title: Systemic interventions for recurrent aphthous stomatitis (mouth ulcers).
abstract: BACKGROUND
  Recurrent aphthous stomatitis (RAS) is the most frequent form of oral ulceration, characterised by recurrent oral mucosal ulceration in an otherwise healthy individual. At its worst RAS can cause significant difficulties in eating and drinking. Treatment is primarily aimed at pain relief and the promotion of healing to reduce the duration of the disease or reduce the rate of recurrence. A variety of topical and systemic therapies have been utilised.
  
  
  OBJECTIVE
  To determine the clinical effect of systemic interventions in the reduction of pain associated with RAS, a reduction in episode duration or frequency.
  
  
  METHODS
  We undertook electronic searches of: Cochrane Oral Health Group and PaPaS Trials Registers (to 6 June 2012); CENTRAL via The Cochrane Library (to Issue 4, 2012); MEDLINE via OVID (1950 to 6 June 2012); EMBASE via OVID (1980 to 6 June 2012); CINAHL via EBSCO (1980 to 6 June 2012); and AMED via PubMed (1950 to 6 June 2012). We searched reference lists from relevant articles and contacted the authors of eligible trials to identify further trials and obtain additional information.
  
  
  METHODS
  We included randomised controlled trials (RCTs) in which the primary outcome measures assess a reduction of pain associated with RAS, a reduction in episode duration or a reduction in episode frequency. Trials were not restricted by outcome alone. We also included RCTs of a cross-over design.
  
  
  METHODS
  Two review authors independently extracted data in duplicate. We contacted trial authors for details of randomisation, blindness and withdrawals. We carried out risk of bias assessment on six domains. We followed The Cochrane Collaboration statistical guidelines and risk ratio (RR) values were to be calculated using fixed-effect models (if two or three trials in each meta-analysis) or random-effects models (if four or more trials in each meta-analysis).
  
  
  RESULTS
  A total of 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Dentistry, The University of Manchester, Manchester, UK. paul.brocklehurst@manchester.ac.uk
authors.forename: Paul
authors.initials: P
authors.lastname: Brocklehurst
authors.forename: Martin
authors.initials: M
authors.lastname: Tickle
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Glenny
authors.forename: Michael A
authors.initials: MA
authors.lastname: Lewis
authors.forename: Michael N
authors.initials: MN
authors.lastname: Pemberton
authors.forename: Jennifer
authors.initials: J
authors.lastname: Taylor
authors.forename: Tanya
authors.initials: T
authors.lastname: Walsh
authors.forename: Philip
authors.initials: P
authors.lastname: Riley
authors.forename: Julian M
authors.initials: JM
authors.lastname: Yates
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D006801:Humans; D056747:Immunomodulation / Q000276:immunology; D019226:Oral Ulcer / Q000628:therapy*; D008517:Phytotherapy / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D013281:Stomatitis, Aphthous / Q000628:therapy*
chemical_list: D000893:Anti-Inflammatory Agents