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Meta-Analysis
. 2012 Sep 12;2012(9):CD005411.
doi: 10.1002/14651858.CD005411.pub2.

Systemic interventions for recurrent aphthous stomatitis (mouth ulcers)

Paul Brocklehurst  1 , Martin Tickle, Anne-Marie Glenny, Michael A Lewis, Michael N Pemberton, Jennifer Taylor, Tanya Walsh, Philip Riley, Julian M Yates
Affiliations
Meta-Analysis

Systemic interventions for recurrent aphthous stomatitis (mouth ulcers)

Paul Brocklehurst et al. Cochrane Database Syst Rev. .

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.

Objectives: To determine the clinical effect of systemic interventions in the reduction of pain associated with RAS, a reduction in episode duration or frequency.

Search 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.

Selection criteria: 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.

Data collection and analysis: 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).

Main 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.

Authors' 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.

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Conflict of interest statement

There are no financial conflicts of interest and the authors declare that they do not have any associations with any parties who may have vested interests in the results of this review.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Intervention versus control, Outcome 1 Recurrence.
1.2
1.2. Analysis
Comparison 1 Intervention versus control, Outcome 2 Episode duration (days).
1.3
1.3. Analysis
Comparison 1 Intervention versus control, Outcome 3 Number of new lesions.
1.4
1.4. Analysis
Comparison 1 Intervention versus control, Outcome 4 Number of new lesions per day.
1.5
1.5. Analysis
Comparison 1 Intervention versus control, Outcome 5 Number of new lesions per week.
1.6
1.6. Analysis
Comparison 1 Intervention versus control, Outcome 6 Number of new lesions per month (6 month tx).
1.7
1.7. Analysis
Comparison 1 Intervention versus control, Outcome 7 Levamisole versus placebo.
1.8
1.8. Analysis
Comparison 1 Intervention versus control, Outcome 8 Number of episodes per month.
1.9
1.9. Analysis
Comparison 1 Intervention versus control, Outcome 9 Ulcer‐free status.
1.10
1.10. Analysis
Comparison 1 Intervention versus control, Outcome 10 Number of days of pain per month (6 month tx).
1.11
1.11. Analysis
Comparison 1 Intervention versus control, Outcome 11 Mean size of aphthae per month (6 month tx).
1.12
1.12. Analysis
Comparison 1 Intervention versus control, Outcome 12 General discomfort per month (6 month tx).
1.13
1.13. Analysis
Comparison 1 Intervention versus control, Outcome 13 Number of ulcers at completion.
1.14
1.14. Analysis
Comparison 1 Intervention versus control, Outcome 14 Pain (VAS).
See this image and copyright information in PMC

Comment in

References

References to studies included in this review

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Dolby 1975 {published data only}
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