No single systemic treatment was found to be effective for treatment of mouth ulcers

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The prevalence of mouth ulcers (recurrent aphthous stomatitis , RAS) has been estimated at between 5 – 60%. They can be painful and slow to heal.  There are three recognized forms; minor, major and herpetiform.  The peak age at onset is between 10 and 19 years of age but they can persist through adulthood. The aim of this review was to determine the clinical effect of systemic interventions in the reduction of pain associated with RAS, a reduction in episode duration or frequency.

Cochrane methodology was followed with searches of the Cochrane Oral Health Group and PaPaS Trials Registers CENTRAL, Medline; Embase, CINAHL and AMED databases , reference lists and trial authors were also contacted. randomised controlled trials (RCTs) with a primary outcome of  reduction of pain, or reduction in episode duration or frequency associated with RAS were included

  • 25 trials were included, 22 of which were placebo controlled and eight made head-to-head comparisons (five trials had more than two treatment arms).
  • Twenty-one different interventions were assessed.
  • The interventions were grouped into two categories: immunomodulatory/anti-inflammatory and uncertain.
  • Only one study was assessed as being at low risk of bias. There was insufficient evidence to support or refute the use of any intervention.

The Authors concluded

No single treatment was found to be effective and therefore the results remain inconclusive in regard to the best systemic intervention for RAS. This is likely to reflect the poor methodological rigour of trials, and lack of studies for certain drugs, rather than the true effect of the intervention. It is also recognised that in clinical practice, individual drugs appear to work for individual patients and so the interventions are likely to be complex in nature. In addition, it is acknowledged that systemic interventions are often reserved for those patients who have been unresponsive to topical treatments, and therefore may represent a select group of patients.


Brocklehurst P, Tickle M, Glenny AM, Lewis MA, Pemberton MN, Taylor J, Walsh T, Riley P, Yates JM. Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No.: CD005411. DOI: 10.1002/14651858.CD005411.pub2.


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