The main goals are to exclude serious and/or systemic disease, and to provide therapy to achieve pain relief, reduction of ulcer duration, and reduction in frequency of episodes.[44]Tarakji B, Gazal G, Al-Maweri SA, et al. Guideline for the diagnosis and treatment of recurrent aphthous stomatitis for dental practitioners. J Int Oral Health. 2015 May;7(5):74-80.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441245
http://www.ncbi.nlm.nih.gov/pubmed/26028911?tool=bestpractice.com
Initial treatment consists of simple options, including changing the patient's toothpaste to a sodium lauryl sulfate-free formulation, antibacterial mouthwash (e.g., chlorhexidine), and symptom relief (e.g., topical lidocaine). Patients should be instructed to avoid recognized trigger foods, and acidic foods and drinks.[1]Scully C. Clinical practice. Aphthous ulceration. N Engl J Med. 2006 Jul 13;355(2):165-72.
http://www.ncbi.nlm.nih.gov/pubmed/16837680?tool=bestpractice.com
If simple measures alone do not work to reduce the symptoms, topical corticosteroids are still the mainstay of treatment, with adjunctive topical antimicrobials, which may reduce the inflammatory component. However, if recurrent aphthous stomatitis (RAS) fails to respond to topical therapies, systemic therapies may be required.[3]Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc. 2003 Feb;134(2):200-7.
http://www.ncbi.nlm.nih.gov/pubmed/12636124?tool=bestpractice.com
[45]Letsinger JA, McCarty MA, Jorizzo JL. Complex aphthosis: a large case series with evaluation algorithm and therapeutic ladder from topicals to thalidomide. J Am Acad Dermatol. 2005 Mar;52(3 Pt 1):500-8.
http://www.ncbi.nlm.nih.gov/pubmed/15761429?tool=bestpractice.com
For all patients, the possibility of local trauma (e.g., from sharp and/or broken teeth, dentures and orthodontic appliances, and biting during chewing) should be assessed and appropriate dental treatment undertaken.[3]Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc. 2003 Feb;134(2):200-7.
http://www.ncbi.nlm.nih.gov/pubmed/12636124?tool=bestpractice.com
There is some evidence of benefit from vitamin B12, even in the absence of any deficiency; supplementation with oral vitamin B12 (cyanocobalamin) has been shown to be effective in studies, irrespective of serum B12 levels.[46]Volkov I, Rudoy I, Freud T, et al. Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled trial. J Am Board Fam Med. 2009 Jan-Feb;22(1):9-16.
https://www.jabfm.org/content/22/1/9
http://www.ncbi.nlm.nih.gov/pubmed/19124628?tool=bestpractice.com
[47]Gulcan E, Toker S, Hatipoğlu H, et al. Cyanocobalamin may be beneficial in the treatment of recurrent aphthous ulcers even when vitamin B12 levels are normal. Am J Med Sci. 2008 Nov;336(5):379-82.
http://www.ncbi.nlm.nih.gov/pubmed/19011392?tool=bestpractice.com
[48]Liu HL, Chiu S, Chen KH. Effectiveness of vitamin B12 on recurrent aphthous stomatitis in long term care: a systematic review. JBI Database System Rev Implement Rep. 2013 Feb;11(2):281-307.
https://journals.lww.com/jbisrir/Abstract/2013/11020/Effectiveness_of_Vitamin_B12_on_Recurrent_Aphthous.3.aspx
Consider iron supplements if iron deficiency anemia occurs.[37]Lopez-Jornet P, Camacho-Alonso F, Martos N. Hematological study of patients with aphthous stomatitis. Int J Dermatol. 2014 Feb;53(2):159-63.
http://www.ncbi.nlm.nih.gov/pubmed/23879674?tool=bestpractice.com
[49]Sumathi K, Shanthi B, Subha Palaneeswari M, et al. Significance of ferritin in recurrent oral ulceration. J Clin Diagn Res. 2014 Mar;8(3):14-5.
https://www.jcdr.net/article_fulltext.asp?issn=0973-709x&year=2014&volume=8&issue=3&page=14&issn=0973-709x&id=4091
http://www.ncbi.nlm.nih.gov/pubmed/24783067?tool=bestpractice.com
However, it is important to consider the cause of iron deficiency before treating it because this can often be the first sign of malabsorption or occult blood loss. Iron supplementation in adults and children may be necessary to prevent ulcers that are a result of iron deficiency anemia. Initial treatment is daily oral iron replacement therapy.[49]Sumathi K, Shanthi B, Subha Palaneeswari M, et al. Significance of ferritin in recurrent oral ulceration. J Clin Diagn Res. 2014 Mar;8(3):14-5.
https://www.jcdr.net/article_fulltext.asp?issn=0973-709x&year=2014&volume=8&issue=3&page=14&issn=0973-709x&id=4091
http://www.ncbi.nlm.nih.gov/pubmed/24783067?tool=bestpractice.com
Topical therapies
Topical corticosteroids are the mainstay of treatment when simple measures alone do not work to improve the symptoms. A variety of different agents can be used, including a corticosteroid paste (a combination of a potent topical corticosteroid such as triamcinolone and dental paste), hydrocortisone buccal tablets, and betamethasone soluble tablets.[50]Liu C, Zhou Z, Liu G, et al. Efficacy and safety of dexamethasone ointment on recurrent aphthous ulceration. Am J Med. 2012 Mar;125(3):292-301.
http://www.ncbi.nlm.nih.gov/pubmed/22340928?tool=bestpractice.com
However, these specific formulations of hydrocortisone and betamethasone are not available in the US and corticosteroid mouth rinses may need to be specially compounded. More potent topical corticosteroids (such as betamethasone dipropionate, clobetasol, or fluocinonide) may also be used.[3]Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc. 2003 Feb;134(2):200-7.
http://www.ncbi.nlm.nih.gov/pubmed/12636124?tool=bestpractice.com
Treatment duration is case-dependent but there is no evidence of adrenal suppression with low-potency corticosteroids.
Topical therapies for symptom relief may be of benefit. These include topical anesthetics (e.g., lidocaine) and topical anti-inflammatory agents. Adjunctive antimicrobial agents may also be of some value, in part by reducing secondary infection. These may reduce the severity and pain of ulceration. For example, randomized controlled trials have shown that chlorhexidine oral solution may reduce the duration of RAS and increase the number of ulcer-free days.[51]Addy M, Tapper-Jones L, Seal M. Trial of astringent and antibacterial mouthwashes in the management of recurrent aphthous ulceration. Br Dent J. 1974 Jun 4;136(11):452-5.
http://www.ncbi.nlm.nih.gov/pubmed/4531936?tool=bestpractice.com
[52]Addy M, Carpenter R, Roberts WR. Management of recurrent aphthous ulceration: a trial of chlorhexidine gluconate gel. Br Dent J. 1976 Aug 17;141(4):118-20.
http://www.ncbi.nlm.nih.gov/pubmed/786339?tool=bestpractice.com
[53]Addy M. Hibitane in the treatment of aphthous ulceration. J Clin Periodontol. 1977 Dec;4(5):108-16.
http://www.ncbi.nlm.nih.gov/pubmed/350904?tool=bestpractice.com
[54]Hunter L, Addy M. Chlorhexidine gluconate mouthwash in the management of minor aphthous ulceration: a double-blind, placebo controlled cross-over trial. Br Dent J. 1987 Feb 7;162(3):106-10.
http://www.ncbi.nlm.nih.gov/pubmed/3545267?tool=bestpractice.com
Topical tetracyclines used as rinses may also be effective.[55]Graykowski EA, Kingman A. Double-blind trial of tetracycline in recurrent aphthous ulceration. J Oral Pathol. 1978;7(6):376-82.
http://www.ncbi.nlm.nih.gov/pubmed/105096?tool=bestpractice.com
[56]Häyrinen-Immonen R, Sorsa T, Pettila J, et al. Effect of tetracyclines on collagenase activity in patients with recurrent aphthous ulcers. J Oral Pathol Med. 1994 Jul;23(6):269-72.
http://www.ncbi.nlm.nih.gov/pubmed/7932246?tool=bestpractice.com
However, they must be compounded, and they should be avoided in children less than 8 years of age as they may cause tooth discoloration.[57]Vennila V, Madhu V, Rajesh R, et al. Tetracycline-induced discoloration of deciduous teeth: case series. J Int Oral Health. 2014 Jun;6(3):115-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109251
http://www.ncbi.nlm.nih.gov/pubmed/25083046?tool=bestpractice.com
Systemic therapies
If RAS fails to respond to topical therapies, systemic therapies may be required. However, studies are lacking to assess their efficacy (or their adverse effects).[58]Brocklehurst P, Tickle M, Glenny AM, et al. Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database Syst Rev. 2012 Sep 12;(9):CD005411.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005411.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/22972085?tool=bestpractice.com
For patients with severe RAS, a short course of systemic corticosteroids, systemic immunomodulators, or anti-inflammatory agents, such as colchicine, azathioprine, or thalidomide, may be necessary.[1]Scully C. Clinical practice. Aphthous ulceration. N Engl J Med. 2006 Jul 13;355(2):165-72.
http://www.ncbi.nlm.nih.gov/pubmed/16837680?tool=bestpractice.com
[3]Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc. 2003 Feb;134(2):200-7.
http://www.ncbi.nlm.nih.gov/pubmed/12636124?tool=bestpractice.com
[45]Letsinger JA, McCarty MA, Jorizzo JL. Complex aphthosis: a large case series with evaluation algorithm and therapeutic ladder from topicals to thalidomide. J Am Acad Dermatol. 2005 Mar;52(3 Pt 1):500-8.
http://www.ncbi.nlm.nih.gov/pubmed/15761429?tool=bestpractice.com
[59]Hello M, Barbarot S, Bastuji-Garin S, et al. Use of thalidomide for severe recurrent aphthous stomatitis: a multicenter cohort analysis. Medicine (Baltimore). 2010 May;89(3):176-82.
https://journals.lww.com/md-journal/Fulltext/2010/05000/Use_of_Thalidomide_for_Severe_Recurrent_Aphthous.5.aspx
http://www.ncbi.nlm.nih.gov/pubmed/20453604?tool=bestpractice.com
[60]Toader MP, Esanu IM, Taranu T, et al. Colchicine in the treatment of refractory aphthous ulcerations: review of the literature and two case reports. Exp Ther Med. 2021 Mar;21(3):281.
https://www.spandidos-publications.com/10.3892/etm.2021.9712
http://www.ncbi.nlm.nih.gov/pubmed/33603888?tool=bestpractice.com
Oral prednisone as a 1-week course tapered over a second week is one suggested regimen.[3]Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc. 2003 Feb;134(2):200-7.
http://www.ncbi.nlm.nih.gov/pubmed/12636124?tool=bestpractice.com
The first-line systemic immunomodulator used in RAS and the mucocutaneous manifestations of Behcet syndrome is colchicine.[61]Taylor J, Glenny AM, Walsh T, et al. Interventions for managing oral ulcers in Behçet's disease. Cochrane Database Syst Rev. 2014 Sep 25;(9):CD011018.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011018.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/25254615?tool=bestpractice.com
There is weak evidence to support the use of azathioprine.
Thalidomide is rarely used; great caution is required for its use, and specialist referral and prescription is recommended.[1]Scully C. Clinical practice. Aphthous ulceration. N Engl J Med. 2006 Jul 13;355(2):165-72.
http://www.ncbi.nlm.nih.gov/pubmed/16837680?tool=bestpractice.com
[3]Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc. 2003 Feb;134(2):200-7.
http://www.ncbi.nlm.nih.gov/pubmed/12636124?tool=bestpractice.com
However, the use of thalidomide in RAS is supported by data in both RAS and in patients with aphthous-like ulceration in HIV infection.[62]Revuz J, Guillaume JC, Janier M, et al. Crossover study of thalidomide vs placebo in severe recurrent aphthous stomatitis. Arch Dermatol. 1990 Jul;126(7):923-7.
http://www.ncbi.nlm.nih.gov/pubmed/2193629?tool=bestpractice.com
[63]Nicolau DP, West TE. Thalidomide: treatment of severe recurrent aphthous stomatitis in patients with AIDS. DICP. 1990 Nov;24(11):1054-6.
http://www.ncbi.nlm.nih.gov/pubmed/2275226?tool=bestpractice.com
In these patient groups, open and double-blind studies have shown that thalidomide is an effective agent available for the management of severe, refractory RAS.[6]Jurge S, Kuffer R, Scully C, et al. Mucosal disease series. Number VI. Recurrent aphthous stomatitis. Oral Dis. 2006 Jan;12(1):1-21.
http://www.ncbi.nlm.nih.gov/pubmed/16390463?tool=bestpractice.com
[59]Hello M, Barbarot S, Bastuji-Garin S, et al. Use of thalidomide for severe recurrent aphthous stomatitis: a multicenter cohort analysis. Medicine (Baltimore). 2010 May;89(3):176-82.
https://journals.lww.com/md-journal/Fulltext/2010/05000/Use_of_Thalidomide_for_Severe_Recurrent_Aphthous.5.aspx
http://www.ncbi.nlm.nih.gov/pubmed/20453604?tool=bestpractice.com
Thalidomide would never be commenced in primary care - there is tight legislation around prescribing of it. For example, in the UK its use is approved only on case-by-case discussion with various health boards/trusts.
Results with other immunomodulatory agents used to treat severe or refractory RAS, such as levamisole or pentoxifylline, have shown either poor clinical response or a significant incidence of treatment-related adverse effects.[6]Jurge S, Kuffer R, Scully C, et al. Mucosal disease series. Number VI. Recurrent aphthous stomatitis. Oral Dis. 2006 Jan;12(1):1-21.
http://www.ncbi.nlm.nih.gov/pubmed/16390463?tool=bestpractice.com
Management of children under the age of 12 years
As with adults, the first-line treatment in children is the introduction of simple measures (i.e., change of toothpaste, avoidance of triggers, or assessment for trauma). In addition to this, there are a number of over-the-counter anti-inflammatory treatments available for the relief of symptoms. A suitable formulation that is licensed for use in children should be selected.[64]Crighton AJ. Oral medicine in children. Br Dent J. 2017 Dec;223(9):706-12.
http://www.ncbi.nlm.nih.gov/pubmed/29097798?tool=bestpractice.com
There are a limited number of topical corticosteroids that are licensed for oral use in children. If topical corticosteroids are needed, they can be used off-label, but only in children who can follow instructions with regards to spitting out the medication. This means that they usually cannot be used in children under 6 years of age. These treatments should only be started under specialist care after the child has been assessed and other causes of oral ulcers have been excluded. Oral asthma inhalers have been used off-label as a topical application for this indication.[64]Crighton AJ. Oral medicine in children. Br Dent J. 2017 Dec;223(9):706-12.
http://www.ncbi.nlm.nih.gov/pubmed/29097798?tool=bestpractice.com
Systemic treatments for RAS are rarely used in children under the age of 12 years, and are only commenced under specialist care.