS patients according to clinical characteristics of oral ulcers, a significant association was observed between C677T mutation and number of oral ulcers of RAS patients (p = 0.006).

CONCLUSIONS:

As a result, a high association between MTHFR gene C677T mutation and RAS was observed in the present study. Also number of oral ulcers was found to be associated with MTHFR C677T mutation in RAS patients.

CLINICAL RELEVANCE:

If our observation can be substantiated with further studies, evaluation for MTHFR mutations and perhaps folate supplementation may become necessary in selected patients.

PROJECT: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disorder characterized by recurrent, painful oral aphthae, and oxidative stress presumably contributes to its pathogenesis. The aim of this study is to scrutinize the relationship between oxidative stress and serum trace elements (copper, Cu; zinc, Zn; selenium, Se), and to evaluate the ratios of Cu/Zn and Cu/Se in this disorder.

PROCEDURE:

Patients with RAS (n=33) and age- and sex-matched healthy control subjects (n=30) were enrolled in this study. Malondialdehyde (MDA) concentrations in plasma and the activities of superoxide dismutase (SOD1; CuZnSOD), glutathione peroxidase (GPx) and catalase (CAT) in erythrocyte were determined as spectrophotometric. Also, the levels of Se, Zn and Cu in serum were determined on flame and furnace atomic absorption spectrophotometer using Zeeman background correction.

RESULTS AND CONCLUSIONS:

Oxidative stress was confirmed by the significant elevation in plasma MDA, and by the significant decrease in CAT, SOD1, and GPx (p<0.05). When compared to controls, Zn and Se levels were significantly lower in patients, whereas Cu levels was higher in RAS patients than those in controls (p<0.05). In addition, the correlation results of this study were firstly shown that there were significant and positive correlations between Se-CAT, Se-GPx, and Cu-MDA parameters, but negative correlations between Se-Cu, Se-MDA, Cu-CAT, Cu-SOD1 and Cu-GPx parameters in RAS patients. Furthermore, the ratios of Cu/Zn and Cu/Se were significantly higher in the patients than the control subjects (p<0.05). Our results indicated that lipid peroxidation associated with the imbalance of the trace elements seems to play a crucial role in the pathogenesis of RAS. Furthermore, the serum Cu/Zn and Cu/Se ratios may be used as biochemical markers in these patients.

Recurrent aphthous stomatitis (RAS) has a multifactorial etiopathogenesis, an interaction between predisposing factors and/or systemic conditions and immunological components in genetically predisposed subjects. The Mediterranean fever (MEFV) gene has already been identified as being responsible for familial Mediterranean fever. Because the association between MEFV gene mutations and Behçet's disease has been reported before in several studies, we considered that the role of MEFV gene mutations should be studied in patients with RAS, because of the clinical similarities of both diseases. The aim of this study was to explore the frequency and clinical significance of MEFV gene mutations in a cohort of Turkish patients with RAS. The study population comprised 100 unrelated patients with a clinical diagnosis of RAS and 156 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction and restriction fragment length polymorphism for the four MEFV gene mutations (M694V, M680I, V726A and E148Q). There were statistically significant differences of the MEFV gene mutation carrier rates and allele frequencies between RAS patients and healthy controls (P = 0.042, odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.01-3.41; and P = 0.039, OR = 1.8, 95% CI = 1.02-3.14, respectively). Even if it is not statistically significant, the E148Q allele frequency was higher in patients with RAS than the control group. A statistically significant increased prevalence of MEFV variants in RAS patients was found. This is the first study to report that missense mutations of MEFV is associated with RAS in the Turkish population.

The paper describes a clinical case of celiac disease with grade 3 malabsorption, which is associated with recurrent aphthous stomatitis and schizophrenia. On readmission after 8 months of strict adherence to his gluten-free diet, the patient was observed to be in clinical remission and to have normalized laboratory indices and immunological tests. The signs of recurrent stomatitis disappeared. However, the symptoms of the mental disease remained.

OBJECTIVES:

To compare immediate pain relief, healing time between minor recurrent aphthous ulcers treated with a single session of carbon dioxide (CO2) laser and a placebo.

STUDY DESIGN:

A prospective clinical study was performed on 25 patients with minor recurrent aphthous stomatitis. Pretreatment pain levels were recorded using a numerical rating scale. Ulcers were randomized to either receive treatment or placebo. Pain levels were assessed immediately after treatment and after 24 h. Healing was assessed on days 3 and 4, and once every 2 days thereafter for 2 weeks.

RESULTS:

Mean pain scores in the laser group were significantly reduced immediately after treatment (0.68 ± 0.6) compared with pretreatment (8.48 ± 0.71; P < .001). In contrast, the placebo group showed little difference in pain scores between pretreatment (8.08 ± 0.70) and immediately after treatment (7.96 ± 0.84). In the laser group, significant improvements in healing times were observed (4.08 ± 0.81 vs. 7.84 ± 0.90 days; P < .001).

CONCLUSION:

CO2 laser therapy in recurrent aphthous stomatitis (RAS) provides immediate pain relief sustained over 24 h, along with accelerated healing time.

DesignRandomised controlled trial.InterventionPatients with a validated history of at least three episodes of idiopathic recurrent aphthous stomatitis were randomised to either a once-daily multivitamin containing 100% of the U.S. reference daily intake (RDI) of essential vitamins or a placebo for at least one year.Outcome measureNumber of new RAS episodes, mouth pain, normalcy of diet and medication compliance.ResultsThere were no significant differences in mean number of new RAS episodes between the multivitamin (4.19 episodes) and placebo (4.60 episodes) groups. Mean duration of new episodes was similar for the two groups at 8.66 days for multivitamin group and 8.99 days for placebo(P = .60). There were no differences with other measures.ConclusionsDaily multivitamin supplementation, with the RDI of essential vitamins, did not result in a reduction in the number or duration of RAS episodes.

DesignRandomised controlled trial (RCT).InterventionOne hundred and sixty patients participating in a RCT in which they were randomised to multivitamins (n=81) or placebo (n=79) completed ulcer diaries and a weekly telephone survey by calling an automated interactive voice response (IVR) system. Stressful events were quantified using the validated Recent Life Changes Questionnaire (RLCQ) and were classified as mental or physical stressors.Outcome measureOnset and duration of RAS episodesResultsStressful life events were significantly associated with the onset of RAS episodes (P < 0.001), but not with the duration of the RAS episodes. Experiencing a stressful life event increased the odds of an RAS episode by almost three times (OR = 2.72; 95% CI = 2.04-3.62). When controlled for each other, mental stressors had a larger effect (OR = 3.46, 95% CI = 2.54- 4.72) than physical stressors (OR = 1.44; 95% CI = 1.04- 1.99) on the occurrence of RAS episodes. RAS episodes did not occur more frequently or last longer with increasing stress severity.ConclusionsIn patients with a history of RAS, stressful events may mediate changes involved in the initiation of new RAS episodes. Mental stressors are more strongly associated with RAS episodes than physical stressors.