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Medication

Medication Summary

Therapy for this condition is aimed at palliating symptoms, shortening healing time, and reducing the number of episodes (prophylaxis)

Class Summary

Topical steroids are the first-line therapy. They are used to suppress immunologic- and inflammatory-mediated attacks resulting in ulceration. They are used to treat idiopathic and acquired autoimmune disorders.

Prednisone (Deltasone)

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Prednisone is a systemic corticosteroid for cases of severe aphthae; it is inactive and must be metabolized to the active metabolite prednisolone. Close follow-up care and monitoring are required to monitor for candidiasis and other secondary infections and adverse reactions. Prednisone is available in a 5 mg/5 mL solution.

Dexamethasone (Decadron, Dexasone)

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Dexamethasone is the drug of choice for recurrent aphthous ulcers and various inflammatory diseases. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reducing capillary permeability. An elixir of 0.5 mg/5 mL (high potency, substituted, fluorinated) may be used.

Triamcinolone topical (Aristocort)

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Topical triamcinolone is for inflammatory dermatoses responsive to steroids; it decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability. It is advisable when local disease is accessible to the patient. Use 0.1% gel.

Fluocinonide (Fluonex, Lidex)

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Fluocinonide is a high-potency topical corticosteroid that inhibits cell proliferation; it is immunosuppressive and anti-inflammatory. It is advisable when local disease is accessible to the patient. Use 0.05% gel.

Clobetasol propionate (Temovate)

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Clobetasol propionate is a class I superpotent topical steroid that suppresses mitosis and increases the synthesis of proteins that decrease inflammation and cause vasoconstriction. Use 0.05% gel.

Class Summary

These agents locally relieve pain of recurrent aphthous ulcers.

Lidocaine anesthetic (Xylocaine)

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Lidocaine anesthetic is an amide-type local anesthetic. It decreases permeability to sodium ions in neuronal membranes and inhibits depolarization, blocking the transmission of nerve impulses. Use 2% viscous solution.

Benzocaine (Americaine, Anbesol)

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Benzocaine is a para-aminobenzoic acid (PABA) derivative, ester-type local anesthetic that is minimally absorbed. It inhibits neuronal membrane depolarization, blocking nerve impulses.

Class Summary

These agents protect and bolster natural mucosal barrier.

Sucralfate (Carafate)

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Sucralfate is a sulfate-aluminum complex, which coats ulcer surfaces, forming a physical barrier. In this way, it protects the ulcer surface from irritation. Some studies have reported improvement in symptomology and duration of ulcers, while other studies have found that sucralfate is not effective in the treatment of recurrent aphthous ulcers.

Bismuth subsalicylate (Kaopectate, Kaopectate Extra Strength, Maalox Total Relief)

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Bismuth subsalicylate has been used to reduce pain from oral ulcers by protecting raw mucosa. It may also accelerate reepithelialization, although its mechanism of action is largely unknown. Some clinicians advise patients to include bismuth subsalicylate in mouthwash recipes along with other ingredients, such as liquid diphenhydramine.

Bioadherent oral (Gelclair)

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This oral bioadherent adheres to the mucosal surface of mouth and forms a protective coating that shields exposed and overstimulated nerve endings. Ingredients include water, maltodextrin, propylene glycol, polyvinylpyrrolidone (PVP), sodium hyaluronate, potassium sorbate, sodium benzoate, hydroxy ethylcellulose, polyethylene glycol (PEG)–40, hydrogenated castor oil, disodium edetate, benzalkonium chloride, flavoring, saccharin sodium, and glycyrrhetinic acid.

Class Summary

These agents are indicated for topical application to hold closed easily approximated skin edges of wounds. They may be helpful in aphthous ulcers.

2-Octyl cyanoacrylate

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Over-the-counter formulations of cyanoacrylate (essentially Super Glue) form a waterproof occlusive barrier over ulcers.

Class Summary

These agents blunt immunologically mediated destruction leading to mucosal ulceration. Systemic immunosuppressants are indicated for severe and recalcitrant cases of aphthous stomatitis.

Colchicine (Colcrys, Mitigare)

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Colchicine is an anti-inflammatory agent that inhibits microtubule polymerization. Studies have shown that colchicine is effective in reducing pain from aphthous ulcers, as well as decreasing the frequency of ulcer formation. Adverse effects include gastrointestinal upset, such as diarrhea, and neutropenia. Use 0.6 mg thrice daily.

Montelukast (Singulair)

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Montelukast sodium is an immunosuppressive agent that acts via leukotriene receptor antagonism. It blocks leukotrienes, downstream metabolic products of arachidonic acid, from binding to receptors located on neutrophils and macrophages and thereby blocks their activation, chemotaxis, and degranulation. It is reported to have equal efficacy as prednisone in the treatment of recurrent aphthous stomatitis, with fewer adverse effects.

Clofazimine (Lamprene)

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Clofazimine is an immunosuppressive and anti-inflammatory agent with antibacterial properties that has shown efficacy in reducing the frequency of ulcers and symptoms in patients who continue to experience ulcers. Although its precise mechanism of action is unclear, it has been shown to accumulate in phagocytes, increase lysosomal enzyme production, and inhibit neutrophil migration.

Azathioprine (Imuran)

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Azathioprine is largely converted to the active metabolites 6-mercaptopurine and 6-thioinosinic acid; it antagonizes purine metabolism and inhibits the synthesis of DNA, RNA, and proteins. It may decrease the proliferation of immune cells, lowering autoimmune activity. It may decrease the proliferation of immune cells, lowering autoimmune activity.

Thalidomide (Thalomid)

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Thalidomide was the first FDA-approved therapy for recurrent aphthous ulcer. It is an immunomodulatory agent that may suppress excessive production of tumor necrosis factor (TNF)‒alpha and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration. Close follow-up, including nerve conduction studies and electromyography every 6 months, is recommended in patients using thalidomide.

Class Summary

These agents are inhibitors of the formation and/or release of inflammatory mediators.

Cyclosporine (Gengraf, Neoral, Sandimmune)

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Cyclosporine is a potent immunosuppressant that binds cyclophilin on lymphocytes to inhibit calcineurin and thereby prevent the production of interleukin 2. In this way, it dampens the immune response and particularly the action of T cells. Cyclosporine has been tested as a systemic agent and a topical paste with mixed reports of efficacy, but it is now most often used effectively as an oral rinse.

Amlexanox (Aphthasol)

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Amlexanox is an adhesive oral paste whose mechanism of action is unknown. It appears to accelerate the healing of aphthous ulcers. Amlexanox appears as a beige-colored paste. It is a potent inhibitor of the formation and release of inflammatory mediators (histamine and leukotrienes) from mast cells, neutrophils, and mononuclear cells in in vitro studies. Amlexanox is FDA approved for the treatment of recurrent aphthous stomatitis.

Class Summary

Retinoids are a class of drugs closely related to vitamin A. They are used to regulate epithelial cell differentiation and have also been shown to have immunomodulatory and anti-inflammatory effects.

Isotretinoin (Absorica, Amnesteem, Claravis)

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Researchers have found systemic isotretinoin to be an effective therapy for recurrent aphthous ulcers. Additionally, isotretinoin (0.1% gel) has been used in the treatment of oral lichen planus with reported efficacy, and it may also be useful in the treatment of recurrent aphthous ulcers.

Tretinoin topical (Atralin, Avita, Refissa)

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Tretinoin in an adhesive base (0.1%) has been used in the treatment of oral lichen planus with reported efficacy, and it may also be useful in the treatment of recurrent aphthous ulcers.

Retinoic acid

Retinoic acid in an oral base (0.05%) has been used in the treatment of oral lichen planus with reported efficacy, and it may also be useful in the treatment of recurrent aphthous ulcers.

Class Summary

These agents treat inflammation of the oral mucosa caused by bacterial or fungal actions.

Chlorhexidine oral (Peridex, PerioChip, PerioGard)

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Chlorhexidine gluconate is an adjunct treatment for gingival disease; it binds to negatively charged bacterial cell walls and extramicrobial complex, causing bacteriostatic and bactericidal effects. Chlorhexidine gluconate is an effective, safe, and reliable topical wash or oral mouthwash antiseptic.

Tetracycline

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Tetracycline treats gram-positive and gram-negative organisms and mycoplasmal, chlamydial, and rickettsial infections. It inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits. Use the oral suspension. It may have an anti-inflammatory in addition to antibacterial mechanism of action.

Class Summary

Hemorheologic agents may be beneficial in patients who do not respond to other therapies; they are not first-line treatment.

Pentoxifylline (Pentoxil, Trental)

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Pentoxifylline inhibits the production of TNF-alpha and reduces the migration of neutrophils. Its specific action in aphthous stomatitis is unclear, but it has been shown to reduce the severity and frequency of episodes.

Class Summary

As xerostomia may exacerbate or even contribute to the development of aphthous ulcers, treatment with agents known to increase saliva production may be of benefit to some patients.

Cevimeline (Evoxac)

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Cevimeline is a parasympathomimetic agent that acts via muscarinic acetylcholine receptors to induce salivation. Use cevimeline at 30 mg orally thrice daily.

Pilocarpine (Pilocarpine PO, Salagen)

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Pilocarpine is a parasympathomimetic agent that acts via muscarinic acetylcholine receptors to induce salivation. Use 5 mg, 1-2 tablets, 3-4 times per day, not to exceed 30 g/day.

Class Summary

These agents may be used as adjunct topical treatments to shorten healing time and reduce pain.

Quercetin

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Quercetin is a plant flavonoid that has been shown to stimulate gastric epithelial cell proliferation and may be used as an adjunct topical agent to shorten healing time and reduce pain.

Questions

Crivelli MR, Aguas S, Adler I, Quarracino C, Bazerque P. Influence of socioeconomic status on oral mucosa lesion prevalence in schoolchildren. Community Dent Oral Epidemiol. 1988 Feb. 16(1):58-60. [QxMD MEDLINE Link].
Shulman JD. An exploration of point, annual, and lifetime prevalence in characterizing recurrent aphthous stomatitis in USA children and youths. J Oral Pathol Med. 2004 Oct. 33 (9):558-66. [QxMD MEDLINE Link].
Axéll T, Henricsson V. The occurrence of recurrent aphthous ulcers in an adult Swedish population. Acta Odontol Scand. 1985 May. 43(2):121-5. [QxMD MEDLINE Link].
Embil JA, Stephens RG, Manuel FR. Prevalence of recurrent herpes labialis and aphthous ulcers among young adults on six continents. Can Med Assoc J. 1975 Oct 4. 113 (7):627-30. [QxMD MEDLINE Link].
Axéll T. A prevalence study of oral mucosal lesions in an adult Swedish population. Odontol Revy Suppl. 1976. 36:1-103. [QxMD MEDLINE Link].
Robledo-Sierra J, Mattsson U, Svedensten T, Jontell M. The morbidity of oral mucosal lesions in an adult Swedish population. Med Oral Patol Oral Cir Bucal. 2013 Sep 1. 18 (5):e766-72. [QxMD MEDLINE Link].
Cebeci AR, Gülşahi A, Kamburoglu K, Orhan BK, Oztaş B. Prevalence and distribution of oral mucosal lesions in an adult Turkish population. Med Oral Patol Oral Cir Bucal. 2009 Jun 1. 14 (6):E272-7. [QxMD MEDLINE Link].
Mumcu G, Cimilli H, Sur H, Hayran O, Atalay T. Prevalence and distribution of oral lesions: a cross-sectional study in Turkey. Oral Dis. 2005 Mar. 11 (2):81-7. [QxMD MEDLINE Link].
Safadi RA. Prevalence of recurrent aphthous ulceration in Jordanian dental patients. BMC Oral Health. 2009 Nov 22. 9:31. [QxMD MEDLINE Link].
Davatchi F, Tehrani-Banihashemi A, Jamshidi AR, et al. The prevalence of oral aphthosis in a normal population in Iran: a WHO-ILAR COPCORD study. Arch Iran Med. 2008 Mar. 11 (2):207-9. [QxMD MEDLINE Link].
Abdullah MJ. Prevalence of recurrent aphthous ulceration experience in patients attending Piramird dental speciality in Sulaimani City. J Clin Exp Dent. 2013 Apr 1. 5 (2):e89-94. [QxMD MEDLINE Link].
Bhatnagar P, Rai S, Bhatnagar G, Kaur M, Goel S, Prabhat M. Prevalence study of oral mucosal lesions, mucosal variants, and treatment required for patients reporting to a dental school in North India: In accordance with WHO guidelines. J Family Community Med. 2013 Jan. 20 (1):41-8. [QxMD MEDLINE Link].
Thangadurai M, Andamuthu Y, Srinivasan A, Abikshyeet P, Kumar SJS, Vilvanathan V. Prevalence and family history of recurrent aphthous stomatitis among the students of a dental institution in south India. J Indian Acad Dental Specialist Researchers. 2014. 1(2):53-55.
Field EA, Brookes V, Tyldesley WR. Recurrent aphthous ulceration in children--a review. Int J Paediatr Dent. 1992 Apr. 2 (1):1-10. [QxMD MEDLINE Link].
Lopez-Jornet P, Camacho-Alonso F, Martos N. Hematological study of patients with aphthous stomatitis. Int J Dermatol. 2014 Feb. 53 (2):159-63. [QxMD MEDLINE Link].
Sun A, Chen HM, Cheng SJ, Wang YP, Chang JY, Wu YC, et al. Significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high homocysteine level with recurrent aphthous stomatitis. J Oral Pathol Med. 2015 Apr. 44 (4):300-5. [QxMD MEDLINE Link].
Gallo Cde B, Mimura MA, Sugaya NN. Psychological stress and recurrent aphthous stomatitis. Clinics (Sao Paulo). 2009. 64(7):645-8. [QxMD MEDLINE Link]. [Full Text].
Huling LB, Baccaglini L, Choquette L, Feinn RS, Lalla RV. Effect of stressful life events on the onset and duration of recurrent aphthous stomatitis. J Oral Pathol Med. 2012 Feb. 41(2):149-52. [QxMD MEDLINE Link]. [Full Text].
MacPhail LA, Greenspan D, Feigal DW, Lennette ET, Greenspan JS. Recurrent aphthous ulcers in association with HIV infection. Description of ulcer types and analysis of T-lymphocyte subsets. Oral Surg Oral Med Oral Pathol. 1991 Jun. 71(6):678-83. [QxMD MEDLINE Link].
Burton-Kee JE, Mowbray JF, Lehner T. Different cross-reacting circulating immune complexes in Behçet's syndrome and recurrent oral ulcers. J Lab Clin Med. 1981 Apr. 97(4):559-67. [QxMD MEDLINE Link].
Eglin RP, Lehner T, Subak-Sharpe JH. Detection of RNA complementary to herpes-simplex virus in mononuclear cells from patients with Behçet's syndrome and recurrent oral ulcers. Lancet. 1982 Dec 18. 2(8312):1356-61. [QxMD MEDLINE Link].
Jorizzo JL. Behcet's disease. Freedberg IM, Eisen AZ, Wolff K, et al, eds. Dermatology in General Medicine. New York: McGraw-Hill Professional; 1999. Vol 2: 2161-5.
Sakane T, Takeno M, Suzuki N, Inaba G. Behçet's disease. N Engl J Med. 1999 Oct 21. 341(17):1284-91. [QxMD MEDLINE Link].
Studd M, McCance DJ, Lehner T. Detection of HSV-1 DNA in patients with Behçet's syndrome and in patients with recurrent oral ulcers by the polymerase chain reaction. J Med Microbiol. 1991 Jan. 34(1):39-43. [QxMD MEDLINE Link].
Adisen E, Aral A, Aybay C, Gürer MA. Salivary epidermal growth factor levels in Behçet's disease and recurrent aphthous stomatitis. Dermatology. 2008. 217(3):235-40. [QxMD MEDLINE Link].
Hazzaa HH, Rashwan WA, Attia EA. IL-18 gene polymorphisms in aphthous stomatitis vs. Behçet's disease in a cohort of Egyptian patients. J Oral Pathol Med. 2014 Nov. 43 (10):746-53. [QxMD MEDLINE Link].
Ferguson MM, Wray D, Carmichael HA, Russell RI, Lee FD. Coeliac disease associated with recurrent aphthae. Gut. 1980 Mar. 21(3):223-6. [QxMD MEDLINE Link].
Ferguson R, Basu MK, Asquith P, Cooke WT. Jejunal mucosal abnormalities in patients with recurrent aphthous ulceration. Br Med J. 1976 Jan 3. 1(6000):11-13. [QxMD MEDLINE Link].
Wray D. Gluten-sensitive recurrent aphthous stomatitis. Dig Dis Sci. 1981 Aug. 26(8):737-40. [QxMD MEDLINE Link].
Yasar S, Yasar B, Abut E, Asiran Serdar Z. Clinical importance of celiac disease in patients with recurrent aphthous stomatitis. Turk J Gastroenterol. 2012 Feb. 23(1):14-8. [QxMD MEDLINE Link].
de Carvalho FK, de Queiroz AM, Bezerra da Silva RA, Sawamura R, Bachmann L, Bezerra da Silva LA, et al. Oral aspects in celiac disease children: clinical and dental enamel chemical evaluation. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015 Jun. 119 (6):636-43. [QxMD MEDLINE Link].
Zunt S. Severe/frequent recurrent aphthous ulcers and salivary flow rates. Oral Surg, Oral Med, Oral Pathol and Oral Rad. 2004. 98(2):
Miller MF, Garfunkel AA, Ram C, Ship II. Inheritance patterns in recurrent aphthous ulcers: twin and pedigree data. Oral Surg Oral Med Oral Pathol. 1977 Jun. 43(6):886-91. [QxMD MEDLINE Link].
Slebioda Z, Szponar E, Kowalska A. Recurrent aphthous stomatitis: genetic aspects of etiology. Postepy Dermatol Alergol. 2013 Apr. 30 (2):96-102. [QxMD MEDLINE Link].
Bidoki AZ, Harsini S, Sadr M, Soltani S, Mohammadzadeh M, Najafi S, et al. NLRP3 gene polymorphisms in Iranian patients with recurrent aphthous stomatitis. J Oral Pathol Med. 2015 May 28. [QxMD MEDLINE Link].
Najafi S, Yousefi H, Mohammadzadeh M, Bidoki AZ, Firouze Moqadam I, Farhadi E, et al. Association study of interleukin-1 family and interleukin-6 gene single nucleotide polymorphisms in recurrent aphthous stomatitis. Int J Immunogenet. 2015 Dec. 42 (6):428-31. [QxMD MEDLINE Link].
Wilhelmsen NS, Weber R, Monteiro F, Kalil J, Miziara ID. Correlation between histocompatibility antigens and recurrent aphthous stomatitis in the Brazilian population. Braz J Otorhinolaryngol. 2009 May-Jun. 75(3):426-31. [QxMD MEDLINE Link].
Kozlak ST, Walsh SJ, Lalla RV. Reduced dietary intake of vitamin B12 and folate in patients with recurrent aphthous stomatitis. J Oral Pathol Med. 2010 Feb 7. [QxMD MEDLINE Link].
Carrozzo M. Vitamin B12 for the treatment of recurrent aphthous stomatitis. Evid Based Dent. 2009. 10(4):114-5. [QxMD MEDLINE Link].
Baccaglini L, Lalla RV, Bruce AJ, Sartori-Valinotti JC, Latortue MC, Carrozzo M, et al. Urban legends: recurrent aphthous stomatitis. Oral Dis. 2011 Nov. 17(8):755-70. [QxMD MEDLINE Link]. [Full Text].
Yasui K, Kurata T, Yashiro M, Tsuge M, Ohtsuki S, Morishima T. The effect of ascorbate on minor recurrent aphthous stomatitis. Acta Paediatr. 2009 Dec 10. [QxMD MEDLINE Link].
Khabbazi A, Ghorbanihaghjo A, Fanood F, Kolahi S, Hajialiloo M, Rashtchizadeh N. A comparative study of vitamin D serum levels in patients with recurrent aphthous stomatitis. Egyptian Rheumatol. 2015. 37(3):133-37.
Sun A, Chu CT, Wu YC, Yuan JH. Mechanisms of depressed natural killer cell activity in recurrent aphthous ulcers. Clin Immunol Immunopathol. 1991 Jul. 60(1):83-92. [QxMD MEDLINE Link].
Lewkowicz N, Kur B, Kurnatowska A, Tchorzewski H, Lewkowicz P. Expression of Th1/Th2/Th3/Th17-related genes in recurrent aphthous ulcers. Arch Immunol Ther Exp (Warsz). 2011 Oct. 59(5):399-406. [QxMD MEDLINE Link].
Taylor LJ, Bagg J, Walker DM, Peters TJ. Increased production of tumour necrosis factor by peripheral blood leukocytes in patients with recurrent oral aphthous ulceration. J Oral Pathol Med. 1992 Jan. 21(1):21-5. [QxMD MEDLINE Link].
Hasan A, Childerstone A, Pervin K, et al. Recognition of a unique peptide epitope of the mycobacterial and human heat shock protein 65-60 antigen by T cells of patients with recurrent oral ulcers. Clin Exp Immunol. 1995 Mar. 99(3):392-7. [QxMD MEDLINE Link].
Miyamoto NT Jr, Borra RC, Abreu M, Weckx LL, Franco M. Immune-expression of HSP27 and IL-10 in recurrent aphthous ulceration. J Oral Pathol Med. 2008 Sep. 37(8):462-7. [QxMD MEDLINE Link].
Albanidou-Farmaki E, Poulopoulos AK, Epivatianos A, Farmakis K, Karamouzis M, Antoniades D. Increased anxiety level and high salivary and serum cortisol concentrations in patients with recurrent aphthous stomatitis. Tohoku J Exp Med. 2008 Apr. 214(4):291-6. [QxMD MEDLINE Link].
Borra RC, de Mesquita Barros F, de Andrade Lotufo M, Villanova FE, Andrade PM. Toll-like receptor activity in recurrent aphthous ulceration. J Oral Pathol Med. 2009 Mar. 38(3):289-98. [QxMD MEDLINE Link].
Arikan S, Durusoy C, Akalin N, Haberal A, Seckin D. Oxidant/antioxidant status in recurrent aphthous stomatitis. Oral Dis. 2009 Oct. 15(7):512-5. [QxMD MEDLINE Link].
Bagan J, Saez G, Tormos C, Gavalda C, Sanchis JM, Bagan L, et al. Oxidative stress and recurrent aphthous stomatitis. Clin Oral Investig. 2014 Nov. 18 (8):1919-23. [QxMD MEDLINE Link].
Ozdemir IY, Calka O, Karadag AS, Akdeniz N, Ozturk M. Thyroid autoimmunity associated with recurrent aphthous stomatitis. J Eur Acad Dermatol Venereol. 2012 Feb. 26(2):226-30. [QxMD MEDLINE Link].
Ghodratnama F, Wray D, Bagg J. Detection of serum antibodies against cytomegalovirus, varicella zoster virus and human herpesvirus 6 in patients with recurrent aphthous stomatitis. J Oral Pathol Med. 1999 Jan. 28(1):12-5. [QxMD MEDLINE Link].
Pedersen A, Hornsleth A. Recurrent aphthous ulceration: a possible clinical manifestation of reactivation of varicella zoster or cytomegalovirus infection. J Oral Pathol Med. 1993 Feb. 22(2):64-8. [QxMD MEDLINE Link].
Li L, Gu H, Zhang G. Association between recurrent aphthous stomatitis and Helicobacter pylori infection: a meta-analysis. Clin Oral Investig. 2014 Jul. 18 (6):1553-60. [QxMD MEDLINE Link].
Albanidou-Farmaki E, Giannoulis L, Markopoulos A, et al. Outcome following treatment for Helicobacter pylori in patients with recurrent aphthous stomatitis. Oral Dis. 2005 Jan. 11(1):22-6. [QxMD MEDLINE Link].
Birek C, Grandhi R, McNeill K, Singer D, Ficarra G, Bowden G. Detection of Helicobacter pylori in oral aphthous ulcers. J Oral Pathol Med. 1999 May. 28(5):197-203. [QxMD MEDLINE Link].
Elsheikh MN, Mahfouz ME. Prevalence of Helicobacter pylori DNA in recurrent aphthous ulcerations in mucosa-associated lymphoid tissues of the pharynx. Arch Otolaryngol Head Neck Surg. 2005 Sep. 131(9):804-8. [QxMD MEDLINE Link].
Mansour-Ghanaei F, Asmar M, Bagherzadeh AH, Ekbataninezhad S. Helicobacter pylori infection in oral lesions of patients with recurrent aphthous stomatitis. Med Sci Monit. 2005 Dec. 11(12):CR576-9. [QxMD MEDLINE Link].
Porter SR, Barker GR, Scully C, Macfarlane G, Bain L. Serum IgG antibodies to Helicobacter pylori in patients with recurrent aphthous stomatitis and other oral disorders. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997 Mar. 83(3):325-8. [QxMD MEDLINE Link].
Hijazi K, Lowe T, Meharg C, Berry SH, Foley J, Hold GL. Mucosal microbiome in patients with recurrent aphthous stomatitis. J Dent Res. 2015 Mar. 94 (3 Suppl):87S-94S. [QxMD MEDLINE Link].
Hay KD, Reade PC. The use of an elimination diet in the treatment of recurrent aphthous ulceration of the oral cavity. Oral Surg Oral Med Oral Pathol. 1984 May. 57 (5):504-7. [QxMD MEDLINE Link].
Shim YJ, Choi JH, Ahn HJ, Kwon JS. Effect of sodium lauryl sulfate on recurrent aphthous stomatitis: a randomized controlled clinical trial. Oral Dis. 2012 Oct. 18 (7):655-60. [QxMD MEDLINE Link].
Herlofson BB, Barkvoll P. Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study. Acta Odontol Scand. 1994 Oct. 52 (5):257-9. [QxMD MEDLINE Link].
Hasan AA, Ciancio S. Association between ingestion of nonsteroidal anti-inflammatory drugs and the emergence of aphthous-like ulcers. J Int Acad Periodontol. 2009 Jan. 11(1):155-9. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Samaranayake LPK, Cheung L. Samaranayake YH. Candidiasis and other fungal diseases of the mouth. Dermatol Ther. 2001. 15:251-69.
Abahussein O. Ulceration in Rheumatic Disease. Matucci-Cerinic M, Furst D, Fiorentino E, eds. Skin Manifestations in Rheumatic Disease. 1st ed. New York, NY: Springer-Verlag; 2014. 63-70.
Daley TD, Armstrong JE. Oral manifestations of gastrointestinal diseases. Can J Gastroenterol. 2007 Apr. 21 (4):241-4. [QxMD MEDLINE Link].
Cohen PR. Sweet's syndrome--a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007 Jul 26. 2:34. [QxMD MEDLINE Link].
Boxer L, Dale DC. Neutropenia: causes and consequences. Semin Hematol. 2002 Apr. 39 (2):75-81. [QxMD MEDLINE Link].
Padeh S, Stoffman N, Berkun Y. Periodic fever accompanied by aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA syndrome) in adults. Isr Med Assoc J. 2008 May. 10(5):358-60. [QxMD MEDLINE Link].
Cantarini L, Vitale A, Bartolomei B, Galeazzi M, Rigante D. Diagnosis of PFAPA syndrome applied to a cohort of 17 adults with unexplained recurrent fevers. Clin Exp Rheumatol. 2012 Mar-Apr. 30(2):269-71. [QxMD MEDLINE Link].
Imai H, Motegi M, Mizuki N, Ohtani H, Komatsuda A, Hamai K, et al. Mouth and genital ulcers with inflamed cartilage (MAGIC syndrome): a case report and literature review. Am J Med Sci. 1997 Nov. 314 (5):330-2. [QxMD MEDLINE Link].
Ramírez-Amador V, Esquivel-Pedraza L, Sierra-Madero J, Anaya-Saavedra G, González-Ramírez I, Ponce-de-León S. The Changing Clinical Spectrum of Human Immunodeficiency Virus (HIV)-Related Oral Lesions in 1,000 Consecutive Patients: A 12-Year Study in a Referral Center in Mexico. Medicine (Baltimore). 2003 Jan. 82 (1):39-50. [QxMD MEDLINE Link].
Kimura S, Kuroda J, Akaogi T, Hayashi H, Kobayashi Y, Kondo M. Trisomy 8 involved in myelodysplastic syndromes as a risk factor for intestinal ulcers and thrombosis--Behçet's syndrome. Leuk Lymphoma. 2001 Jun. 42 (1-2):115-21. [QxMD MEDLINE Link].
Davatchi F. Diagnosis/Classification Criteria for Behcet's Disease. Patholog Res Int. 2012. 2012:607921. [QxMD MEDLINE Link].
O'Neill TW, Rigby AS, Silman AJ, Barnes C. Validation of the International Study Group criteria for Behçet's disease. Br J Rheumatol. 1994 Feb. 33 (2):115-7. [QxMD MEDLINE Link].
Tappuni AR, Kovacevic T, Shirlaw PJ, Challacombe SJ. Clinical assessment of disease severity in recurrent aphthous stomatitis. J Oral Pathol Med. 2013 Sep. 42 (8):635-41. [QxMD MEDLINE Link].
Challacombe SJ, Alsahaf S, Tappuni A. Recurrent Aphthous Stomatitis: Towards Evidence-Based Treatment?. Curr Oral Health Rep. 2015. 2:158-67.
Ekiz O, Balta I, Sen BB, Rifaioglu EN, Ergin C, Balta S, et al. Mean platelet volume in recurrent aphthous stomatitis and Behçet disease. Angiology. 2014 Feb. 65 (2):161-5. [QxMD MEDLINE Link].
Rogers RS 3rd, Hutton KP. Screening for haematinic deficiencies in patients with recurrent aphthous stomatitis. Australas J Dermatol. 1986 Dec. 27(3):98-103. [QxMD MEDLINE Link].
Alidaee MR, Taheri A, Mansoori P, Ghodsi SZ. Silver nitrate cautery in aphthous stomatitis: a randomized controlled trial. Br J Dermatol. 2005 Sep. 153(3):521-5. [QxMD MEDLINE Link].
Brice SL. Clinical evaluation of the use of low-intensity ultrasound in the treatment of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997 Jan. 83(1):14-20. [QxMD MEDLINE Link].
Brocklehurst P, Tickle M, Glenny AM, Lewis MA, Pemberton MN, Taylor J, et al. Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database Syst Rev. 2012 Sep 12. 9:CD005411. [QxMD MEDLINE Link].
Liu C, Zhou Z, Liu G, Wang Q, Chen J, Wang L, et al. Efficacy and safety of dexamethasone ointment on recurrent aphthous ulceration. Am J Med. 2012 Mar. 125 (3):292-301. [QxMD MEDLINE Link].
Meng W, Dong Y, Liu J, Wang Z, Zhong X, Chen R, et al. A clinical evaluation of amlexanox oral adhesive pellicles in the treatment of recurrent aphthous stomatitis and comparison with amlexanox oral tablets: a randomized, placebo controlled, blinded, multicenter clinical trial. Trials. 2009 May 6. 10:30. [QxMD MEDLINE Link].
Khandwala A, Van Inwegen RG, Charney MR, Alfano MC. 5% amlexanox oral paste, a new treatment for recurrent minor aphthous ulcers: II. Pharmacokinetics and demonstration of clinical safety. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997 Feb. 83 (2):231-8. [QxMD MEDLINE Link].
Bonitsis NG, Altenburg A, Krause L, Stache T, Zouboulis CC. Current concepts in the treatment of Adamantadies-Behçet’s disease. Drugs Future. 2009. 34:749–63.
Chavan M, Jain H, Diwan N, Khedkar S, Shete A, Durkar S. Recurrent aphthous stomatitis: a review. J Oral Pathol Med. 2012 Sep. 41 (8):577-83. [QxMD MEDLINE Link].
Altenburg A, Abdel-Naser MB, Seeber H, Abdallah M, Zouboulis CC. Practical aspects of management of recurrent aphthous stomatitis. J Eur Acad Dermatol Venereol. 2007 Sep. 21 (8):1019-26. [QxMD MEDLINE Link].
Elad S, Epstein JB, von Bültzingslöwen I, Drucker S, Tzach R, Yarom N. Topical immunomodulators for management of oral mucosal conditions, a systematic review; Part II: miscellaneous agents. Expert Opin Emerg Drugs. 2011 Mar. 16 (1):183-202. [QxMD MEDLINE Link].
Belenguer-Guallar I, Jiménez-Soriano Y, Claramunt-Lozano A. Treatment of recurrent aphthous stomatitis. A literature review. J Clin Exp Dent. 2014 Apr. 6 (2):e168-74. [QxMD MEDLINE Link].
Sharquie KE, Helmi RM, Noaimi AA, Kadhom AA, Al-Hayani RK. Therapeutic role of isotretinoin in the management of recurrent aphthous stomatitis (Single-Blind Controlled Therapeutic Study). J Cosmetics Dermatological Sciences and Applications. 2015. 5:15-21.
Gorsky M, Epstein J, Rabenstein S, Elishoov H, Yarom N. Topical minocycline and tetracycline rinses in treatment of recurrent aphthous stomatitis: a randomized cross-over study. Dermatol Online J. 2007 May 1. 13 (2):1. [QxMD MEDLINE Link].
Clemente Rodríguez de Rivera E, Rodríguez de Rivera Campillo E, E. Jané Salas, Albuquerque R, López JL. O10364 Effectiveness of Bexident Post in the treatment of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Rad. 2014. 117(5):e382.
Descroix V, Coudert AE, Vigé A, Durand JP, Toupenay S, Molla M, et al. Efficacy of topical 1% lidocaine in the symptomatic treatment of pain associated with oral mucosal trauma or minor oral aphthous ulcer: a randomized, double-blind, placebo-controlled, parallel-group, single-dose study. J Orofac Pain. 2011 Fall. 25 (4):327-32. [QxMD MEDLINE Link].
Buchsel PC. Polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair): a bioadherent oral gel for the treatment of oral mucositis and other painful oral lesions. Expert Opin Drug Metab Toxicol. 2008 Nov. 4 (11):1449-54. [QxMD MEDLINE Link].
Ludlow JB, Kutcher MJ, Samuelson A. Intraoral digital imaging documenting recurrent aphthous ulcer healing in 2-octyl cyanoacrylate versus sham-treated lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 Apr. 89 (4):425-31. [QxMD MEDLINE Link].
Campisi G, Spadari F, Salvato A. [Sucralfate in odontostomatology. Clinical experience]. Minerva Stomatol. 1997 Jun. 46 (6):297-305. [QxMD MEDLINE Link].
Ricer RE. Sucralfate vs. placebo for the treatment of aphthous ulcers: a double-blinded prospective clinical trial. Fam Pract Res J. 1989 Fall-Winter. 9 (1):33-41. [QxMD MEDLINE Link].
Halaszynski T. Management of Oral Ulcers and Burning Mouth Syndrome. Vadivelu N, Vadivelu A, Kaye AD, eds. Orofacial Pain: A Clinician’s Guide. Cham, Switzerland: Springer; 2014. 103-14.
Pinto A, Lindemeyer RG, Sollecito TP. The PFAPA syndrome in oral medicine: differential diagnosis and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 Jul. 102 (1):35-9. [QxMD MEDLINE Link].
Femiano F, Buonaiuto C, Gombos F, Lanza A, Cirillo N. Pilot study on recurrent aphthous stomatitis (RAS): a randomized placebo-controlled trial for the comparative therapeutic effects of systemic prednisone and systemic montelukast in subjects unresponsive to topical therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Mar. 109 (3):402-7. [QxMD MEDLINE Link].
Katz J, Langevitz P, Shemer J, Barak S, Livneh A. Prevention of recurrent aphthous stomatitis with colchicine: an open trial. J Am Acad Dermatol. 1994 Sep. 31 (3 Pt 1):459-61. [QxMD MEDLINE Link].
Dixon AJ, Wall GC. Probable colchicine-induced neutropenia not related to intentional overdose. Ann Pharmacother. 2001 Feb. 35 (2):192-5. [QxMD MEDLINE Link].
Brown RS, Bottomley WK. Combination immunosuppressant and topical steroid therapy for treatment of recurrent major aphthae. A case report. Oral Surg Oral Med Oral Pathol. 1990 Jan. 69 (1):42-4. [QxMD MEDLINE Link].
de Abreu MA, Hirata CH, Pimentel DR, Weckx LL. Treatment of recurrent aphthous stomatitis with clofazimine. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Nov. 108(5):714-21. [QxMD MEDLINE Link].
Femiano F, Gombos F, Scully C. Recurrent aphthous stomatitis unresponsive to topical corticosteroids: a study of the comparative therapeutic effects of systemic prednisone and systemic sulodexide. Int J Dermatol. 2003 May. 42 (5):394-7. [QxMD MEDLINE Link].
Jacobson JM, Greenspan JS, Spritzler J, Ketter N, Fahey JL, Jackson JB, et al. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med. 1997 May 22. 336 (21):1487-93. [QxMD MEDLINE Link].
Thornhill MH, Baccaglini L, Theaker E, Pemberton MN. A randomized, double-blind, placebo-controlled trial of pentoxifylline for the treatment of recurrent aphthous stomatitis. Arch Dermatol. 2007 Apr. 143(4):463-70. [QxMD MEDLINE Link].
Hamdy AA, Ibrahem MA. Management of aphthous ulceration with topical quercetin: a randomized clinical trial. J Contemp Dent Pract. 2010 Jul 1. 11 (4):E009-16. [QxMD MEDLINE Link].
Mostafa AAE, Ibrahem MAE. Management of aphthous ulceration with topical quercetin. Cairo Dental J. 2009. 25(1):
Al-Maweri SA, Alaizari N, Alharbi AA, Alotaibi SA, AlQuhal A, Almutairi BF, et al. Efficacy of curcumin for recurrent aphthous stomatitis: a systematic review. J Dermatolog Treat. 2020 Sep 9. 1-6. [QxMD MEDLINE Link].
Aggour RL, Mahmoud SH, Abdelwhab A. Evaluation of the effect of probiotic lozenges in the treatment of recurrent aphthous stomatitis: a randomized, controlled clinical trial. Clin Oral Investig. 2020 Aug 20. [QxMD MEDLINE Link].
Pedersen AML, Bukkehave KH, Bennett EP, Twetman S. Effect of Lozenges Containing Lactobacillus reuteri on the Severity of Recurrent Aphthous Ulcers: a Pilot Study. Probiotics Antimicrob Proteins. 2020 Sep. 12 (3):819-823. [QxMD MEDLINE Link].
Al-Maweri SA, Halboub E, Ashraf S, Alqutaibi AY, Qaid NM, Yahya K, et al. Single application of topical doxycycline in management of recurrent aphthous stomatitis: a systematic review and meta-analysis of the available evidence. BMC Oral Health. 2020 Aug 24. 20 (1):231. [QxMD MEDLINE Link].
Albrektson M, Hedström L, Bergh H. Recurrent aphthous stomatitis and pain management with low-level laser therapy: a randomized controlled trial. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014 May. 117 (5):590-4. [QxMD MEDLINE Link].
Demetriades N, Hanford H, Laskarides C. General manifestations of Behçet's syndrome and the success of CO2-laser as treatment for oral lesions: a review of the literature and case presentation. J Mass Dent Soc. 2009 Fall. 58(3):24-7. [QxMD MEDLINE Link].
Arikan OK, Birol A, Tuncez F, Erkek E, Koc C. A prospective randomized controlled trial to determine if cryotherapy can reduce the pain of patients with minor form of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 Jan. 101(1):e1-5. [QxMD MEDLINE Link].
Eversole LR, Shopper TP, Chambers DW. Effects of suspected foodstuff challenging agents in the etiology of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol. 1982 Jul. 54(1):33-8. [QxMD MEDLINE Link].
Hay KD, Reade PC. The use of an elimination diet in the treatment of recurrent aphthous ulceration of the oral cavity. Oral Surg Oral Med Oral Pathol. 1984 May. 57(5):504-7. [QxMD MEDLINE Link].
Wright A, Ryan FP, Willingham SE, et al. Food allergy or intolerance in severe recurrent aphthous ulceration of the mouth. Br Med J (Clin Res Ed). 1986 May 10. 292(6530):1237-8. [QxMD MEDLINE Link].
Lalla RV, Choquette LE, Feinn RS, Zawistowski H, Latortue MC, Kelly ET, et al. Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double-masked, placebo-controlled trial. J Am Dent Assoc. 2012 Apr. 143(4):370-6. [QxMD MEDLINE Link].
Axell T, Henricsson V. Association between recurrent aphthous ulcers and tobacco habits. Scand J Dent Res. 1985 Jun. 93(3):239-42. [QxMD MEDLINE Link].
Bittoun R. Recurrent aphthous ulcers and nicotine. Med J Aust. 1991 Apr 1. 154(7):471-2. [QxMD MEDLINE Link].
Sawair FA. Does smoking really protect from recurrent aphthous stomatitis?. Ther Clin Risk Manag. 2010 Nov 22. 6:573-7. [QxMD MEDLINE Link]. [Full Text].
Hill SC, Stavrakoglou A, Coutts IR. Nicotine replacement therapy as a treatment for complex aphthosis. J Dermatolog Treat. 2009 Oct 13. [QxMD MEDLINE Link].

Media Gallery

Minor aphthous ulcer: Small superficial oval erosions with yellow pseudomembrane and an erythematous border are evident on the labial aspect of the left lower lip.
Major aphthous ulcer: Large oval ulcer with white pseudomembrane and raised red border located on the right upper labial mucosa adjacent to the buccal commissure. Note the irregular margin so typical in major aphthae.
Herpetiform aphthous ulcer: Grouped and single tiny white to yellow ulcers scattered on the labial mucosa and on the ventral aspect of the tongue.

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Author

Ginat W Mirowski, MD, DMD Adjunct Associate Professor, Departments of Oral Pathology, Medicine, and Radiology, Indiana University School Medicine

Ginat W Mirowski, MD, DMD is a member of the following medical societies: American Academy of Dermatology, American Medical Women's Association

Disclosure: Nothing to disclose.

Coauthor(s)

Heather C Rosengard, MPH Johns Hopkins University School of Medicine

Disclosure: Nothing to disclose.

Diana V Messadi, DDS, MMSc, DMSc Professor of Dentistry, Associate Dean for Education and Faculty Development, Chair, Section of Oral Medicine and Orofacial Pain, University of California, Los Angeles, School of Dentistry

Diana V Messadi, DDS, MMSc, DMSc is a member of the following medical societies: American Academy of Oral and Maxillofacial Pathology, American Academy of Oral Medicine, American Association for Cancer Research, American Association for Cancer Research, Women in Cancer Research, American Association for Dental Research, American Association of University Women, American Dental Association, American Dental Education Association, Arab American Dental Society, Association of Egyptian-American Scholars, California Dental Association, Egyptian Dental Association, International Association for Dental Research, Southern California Academy of Oral Pathology, West Los Angeles Dental Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

David P Fivenson, MD Associate Director, St Joseph Mercy Hospital Dermatology Program, Ann Arbor, Michigan

David P Fivenson, MD is a member of the following medical societies: American Academy of Dermatology, Michigan State Medical Society, Society for Investigative Dermatology, Photomedicine Society, Wound Healing Society, Michigan Dermatological Society, Medical Dermatology Society

Disclosure: Nothing to disclose.

Christy L Nebesio, MD Dermatologist

Christy L Nebesio, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Jeffrey M Casiglia, DMD, DMSc Lecturer, Harvard School of Dental Medicine; Private Practice, Salem, Massachusetts

Jeffrey M Casiglia, DMD, DMSc is a member of the following medical societies: American Academy of Oral Medicine, American Dental Association

Disclosure: Nothing to disclose.

Aphthous Stomatitis Medication

Medication Summary

Corticosteroids

Class Summary

Prednisone (Deltasone)

Dexamethasone (Decadron, Dexasone)

Triamcinolone topical (Aristocort)

Fluocinonide (Fluonex, Lidex)

Clobetasol propionate (Temovate)

Anesthetics

Class Summary

Lidocaine anesthetic (Xylocaine)

Benzocaine (Americaine, Anbesol)

Coating agents

Class Summary

Sucralfate (Carafate)

Bismuth subsalicylate (Kaopectate, Kaopectate Extra Strength, Maalox Total Relief)

Bioadherent oral (Gelclair)

Topical occlusives

Class Summary

2-Octyl cyanoacrylate

Immunosuppressants

Class Summary

Colchicine (Colcrys, Mitigare)

Montelukast (Singulair)

Clofazimine (Lamprene)

Azathioprine (Imuran)

Thalidomide (Thalomid)

Topical immunomodulators

Class Summary

Cyclosporine (Gengraf, Neoral, Sandimmune)

Amlexanox (Aphthasol)

Retinoids

Class Summary

Isotretinoin (Absorica, Amnesteem, Claravis)

Tretinoin topical (Atralin, Avita, Refissa)

Retinoic acid

Antibacterial agents

Class Summary

Chlorhexidine oral (Peridex, PerioChip, PerioGard)

Tetracycline

Hemorheologic agents

Class Summary

Pentoxifylline (Pentoxil, Trental)

Secretagogues

Class Summary

Cevimeline (Evoxac)

Pilocarpine (Pilocarpine PO, Salagen)

Ear, Eye, Nose & Throat, Herbals

Class Summary

Quercetin

References

Tables

Contributor Information and Disclosures

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