Recurrent aphthous stomatitis – topical medications


Recurrent aphthous stomatitis or recurrent aphthous ulceration is a common problem with a prevalence estimated to vary between 5 – 60%. Peak onset is between the ages of 10 – 19 years of age but they can persist into adulthood. Three major forms are described, minor, major and herpetiform. While common the aetiopathogenesis of recurrent aphthous stomatitis in not fully understood and treatments are mainly symptomatic.

The aim of this review was to investigate and compare the efficacy of different topical medications in the management of recurrent aphthous stomatitis (RAS) using a network meta-analysis (NMA) .


A protocol for the review was registered on the PROSPERO database. Searches were undertaken on the PubMed, Embase, Cochrane Central, Scopus, and China National Knowledge Infrastructure databases. Randomised controlled trials (RCTs)evaluating the use of Triamcinolone acetonide, Doxycycline, Curcumin, Amlexanox, Hyaluronic acid, Chlorhexidine, N-acetylcysteine, Sucralfate, Placebo, Chamomile, Coconut oil, Diosmectite (DS) paste, Basic fibroblast growth factor (bFGF) paste, Benzocaine, Dexamethasone, Berberine, Triester glycerol oxide, Myrrh, and Aloe vera for RAS were considered. Two reviewers independently searched and selected studies extracted data and assessed risk of bias using the Cochrane tool (RoB2). The primary outcomes were pain reduction and/or healing time Standardised mean difference (SMD) and 95% CI were calculated, and pairwise meta-analysis carried out. A Bayesian network meta-analysis with 95% credible intervals was also conducted.


  • 43 RCTs involving a total of 3,067 patients were included.
  • 20 different interventions were tested.
  • Mean age of patients ranged from 41 to 40.09 years.
  • Most studies involved patients with minor RAS with a follow up period of 7 days.
  • 4 studies reported side effects with remainder reporting no side effects or not mentioning them.
  • 29 RCTs were considered to have a high risk of bias and 14 an unclear risk.
  • For pain reduction – NMA did not show any statistically significant differences when different topical treatments were compared together or even with a placebo at different time intervals.
  • For healing time – doxycycline showed a significant difference compared to placebo, but no significant differences were seen for other topical medications when compared together or with placebo.


The authors concluded: –

… very low to moderate evidence to provide a recommendation regarding which topical treatment is the best for alleviating the symptoms of RAS. Rank probability tests concerning pain reduction revealed sucralfate, doxycycline, hyaluronic acid, chamomile, and diosmectite combined with basic fibroblast growth factor paste as the most efficacious treatment options at different evaluation times; therefore, no single therapy was found to be superior to others at different assessment times. Doxycycline followed by curcumin and sucralfate were shown to be the most efficacious treatment options in reducing ulcer healing time. Taking this into consideration, the current NMA cannot provide a definitive conclusion regarding which topical medication is the best for RAS, and further high-quality RCTs with large sample sizes and standardized methodologies are still required.


The authors registered the protocol in the PROSPERO database and followed a typical review and NMA process and number if major databases. In all 43 RCTs were included in the review which is fewer than an earlier review by Lui et al (Dental Elf – 28th Nov 2022) which included 73 studies.  None of the studies included in this new review were considered to be at low risk of bias and 29 of the 43 studies (76%) were considered to be at high risk of bias. Both the Lui et al review and this current review found no significant differences amongst the topical intervention. However, the poor methodological rigour of the trials is a concern. In addition, there was heterogeneity in relation to the size, number, sites, and duration of the ulcers as well as variation in the dosages and concentration of the active ingredients as well as the timing and assessment of the outcome measures.  As the authors note high quality well -conducted trials of appropriate size and duration are needed to provide better evidence on topical measures for the management of RAS.  The use of agreed common outcome measures (COMET ) would also be beneficial for future comparisons.


Primary Paper

Mashrah MA, Fang Y, Song W, Al-Maweri SA, Lan Y, Linhu G, Wang L. Topical medications for the treatment of recurrent aphthous stomatitis: A network meta-analysis. J Oral Pathol Med. 2023 Oct;52(9):811-825. doi: 10.1111/jop.13480. Epub 2023 Sep 27. PMID: 37753744.

Review protocol on PROSPERO

Other references

Dental Elf – 28th Nov 2022

Recurrent aphthous stomatitis – topical interventions

Dental Elf RAS blogs


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