Review question
This review has been conducted to assess the effects of different interventions, administered systemically or topically, for the prevention or treatment of oral ulcers in people with Behçet's disease. The interventions could be compared with an alternative intervention, no intervention or the administration of a placebo.
Background
Behçet's disease is a chronic disease characterised by a multitude of signs and symptoms including oral and genital ulcerations, skin lesions and inflammatory vascular involvement of the central nervous system and gastrointestinal tract. Although the underlying cause of Behçet’s disease is unknown it is thought to involve a genetic predisposition combined with environmental factors.
Behçet's disease most commonly presents in the third decade. The disease is rare in individuals older than age 50 years and during childhood. Although both sexes are equally affected, it is thought that the disease has a more severe course amongst men.
The oral ulceration that occurs in Behçet's disease can be painful and slow to heal. At its worst, this can cause significant difficulties in eating and drinking.
Study characteristics
Authors from Cochrane Oral Health carried out this review of existing studies and the evidence is current up to 4 October 2013. The review includes 15 studies published from 1980 to 2012 in which 888 participants were randomised. Eleven of the trials were conducted in Turkey, two in Japan, one in Iran, and one in the UK. Thirteen different interventions were assessed, administered either topically or systemically.
Topical interventions: sucralfate, interferon–alpha (different doses), cyclosporin A, triamcinolone acetonide ointment, phenytoin syrup mouthwash.
Systemic interventions: aciclovir, thalidomide (different doses), corticosteroids, rebamipide, etanercept, colchicine, interferon–alpha, cyclosporin.
Key results
There was insufficient evidence to support or refute the use of any included intervention with regard to pain, episode duration or episode frequency associated with oral ulcers, or the safety of the interventions.
Quality of the evidence
The quality of the evidence ranged from moderate to very low.
Due to the heterogeneity of trials including trial design, choice of intervention, choice and timing of outcome measures, it was not possible to carry out a meta-analysis. Several interventions show promise and future trials should be planned and reported according to the CONSORT guidelines. Whilst the primary aim of many trials for Behç̧et's disease is not necessarily reduction of oral ulceration, reporting of oral ulcers in these studies should be standardised and pre-specified in the methodology. The use of a core outcome set for oral ulcer trials would be beneficial.
Behçet's disease is a chronic inflammatory vasculitis that can affect multiple systems. Mucocutaneous involvement is common, as is the involvement of many other systems such as the central nervous system and skin. Behç̧et's disease can cause significant morbidity, such as loss of sight, and can be life threatening. The frequency of oral ulceration in Behçet's disease is thought to be 97% to 100%. The presence of mouth ulcers can cause difficulties in eating, drinking, and speaking leading to a reduction in quality of life. There is no cure for Behçet's disease and therefore treatment of the oral ulcers that are associated with Behçet's disease is palliative.
To determine the clinical effectiveness and safety of interventions on the pain, episode duration, and episode frequency of oral ulcers and on quality of life for patients with recurrent aphthous stomatitis (RAS)-type ulceration associated with Behçet's disease.
We undertook electronic searches of the Cochrane Oral Health Group Trials Register (to 4 October 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9); MEDLINE via Ovid (1946 to 4 October 2013); EMBASE via Ovid (1980 to 4 October 2013); CINAHL via EBSCO (1980 to 4 October 2013); and AMED via Ovid (1985 to 4 October 2013). We searched the US National Institutes of Health trials register (http://clinicaltrials.gov) and the World Health Organization (WHO) Clinical Trials Registry Platform for ongoing trials. There were no restrictions on language or date of publication in the searches of the electronic databases. We contacted authors when necessary to obtain additional information.
We included randomised controlled trials (RCTs) that looked at pre-specified oral outcome measures to assess the efficacy of interventions for mouth ulcers in Behçet's disease. The oral outcome measures included pain, episode duration, episode frequency, safety, and quality of life. Trials were not restricted by outcomes alone.
All studies meeting the inclusion criteria underwent data extraction and an assessment of risk of bias, independently by two review authors and using a pre-standardised data extraction form. We used standard methodological procedures expected by Cochrane.
A total of 15 trials (n = 888 randomised participants) were included, 13 were placebo controlled and three were head to head (two trials had more than two treatment arms). Eleven of the trials were conducted in Turkey, two in Japan, one in Iran and one in the UK. Most trials used the International Study Group criteria for Behçet's disease. Eleven different interventions were assessed. The interventions were grouped into two categories, topical and systemic. Only one study was assessed as being at low risk of bias. It was not possible to carry out a meta-analysis. The quality of the evidence ranged from moderate to very low and there was insufficient evidence to support or refute the use of any included intervention with regard to pain, episode duration, or episode frequency associated with oral ulcers, or safety of the interventions.