Systemic interventions for recurrent aphthous stomatitis (mouth ulcers)

School of Dentistry, The University of Manchester, Manchester, UK.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 09/2012; 9(9):CD005411. DOI: 10.1002/14651858.CD005411.pub2
Source: PubMed


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.
To determine the clinical effect of systemic interventions in the reduction of pain associated with RAS, a reduction in episode duration or frequency.
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.
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.
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).
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.
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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Available from: Philip Riley, Jan 03, 2014
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    • "Oral aphthae are also known as Minor recurrent aphthous stomatitis (MiRAS), gumboils, mouth ulcers, aphthous ulcer, and are characterized by presenting a vesiculous-ulcerous state on a erythmatous base with a yellowish background, which passes through the following three periods: 1) vesiculous period; 2) ulcerous period (a period with intense, stinging pain with a burning sensation, which is accompanied by difficulty in chewing and even in speaking, and 3) the scarring period (Rioboo and Bascones, 2001; Benslama, 2002). These are primary lesions, oral mucous ulcers, benign, not contagious, and of unknown etiology (Carrozzo et al., 1995; Brocklehurst et al., 2012; Scully and Poster, 1989). Pain comprises the most important symptom of the disease; its intensity will depend on the size of the ulcer, which also increases with the ingestion of foods and beverages. "
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    ABSTRACT: The plant species Ageratina pichinchensis (Schauer) R.M.King & H.Rob. (Asteraceae) in a wild plant native to Mexico that is utilized in traditional medicine for the treatment of skin problems and for mouth ulcers. The objective of the present study was to evaluate the clinical effectiveness and therapeutic safety of a phytopharmaceutical elaborated with a depigmented hexane-ethyl acetate extract of A. pichinchensis at a concentration of 5% in patients with a clinical condition of Minor Recurrent aphthous stomatitis (MiRAS). We conducted a double-blind, randomized, and controlled pilot study in which the experimental treatment was a phytopharmaceutical elaborated with a unpigmented hexane-ethyl acetate extract of A. pichinchensis at a 5% concentration and, as control treatment, we utilized Triamcinolone at 0.1%. Study participants were patients with a diagnosis of MiRAS, elderly males and females, with a disease evolution of no >3 days. Lesion size was measured by means of a tracing sheet and pain, by the Visual analogue scale (VAS). Output variables comprised clinical effectiveness, treatment adherence, therapeutic failure, and therapeutic success. Fifty six patients participated in the study and we distributed these into two study groups (28 in each group). The results obtained did not show statistically significant differences between the experimental and the control treatments. Among patients treated with the A. pichinchensis extract, the time required for achieving the absence of pain was 4.0 days, while that of the control treatment was 4.1 days. In patients treated with A. pichinchensis, the time necessary for healing was 4.5 days and for the Triamcinolone 0.1%-treated group, this was 4.7 days. Greater clinical effectiveness was evidenced on days 2, 3, and 4 of treatment. During the first 7 follow-up days, there was clinical effectiveness in 92.8% of experimental-group and in 89.2% of control-group patients. At the end of the study, 100% therapeutic effectiveness was able to be scored. Copyright © 2015. Published by Elsevier Ireland Ltd.
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    • "Pentoxifylline, colchicine, dapsone and thalidomide have also been used, but require caution because of possible adverse effects. These treatments are essentially palliative, since none of them have been able to secure permanent disease remission (26). "
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    ABSTRACT: Recurrent aphthous stomatitis (RAS) is the most common chronic disease of the oral cavity, affecting 5-25% of the population. The underlying etiology remains unclear, and no curative treatment is available. The present review examines the existing treatments for RAS with the purpose of answering a number of questions: How should these patients be treated in the dental clinic? What topical drugs are available and when should they be used? What systemic drugs are available and when should they be used? A literature search was made of the PubMed, Cochrane and Scopus databases, limited to articles published between 2008-2012, with scientific levels of evidence 1 and 2 (metaanalyses, systematic reviews, phase I and II randomized clinical trials, cohort studies and case-control studies), and conducted in humans. The results obtained indicate that the management of RAS should be based on identification and control of the possible predisposing factors, with the exclusion of possible underlying systemic causes, and the use of a detailed clinical history along with complementary procedures such as laboratory tests, where required. Only in the case of continuous outbreaks and symptoms should drug treatment be prescribed, with the initial application of local treatments in all cases. A broad range of topical medications are available, including antiseptics (chlorhexidine), antiinflammatory drugs (amlexanox), antibiotics (tetracyclines) and corticosteroids (triamcinolone acetonide). In patients with constant and aggressive outbreaks (major aphthae), pain is intense and topical treatment is unable to afford symptoms relief. Systemic therapy is indicated in such situations, in the form of corticosteroids (prednisone) or thalidomide, among other drugs. Key words:Recurrent aphthous stomatitis, treatment, clinical management.
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