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Aphthous Stomatitis Clinical Presentation

  • Author: Ginat W Mirowski, MD, DMD; Chief Editor: William D James, MD  more...
 
Updated: Feb 09, 2016
 

History

Recurrent aphthous ulcers consist of one or multiple round-to-ovoid, shallow, punched-out–appearing, painful oral ulcers that recur at intervals of a few days to a few months. To evaluate oral ulcers as recurrent aphthous ulcers, ascertain the following information:

  • Nature of the lesions (number, size, duration, recurrence): The prodromal stage (when present) may begin with a pricking or burning sensation on the mucosa. The ulcers develop within 24-48 hours. Pain lasts 3-4 days or until a thicker fibrinous cover develops or early epithelialization occurs. Healing is complete in 7-14 days.
  • Age of the patient at onset
  • Cutaneous or mucosal changes
  • Symptoms of other organ system involvement
  • Current medications, including herbal medications and vitamins
  • Host factors associated with recurrent aphthous ulcer (see Causes): With regard to genetic factors, a family history is evident in some cases. Hematinic deficiency may play a role. Iron, folic acid, or vitamin B-6 and B-12 deficiencies are possible. [15, 16] Immune dysregulation may play possibly play a role. Physical or emotional stress is often reported by patients as associated with recurrent outbreaks. [17] This stress appears to affect onset but not duration or severity of episodes. [18]
  • Environmental factors associated with recurrent aphthous ulcer: Local, chemical, or physical trauma may initiate ulcer development in patients who are susceptible (pathergy). Allergy or sensitivity to chemicals or food additives may stimulate an outbreak. The role of microbial infection is debated.
  • HIV infection (associated with lesions) [19] : Aphthouslike oral ulcerations involving all 3 types of recurrent aphthous ulcers are observed. Approximately 66% of patients who are HIV positive have herpetiform and major recurrent aphthous ulcers. Unlike in healthy individuals, these ulcerations may be present on both keratinized and nonkeratinized surfaces, making it even more critical to rule out opportunistic infections. Ulcerations must be distinguished from those caused by HIV medications and fungal, viral, or bacterial infections. Tissue biopsy for pathologic evaluation and for culture is indicated.
  • Behçet syndrome (associated with lesions) [20, 21, 22, 23, 24, 25] : This complex, multisystemic inflammatory disorder of unknown cause is characterized by recurrent oral aphthae and at least 2 of the following findings: genital aphthae, synovitis, cutaneous pustular vasculitis, posterior uveitis, or meningoencephalitis. Oral aphthae of Behçet syndrome are clinically similar to those in recurrent aphthous ulcers but are accompanied by ocular and genital lesions. The incidence is highest in Japan, Southeast Asia, the Middle East, and southern Europe and in persons aged 30-40 years. Behçet syndrome is strongly associated with HLA-B51. Studies also demonstrate an association between IL-18 gene polymorphisms and Behçet syndrome, which was not observed in patients with aphthous stomatitis. [26]
  • Gluten-sensitive enteropathy (also known as celiac sprue) [27, 28, 29] : Oral lesions occur in most cases of gluten-sensitive enteropathy (GSE) and can often precede abdominal symptoms. Less than 5% of patients with recurrent aphthous ulcers have GSE, also known as celiac disease, or other minor mucosal abnormalities of the small intestine. However, celiac disease is not universally agreed to be causative; thus, the need for patients with aphthosis to be screened for celiac disease is unclear. [30, 31] Bowel symptoms may not be present, but patients may have folate deficiency, and they sometimes have reticulin antibodies.
  • Xerostomia or dry mouth: This may be a precipitating or aggravating factor in many patients since saliva is a lubricating agent with antimicrobial properties. [32]

No specific laboratory tests are available. It is important to exclude other disorders by medical history and a comprehensive laboratory evaluation when indicated.

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Physical

Regardless of the clinical form of recurrent aphthous ulcer, ulcers are confined to the nonkeratinized mucosa of the mouth, sparing the dorsum of the tongue, the attached gingiva, and the hard palate mucosae, which are keratinized unless the patient is HIV positive. Although patients may have submandibular lymphadenopathy, fever is rare. Most patients are otherwise well. Different gradations and their findings are as follows:

  • Recurrent aphthous ulcer minor (see image below): Recurrent aphthous ulcer minor is characterized by discrete shallow ulcers smaller than 1 cm in diameter. The ulcers are covered by a yellow-gray pseudomembrane (fibrinous exudate) and are surrounded by an erythematous halo.
  • Minor aphthous ulcer: Small superficial oval erosi 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.
  • Recurrent aphthous ulcer major (see image below): Recurrent aphthous ulcer major is characterized by oval ulcers that are larger (>1 cm in diameter; often 2-3 cm) and deeper than those observed in recurrent aphthous ulcer minor. The ulcers may coalesce and often have an irregular border.
  • Major aphthous ulcer: Large oval ulcer with white 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 recurrent aphthous ulcer (see image below): Herpetiform recurrent aphthous ulcer is characterized by crops of smaller ulcers; tens of ulcerations may be present in clusters. The ulcers can coalesce to produce a widespread area of irregular ulceration.
  • Herpetiform aphthous ulcer: Grouped and single tin 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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Causes

Although the clinical characteristics of recurrent aphthous ulcer are well defined, the precise etiology and the pathogenesis of recurrent aphthous ulcer remain unclear. Many possibilities have been investigated. Recurrent aphthous ulcer is a multifactorial condition, and it is likely that immune-mediated destruction of the epithelium is the common factor in recurrent aphthous ulcer pathogenesis. Host risk factors associated with recurrent aphthous ulcer are described below.

Genetics

A family history of recurrent aphthous ulcers is evident in some patients. A familial connection includes a young age of onset and symptoms of increased severity. Recurrent aphthous ulcer is highly correlated in identical twins.[33, 34]

Associations between specific HLA haplotypes (eg, HLA- B51) and recurrent aphthous ulcer have been investigated. No consistent association has been demonstrated. However, in two Iranian studies, polymorphisms in an inflammasome-related gene, NLRP3, and in the promoter region for the IL6 gene were found to be significantly associated with recurrent aphthous in a small cohort of patients.[35, 36] Still, host susceptibility is clearly variable, with a polygenic inheritance pattern, and penetrance likely depends on other factors.[37]

Hematinic deficiency

In several studies, hematinic (iron, folic acid, vitamins B-6 and B-12) deficiencies were twice as common in patients with recurrent aphthous ulcers as in control subjects. As many as 20% of patients with recurrent aphthous ulcer have a hematinic deficiency, with some studies also reporting notable elevations of blood homocysteine.[16] Lower dietary intake of folate and vitamin B-12 is more common among persons with aphthous ulcers[38] and treatment with 1000 mcg/d has shown benefit in individuals regardless of serum B-12 levels.[39, 40] A small group of adolescents were shown to have reduced incidence and pain from recurrent aphthous stomatitis when given 2000 mg/d of ascorbic acid.[41] Vitamin D deficiency is also more prevalent in patients with recurrent aphthous stomatitis, although there is no correlation between vitamin D levels and a patient’s clinical course, including number of ulcers, duration of ulcers, or frequency of ulcer development.[42]

Thus, serologic workup is warranted. Hemoglobin and RBC indices are not sufficient in all cases.

Immune dysregulation

At present, no unifying theory of the immunopathogenesis of recurrent aphthous ulcer exists, but immune dysregulation may play a significant role. Cytotoxic action of lymphocytes and monocytes on the oral epithelium seems to cause the ulceration, but the trigger remains unclear. Upon histologic analysis, recurrent aphthous ulcer consists of mucosal ulcerations with mixed inflammatory cell infiltrates. T-helper cells predominate in the preulcerative and healing phases, whereas T-suppressor cells predominate in the ulcerative phase.

Other findings associated with immune dysregulation include the following:

  • Reduced response of patients' lymphocytes to mitogens
  • Circulating immune complexes
  • Alterations in the activity of natural killer cells in various stages of disease [43]
  • Increased adherence of neutrophils
  • Reduced quantities and functionality of regulatory T cells in lesional tissue
  • Increased expression of pro-inflammatory Th1 genes [44]
  • Release of tumor necrosis factor-alpha (TNF-alpha) [45]
  • Significant involvement of mast cells in the pathogenesis of recurrent aphthous ulcer
  • Reduced cellular expression of heat shock protein 27 and interleukin 10 in aphthous lesions [46, 47]
  • Elevated levels of salivary and serum cortisol, as well as increased anxiety [48]
  • Increased Toll-like receptor activity [49]
  • Oxidative stress (altered levels and balance of glutathione and malondialdehyde) [50, 51]
  • Increased levels of autoimmune thyroid-related problems and antithyroid antibodies, although the significance is unclear [52]
  • Immunogenetic factors, including single nucleotide polymorphisms in immune modulatory genes [35, 36]

Microbial infection

Researchers disagree about the role of microbes in the development of recurrent aphthous ulcers. Emphasis has been on a microbial agent as a primary pathogen or an antigenic stimulus. Numerous studies have failed to provide strong evidence to support the role of herpes simplex virus, human herpesvirus, varicella-zoster virus, or cytomegalovirus in the development of aphthous ulcers.[53, 54]

Recurrent aphthous ulcer formation may be a T-cell–mediated response to antigens of Streptococcus sanguis that cross-react with the mitochondrial heat shock proteins and induce oral mucosa damage. Helicobacter pylori has been detected in lesional tissue of oral ulcers, and a 2014 meta-analysis found H pylori infection was associated with an increased risk of recurrent aphthous stomatitis.[55] Still, the frequency of serum immunoglobulin G antibodies to H pylori is not increased in recurrent aphthous ulcers, and the organisms have never proven causative.[56, 57, 58, 59, 60]

Imbalances in the oral mucosal microbiome have been identified in patients with recurrent aphthous stomatitis. Although no phylum-level differences were appreciated between nonulcerated sites in these patients and healthy controls, patients with recurrent aphthous stomatitis did exhibit an increased abundance of Bacteroidales species. Further investigation is required to understand if these microbiome imbalances play a causative role in aphthous stomatitis and how diet and oral hygiene influence the oral mucosal microbiome.[61]

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Contributor Information and Disclosures
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 Womens Association

Disclosure: Nothing to disclose.

Coauthor(s)

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.

Heather C Rosengard, MPH Johns Hopkins University School of Medicine

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: Nothing to disclose.

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.

References
  1. 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. [Medline].

  2. 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. [Medline].

  3. Axéll T, Henricsson V. The occurrence of recurrent aphthous ulcers in an adult Swedish population. Acta Odontol Scand. 1985 May. 43(2):121-5. [Medline].

  4. 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. [Medline].

  5. Axéll T. A prevalence study of oral mucosal lesions in an adult Swedish population. Odontol Revy Suppl. 1976. 36:1-103. [Medline].

  6. 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. [Medline].

  7. 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. [Medline].

  8. 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. [Medline].

  9. Safadi RA. Prevalence of recurrent aphthous ulceration in Jordanian dental patients. BMC Oral Health. 2009 Nov 22. 9:31. [Medline].

  10. 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. [Medline].

  11. 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. [Medline].

  12. 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. [Medline].

  13. 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.

  14. Field EA, Brookes V, Tyldesley WR. Recurrent aphthous ulceration in children--a review. Int J Paediatr Dent. 1992 Apr. 2 (1):1-10. [Medline].

  15. Lopez-Jornet P, Camacho-Alonso F, Martos N. Hematological study of patients with aphthous stomatitis. Int J Dermatol. 2014 Feb. 53 (2):159-63. [Medline].

  16. 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. [Medline].

  17. Gallo Cde B, Mimura MA, Sugaya NN. Psychological stress and recurrent aphthous stomatitis. Clinics (Sao Paulo). 2009. 64(7):645-8. [Medline]. [Full Text].

  18. 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. [Medline]. [Full Text].

  19. 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. [Medline].

  20. 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. [Medline].

  21. 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. [Medline].

  22. 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.

  23. Sakane T, Takeno M, Suzuki N, Inaba G. Behçet's disease. N Engl J Med. 1999 Oct 21. 341(17):1284-91. [Medline].

  24. 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. [Medline].

  25. 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. [Medline].

  26. 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. [Medline].

  27. Ferguson MM, Wray D, Carmichael HA, Russell RI, Lee FD. Coeliac disease associated with recurrent aphthae. Gut. 1980 Mar. 21(3):223-6. [Medline].

  28. 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. [Medline].

  29. Wray D. Gluten-sensitive recurrent aphthous stomatitis. Dig Dis Sci. 1981 Aug. 26(8):737-40. [Medline].

  30. 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. [Medline].

  31. 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. [Medline].

  32. Zunt S. Severe/frequent recurrent aphthous ulcers and salivary flow rates. Oral Surg, Oral Med, Oral Pathol and Oral Rad. 2004. 98(2):

  33. 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. [Medline].

  34. Slebioda Z, Szponar E, Kowalska A. Recurrent aphthous stomatitis: genetic aspects of etiology. Postepy Dermatol Alergol. 2013 Apr. 30 (2):96-102. [Medline].

  35. 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. [Medline].

  36. 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. [Medline].

  37. 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. [Medline].

  38. 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. [Medline].

  39. Carrozzo M. Vitamin B12 for the treatment of recurrent aphthous stomatitis. Evid Based Dent. 2009. 10(4):114-5. [Medline].

  40. 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. [Medline]. [Full Text].

  41. 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. [Medline].

  42. 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.

  43. 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. [Medline].

  44. 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. [Medline].

  45. 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. [Medline].

  46. 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. [Medline].

  47. 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. [Medline].

  48. 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. [Medline].

  49. 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. [Medline].

  50. 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. [Medline].

  51. 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. [Medline].

  52. 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. [Medline].

  53. 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. [Medline].

  54. 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. [Medline].

  55. 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. [Medline].

  56. 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. [Medline].

  57. 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. [Medline].

  58. 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. [Medline].

  59. 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. [Medline].

  60. 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. [Medline].

  61. 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. [Medline].

  62. 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. [Medline].

  63. 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. [Medline].

  64. Herlofson BB, Barkvoll P. Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study. Acta Odontol Scand. 1994 Oct. 52 (5):257-9. [Medline].

  65. 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. [Medline].

  66. 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. [Medline].

  67. Samaranayake LPK, Cheung L. Samaranayake YH. Candidiasis and other fungal diseases of the mouth. Dermatol Ther. 2001. 15:251-69.

  68. 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.

  69. Daley TD, Armstrong JE. Oral manifestations of gastrointestinal diseases. Can J Gastroenterol. 2007 Apr. 21 (4):241-4. [Medline].

  70. Cohen PR. Sweet's syndrome--a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007 Jul 26. 2:34. [Medline].

  71. Boxer L, Dale DC. Neutropenia: causes and consequences. Semin Hematol. 2002 Apr. 39 (2):75-81. [Medline].

  72. 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. [Medline].

  73. 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. [Medline].

  74. 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. [Medline].

  75. 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. [Medline].

  76. 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. [Medline].

  77. Davatchi F. Diagnosis/Classification Criteria for Behcet's Disease. Patholog Res Int. 2012. 2012:607921. [Medline].

  78. 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. [Medline].

  79. 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. [Medline].

  80. Challacombe SJ, Alsahaf S, Tappuni A. Recurrent Aphthous Stomatitis: Towards Evidence-Based Treatment?. Curr Oral Health Rep. 2015. 2:158-67.

  81. 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. [Medline].

  82. Rogers RS 3rd, Hutton KP. Screening for haematinic deficiencies in patients with recurrent aphthous stomatitis. Australas J Dermatol. 1986 Dec. 27(3):98-103. [Medline].

  83. 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. [Medline].

  84. 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. [Medline].

  85. 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. [Medline].

  86. 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. [Medline].

  87. 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. [Medline].

  88. 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. [Medline].

  89. 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.

  90. 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. [Medline].

  91. 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. [Medline].

  92. 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. [Medline].

  93. 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. [Medline].

  94. 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.

  95. 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. [Medline].

  96. 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.

  97. 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. [Medline].

  98. 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. [Medline].

  99. 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. [Medline].

  100. Campisi G, Spadari F, Salvato A. [Sucralfate in odontostomatology. Clinical experience]. Minerva Stomatol. 1997 Jun. 46 (6):297-305. [Medline].

  101. 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. [Medline].

  102. 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.

  103. 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. [Medline].

  104. 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. [Medline].

  105. 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. [Medline].

  106. Dixon AJ, Wall GC. Probable colchicine-induced neutropenia not related to intentional overdose. Ann Pharmacother. 2001 Feb. 35 (2):192-5. [Medline].

  107. 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. [Medline].

  108. 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. [Medline].

  109. 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. [Medline].

  110. 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. [Medline].

  111. 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. [Medline].

  112. 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. [Medline].

  113. Mostafa AAE, Ibrahem MAE. Management of aphthous ulceration with topical quercetin. Cairo Dental J. 2009. 25(1):

  114. 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. [Medline].

  115. 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. [Medline].

  116. 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. [Medline].

  117. 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. [Medline].

  118. 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. [Medline].

  119. 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. [Medline].

  120. 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. [Medline].

  121. Axell T, Henricsson V. Association between recurrent aphthous ulcers and tobacco habits. Scand J Dent Res. 1985 Jun. 93(3):239-42. [Medline].

  122. Bittoun R. Recurrent aphthous ulcers and nicotine. Med J Aust. 1991 Apr 1. 154(7):471-2. [Medline].

  123. Sawair FA. Does smoking really protect from recurrent aphthous stomatitis?. Ther Clin Risk Manag. 2010 Nov 22. 6:573-7. [Medline]. [Full Text].

  124. Hill SC, Stavrakoglou A, Coutts IR. Nicotine replacement therapy as a treatment for complex aphthosis. J Dermatolog Treat. 2009 Oct 13. [Medline].

 
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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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