Cochrane · intervention · CD005411
Systemic interventions for recurrent aphthous stomatitis (mouth ulcers)
Brocklehurst, P, Tickle, M, Glenny, AM, et al. · Cochrane Database of Systematic Reviews · 2012 · Cochrane Library
Full textEvery question was extracted from the full review (methods and results), not only its Summary of Findings table.
Questions
82
current version
GRADE rated
0
No studies
4
Included studies
25
as reported
No studies 4 · 4.9%Ungraded 78 · 95.1%Very low 0 · 0%Low 0 · 0%Moderate 0 · 0%High 0 · 0%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency | Participants with a previous or current history of RAS diagnosed on history and clinical examination (n=25 trials) |
| Intervention | Any preventive, palliative or curative intervention administered systemically | Beta-glucan (n=1); Clofazimine (n=1); Colchicine (n=2); Levamisole (n=8); Montelukast (n=1); Pentoxifylline (n=1); Prednisone (n=2); Sulodexide (n=1); Camel thorn (n=1); Homeopathy (n=1); LongoVital herbal+vitamin (n=1); LongoVital herbal alone (n=2); Multivitamin (n=1); Propolis (n=1); Subantimicrobial doxycycline (n=1); Tetracycline (n=1); Vitamin B12 (n=1); Rofecoxib (n=1); Tinidazole (n=1); Perilla oil (n=1); Soybean oil (n=1) |
| Comparison | No active treatment or placebo; head-to-head trials of different interventions also included | Placebo (n=22 trials); active comparator in head-to-head trials (n=8 trials) |
| Outcomes | Primary: pain associated with RAS; episode duration; episode frequency; safety including adverse effects. Secondary: patient reported outcomes measuring quality of life and reduction in morbidity | Pain (n reported narratively/quantitatively across trials); episode duration; episode frequency / number of new ulcers; ulcer size; complete healing/remission; quality of life; adverse effects |
| Study designs | Randomised controlled trials (RCTs), including cross-over RCTs with a suitable washout period and no evident carry-over effects | 25 RCTs (22 placebo controlled; 8 head-to-head; five trials with more than two treatment arms) |
| Timing | Measurements closest to the end of treatment; cumulative measurements over the total treatment period | Treatment/follow-up durations ranged from 4 days to 8 months across trials; outcomes taken closest to end of treatment or as cumulative totals |
Search date: 2012-06. Databases: Cochrane Oral Health Group Trials Register; Cochrane PaPaS Trials Register; CENTRAL; MEDLINE via OVID; EMBASE via OVID; CINAHL via EBSCO; AMED via PubMed
Questions and results
Show all 2 versionsBeta-glucan (1.3/1.6 beta-glucan 10 mg twice daily for 20 days) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Ulcer severity score (USS) 20 days | MD -4.38 [-6.17, -2.59] | 1 study · 31 participants | Ungraded |
Adverse effects 20 days | There was no reporting of adverse effects. | 1 study · 31 participants | Ungraded |
Clofazimine (100 mg daily for 30 days, then 100 mg every other day) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Complete remission (no further aphthous episodes to 6 months) 6 months | One trial at high risk of bias compared clofazimine (n=23) with placebo (n=20). The number of individuals in the clofazimine group who had no further aphthous episodes from beginning treatment until completion at 6… | 1 study · 43 participants | Ungraded |
Adverse effects 6 months | Clofazimine was associated with an increase in cutaneous adverse effects (skin pigmentation and drying) (Fisher's exact test P=0.015), but these were reported to be easily controlled. | 1 study · 43 participants | Ungraded |
Colchicine (0.5 mg three times per day) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Complete remission (no further aphthous episodes to 6 months) 6 months | The trial by de Abreu 2009 (high risk of bias) also assessed colchicine (n=23) versus placebo (n=20). The number with no further aphthous episodes at 6 months was not significantly different from placebo (Fisher's… | 1 study · 43 participants | Ungraded |
Adverse effects 6 months | There was a greater percentage of treatment interruptions in the colchicine group due to gastrointestinal adverse effects (Fisher's exact test P=0.009). The review noted potential evidence of harm at a dose of 1.5 mg… | 1 study · 43 participants | Ungraded |
Levamisole (150 mg per day) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Decrease in frequency of attacks | RR 4.29 [0.72, 25.39] | 1 study | Ungraded |
Overall effectiveness (episodes, lesions, duration, pain) | Eight trials (seven high, one unclear risk of bias) compared levamisole 150 mg/day with placebo (De Cree 1978; Drinnan 1978; Meyer 1977; Miller 1978; Olson 1978; Van de Heyning 1978; Weckx 2009; Zissis 1983).… | 8 studies | Ungraded |
Decrease in pain | RR 4.29 [0.67, 27.24] | 1 study | Ungraded |
Adverse effects | Patients receiving levamisole reported more adverse effects than those receiving placebo (mild stomach upset/nausea, diarrhoea, sleeplessness, dysgeusia/dysosmia), however no adverse effects were reported as requiring… | 8 studies | Ungraded |
Decrease in duration of attacks | RR 4.29 [0.67, 27.24] | 1 study | Ungraded |
Decrease in number of ulcers | RR 7.88 [0.51, 121.96] | 1 study | Ungraded |
Montelukast (leukotriene receptor antagonist; 10 mg daily for 1 month then alternate days for the second month) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Time to resolution of first ulcer (days) 2 months | MD -3.95 [-4.38, -3.52] | 1 study · 40 participants | Ungraded |
Adverse effects 2 months | The study reported equal drug-related adverse effects for those treated with montelukast and placebo. | 1 study · 40 participants | Ungraded |
Total number of new lesions over 2-month treatment period 2 months | MD -3.90 [-4.55, -3.25] | 1 study · 40 participants | Ungraded |
Pain (visual analogue scale) 2 months | MD -1.15 [-1.46, -0.84] | 1 study · 40 participants | Ungraded |
Pentoxifylline (400 mg three times daily for 60 days) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Pain, number of ulcers, ulcer-free days and ulcer size 60 days (plus 60-day follow-up) | A single trial at high risk of bias compared pentoxifylline 400 mg three times daily (n=14) with placebo (n=12). No statistically significant differences were reported for pain, number of ulcers and ulcer-free days at… | 1 study · 26 participants | Ungraded |
Adverse effects 60 days (plus 60-day follow-up) | Patients receiving pentoxifylline reported more adverse events than those in the placebo group but this was not statistically significant (69% reported adverse effects: dizziness, headaches, stomach upset, increased… | 1 study · 26 participants | Ungraded |
Prednisone (oral, commencing 25 mg with phased dose reduction over 2 months) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Time to resolution of first ulcer (days) 2 months | MD -6.35 [-6.74, -5.96] | 1 study · 40 participants | Ungraded |
Total number of new lesions over 2-month treatment period 2 months | MD -4.20 [-4.84, -3.56] | 1 study · 40 participants | Ungraded |
Days to resolution of pain and epithelialization of aphthae; number of aphthae per month 2 months | Femiano 2003 (high risk of bias) reports days to resolution of pain and days to epithelialization of aphthae at 1 month, and number of aphthae per month after the first and second months; data presented as… | 1 study · 20 participants | Ungraded |
Adverse effects 2 months | Femiano 2003: one significant adverse event (gastritis) for the prednisone group versus none for placebo. Femiano 2010: more drug-related adverse effects for those treated with prednisone than placebo. | 2 studies | Ungraded |
Sulodexide (heparin plus dermatan sulphate chains) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Days to resolution of pain / epithelialization; number of aphthae per month | The trial by Femiano 2003 (high risk of bias) also compared sulodexide with placebo. Data were incompletely presented (ranges/totals only) precluding further analysis. | 1 study · 20 participants | Ungraded |
Adverse effects | Sulodexide was not associated with significant adverse events. | 1 study · 20 participants | Ungraded |
Camel thorn (plant distillate) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Pain intensity and lesion diameter up to 14 days | The authors report lower pain and smaller lesions in the camel thorn group up to 10 days after referral; a statistically significant difference in pain intensity was also reported. | 1 study · 93 participants | Ungraded |
Time to complete resolution of ulcer (days) up to 14 days | A single trial (Pourahmad 2010, unclear risk of bias) randomised 93 participants to camel thorn distillate (n=49) or placebo (n=44). Mean time to complete resolution was 4.02 days (range 3 to 7) for camel thorn… | 1 study · 93 participants | Ungraded |
Adverse effects up to 14 days | No evidence of drug side effects was observed. | 1 study · 93 participants | Ungraded |
Individualised homeopathic medicine (two doses over 24 hours) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Adverse effects 6 days | No participant needed to discontinue treatment due to adverse events. | 1 study · 100 participants | Ungraded |
Mean pain score and mean ulcer size 6 days | A statistically significant difference was reported in mean pain score and mean ulcer size favouring the homeopathic group (P<0.05). Summary data not presented, precluding further analysis. | 1 study · 100 participants | Ungraded |
Complete ulcer healing by end of study (day 6) 6 days | RR 2.00 [1.39, 2.89] | 1 study · 100 participants | Ungraded |
Pain free by end of study (day 6) 6 days | RR 2.00 [1.39, 2.89] | 1 study · 100 participants | Ungraded |
LongoVital (herbal plus vitamin supplement) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Number of ulcer-free days and number of new ulcers 4 months | Forty patients were randomised to receive LongoVital (herbal plus vitamin) or placebo (Kolseth 2005). Data presented as medians with 95% confidence intervals, unsuitable for further analysis. The authors report no… | 1 study · 40 participants | Ungraded |
Adverse effects 4 months | Reported adverse events were minor and evenly distributed between the groups. | 1 study · 40 participants | Ungraded |
LongoVital (herbal component alone) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Mean size of ulcers 4 to 6 months | MD -0.30 [-0.56, 0.04] | 1 study · 50 participants | Ungraded |
General degree of discomfort 4 to 6 months | MD -0.30 [-0.37, 0.97] | 1 study · 50 participants | Ungraded |
Number of days of pain (monthly average) 4 to 6 months | MD -3.80 [-9.39, 1.79] | 1 study · 50 participants | Ungraded |
Number of days of ulcers (monthly average) 4 to 6 months | MD -0.80 [-3.30, 1.70] | 1 study · 50 participants | Ungraded |
Number of ulcer-free days and number of new ulcers 4 months | Kolseth 2005 (high risk of bias): 40 patients randomised to the herbal component of LongoVital alone or placebo; data presented as medians with 95% CIs, unsuitable for further analysis; no statistically significant… | 1 study · 40 participants | Ungraded |
Adverse effects | Reported adverse events were minor and evenly distributed between the groups (Kolseth 2005). 'Very few and mostly harmless side-effects' were observed (Bratel 2005). | 2 studies | Ungraded |
Daily multivitamin vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Average mouth pain during RAS episodes | MD -0.05 [-0.71, 0.61] | 1 study | Ungraded |
Mean number of new lesions | MD -0.41 [-1.85, 1.03] | 1 study | Ungraded |
Duration of episodes | MD -0.33 [-2.06, 1.40] | 1 study | Ungraded |
Bee propolis (one 500 mg capsule per day) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Quality of life 6 months (minimum) | Patients in the propolis group self-reported a significant improvement in their quality of life (P=0.03), based on volunteered statements of self-reported improvement. | 1 study · 19 participants | Ungraded |
Reduction of outbreaks (expected vs observed ulcers) 6 months (minimum) | The authors report a statistically significant difference in the reduction of outbreaks based on the difference between expected and observed number of ulcers (Fisher's exact test, one sided, P=0.04). | 1 study · 19 participants | Ungraded |
Adverse effects 6 months (minimum) | Propolis was associated with low rates of minimal side effects. | 1 study · 19 participants | Ungraded |
Mean number of lesions over treatment period 6 months (minimum) | MD -2.6 [-7.30, 2.10] | 1 study · 19 participants | Ungraded |
Subantimicrobial dose doxycycline (20 mg twice daily for 90 days) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total number of new ulcers over 90 days 90 days | MD -16.40 [-30.44, -2.36] | 1 study · 50 participants | Ungraded |
Adverse effects 90 days | No differences in adverse events were reported. | 1 study · 50 participants | Ungraded |
Mean VAS pain per day 90 days | MD -5.00 [-11.93, 1.93] | 1 study · 50 participants | Ungraded |
Number of ulcers at end of 90-day treatment 90 days | MD -0.5 [-1.10, 0.10] | 1 study · 50 participants | Ungraded |
Number of new lesions per day 90 days | MD -0.19 [-0.35, -0.03] | 1 study · 50 participants | Ungraded |
Tetracycline suspension (250 mg, held in mouth 2 minutes then swallowed, four times daily for 5 days) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Adjusted maximum ulcer size and adjusted maximum pain 5 days per outbreak | A statistically significant difference was shown, in favour of tetracycline, for adjusted maximum ulcer size (P=0.034) and adjusted maximum pain (P=0.017). | 1 study | Ungraded |
Average number of new lesions per week 5 days per outbreak | MD -0.47 [-1.34, 0.40] | 1 study | Ungraded |
Adverse effects 5 days per outbreak | Adverse event rates were comparable between groups. | 1 study | Ungraded |
Vitamin B12 (sublingual, 1000 mcg daily for 6 months) vs Placebo
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Adverse effects 6 months | No adverse events were associated with receiving vitamin B12 or placebo in this study. | 1 study · 58 participants | Ungraded |
'No ulcer' status during last 2 months of treatment 6 months | RR 3.27 [1.23, 8.66] | 1 study · 58 participants | Ungraded |
Pain score 6 months | MD -1.72 [-2.70, -0.74] | 1 study · 58 participants | Ungraded |
Average duration of RAS episode (days) 6 months | MD -2.86 [-5.39, -0.33] | 1 study · 58 participants | Ungraded |
Frequency of outbreaks per month 6 months | MD -8.74 [-16.62, -0.86] | 1 study · 58 participants | Ungraded |
Colchicine (0.5 mg three times per day) vs Clofazimine (100 mg daily for 30 days, then 100 mg every other day)
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Adverse effects 6 months | Clofazimine was associated with an increase in cutaneous adverse effects (Fisher's exact test P=0.015), easily controlled; there was a greater percentage of treatment interruptions in the colchicine group due to… | 1 study · 46 participants | Ungraded |
Complete remission, pain intensity, patient and physician evaluation 6 months | One trial at high risk of bias (de Abreu 2009) compared clofazimine (n=23) with colchicine (n=23). The number with no further aphthous episodes at 6 months was significantly greater in the clofazimine group than the… | 1 study · 46 participants | Ungraded |
Colchicine (0.5 mg per day for 3 months) vs Prednisolone (5 mg per day for 3 months)
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Pain at completion of treatment 3 months | MD -0.16 [-1.18, 0.86] | 1 study · 34 participants | Ungraded |
Number of aphthous ulcers at completion 3 months | MD -0.13 [-0.50, 0.24] | 1 study · 34 participants | Ungraded |
Recurrence during treatment period 3 months | RR 1.30 [0.98, 1.71] | 1 study · 34 participants | Ungraded |
Adverse effects 3 months | Colchicine was associated with statistically significantly more adverse effects than prednisolone (nine participants reporting adverse effects on colchicine versus two on prednisolone). | 1 study · 34 participants | Ungraded |
Prednisone (oral, commencing 25 mg with phased dose reduction over 2 months) vs Montelukast (leukotriene receptor antagonist)
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Time to resolution of first ulcer (days) 2 months | MD -2.40 [-2.76, -2.04] | 1 study · 40 participants | Ungraded |
Adverse effects 2 months | The study reported more drug-related adverse effects for those treated with prednisone than montelukast. | 1 study · 40 participants | Ungraded |
Total number of new lesions over 2-month treatment period 2 months | MD -0.30 [-0.90, 0.30] | 1 study · 40 participants | Ungraded |
Levamisole 50 mg three times per day for days 1 and 2 vs Levamisole 50 mg three times per day for day 1 and placebo for day 2 (lower dose)
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Adverse effects 16 weeks | Two patients in each group reported unwanted effects. | 1 study | Ungraded |
Overall effectiveness (all parameters) 16 weeks | A trial at high risk of bias (Zissis 1983) compared two different dose regimens of levamisole (treatment 2 days per week for 16 weeks; a third group received placebo). There was inconsistency in the presentation of the… | 1 study | Ungraded |
Rofecoxib (oral, 50 mg on first day then 25 to 50 mg per day for 4 days) vs Tinidazole (1 g per day for 3 days)
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total effective rate at 4 days 4 days | RR 1.17 [0.95, 1.43] | 1 study · 60 participants | Ungraded |
Adverse effects 4 days | No adverse effects reported in translation. | 1 study · 60 participants | Ungraded |
Sulodexide (heparin plus dermatan sulphate chains) vs Prednisone (oral)
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Overall effectiveness (days to resolution; number of aphthae per month) | A comparison between sulodexide (n=10) and prednisone (n=10) was made in a trial at high risk of bias (Femiano 2003). Data presented as ranges/totals only with no estimate of variability, precluding further analysis.… | 1 study · 20 participants | Ungraded |
Adverse effects | Sulodexide was without significant adverse events; one significant adverse event (gastritis) was reported for the prednisone group. | 1 study · 20 participants | Ungraded |
LongoVital (herbal plus vitamin component) vs LongoVital (herbal component alone)
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Number of ulcer-free days and number of new ulcers 4 months | A single trial at high risk of bias (Kolseth 2005) randomised participants to the herbal component of LongoVital alone or LongoVital with herbal plus vitamin component. Data presented as medians with 95% CIs,… | 1 study · 40 participants | Ungraded |
Adverse effects 4 months | Reported adverse events were minor and evenly distributed between the groups (Kolseth 2005). | 1 study · 40 participants | Ungraded |
Perilla cooking oil vs Soybean cooking oil
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Average number of days for resolution of ulcers 8 months | MD 0.80 [-1.83, 3.43] | 1 study · 33 participants | Ungraded |
Adverse effects 8 months | No adverse events were reported. | 1 study · 33 participants | Ungraded |
Betamethasone (systemic corticosteroid) vs Placebo or no treatment
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | Table 1 (Systemic agents used in the management of aphthous stomatitis): 'Studies of these corticosteroids were not found or included in the review but are included here for completeness. They are not given orally for… | 0 studies | No studies |
Beclometasone dipropionate (systemic corticosteroid) vs Placebo or no treatment
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | Table 1: 'Studies of these corticosteroids were not found or included in the review but are included here for completeness.' No trial of beclometasone dipropionate for RAS was identified. | 0 studies | No studies |
Hydrocortisone (systemic corticosteroid) vs Placebo or no treatment
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | Table 1: 'Studies of these corticosteroids were not found or included in the review but are included here for completeness.' No trial of hydrocortisone for RAS was identified. | 0 studies | No studies |
Thalidomide (immunomodulator) vs Placebo or no treatment
Population: Participants with a previous or current history of recurrent aphthous stomatitis (RAS), diagnosed on history and clinical examination; excluding those with Behcet's disease, Reiter's syndrome, recurrent erythema multiforme, viral infection, coeliac disease, Crohn's disease, ulcerative colitis, anaemia or haematinic deficiency
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | Authors' conclusions: 'this review did not find trials involving several of other systemic interventions used for RAS, for example thalidomide in the absence of any systemic condition, despite its limitations on… | 0 studies | No studies |