UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Recurrent aphthous stomatitis

Author
Sylvia Brice, MD
Section Editor
Robert P Dellavalle, MD, PhD, MSPH
Deputy Editor
Rosamaria Corona, MD, DSc

INTRODUCTION

Recurrent aphthous stomatitis (RAS), also known as "canker sores," is a common disease of the oral and, occasionally, genital mucosa characterized by the repeated development of one to many discrete, painful ulcers that usually heal within 7 to 14 days [1-6]. The lesions are typically 3 to 5 mm, round to oval ulcers with a peripheral rim of erythema and a yellowish adherent exudate centrally. The process may range in severity, with some patients noting only an occasional lesion and others experiencing such frequent episodes that they have almost continuous ulcer activity [1-6].

This topic will discuss the pathogenesis, clinical manifestations, and management of RAS. Other causes of oral and/or genital ulceration are discussed separately.

(See "Oral lesions".)

(See "Clinical manifestations and diagnosis of Behçet's syndrome".)

(See "Approach to the patient with genital ulcers".)

                           
To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Sep 16, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. Edgar NR, Saleh D, Miller RA. Recurrent Aphthous Stomatitis: A Review. J Clin Aesthet Dermatol 2017; 10:26.
  2. Cui RZ, Bruce AJ, Rogers RS 3rd. Recurrent aphthous stomatitis. Clin Dermatol 2016; 34:475.
  3. 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; 7:74.
  4. Akintoye SO, Greenberg MS. Recurrent aphthous stomatitis. Dent Clin North Am 2014; 58:281.
  5. Scully C, Porter S. Oral mucosal disease: recurrent aphthous stomatitis. Br J Oral Maxillofac Surg 2008; 46:198.
  6. Chattopadhyay A, Shetty KV. Recurrent aphthous stomatitis. Otolaryngol Clin North Am 2011; 44:79.
  7. Chattopadhyay A, Chatterjee S. Risk indicators for recurrent aphthous ulcers among adults in the US. Community Dent Oral Epidemiol 2007; 35:152.
  8. 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; 52:500.
  9. Alpsoy E. Behçet's disease: A comprehensive review with a focus on epidemiology, etiology and clinical features, and management of mucocutaneous lesions. J Dermatol 2016; 43:620.
  10. Baccaglini L, Lalla RV, Bruce AJ, et al. Urban legends: recurrent aphthous stomatitis. Oral Dis 2011; 17:755.
  11. Slebioda Z, Szponar E, Kowalska A. Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: literature review. Arch Immunol Ther Exp (Warsz) 2014; 62:205.
  12. Najafi S, Firooze Moqadam I, Mohammadzadeh M, et al. Interleukin-10 gene polymorphisms in recurrent aphthous stomatitis. Immunol Invest 2014; 43:405.
  13. Buño IJ, Huff JC, Weston WL, et al. Elevated levels of interferon gamma, tumor necrosis factor alpha, interleukins 2, 4, and 5, but not interleukin 10, are present in recurrent aphthous stomatitis. Arch Dermatol 1998; 134:827.
  14. Ozyurt K, Celik A, Sayarlıoglu M, et al. Serum Th1, Th2 and Th17 cytokine profiles and alpha-enolase levels in recurrent aphthous stomatitis. J Oral Pathol Med 2014; 43:691.
  15. Günhan Ö, Günal A, Avcı A, et al. Oral epithelial barrier function and the role of nuclear factor kappa-β pathway in the pathogenesis of aphthous ulceration. Turk J Gastroenterol 2013; 24:508.
  16. Gallo C, Barros F, Sugaya N, et al. Differential expression of toll-like receptor mRNAs in recurrent aphthous ulceration. J Oral Pathol Med 2012; 41:80.
  17. Keogan MT. Clinical Immunology Review Series: an approach to the patient with recurrent orogenital ulceration, including Behçet's syndrome. Clin Exp Immunol 2009; 156:1.
  18. Lalla RV, Choquette LE, Feinn RS, et al. Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double-masked, placebo-controlled trial. J Am Dent Assoc 2012; 143:370.
  19. Wray D, Graykowski EA, Notkins AL. Role of mucosal injury in initiating recurrent aphthous stomatitis. Br Med J (Clin Res Ed) 1981; 283:1569.
  20. Keenan AV, Spivakovksy S. Stress associated with onset of recurrent aphthous stomatitis. Evid Based Dent 2013; 14:25.
  21. Bratel J, Hakeberg M. Anamnestic findings from patients with recurrent aphthous stomatitis. Swed Dent J 2014; 38:143.
  22. Sawair FA. Does smoking really protect from recurrent aphthous stomatitis? Ther Clin Risk Manag 2010; 6:573.
  23. Marakoğlu K, Sezer RE, Toker HC, Marakoğlu I. The recurrent aphthous stomatitis frequency in the smoking cessation people. Clin Oral Investig 2007; 11:149.
  24. Stenman G, Heyden G. Premonitory stages of recurrent aphthous stomatitis. I. Histological and enzyme histochemical investigations. J Oral Pathol 1980; 9:155.
  25. Rogers RS 3rd. Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders. Semin Cutan Med Surg 1997; 16:278.
  26. Chen H, Sui Q, Chen Y, et al. Impact of haematologic deficiencies on recurrent aphthous ulceration: a meta-analysis. Br Dent J 2015; 218:E8.
  27. Kaneko Y, Nakai N, Kida T, et al. Mouth and Genital Ulcers with Inflamed Cartilage Syndrome: Case Report and Review of the Published Work. Indian J Dermatol 2016; 61:347.
  28. Hidalgo-Tenorio C, Sabio-Sánchez JM, Linares PJ, et al. Magic syndrome and true aortic aneurysm. Clin Rheumatol 2008; 27:115.
  29. Mekinian A, Lambert M, Beregi JP, et al. Aortic aneurysm in MAGIC syndrome successfully managed with combined anti-TNF-alpha and stent grafting. Rheumatology (Oxford) 2009; 48:1169.
  30. Ng CS, Hogan P, McKenzie S, et al. Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome complicated by aneurysmal aortitis. J Clin Rheumatol 2007; 13:221.
  31. Jorizzo JL, Salisbury PL, Rogers RS 3rd, et al. Oral lesions in systemic lupus erythematosus. Do ulcerative lesions represent a necrotizing vasculitis? J Am Acad Dermatol 1992; 27:389.
  32. Shakeri R, Zamani F, Sotoudehmanesh R, et al. Gluten sensitivity enteropathy in patients with recurrent aphthous stomatitis. BMC Gastroenterol 2009; 9:44.
  33. Bucci P, Carile F, Sangianantoni A, et al. Oral aphthous ulcers and dental enamel defects in children with coeliac disease. Acta Paediatr 2006; 95:203.
  34. Nieri M, Tofani E, Defraia E, et al. Enamel defects and aphthous stomatitis in celiac and healthy subjects: Systematic review and meta-analysis of controlled studies. J Dent 2017; 65:1.
  35. Greuter T, Bertoldo F, Rechner R, et al. Extraintestinal Manifestations of Pediatric Inflammatory Bowel Disease: Prevalence, Presentation, and Anti-TNF Treatment. J Pediatr Gastroenterol Nutr 2017; 65:200.
  36. Field EA, Allan RB. Review article: oral ulceration--aetiopathogenesis, clinical diagnosis and management in the gastrointestinal clinic. Aliment Pharmacol Ther 2003; 18:949.
  37. Patil N, Chaurasia VR, Babaji P, et al. The effect of highly active antiretroviral therapy on the prevalence of oral manifestation in human immunodeficiency virus-infected patients in Karnataka, India. Eur J Dent 2015; 9:47.
  38. Kerr AR, Ship JA. Management strategies for HIV-associated aphthous stomatitis. Am J Clin Dermatol 2003; 4:669.
  39. Jacobson JM, Greenspan JS, Spritzler J, 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; 336:1487.
  40. Arduino PG, Porter SR. Oral and perioral herpes simplex virus type 1 (HSV-1) infection: review of its management. Oral Dis 2006; 12:254.
  41. Ródenas JM, Ortego N, Herranz MT, et al. Cyclic neutropenia: a cause of recurrent aphthous stomatitis not to be missed. Dermatology 1992; 184:205.
  42. Ali NS, Sartori-Valinotti JC, Bruce AJ. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. Clin Dermatol 2016; 34:482.
  43. van der Hilst JC, Bodar EJ, Barron KS, et al. Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome. Medicine (Baltimore) 2008; 87:301.
  44. Rosman IS, Berk DR, Bayliss SJ, et al. Acute genital ulcers in nonsexually active young girls: case series, review of the literature, and evaluation and management recommendations. Pediatr Dermatol 2012; 29:147.
  45. Ranganath SP, Pai A. Is Optimal Management of Recurrent Aphthous Stomatitis Possible? A Reality Check. J Clin Diagn Res 2016; 10:ZE08.
  46. Brocklehurst P, Tickle M, Glenny AM, et al. Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database Syst Rev 2012; :CD005411.
  47. Spivakovsky S. Inconclusive evidence on systemic treatments for recurrent aphthous stomatitis. Evid Based Dent 2012; 13:120.
  48. Belenguer-Guallar I, Jiménez-Soriano Y, Claramunt-Lozano A. Treatment of recurrent aphthous stomatitis. A literature review. J Clin Exp Dent 2014; 6:e168.
  49. Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc 2003; 134:200.
  50. Suter VGA, Sjölund S, Bornstein MM. Effect of laser on pain relief and wound healing of recurrent aphthous stomatitis: a systematic review. Lasers Med Sci 2017; 32:953.
  51. Han M, Fang H, Li QL, et al. Effectiveness of Laser Therapy in the Management of Recurrent Aphthous Stomatitis: A Systematic Review. Scientifica (Cairo) 2016; 2016:9062430.
  52. Pavlić V, vujić-Aleksić V, Aoki A, Nežić L. Treatment of recurrent aphthous stomatitis by laser therapy: A systematic review of the literature. Vojnosanit Pregl 2015; 72:722.
  53. Liu C, Zhou Z, Liu G, et al. Efficacy and safety of dexamethasone ointment on recurrent aphthous ulceration. Am J Med 2012; 125:292.
  54. Alpsoy E, Er H, Durusoy C, Yilmaz E. The use of sucralfate suspension in the treatment of oral and genital ulceration of Behçet disease: a randomized, placebo-controlled, double-blind study. Arch Dermatol 1999; 135:529.
  55. Rattan J, Schneider M, Arber N, et al. Sucralfate suspension as a treatment of recurrent aphthous stomatitis. J Intern Med 1994; 236:341.
  56. Bhat S, Sujatha D. A clinical evaluation of 5% amlexanox oral paste in the treatment of minor recurrent aphthous ulcers and comparison with the placebo paste: a randomized, vehicle controlled, parallel, single center clinical trial. Indian J Dent Res 2013; 24:593.
  57. Rodríguez M, Rubio JA, Sanchez R. Effectiveness of two oral pastes for the treatment of recurrent aphthous stomatitis. Oral Dis 2007; 13:490.
  58. 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; 22:9.
  59. Femiano F, Buonaiuto C, Gombos F, et al. 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; 109:402.
  60. 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; 42:394.
  61. Pakfetrat A, Mansourian A, Momen-Heravi F, et al. Comparison of colchicine versus prednisolone in recurrent aphthous stomatitis: A double-blind randomized clinical trial. Clin Invest Med 2010; 33:E189.
  62. Davatchi F, Sadeghi Abdollahi B, Tehrani Banihashemi A, et al. Colchicine versus placebo in Behçet's disease: randomized, double-blind, controlled crossover trial. Mod Rheumatol 2009; 19:542.
  63. Lynde CB, Bruce AJ, Rogers RS 3rd. Successful treatment of complex aphthosis with colchicine and dapsone. Arch Dermatol 2009; 145:273.
  64. Sharquie KE, Najim RA, Al-Hayani RK, et al. The therapeutic and prophylactic role of oral zinc sulfate in management of recurrent aphthous stomatitis (ras) in comparison with dapsone. Saudi Med J 2008; 29:734.
  65. Sharquie KE, Najim RA, Abu-Raghif AR. Dapsone in Behçet's disease: a double-blind, placebo-controlled, cross-over study. J Dermatol 2002; 29:267.
  66. Wu JJ, Huang DB, Pang KR, et al. Thalidomide: dermatological indications, mechanisms of action and side-effects. Br J Dermatol 2005; 153:254.
  67. Hello M, Barbarot S, Bastuji-Garin S, et al. Use of thalidomide for severe recurrent aphthous stomatitis: a multicenter cohort analysis. Medicine (Baltimore) 2010; 89:176.
  68. www.fda.gov/downloads/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm222649.pdf (Accessed on August 09, 2017).
  69. 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; 143:463.
  70. Sand FL, Thomsen SF. Efficacy and safety of TNF-α inhibitors in refractory primary complex aphthosis: a patient series and overview of the literature. J Dermatolog Treat 2013; 24:444.
  71. O'Neill ID, Scully C. Biologics in oral medicine: ulcerative disorders. Oral Dis 2013; 19:37.
  72. Yilmaz HG, Albaba MR, Caygur A, et al. Treatment of recurrent aphthous stomatitis with Er,Cr:YSGG laser irradiation: A randomized controlled split mouth clinical study. J Photochem Photobiol B 2017; 170:1.
  73. Alidaee MR, Taheri A, Mansoori P, Ghodsi SZ. Silver nitrate cautery in aphthous stomatitis: a randomized controlled trial. Br J Dermatol 2005; 153:521.