Evidence-based answers from the Family Physicians Inquiries Network Justin Bailey, MD; Claire McCarthy, MD What is the most effective way Family Medicine Residency of Idaho, Boise (Dr. Bailey); David Grant Medical to treat recurrent canker sores? Center, Travis Air Force Base, Calif (Dr. McCarthy) EvidEncE-basEd answEr Rita F. Smith, MLS Wilford Hall Medical Center Library, Lackland amlexanox appears to be most ef- RCTs on differing agents), and chlorhexi- Air Force Base, Tex A fective overall. Amlexanox 5% paste dine mouthwashes may reduce overall ul- reduces ulcer size, pain duration, and cer burden (SOR: B, heterogeneous RCTs). ASSISTANT EDITOR healing time (strength of recommendation The herbal preparation Eupatorium laevig- Peter C. Smith, MD University of Colorado, [SOR]: A, multiple randomized controlled atum alleviates pain and improves healing Rose Family Medicine trials [RCTs]). (SOR: B, single RCT). Residency, Denver Topical steroids may alleviate pain Oral vitamin B12 supplements and and decrease ulcer burden, defined as to- avoiding toothpastes containing sodium tal number of ulcers over a measured time, lauryl sulfate may prevent recurrent ulcers usually 4 to 6 weeks (SOR: B, multiple (SOR: B, small RCTs). The TABLE compares small heterogenous RCTs). Chemical cau- ulcer treatments. tery agents also lessen pain (SOR: A, single Evidence summary 4 RCTs reported significant pain relief. One A systematic review of 4 double-blind RCTs trial found that 11 of 15 patients treated with found that the anti-inflammatory amlexanox 5% beclomethasone spray experienced less pain paste significantly reduced ulcer size compared compared with 0 of 15 patients in the placebo with placebo (−1 vs 0 mm on Day 3 and −3 vs group (P<.05).3 −1 mm on Day 5; P<.01). It also decreased heal- Beclomethasone also decreased the ul- ing time by Day 3 and duration of pain. When cer index (number of ulcers each day over applied during the prodromal stage, amlexanox time) in 2 of 4 RCTS (eg, 13 of 15 patients dramatically reduced the number of patients [drug] vs 0 of 15 patients [placebo]; P<.01).3 who progressed to full ulcers.1 Chemical cautery relieves pain Clobetasol also reduces pain, ulcer size but may not speed healing A double-blind RCT comparing amlexanox An RCT of 97 patients compared physician- 5% with another anti-inflammatory, clobeta- applied silver nitrate with placebo after pa- sol propionate 0.05% paste, showed equal tients in each group received a 2% lidocaine declines in visual analog pain scores (an aver- swab. Silver nitrate treatment was associated age drop from 6 to 2 points out of 10 for each with more pain-free patients at Day 1 but treatment by Day 3 compared with baseline; didn’t decrease time until resolution.4 P<.001). Both treatments produced equiva- Debacterol reduced pain more than pla- lent reductions in ulcer size from baseline by cebo by Day 3 (−45 vs −15 points on a visual Day 5 (P<.001).2 analog scale; P<.001) and resolved symptoms more effectively by Day 6.5 Corticosteroids decrease pain, number of ulcers Antiseptic mouthwashes In a systematic review of 9 small RCTs com- lower ulcer index paring corticosteroids with placebo, 3 out of A systematic review of 5 low-quality RCTs jfpoNline.com Vol 60, No 10 | OCToBER 2011 | ThE journal oF FamIly PRacticE 621 TABLE How canker sore treatments compare Total patients Treatment Route/comparison studied outcomes Benefit cost* amlexanox 5% Topical qid/placebo 1335 Pain-free NNT=5 1 wk of therapy: paste1 by Day 3 (42% vs 22%; $30 P<.05) ulcer resolution NNT=1.6 at prodromal (97% vs 35%; stage P<.01) ulcer healed NNT=7 by Day 3 (47% vs 21%; P<.05) Silver nitrate4 1-time topical 97 Pain reduction NNT=1.7 1 stick: 15 cents application/placebo by Day 1 (70% vs 10%; P<.001) Debacterol5 1-time topical 60 complete ulcer NNT=1.4 $6.95 application/placebo resolution by (100% vs 30%; Day 6 P<.01) corticosteroids Topical qid 116 Pain reduction 3 of 4 clinical trials Varies; (various)2 show benefit triamcinolone: $10.99 chlorhexidine4 mouthwash qid 77 Reduction 2 of 3 trials $3-$5 in total days show benefit with ulcers 6 Vitamin B12 oral daily for 58 No new ulcers NNT=2.3 6-month prophylaxis by 6 mo (74% vs 32%; supply: $10-$20 P<.01) Eupatorium Topical steroid qid 60 Decreased pain NNT=2.3 (93% vs Not commercially laevigatum7 by Day 5 50%; P<.001) available healed by Day 5 NNT=7.6 (40% vs 27%; P<.001) magic oral rinses qid No patients No trials uncertain $5-$10 mouthwash8 studied available (estimated) NNT, number needed to treat. *Pricing from drugstore.com. (small size, incomplete reporting of data, with placebo; P>.05).2 varied outcomes) comparing chlorhexidine One small RCT found that a commercial with placebo reported that in 2 of 3 studies mouthwash (Listerine antiseptic containing that measured the ulcer index, chlorhexidine menthol, thymol, methyl salicylate, and eu- reduced the index more than placebo (eg, calyptol) modestly decreased ulcer duration 0.83 with chlorhexidine vs 1.66 with placebo; (−1.43 days per outbreak for Listerine compared P<.05). Three of 4 studies that evaluated ulcer with −0.54 days for placebo; P<.001) and sever- duration didn’t show a significant decrease ity (−0.53 points on a 10-point pain scale with (5.02 days with chlorhexidine vs 5.78 days mouthwash vs 0 points with placebo; P<.001).6 continued oN PagE 632 622 ThE journal oF FamIly PRacticE | OCToBER 2011 | Vol 60, No 10 continued from PagE 622 Herbal preparation relieves pain, adherent agents such as Rincinol appear to improves healing have minimal benefit.9 In a small double-blind trial, Eupatorium laevig- atum paste improved 5-day cure rates and pain “Magic mouthwashes” relief more than triamcinolone 0.1% paste.7 lack efficacy data Clinicians often prescribe “magic mouth- Vitamin B12, avoiding certain washes” (various combinations of viscous toothpastes, helps prevent recurrence lidocaine, benzocaine, milk of magnesia, A small RCT comparing 1000 mcg of oral vi- kaolin pectate, chlorhexidine, or diphenhy- tamin B12 daily with placebo for prophylaxis dramine), but we found no studies evaluating found that B12 reduced ulcer duration more their effectiveness. than placebo (1.98±3.77 vs 4.84±5.71 days; P<.05), number of ulcers (3.88±7.98 vs 13.39±23; P<.05), and pain (0.64±1.45 vs Recommendations 2.36 ±2.21 points; P<.01) by 5 months of treat- The British National Health Service Clinical ment and increased the percentage of ulcer- Knowledge Summary suggests avoiding ag- free patients by 6 months.8 gravating foods and life stressors, using a soft In 3 of 4 small trials, avoiding toothpaste bristled toothbrush, quitting smoking, and containing sodium lauryl sulfate slightly but using topical corticosteroids, antimicrobial Amlexanox 5% significantly reduced recurrent ulcers.9 Bio- mouthwashes, and topical anesthetics.10 JFP paste reduced ulcer size, pain duration, and References healing time. 1. Bell J. Amlexanox for the treatment of recurrent aphthous ulcers. 7. Paulo Filho W, Ribeiro JE, Pinto DS. Safety and efficacy of Eupa- Clin Drug Investig. 2005;25:555566. torium laevigatum paste as therapy for buccal aphthae: random- ized, double-blind comparison with triamcinolone 0.1% orabase. 2. Rodriguez M, Rubio JA, Sanchez R. Effectiveness of two oral Adv Ther. 2000;17:272-281. pastes for the treatment of recurrent aphthous stomatitis. Oral Dis. 2007;13:490-494. 8. Volkov I, Rudoy I, Freud T, et al. Effectiveness of vitamin B12 in 3. Porter S, Scully C. Aphthous ulcers (recurrent). BMJ Clin Evid. treating recurrent aphthous stomatitis: a randomized, double 2007;12(1303):1-9. blind placebo-controlled trial. J Am Board Fam Med. 2009; 22:9-16. 4. Alidaee MR, Taheri A, Mansoori P, et al. Silver nitrate cautery in aphthous stomatitis: a randomized controlled trial. Br J 9. DynaMed Editorial Team. Aphthous ulcers, treatment and Dermatol. 2005;153:521-525. prevention. Last updated October 27, 2009. Available at: 5. Rhodus NL, Bereuter J. An evaluation of a chemical cautery agent www.ebscohost.com/dynamed. Accessed November 6, and an anti-inflammatory ointment for the treatment of recur- 2009. rent aphthous stomatitis: a pilot study. Quintessence Int. 1998; 10. National Health Service Clinical Knowledge Summaries: 29:769-773. aphthous ulcer—management: how should I manage aph- 6. Meiller TF, Kutcher MJ, Overholser CD, et al. Effect of an antimi- thous ulcers? Available at: www.cks.nhs.uk/aphthous_ulcer/ crobial mouth rinse on recurrent aphthous ulcerations. Oral Surg management/detailed_answers/managing_aphthous_ulcers#. Oral Med Oral Pathol. 1991;72:425-429. Accessed January 28, 2010. 632 ThE journal oF FamIly PRacticE | OCToBER 2011 | Vol 60, No 10.