Recurrent aphthous stomatitis. A study of the clinical characteristics of lesions in 93 cases

We studied the clinical characteristics of 93 patients with recurrent aphthous stomatitis (RAS); 66 corresponded to minor aphthae (MiRAS), 20 to major aphthae (MaRAS), and 7 to herpes-like ulcerations (HU). MiRAS was seen to present the lowest rate of recurrences, as well as the shortest duration and the fewest lesions per episode. In turn, MaRAS presented the longest duration per recurrence, along with a number of lesions and recurrences that was lower than in HU but greater than in cases of MiRAS. Finally, HU developed the greatest number of lesions and recurrences. When we classified RAS according to the rate of episodes, no statistically significant differences were observed among the three types in terms of patient age, number and duration of lesions, or evolution time of the oral disorder.     

Randomised controlled trial of the efficacy of HybenX in the symptomatic treatment of recurrent aphthous stomatitis

Background:  The treatment of recurrent aphthous stomatitis (RAS) is principally directed towards reducing the pain and duration of each episode of ulceration; however, there remain few agents for which there is definitive evidence of benefit.
Aims:  The aims of the present study were to determine the efficacy of HybenX (Epien Medical Inc., Minneapolis, MN, USA), vs another device used for the treatment of RAS (Salicept; Carrington Laboratories Inc., lrving, TX, USA) to reduce the symptoms and duration of RAS and determine the safety of HybenX for this clinical application.
Material and methods:  Sixty-three individuals (36 male, 27 female, group median age 25years, range 17.8–57.9years) were entered into a prospective randomised controlled trial of HybenX vs an occlusive covering device (Salicept oral patches; Carrington Laboratories).
Results:  Painful symptoms over a 5-day posttreatment period were reduced by both agents although HybenX was statistically more effective at day 2 than Salicept, and there was a trend for HybenX to cause greater pain reduction than Salicept over this 5-day period. Both agents gave rise to few adverse side effects – a total of nine adverse events in eight patients were recorded. All were unlikely to be related to the treatment devices. HybenX was only applied on one occasion to the HybenX group, while individuals in the Salicept group were able to self medicate as required. The mean number of Salicept patches used per day per subject was three (s.d. 3.3) on day 1 posttreatment, 3.4 (s.d. 3.1) on day 2 and 2.7 (s.d. 1.9) on day 3. Thereafter, the number of applications fell to a mean of 0.8 on day 7.
Conclusion:  It is concluded that HybenX safely and effectively reduces the painful symptoms of RAS.     

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 ± 2.19) compared with active BD patients (6.01 ± 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.     

Salivary cortisol and anxiety in recurrent aphthous stomatitis

Anxiety and salivary cortiso) were measured in two groups of patients with recurrent aphthous ulceration. One group of patients had persistent aphthae (Group 1) and the others had been relieved of their aphthae following correction of delected haematinic deficiency states (Group 2). Anxiety was measured using the Hospital Anxiety and Depression scale and radioimmunoassay of salivary cortisol. There was a statistically significant increased proportion of borderline or clinically anxious patients in Group 1 compared to Group 2 ( P <0.05). Median salivary' cortisol levels also showed a statistically significant elevation in Group 1 (P<0.0 1). It is concluded that stress may play a role in the aetiology of recurrent aphthous stomatitis, particularly in patients who have an underlying anxiety trait.     

Efficacy of bioadhesive patches in the treatment of recurrent aphthous stomatitis

This study evaluated the efficacy of bioadhesive hydrogel patches, made of a pharmaceutical grade cellulose derivative, in the control of pain and as an aid to healing of aphthous ulceration. Patients kept a twice daily ulcer diary to record their pain level on a visual analogue scale. The sensitivity of the test ulcer was assessed by a challenge with pure orange juice as a stimulant before and after application of the patch by the patient. A significant reduction in stimulated pain was recorded following application of the patches to the ulcers ( P <0.01). The patches were found to adhere longer to large ulcers in the early stages of ulceration, when they achieved their maximum protective and pain-attenuating effects. The ulcer size was recorded daily by the patient and patients claimed a reduction in healing time following patch therapy.     

Increased production of tumour necrosis factor by peripheral blood leukocytes in patients with recurrent oral aphthous ulceration

Much evidence suggests that recurrent oral aphthous ulceration (RAU) is an immunologically mediated disease. Tumour necrosis factor has multiple biologic properties, some of which may be relevant to the pathogenesis of RAU. This study has assessed its production by peripheral blood leukocytes from aphthous patients in active and remission phases of disease and from patients with nonaphthous ulceration (diseased controls). Each ulcer patient was studied in parallel with a matched healthy control volunteer. A bioassay against the standard mouse fibrosarcoma line, L929, was used to assess the levels of tumour necrosis factor-alpha (TNF). Significantly greater amounts of TNF were released from unstimulated monocyte-enriched and monocyte-depleted leukocyte fractions in active RAU compared with those from healthy control donors, suggesting that this cytokine may be associated with RAU.     

Effectiveness of two oral pastes for the treatment of recurrent aphthous stomatitis

OBJECTIVE: To compare the effectiveness of two topical medications to reduce the pain and size of recurrent minor aphthous ulcers. SETTING: Ten Colombian Dental Faculties' clinics. DESIGN: A double-blind randomized multi-centre clinical study. SUBJECTS: Ninety-six patients complaining of at least five acute aphthous ulcers were randomized to two intervention groups. Sample size was calculated using an alpha error of 0.05 and beta of 0.20. MATERIALS AND METHODS: Participants were randomly assigned to receive 5% amlexanox or a 0.05% clobetasol propionate magistral preparation. Observers at the participating institutions were previously trained to standardize clinical diagnosis and data recollection. Ulcer size and pain were measured on treatment days 0, 2 and 5. RESULTS: No significant differences were found between the two groups studied in any of the studied variables at baseline. Both treatment medications significantly reduced pain magnitude and the index ulcer's size on days 2 and 5 compared with day 0 without adverse reactions (within groups differences). No statistical differences between groups of the study medications were found. CONCLUSION: The two treatments applied had similar effectiveness as they both relieved pain and reduced the size of recurrent aphthous ulcers.     

Recurrent aphthous stomatitis revisited; clinical features,associations, and new association with infant feeding practices?

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease, characterized by painful oral ulcerations whose causes is poorly understood. The aim of the present study was to assess the characteristics of patients suffering from RAS. METHODS: Five hundred and twenty-eight consecutive patients attending an Oral Medicine Specialist Clinic in the UK were examined and 143 specific attributes recorded. RESULTS: Patients with a clinical diagnosis of RAS were significantly more often males (P = 0.001) younger (P < 0.001). Significant correlations were observed between a diagnosis of RAS and trauma (P = 0.044), stress (P = 0.006), non-smoking (P < 0.001), a family history (P < 0.001), breast feeding (P = 0.017) and the site in the mouth (buccal, labial, floor of mouth) (P < 0.007). CONCLUSION: This retrospective analysis of patients attending a tertiary referral center provides evidence to support some long held beliefs about RAS, such as young age of onset, sites affected, and associations with trauma, stress, familial history and hormonal changes, while raising a new and interesting decreased incidence with breast feeding.     

Reduced dietary intake of vitamin B12 and folate in patients with recurrent aphthous stomatitis

J Oral Pathol Med (2010) 39 : 420–423 Background: Recurrent aphthous stomatitis (RAS), commonly referred to as canker sores, is a very common and painful oral mucosal disease. Although the etiology of RAS is not well understood, a number of factors may play a role, including nutritional deficiencies. The objective of this study was to compare dietary vitamin intake in RAS patients to that of a control group. Methods: One hundred subjects, who had suffered at least three episodes of minor RAS in the previous 12 months, completed a detailed Diet History Questionnaire designed and validated by the US National Institutes of Health. DietCalc software was used to calculate daily dietary intakes of nine different vitamins in the study subjects. Daily intakes were energy‐adjusted and compared to age‐ and gender‐matched nutrient intake data on 9033 subjects from the US National Health and Nutrition Examination Survey. Results:  The study subjects had significantly lower daily intake of vitamin B12 (P < 0.0002) and folate (P < 0.0001) as compared to the controls. Conclusions: Our results demonstrate that patients with recurrent aphthous stomatitis are more likely to have lower dietary intakes of vitamin B12 and folate than a control group. These results support and extend previous studies indicating a link between the etiology of RAS and hematological deficiencies of vitamin B12 and folate. These findings suggest that consuming sufficient amounts of these vitamins may be a useful strategy to reduce the number and/or duration of RAS episodes.     

Association between recurrent aphthous stomatitis and inheritance of a single‐nucleotide polymorphism of the NOS2 gene encoding inducible nitric oxide synthase

J Oral Pathol Med (2011) 40 : 715–720 Background: Recurrent aphthous stomatitis is a common ulcerative disease of the oral mucosa. Recurrent oral aphthous ulceration is also a feature of the more serious and systemic Behçet’s disease. Nitric oxide is a free radical synthesized by one of a family of nitric oxide synthase (NOS) enzymes and is an important regulator of inflammation and immunity. Association of NOS3 gene polymorphisms encoding endothelial nitric oxide synthase has been reported in Behçet’s disease but not recurrent aphthous stomatitis. The aim of this study was to investigate any association between NOS2 gene polymorphisms that encode inducible nitric oxide synthase and recurrent aphthous stomatitis. Methods: This is a case control association study. Eighty‐three Jordanian recurrent aphthous stomatitis patients and 83 age, gender and ethnically matched controls were genotyped for three NOS2 single‐nucleotide polymorphisms, rs10459953, rs1060822 and rs2297518. Chi‐squared analysis was used to compare the allele frequencies and genotypes. Results: There was a significant association between recurrent aphthous stomatitis and inheritance of single‐nucleotide polymorphism rs2297518 (P = 0.006). Although no direct association was demonstrated between rs10459953 or rs1060822 and recurrent aphthous stomatitis, a strong linkage disequilibrium was identified between rs1060822 and rs2297518. Conclusion: Inheritence of a NOS2 single‐nucleotide polymorphism rs2297518 is associated with increased risk of recurrent aphthous stomatitis in a Jordanian population. Confirmatory studies in other populations and investigation of other NOS2 gene polymorphisms will enhance our understanding of the functional basis of this association and help elucidate the role of inducible nitric oxide synthase in recurrent aphthous stomatitis.     

Cell-mediated and humoral immunity against oral streptococci, neisseria, staphylococci, and adult human oral mucosa antigens in recurrent aphthous stomatitis

abstract — Cell-mediated immunity (CMI) and humoral immunity (HI) against oral bacteria ( Streptococcus sanguis strain 2A, ATCC 10556, Streptococcus sanguis group H1, Neisseria subflava and Staphylococcus ) and adult human oral mucosa (AHOM) antigens were investigated in relation to exacerbation of recurrent aphthous stomatitis (RAS). The material consisted of 10 patients with RAS and 10 controls. The CMI and HI were assessed by means of the leukocyte migration test (LMT) and a double-layer immunofluorescence (IF) technique. Compared with normal controls the leukocyte migration inhibition against Strep. 2A and AHOM was significantly increased in patients with exacerbation of RAS and the reactivity seemed to develop in relation to the exacerbation of RAS. The leukocyte migration inhibition was not significantly increased when Strep. H1, Neisseria subflava, Staphylococcus or fetal human kidney extracts were used as antigens. The IgG antibodies against Strep. 2A and Strep. H1 were significantly raised in sera from patients with exacerbation of RAS. However, the endpoint titers (EPT) did not increase significantly in relation to the exacerbation of RAS. The distribution of EPT against Neisseria subflava, Staphylococcus and AHOM did not differ significantly when sera from patients with exacerbation of RAS were related to sera from controls. The present investigations support the hypothesis that CMI against streptococcal and AHOM antigens may be involved in the immunopathogenesis of RAS.     

Clearance of sodium lauryl sulphate from the oral cavity

Sodium lauryl sulphate (SLS) is used in toothpaste and mouth rinses as an emulsifying and surface cleaning agent. SLS has been implicated in an increased incidence of oral irritation in subjects predisposed to recurrent aphthous stomatitis (RAU). Hence, the purpose of this study was to determine the levels of SLS found in the oral cavity following rinsing with an SLS containing mouth rinse and brushing with a SLS containing dentifrice. An analytical method to separate SLS from saliva and other complex systems was developed. The method used high performance liquid chromatography (HPLC) and detection performed using conductivity measurements. Standard curves with known concentrations showed a detection limit of less than 0.4 ug SLS/ml of fluid. 2 clinical studies were conducted to determine the amount of SLS retained in the mouth by a healthy population after rinsing or brushing with commercially available products. The results showed, after rinsing, that 96% of the available SLS from the rinse was recovered in the collected samples within 2 min. Similarly, after brushing. 86% of the SLS contained within the toothpaste was recovered from the collected samples within the first 10 min. These results showed that the amount of SLS retained in the oral cavity was minimal and the contact time between SLS and the oral cavity was very short. A 2nd study was conducted to measure the amount of SLS retained in the mouth by a population susceptible to RAU. After rinsing. 91% of the available SLS was recovered within the first 2 min. Following brushing. 89% of the SLS in the dentifrice was recovered within the first 10 min. These results were comparable to those determined by the study involving the healthy population.     

An immunofluorescence study on the cross-reaction between Strep. 2A and human oral mucosa

abstract — Immunologic cross-reactions between Strep. 2A, fetal human oral mucosa (FHOM), and adult human oral mucosa (AHOM) were investigated by the use of a double layer immunofluorescence staining technique. Rabbit sera were prepared against Strep. 2A and FHOM. Seventeen sera from patients with recurrent aphthous stomatitis (RAS) and with known antibodies against Strep. 2A and AHOM were examined for antibodies against FHOM. The distribution of endpoint titers against FHOM in the sera from RAS differed significantly from the distribution in 17 controls. The immune absorptions in the rabbit sera and in the 17 sera from patients with RAS indicate that some cross-reacting antigenic determinants are shared between Strep. 2A, FHOM, and AHOM. Further, the present results indicate that antibodies are produced against antigenic determinants which are not shared by Strep. 2A, FHOM, and AHOM. The role of cross-reacting antigens in the pathogenesis of RAS is discussed but remains obscure.     

食物性过敏原致复发性口腔溃疡的可能性分析

目的探讨复发性阿弗它口腔溃疡(RAU)的发生与食物性过敏原的关系。方法采用酶免疫分析法对42例复发性阿弗它口腔溃疡患者及21例健康人进行食物过敏原的检测。结果实验组19例出现阳性过敏反应,阳性率为45.2%,对照组无一例阳性。实验组19例总IgE升高,阳性率45.2%,易诱发过敏的食物依次为海鲜、鸡蛋、大麦、燕麦、玉米、菇等;对照组仅3例出现总IgE升高,阳性率为14.3%。两组在统计学上差异有显著性(P<0.05)。结论部分RAU的发生与食物过敏密切相关,发现并限制接触过敏食物有助于治疗。     

针刺对口腔复发性溃疡患者Ｔ细胞亚群的影响

目的：研究针刺治疗对口腔复发性溃疡（ＲＡＳ）患者Ｔ细胞群的影响,方法：对ＲＡＳ病人进行针刺治疗,采用矫联免疫法（ＡＰＡＡＰ法）测定治疗前后外周血Ｔ淋巴细胞亚群ＣＤ^ 3,CD^ 4,CD^ 8。结论：治疗后患者ＣＤ^ 3无明显变化,ＣＤ^ 4有所增加（与治疗前及对照组相比较Ｐ＜０．０５）,而ＣＤ^ 8却相对下降（Ｐ＜０．０５）,ＣＤ^ 4/CD^ ８比值明显升高（Ｐ＜０．０５）,结论：针刺治疗能改善患者ＣＤ^ 4,CD^ 48的数量异常,使ＣＤ^ 4/CD^ 8的数量异常,使ＣＤ^ 4/CD^ 8比值恢复到正常。     

Helicobacter pylori and gastric hyperacidity,and their association with recurrent aphthous stomatitis

Helicobacter pylori is an established cause of gastric ulcers. Its role in causing recurrent aphthous stomatitis (RAS) remains controversial. Fifty-two RAS patients and 52 sex-matched controls were recruited in this case–control study. All subjects were screened for hematinic deficiencies and H. pylori. The latter was assessed quantitatively using the ¹⁴C-urea breath test. The χ² test and Wilcoxon signed ranks test were used to compare H. pylori and hematinic indices between cases and controls, while conditional logistic regression was used to assess the associations between the occurrence of RAS and independent factors. H. pylori was positive in 56.7% of the overall sample, with no difference between RAS patients (50.8%) and controls (49.2%) (P = 0.843). The median H. pylori and haematological indices values did not show any association with ulcer diameter, number, or frequency. Interestingly, gastric hyperacidity was significantly associated with RAS, and this association was independent from tobacco smoking, alcohol drinking, and H. pylori (odds ratio 14.99, 95% confidence interval 2.47–90.95; P = 0.003). This study found no association between H. pylori and RAS. The association between RAS and gastric hyperacidity suggests that gastric refluxate, not H. pylori, has an effect on the oral mucosa that favours an ulcerative change.     

壳聚糖口腔贴膜治疗轻型复发性阿弗他溃疡随机对照临床研究

目的通过壳聚糖口腔贴膜对轻型复发性阿弗他溃疡的临床疗效观察,探讨其有效性和安全性。方法本研究共纳入72例患有轻型复发性阿弗他溃疡的受试者。在6日的试验期间,随机分配受试者至试验组或对照组并告知贴膜使用方法,试验组材料为壳聚糖口腔贴膜,对照组材料为聚乙烯醇膜;比较2组受试者溃疡疼痛值、溃疡面积及不良反应。结果在第4天至第6天,试验组溃疡面积缩小(2.91±3.66)mm^2,对照组溃疡面积缩小(1.10±2.26)mm^2,2组差异具有统计学意义(P<0.05),试验期间初诊及每次复查时,组间溃疡面积、溃疡疼痛值、溃疡疼痛缩小值比较差异均没有统计学意义(P>0.05)。试验过程中无不良反应发生。结论壳聚糖口腔贴膜具有一定的促进轻型复发性阿弗他溃疡愈合的作用。