This literature review aims to provide guidance on the treatment of recurrent aphthous stomatitis (RAS) based on studies published over the past 10 years.

This study included randomized clinical trials involving human patients from 2013 and 2023, published in any language. The trials examined both pharmacological and non-pharmacological treatments for aphthous lesions, mainly focusing on the adult population, with pain management as the primary outcome. The research was conducted using PubMed, EMBASE, and CINHAL databases.

Most of the 45 analyzed studies focused on non-pharmacological therapies, which led to positive results with minimal adverse effects or contraindications, even when compared to cortisone-based treatments. Laser therapy also showed excellent results, particularly in the immediate post-treatment period. Non-pharmacological therapies appeared to offer the best risk-benefit ratio for patients suffering from RAS.

Treatment should be individualized based on the patient's specific form of RAS, and laser therapy can be used either as a standalone treatment or as an adjunct to other treatments considered in the review.

Oral diseases, particularly dental caries and periodontal disease, pose significant global health challenges. The imbalance of the oral microbiota plays a key role in the occurrence of these diseases, prompting researchers to seek new strategies to restore oral ecological balance. Lactobacillus reuteri is a Gram-positive rod-shaped bacterium that exists in various body parts of humans, including the gastrointestinal tract, urinary tract, skin, and so on. This species has a potentially positive impact on oral health and plays an important role in maintaining systemic health. Recent studies have explored the application of Lactobacillus reuteri in the prevention and treatment of oral diseases, and its impact on systemic health has also been preliminarily revealed. The current review summarizes the role of Lactobacillus reuteri in oral health and systemic health and outlines its potential applications in the future. Lactobacillus reuteri has shown promising prospects in treating non-communicable biofilm-dependent oral diseases, but its mechanism of action and efficacy still need further research. In addition, Lactobacillus reuteri has also displayed some potential benefits in promoting overall health. Future research should focus on revealing the specific pathways of action of Lactobacillus reuteri, screening for the most beneficial strains, determining the most effective drug delivery strategies, developing oral and systemic health products based on Lactobacillus reuteri, and ensuring their safety in clinical applications.

Mucosal ulcers are a common yet often overlooked complication during orthodontic treatment, significantly impacting patient comfort and compliance. This letter aims to highlight the prevalence, potential causes, and management strategies for mucosal ulcers in orthodontic patients. By reviewing recent literature and clinical observations, we underscore the necessity for proactive measures and tailored interventions to mitigate the incidence and severity of these lesions. Emphasizing the role of patient education and the use of protective devices, we call for a multidisciplinary approach to enhance patient care and treatment outcomes. This discussion is particularly relevant in the context of evolving orthodontic techniques and materials, which necessitate continuous adaptation of clinical practices to ensure patient safety and well-being.

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.

We aimed to assess the therapeutic effects of a topical probiotic nano-formulation derived from Lactobacillus reuteri on treating recurrent aphthous stomatitis.

60 participants were randomly allocated into two groups (control and probiotic). Probiotic group administered topical probiotic nano-formulation three times a day for seven days. The control group administered a standard analgesic oral rinse. The size of ulcer(s) and pain severity were recorded on days 0, 3, 5, and 7 after intervention.

Before the intervention, the groups had no significant differences in terms of pain severity (P-value = 0.28) and lesion size (P-value = 0.24). Both groups exhibited significant reductions in pain severity and lesion size over the course of the intervention. After one week, the probiotic group had a notably larger lesion size reduction than the control group (P-value = 0.01). The probiotic group also showed a significantly greater reduction in pain severity than the control group (P-value = 0.04).

Applying topical probiotic nano-formulation derived from Lactobacillus reuteri three times a day decreased lesion size and pain severity in RAS patients faster than the local analgesic oral rinse.

Lactobacillus reuteri-derived probiotic nano-formulation might be a promising treatment option for RAS.

Biologics are unaffordable to a large majority of the global population because of prohibitively expensive fermentation systems, purification and the requirement for cold chain for storage and transportation. Limitations of current production and delivery systems of biologics were evident during the recent pandemic when <2.5% of vaccines produced were available to low-income countries and ∼19 million doses were discarded in Africa due to lack of cold-chain infrastructure. Among FDA-approved biologics since 2015, >90% are delivered using invasive methods. While oral or topical drugs are highly preferred by patients because of their affordability and convenience, only two oral drugs have been approved by FDA since 2015. A newly launched oral biologic costs only ∼3% of the average cost of injectable biologics because of the simplified regulatory approval process by elimination of prohibitively expensive fermentation, purification, cold storage/transportation. In addition, the cost of developing a new biologic injectable product (∼$2.5 billion) has been dramatically reduced through oral or topical delivery. Topical delivery has the unique advantage of targeted delivery of high concentration protein drugs, without getting diluted in circulating blood. However, only very few topical drugs have been approved by the FDA. Therefore, this review highlights recent advances in oral or topical delivery of proteins at early or advanced stages of human clinical trials using chewing gums, patches or sprays, or nucleic acid drugs directly, or in combination with, nanoparticles and offers future directions.

Background and objectives: To compare the efficacy and safety of topical interventions used for recurrent aphthous stomatitis. Materials and Methods: This network meta-analysis was conducted in accordance with the PRISMA statement. We searched four electronic databases, PubMed, Web of Science (WOS), Cochrane Central Register of Controlled Trials and Embase, for randomized controlled trials reporting efficacy and safety data on topical interventions for recurrent aphthous stomatitis. We performed a quality evaluation using a methodology based on the Cochrane Handbook. Two authors independently extracted data on healing effect, size reduction effect, symptom reduction effect, recurrence and safety assessment. Network meta-analysis was then performed using ADDIS and RevMan. Results: A total of 72 trials (5272 subjects) involving 29 topical interventions were included. Honey, lnsulin liposome gel, laser, amlexanox, glycyrrhiza and triamcinolone had better efficacy performance. Probiotics and chlorhexidine helped to prolong ulcer intervals and reduce recurrence. Doxycycline and penicillin had a high risk of adverse events. Hematologic evaluation showed no preference. The rank possibility of size-reducing effect and symptom-reducing effect supported the short-term effect of laser and the long-term effect of probiotics. Conclusions: We recommend the use of laser as a short-term intervention during the exacerbation phase of RAS and probiotics as a long-term intervention during the exacerbation and remission phases of RAS.

There is currently a lack of effective drugs to cure recurrent aphthous stomatitis. This study aimed to evaluate the efficacy of probiotics alone or as an adjunct in recurrent aphthous stomatitis (RAS) patients. Seven randomized controlled trials (RCTs) were included, of which three were included in quantitative analysis. Of five studies evaluating the efficacy of probiotics alone compared with placebo or Oracure gel, two reported no significant difference in relieving oral pain, while probiotics exhibited a higher capacity for decreasing oral pain in the other three. A significant decrease in ulcer severity was found in one, while no significant difference was found in the other four. The remaining two studies demonstrated that probiotics, as an adjunct to steroids or anaesthetic antiseptic gel, significantly reduced the ulcer severity and oral pain. The meta-analysis showed a significant decrease in oral pain (- 1.72, P = 0.0001) with probiotics compared with placebo. In conclusion, probiotics alone were capable of relieving oral pain but not effective in reducing ulcer severity. A combination of probiotics and steroids or anaesthetic antiseptic gel was more effective than steroids or anaesthetic antiseptic gel alone in RAS patients. Probiotics are promising for the treatment of recurrent aphthous stomatitis.

The study aimed to explore the effectiveness of probiotics in the treatment of minor recurrent aphthous stomatitis (RAS).

We performed a randomized, controlled clinical study. Sixty adult (group A) and 60 children patients (group B) with diagnosis of minor RAS were included. Both groups were divided into two subgroups; AI and BI (test subgroups) and AII and BII (control subgroups). For test subgroups, probiotic lozenges were consecutively administered twice daily, for 5 days. The size and pain level of ulcers were recorded on treatment days 0, 3, and 5. The outbreak frequency of RAS within 6 months was investigated for all subgroups.

Compared with baseline, an improvement was evident for all subgroups. However, for effectiveness in pain reduction, a statistically significant difference in favor of AI was observed for all evaluation periods when compared with control subgroup. Regarding effectiveness in ulcer size reduction, a statistically significant difference in favor of BI was observed at day 5 when compared with control subgroup. No significant difference was observed in the effectiveness index between subgroups AI and BI (test subgroups) except in effectiveness in pain reduction at day 3. The outbreak frequency decreased significantly in subgroup BI.

Topical application of probiotics decreased pain intensity and accelerates RAS healing. The effectiveness in pain reduction is more evident in adult patients while acceleration of healing is more evident in children.

Probiotics could be a well-tolerated, topical therapeutic agent in the treatment of minor RAS.

ClinicalTrials.gov ID: NCT04383236.