Advertisement

Oral Ulcerative Lesions

  • Giovanni LodiEmail author
  • Elena Varoni
  • Jairo Robledo-Sierra
  • Alessandro Villa
  • Mats Jontell
Reference work entry

Abstract

Ulcers are the most common lesions affecting the oral mucosa, and they can be ascribed to a plethora of local or systemic conditions, making differential diagnosis pivotal and often difficult. As oral ulcers dŁ can be a manifestation of local or systemic conditions of very different nature and severity, including trauma (mechanical, chemical, thermal), drug reactions, immune-mediated diseases, infections, and neoplasms; a careful differential diagnosis is mandatory. Recurrent aphthous stomatitis (RAS) is the most frequent ulcerative disorder of the oral cavity, affecting 10–20% of the general population. RAS lesions typically present as round or oval shallow ulcers of the nonkeratinized mucosa, with a yellow-grayish fibrin pseudomembrane and a characteristic erythematous halo. They usually appear first in childhood or adolescence, in subjects without other systemic signs. RAS may present in four main forms based on its clinical appearance (minor, major, herpetiform, and severe), and its management depends on the frequency and severity of the lesions. RAS episodes are self-limiting and in most cases do not need treatment. For severe and painful cases, the aim of therapy is to control pain and to reduce the frequency of episodes. Topical corticosteroids are typically first-line treatment, but they do not affect the rate of recurrence. Less frequently, aphthous stomatitis can be associated with a number of systemic conditions, including gastrointestinal disorders, in particular inflammatory bowel diseases and celiac disease, Behçet syndrome, food allergy, and deficiencies of micronutrients, mainly vitamin B12, folate, ferritin, and iron. In all these cases, the detection of oral lesions can lead to an early diagnosis of the underlying condition, the management of which requires a multi-specialist approach.

Keywords

Oral ulcer Oral ulcerative disease Oral ulcerative conditions Recurrent aphthous ulceration Recurrent aphthous stomatitis Aphthous-like ulcers Crohn’s disease Celiac disease Inflammatory bowel disease Behçet syndrome Food allergy Micronutrient deficiency 

References

  1. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361(21):2066–78.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Abrams EM, Sicherer SH. Diagnosis and management of food allergy. CMAJ. 2016;188(15):1087–93.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Aine L, Mäki M, Collin P, Keyriläinen O. Dental enamel defects in celiac disease. J Oral Pathol Med. 1990;19(6):241–5.PubMedCrossRefGoogle Scholar
  4. Akintoye SO, Greenberg MS. Recurrent aphthous stomatitis. Dent Clin N Am. 2014;58(2):281–97.PubMedCrossRefPubMedCentralGoogle Scholar
  5. Albanidou-Farmaki E, Deligiannidis A, Markopoulos AK, Katsares V, Farmakis K, Parapanissiou E. HLA haplotypes in recurrent aphthous stomatitis: a mode of inheritance? Int J Immunogenet. 2008;35(6):427–32.PubMedCrossRefPubMedCentralGoogle Scholar
  6. Alpsoy E, Zouboulis CC, Ehrlich GE. Mucocutaneous lesions of Behcet’s disease. Yonsei Med J. 2007;48(4):573–85.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Alpsoy E. Behcet’s disease: a comprehensive review with a focus on epidemiology, etiology and clinical features, and management of mucocutaneous lesions. J Dermatol. 2016; 43(6):620–32.PubMedCrossRefGoogle Scholar
  8. Alrashdan MS, Cirillo N, McCullough M. Oral lichen planus: a literature review and update. Arch Dermatol Res. 2016;308(8):539–51.PubMedCrossRefPubMedCentralGoogle Scholar
  9. Andrès E, Nachit M, Guillet-Thibault J. Oral manifestations of vitamin B12 and B9 deficiencies: a prospective study. J Oral Pathol Med. 2016;45(2):154.PubMedCrossRefPubMedCentralGoogle Scholar
  10. Axéll T. A prevalence study of oral mucosal lesions in an adult Swedish population. Odontol Revy Suppl. 1976;36:1–103.PubMedPubMedCentralGoogle Scholar
  11. Azizlerli G, Kose AA, Sarica R. Prevalence of Behcet’s disease in Istanbul, Turkey. Int J Dermatol. 2003;42(10):803–6.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Babaee N, Hosseinkazemi H, Pouramir M, Khakbaz Baboli O, Salehi M, Khadir F, Bijani A, Mehryari M. Salivary oxidant/antioxidant status and haematological parameters in patients with recurrent aphthous stomatitis. Caspian J Int Med. 2016;7(1):13–8.Google Scholar
  13. Baccaglini L, Lalla RV, Bruce AJ, Sartori-Valinotti JC, Latortue MC, Carrozzo M, Rogers RS 3rd. Urban legends: recurrent aphthous stomatitis. Oral Dis. 2011;17(8):755–70.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bachtiar EW, Cornain S, Siregar B, Raharjo TW. Decreased CD4+/CD8+ ratio in major type of recurrent aphthous ulcers: comparing major to minor types of ulcers. Asian Pac J Allergy Immunol. 1998;16(2–3):75–9.PubMedPubMedCentralGoogle Scholar
  15. Balasubramaniam R, Kuperstein AS, Stoopler ET. Update on oral herpes virus infections. Dent Clin N Am. 2014;58(2):265–80.PubMedCrossRefPubMedCentralGoogle Scholar
  16. Ballmer-Weber BK. Food allergy in adolescence and adulthood. Chem Immunol Allergy. 2015;101:51–8.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Bang DS, Oh SH, Lee KH. Influence of sex on patients with Behcet’s disease in Korea. J Korean Med Sci. 2003;18(2):231–5.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Bao ZX, Yang XW, Shi J, Liu LX. Serum zinc levels in 368 patients with oral mucosal diseases: a preliminary study. Med Oral Patol Oral Cir Bucal. 2016;21(3):e335–40.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Barker JM, Liu E. Celiac disease: pathophysiology, clinical manifestations, and associated autoimmune conditions. Adv Pediatr Infect Dis. 2008;55:349–65.Google Scholar
  20. Baumgart DC, Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007;369(9573):1641–57.PubMedCrossRefPubMedCentralGoogle Scholar
  21. Bazrafshani MR, Hajeer AH, Ollier WE, Thornhill MH. IL-1B and IL-6 gene polymorphisms encode significant risk for the development of recurrent aphthous stomatitis (RAS). Genes Immun. 2002;3(5):302–5.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Behçet H. Uber rezidivierende aphthöse, durch ein Virus verursachte Geschwure, am Mund, am Auge, und an den Genitalien. Dermatol Wochenschr. 1937;36:1152–7.Google Scholar
  23. Besu I, Jankovic L, Magdu IU, Konic-Ristic A, Raskovic S, Juranic Z. Humoral immunity to cow’s milk proteins and gliadin within the etiology of recurrent aphthous ulcers? Oral Dis. 2009;15(8):560–4.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Besu I, Jankovic L, Konic-Ristic A, Raskovic S, Besu V, Djuric M, Cakic S, Magdu IU, Juranic Z. The role of specific cow’s milk proteins in the etiology of recurrent aphthous ulcers. J Oral Pathol Med. 2013;42(1):82–8.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Boras VV, Lukac J, Brailo V, Picek P, Kordic D, Zilic IA. Salivary interleukin-6 and tumor necrosis factor-alpha in patients with recurrent aphthous ulceration. J Oral Pathol Med. 2006;35(4):241–3.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Bradley PJ, Ferlito A, Devaney KO, Rinaldo A. Crohn’s disease manifesting in the head and neck. Acta Otolaryngol. 2004;124(3):237–41.PubMedCrossRefPubMedCentralGoogle Scholar
  27. Brennan MT, Valerin MA, Napeñas JJ, Lockhart PB. Oral manifestations of patients with lupus erythematosus. Dent Clin N Am. 2005;49(1):127–41.PubMedCrossRefGoogle Scholar
  28. Brocklehurst P, Tickle M, Glenny AM, Lewis MA, Pemberton MN, Taylor J, Walsh T, Riley P, Yates JM. Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database Syst Rev. 2012;9:CD005411.Google Scholar
  29. Buno IJ, Huff JC, Weston WL, Cook DT, Brice SL. 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(7):827–31.PubMedCrossRefPubMedCentralGoogle Scholar
  30. Burgan SZ, Sawair FA, Amarin ZO. Hematologic status in patients with recurrent aphthous stomatitis in Jordan. Saudi Med J. 2006;27(3):381–4.PubMedPubMedCentralGoogle Scholar
  31. Burisch J, Jess T, Martinato M, Lakatos PL, ECCO -EpiCom. The burden of inflammatory bowel disease in Europe. J Crohns Colitis. 2013;7(4):322–37.PubMedCrossRefPubMedCentralGoogle Scholar
  32. Carrard V, Haas A, Rados P, Filho M, Oppermann R, Albandar J, Susin C. Prevalence and risk indicators of oral mucosal lesions in an urban population from South Brazil. Oral Dis. 2011;17(2):171–9.PubMedCrossRefPubMedCentralGoogle Scholar
  33. Challacombe SJ, Barkhan P, Lehner T. Haematological features and differentiation of recurrent oral ulceration. Br J Oral Surg. 1977;15(1):37–48.PubMedCrossRefPubMedCentralGoogle Scholar
  34. Chen H, Sui Q, Chen Y, Ge L, Lin M. Impact of haematologic deficiencies on recurrent aphthous ulceration: a meta-analysis. Br Dent J. 2015;218(4):E8.PubMedCrossRefPubMedCentralGoogle Scholar
  35. Chi AC, Day TA, Neville BW. Oral cavity and oropharyngeal squamous cell carcinoma–an update. CA Cancer J Clin. 2015;65(5):401–21.PubMedCrossRefPubMedCentralGoogle Scholar
  36. Collet E, Jeudy G, Dalac S. Cheilitis, perioral dermatitis and contact allergy. Eur J Dermatol. 2013;23(3):303–7.PubMedPubMedCentralGoogle Scholar
  37. Compilato D, Carroccio A, Calvino F, Di Fede G, Campisi G. Haematological deficiencies in patients with recurrent aphthosis. J Eur Acad Dermatol Venereol. 2010;24(6):667–73.PubMedCrossRefPubMedCentralGoogle Scholar
  38. Cowan D, Ho B, Sykes KJ, Wei JL. Pediatric oral burns: a ten-year review of patient characteristics, etiologies and treatment outcomes. Int J Pediatr Otorhinolaryngol. 2013;77(8):1325–8.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 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;16(1):58–60.PubMedCrossRefPubMedCentralGoogle Scholar
  40. Dalvi SR, Yildirim R, Yazici Y. Behcet’s syndrome. Drugs. 2012;72(17):2223–41.PubMedCrossRefPubMedCentralGoogle Scholar
  41. Davatchi F, Sadeghi Abdollahi B, Chams-Davatchi C, Shahram F, Shams H, Nadji A, Faezi T, Akhlaghi M, Ghodsi Z, Mohtasham N, Ashofteh F. The saga of diagnostic/classification criteria in Behcet’s disease. Int J Rheum Dis. 2015;18(6):594–605.PubMedCrossRefPubMedCentralGoogle Scholar
  42. de Carvalho FK, de Queiroz AM, Bezerra da Silva RA, Sawamura R, Bachmann L, Bezerra da Silva LA, Nelson-Filho P. Oral aspects in celiac disease children: clinical and dental enamel chemical evaluation. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;119(6):636–43.PubMedCrossRefPubMedCentralGoogle Scholar
  43. de Menthon M, Lavalley MP, Maldini C, et al. HLA-B51/B5 and the risk of Behcet’s disease: a systematic review and meta-analysis of case–control genetic association studies. Arthritis Rheum. 2009;61(10):1287–96.PubMedCrossRefGoogle Scholar
  44. Fairfield KM, Fletcher RH. Vitamins for chronic disease prevention in adults: scientific review. JAMA. 2002;287(23):3116–26.PubMedCrossRefPubMedCentralGoogle Scholar
  45. Fasano A, Catassi C. Clinical practice. Celiac disease. N Engl J Med. 2012;367(25):2419–26.PubMedCrossRefPubMedCentralGoogle Scholar
  46. Gallo C d B, Mimura MA, Sugaya NN. Psychological stress and recurrent aphthous stomatitis. Clinics (Sao Paulo). 2009;64(7):645–8.CrossRefGoogle Scholar
  47. García-Pola Vallejo MJ, Martínez Díaz-Canel AI, García Martín JM, González García M. Risk factors for oral soft tissue lesions in an adult Spanish population. Community Dent Oral Epidemiol. 2002;30(4):277–85.PubMedCrossRefPubMedCentralGoogle Scholar
  48. Gilvetti C, Porter SR, Fedele S. Traumatic chemical oral ulceration: a case report and review of the literature. Br Dent J. 2010;208(7):297–300.PubMedCrossRefPubMedCentralGoogle Scholar
  49. Green PHR, Cellier C. Celiac disease. N Engl J Med. 2007;357(17):1731–43.PubMedCrossRefPubMedCentralGoogle Scholar
  50. Gurler A, Boyvat A, Tursen U. Clinical manifestations of Behcet’s disease: an analysis of 2147 patients. Yonsei Med J. 1997;38(6):423–7.PubMedCrossRefPubMedCentralGoogle Scholar
  51. Gujral N, Freeman HJ, Thomson AB. Celiac disease: prevalence, diagnosis, pathogenesis and treatment. World J Gastroenterol. 2012;18(42):6036–59.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Hello M, Barbarot S, Bastuji-Garin S, Revuz J, Chosidow O. Use of thalidomide for severe recurrent aphthous stomatitis: a multicenter cohort analysis. Medicine (Baltimore). 2010;89(3):176–82.CrossRefGoogle Scholar
  53. Ho MH, Wong WH, Chang C. Clinical spectrum of food allergies: a comprehensive review. Clin Rev Allergy Immunol. 2014;46(3):225–40.PubMedCrossRefPubMedCentralGoogle Scholar
  54. International Study Group for Behçet Disease. Criteria for diagnosis of Behçet disease. Lancet. 1990;335(8697):1078–80.Google Scholar
  55. International Team for the Revision of the International Criteria for Behçet Disease (ITR-ICBD). The international criteria for Behçet disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol. 2014;28(3):338–47.CrossRefGoogle Scholar
  56. Jung SA. Differential diagnosis of inflammatory bowel disease: what is the role of colonoscopy? Clin Endosc. 2012;45(3):254–62.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Kalla R, Ventham NT, Satsangi J, Arnott ID. Crohn’s disease. BMJ. 2014;349:g6670.PubMedCrossRefPubMedCentralGoogle Scholar
  58. Katsanos KH, Torres J, Roda G, Brygo A, Delaporte E, Colombel JF. Review article: non-malignant oral manifestations in inflammatory bowel diseases. Aliment Pharmacol Ther. 2015;42(1):40–60.PubMedCrossRefPubMedCentralGoogle Scholar
  59. Khan NF, Saeed M, Chaudhary S, Khan NF. Haematological parameters and recurrent aphthous stomatitis. J Coll Physicians Surg Pak. 2013;23(2):124–7.PubMedPubMedCentralGoogle Scholar
  60. Keogan MT. Clinical Immunology Review Series: an approach to the patient with recurrent orogenital ulceration, including Behcet’s syndrome. Clin Exp Immunol. 2009;156(1):1–11.PubMedPubMedCentralCrossRefGoogle Scholar
  61. Kim B, LeBoit PE. Histopathologic features of erythema nodosum – like lesions in Behcet disease: a comparison with erythema nodosum focusing on the role of vasculitis. Am J Dermatopathol. 2000;22(5):379–90.PubMedCrossRefPubMedCentralGoogle Scholar
  62. Kitaichi N, Miyazaki A, Iwata D, et al. Ocular features of Behcet’s disease: an international collaborative study. Br J Ophthalmol. 2007;91(12):1579–82.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Krause I, Rosen Y, Kaplan I, et al. Recurrent aphthous stomatitis in Behcet’s disease: clinical features and correlation with systemic disease expression and severity. J Oral Pathol Med. 1999;28(5):193–6.PubMedCrossRefPubMedCentralGoogle Scholar
  64. Koybasi S, Parlak AH, Serin E, Yilmaz F, Serin D. Recurrent aphthous stomatitis: investigation of possible etiologic factors. Am J Otolaryngol. 2006;27(4):229–32.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 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;39(5):420–3.PubMedPubMedCentralGoogle Scholar
  66. Lalla RV, Choquette LE, Feinn RS, Zawistowski H, Latortue MC, Kelly ET, Baccaglini L. Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double-masked, placebo-controlled trial. J Am Dent Assoc. 2012;143(4):370–6.PubMedPubMedCentralCrossRefGoogle Scholar
  67. Lankarani KB, Sivandzadeh GR, Hassanpour S. Oral manifestation in inflammatory bowel disease: a review. World J Gastroenterol. 2013;19:8571–9.PubMedPubMedCentralCrossRefGoogle Scholar
  68. Laranjeira N, Fonseca J, Meira T, Freitas J, Valido S, Leitão J. Oral mucosa lesions and oral symptoms in inflammatory bowel disease patients. Arq Gastroenterol. 2015;52(2):105–10.PubMedCrossRefPubMedCentralGoogle Scholar
  69. Lin SS, Chou MY, Ho CC, Kao CT, Tsai CH, Wang L, Yang CC. Study of the viral infections and cytokines associated with recurrent aphthous ulceration. Microbes Infect. 2005;7(4):635–44.PubMedCrossRefPubMedCentralGoogle Scholar
  70. Lionetti E, Castellaneta S, Francavilla R, Pulvirenti A, Tonutti E, Amarri S, Barbato M, Barbera C, Barera G, Bellantoni A, Castellano E, Guariso G, Limongelli MG, Pellegrino S, Polloni C, Ughi C, Zuin G, Fasano A, Catassi C, SIGENP (Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition) Working Group on Weaning and CD Risk. Introduction of gluten, HLA status, and the risk of celiac disease in children. N Engl J Med. 2014;371(14):1295–303.PubMedCrossRefPubMedCentralGoogle Scholar
  71. Lo Russo L, Fedele S, Guiglia R, Ciavarella D, Lo Muzio L, Gallo P, Di Liberto C, Campisi G. Diagnostic pathways and clinical significance of desquamative gingivitis. J Periodontol. 2008;79(1):4–24.PubMedCrossRefPubMedCentralGoogle Scholar
  72. Lopez-Jornet P, Camacho-Alonso F, Martos N. Hematological study of patients with aphthous stomatitis. Int J Dermatol. 2014;53(2):159–63.PubMedCrossRefPubMedCentralGoogle Scholar
  73. Main DM, Chamberlain MA. Clinical differentiation of oral ulceration in Behcet’s disease. Br J Rheumatol. 1992;31(11):767–70.PubMedCrossRefPubMedCentralGoogle Scholar
  74. Marty M, Bailleul-Forestier I, Vaysse F. Recurrent Aphthous stomatitis as a marker of celiac disease in children. Pediatr Dermatol. 2016;33(2):241.PubMedCrossRefPubMedCentralGoogle Scholar
  75. McCartan BE, Healy CM, McCreary CE, Flint SR, Rogers S, Toner ME. Characteristics of patients with orofacial granulomatosis. Oral Dis. 2011;17(7):696–704.PubMedCrossRefGoogle Scholar
  76. McGowan EC, Peng RD, Salo PM, Zeldin DC, Keet CA. Changes in food-specific IgE over time in the National Health and nutrition examination survey (NHANES). J Allergy Clin Immunol Pract. 2016;4(4):713–20.PubMedPubMedCentralCrossRefGoogle Scholar
  77. McMillan R, Taylor J, Shephard M, Ahmed R, Carrozzo M, Setterfield J, Grando S, Mignogna M, Kuten-Shorrer M, Musbah T, Elia A, McGowan R, Kerr AR, Greenberg MS, Hodgson T, Sirois D. World workshop on oral medicine VI: a systematic review of the treatment of mucocutaneous pemphigus vulgaris. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;120(2):132–42.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Miller MF, Garfunkel AA, Ram CA, Ship II. The inheritance of recurrent aphthous stomatitis. Observations on susceptibility. Oral Surg Oral Med Oral Pathol. 1980;49(5):409–12.PubMedCrossRefPubMedCentralGoogle Scholar
  79. Mortazavi H, Safi Y, Baharvand M, Rahmani S. Diagnostic features of common oral ulcerative lesions: an updated decision tree. Int J Dent. 2016;2016:7278925.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Nahlieli O, Eliav E, Shapira Y, Baruchin AM. Central palatal burns associated with the eating of microwaved pizzas. Burns. 1999;25(5):465–6.PubMedCrossRefPubMedCentralGoogle Scholar
  81. National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention – Epidemiology of the IBD – Inflammatory Bowel Disease. [Internet] 2015 [page last updated: March 31, 2015]. Available from: www.cdc.gov/ibd/ibd-epidemiology.htm. Accessed 19 Aug 2016.
  82. Ogura M, Yamamoto T, Morita M, Watanabe T. A case-control study on food intake of patients with recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91(1):45–9.PubMedCrossRefPubMedCentralGoogle Scholar
  83. Olson JA, Feinberg I, Silverman S Jr, Abrams D, Greenspan JS. Serum vitamin B12, folate, and iron levels in recurrent aphthous ulceration. Oral Surg Oral Med Oral Pathol. 1982;54(5):517–20.PubMedCrossRefPubMedCentralGoogle Scholar
  84. Orbak R, Cicek Y, Tezel A, Dogru Y. Effects of zinc treatment in patients with recurrent aphthous stomatitis. Dent Mater J. 2003;22(1):21–9.PubMedCrossRefPubMedCentralGoogle Scholar
  85. Orbak R, Kara C, Ozbek E, Tezel A, Demir T. Effects of zinc deficiency on oral and periodontal diseases in rats. J Periodontal Res. 2007;42(2):138–43.PubMedCrossRefPubMedCentralGoogle Scholar
  86. Ozler GS. Zinc deficiency in patients with recurrent aphthous stomatitis: a pilot study. J Laryngol Otol. 2014;128(6):531–3.PubMedCrossRefPubMedCentralGoogle Scholar
  87. Ozturk P, Belge Kurutas E, Ataseven A. Copper/zinc and copper/selenium ratios, and oxidative stress as biochemical markers in recurrent aphthous stomatitis. J Trace Elem Med Biol. 2013;27(4):312–6.PubMedCrossRefPubMedCentralGoogle Scholar
  88. Pedersen A, Hornsleth A. Recurrent aphthous ulceration: a possible clinical manifestation of reactivation of varicella zoster or cytomegalovirus infection. J Oral Pathol Med. 1993;22(2):64–8.PubMedCrossRefPubMedCentralGoogle Scholar
  89. Pekiner FN, Aytugar E, Demirel GY, Borahan MO. Interleukin-2, interleukin-6 and T regulatory cells in peripheral blood of patients with Behçet’s disease and recurrent aphthous ulcerations. J Oral Pathol Med. 2012;41(1):73–9.PubMedCrossRefPubMedCentralGoogle Scholar
  90. Pentenero M, Broccoletti R, Carbone M, Conrotto D, Gandolfo S. The prevalence of oral mucosal lesions in adults from the Turin area. Oral Dis. 2008;14(4):356–66.PubMedCrossRefPubMedCentralGoogle Scholar
  91. Piskin S, Sayan C, Durukan N, Senol M. Serum iron, ferritin, folic acid, and vitamin B12 levels in recurrent aphthous stomatitis. J Eur Acad Dermatol Venereol. 2002;16(1):66–7.CrossRefGoogle Scholar
  92. Pittock S, Drumm B, Fleming P, McDermott M, Imrie C, Flint S, Bourke B. The oral cavity in Crohn’s disease. J Pediatr. 2001;138:767–71.PubMedCrossRefGoogle Scholar
  93. Porter SR, Scully C, Flint S. Hematologic status in recurrent aphthous stomatitis compared with other oral disease. Oral Surg Oral Med Oral Pathol. 1988;66(1):41–4.PubMedCrossRefPubMedCentralGoogle Scholar
  94. Preeti L, Magesh KT, Rajkumar K, Karthik R. Recurrent aphthous stomatitis. J Oral Maxillofac Pathol. 2011;15(3):252–6.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Rashid M, Zarkadas M, Anca A, Limeback H. Oral manifestations of celiac disease: a clinical guide for dentists. J Can Dent Assoc. 2011;77:b39.PubMedPubMedCentralGoogle Scholar
  96. Rogers RS 3rd, Hutton KP. Screening for haematinic deficiencies in patients with recurrent aphthous stomatitis. Australas J Dermatol. 1986;27(3):98–103.PubMedCrossRefPubMedCentralGoogle Scholar
  97. Sackett DL, Haynes RB, Guyatt GH, Tugwell P. Clinical epidemiology: a basic science for clinical medicine. 2nd ed. Boston: Little, Brown; 1991.Google Scholar
  98. Sakane T, Takeno M, Suzuki N, et al. Behcet’s disease. N Engl J Med. 1999;341(17):1284–91.PubMedPubMedCentralCrossRefGoogle Scholar
  99. Samim F, Auluck A, Zed C, Williams PM. Erythema multiforme: a review of epidemiology, pathogenesis, clinical features, and treatment. Dent Clin North Am. 2013;57(4):583–96.PubMedCrossRefPubMedCentralGoogle Scholar
  100. Sartor RB. Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2006;3(7):390–407.PubMedCrossRefPubMedCentralGoogle Scholar
  101. Scully C. Clinical practice. Aphthous ulceration. N Engl J Med. 2006;355(2):165–72.PubMedCrossRefPubMedCentralGoogle Scholar
  102. Ship II. Epidemiologic aspects of recurrent aphthous ulcerations. Oral Surg Oral Med Oral Pathol. 1972;33(3):400–6.PubMedCrossRefPubMedCentralGoogle Scholar
  103. Scully C, Felix DH. Oral medicine–update for the dental practitioner. Aphthous and other common ulcers. Br Dent J. 2005;199(5):259–64.PubMedCrossRefPubMedCentralGoogle Scholar
  104. Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc. 2003;134(2):200–7.PubMedCrossRefPubMedCentralGoogle Scholar
  105. Senusi A, Seoudi N, Bergmeier LA, et al. Genital ulcer severity score and genital health quality of life in Behcet’s disease. Orphanet J Rare Dis. 2015;10:117.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Seyedmajidi SA, Seyedmajidi M, Moghadamnia A, Khani Z, Zahedpasha S, Jenabian N, Jorsaraei G, Halalkhor S, Motallebnejad M. Effect of zinc-deficient diet on oral tissues and periodontal indices in rats. Int J Mol Cell Med. 2014;3(2):81–7.PubMedPubMedCentralGoogle Scholar
  107. Shah D, Sachdev HS, Gera T, De-Regil LM, Peña-Rosas JP. Fortification of staple foods with zinc for improving zinc status and other health outcomes in the general population. Cochrane Database Syst Rev. 2016;6:CD010697.Google Scholar
  108. Ship II. Nutrition and food intake in aphthous ulcerations. Arch Environ Health. 1962;5:158–66.PubMedCrossRefPubMedCentralGoogle Scholar
  109. Ship JA, Chavez EM, Doerr PA, Henson BS, Sarmadi M. Recurrent aphthous stomatitis. Quintessence Int. 2000;31(2):95–112.PubMedPubMedCentralGoogle Scholar
  110. Shulman JD, Beach MM, Rivera-Hidalgo F. The prevalence of oral mucosal lesions in U.S. adults: data from the third National Health and nutrition examination survey, 1988–1994. J Am Dent Assoc. 2004;135(9):1279–86.PubMedCrossRefPubMedCentralGoogle Scholar
  111. Singh B, Kedia S, Konijeti G, Mouli VP, Dhingra R, Kurrey L, Srivastava S, Pradhan R, Makharia G, Ahuja V. Extra-intestinal manifestations of inflammatory bowel disease and intestinal tuberculosis: frequency and relation with disease phenotype. Indian J Gastroenterol. 2015;34:43–50.PubMedCrossRefPubMedCentralGoogle Scholar
  112. Slebioda Z, Szponar E, Kowalska A. Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: literature review. Arch Immunol Ther Exp. 2014;62(3):205–15.CrossRefGoogle Scholar
  113. Sun A, Chen HM, Cheng SJ, Wang YP, Chang JY, YC W, Chiang CP. 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;44(4):300–5.PubMedCrossRefPubMedCentralGoogle Scholar
  114. Sun A, Chu CT, Liu BY, Wang JT, Leu JS, Chiang CP. Expression of interleukin-2 receptor by activated peripheral blood lymphocytes upregulated by the plasma level of interleukin-2 in patients with recurrent aphthous ulcers. Proc Natl Sci Counc Repub China B. 2000;24(3):116–22.PubMedPubMedCentralGoogle Scholar
  115. Taylor J, Glenny AM, Walsh T, et al. Interventions for the management of oral ulcers in Behcet’s disease. Cochrane Database Syst Rev. 2014;9:CD011018.Google Scholar
  116. Taylor J, McMillan R, Shephard M, Setterfield J, Ahmed R, Carrozzo M, Grando S, Mignogna M, Kuten-Shorrer M, Musbah T, Elia A, McGowan R, Kerr AR, Greenberg MS, Hodgson T, Sirois D. World workshop on oral medicine VI: a systematic review of the treatment of mucous membrane pemphigoid. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;120(2):161–71.PubMedCrossRefGoogle Scholar
  117. Thongprasom K, Youngnak P, Aneksuk V. Hematologic abnormalities in recurrent oral ulceration. Southeast Asian J Trop Med Public Health. 2002;33(4):872–7.PubMedPubMedCentralGoogle Scholar
  118. Topaloğlu Demir F, Kocatürk E, Yorulmaz E, Adalı G, Kavala M. Mucocutaneous manifestations of inflammatory bowel disease in Turkey. J Cutan Med Surg. 2014;18(6):397–404.PubMedCrossRefPubMedCentralGoogle Scholar
  119. Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, et al. Uveitis in Behcet disease: an analysis of 880 patients. Am J Ophthalmol. 2004;138(3):373–80.PubMedCrossRefGoogle Scholar
  120. Veloso FT, Carvalho J, Magro F. Immune-related systemic manifestations of inflammatory bowel disease. A prospective study of 792 patients. J Clin Gastroenterol. 1996;23(1):29–34.PubMedCrossRefPubMedCentralGoogle Scholar
  121. Victoria JM, Kalapothakis E, Silva Jde F, Gomez RS. Helicobacter pylori DNA in recurrent aphthous stomatitis. J Oral Pathol Med. 2003;32(4):219–23.PubMedCrossRefPubMedCentralGoogle Scholar
  122. Vidal-Alaball J, Butler CC, Cannings-John R, Goringe A, Hood K, McCaddon A, McDowell I, Papaioannou A. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2005;3:CD004655.Google Scholar
  123. Volkov I, Rudoy I, Freud T, Sardal G, Naimer S, Peleg R, Press Y. Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled trial. J Am Board Fam Med. 2009;22(1):9–16.PubMedCrossRefPubMedCentralGoogle Scholar
  124. Wardhana, Datau EA. Recurrent aphthous stomatitis caused by food allergy. Acta Med Indones. 2010;42(4):236–40.PubMedPubMedCentralGoogle Scholar
  125. World Health Organization. Nutrition. Micronutrients. [Internet] 2016. Available from: www.who.int/nutrition/topics/micronutrients/en/#. Accessed 19 Aug 2016.
  126. Wray D. A double-blind trial of systemic zinc sulfate in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol. 1982;53(5):469–72.PubMedCrossRefPubMedCentralGoogle Scholar
  127. Wray D, Ferguson MM, Mason DK, Hutcheon AW, Dagg JH. Recurrent aphthae: treatment with vitamin B12, folic acid, and iron. Br Med J. 1975;2(5969):490–3.PubMedPubMedCentralCrossRefGoogle Scholar
  128. Wray D, Ferguson MM, Hutcheon AW, Dagg JH. Nutritional deficiencies in recurrent aphthae. J Oral Pathol Med. 1978;7(6):418–23.CrossRefGoogle Scholar
  129. Wray D, Vlagopoulos TP, Siraganian RP. Food allergens and basophil histamine release in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol. 1982;54(4):388–95.PubMedCrossRefPubMedCentralGoogle Scholar
  130. Wright A, Ryan FP, Willingham SE, Holt S, Page AC, Hindle MO, Franklin CD. Food allergy or intolerance in severe recurrent aphthous ulceration of the mouth. Br Med J (Clin Res Ed). 1986;292(6530):1237–8.CrossRefGoogle Scholar
  131. Yamamoto T, Yoneda K, Ueta E, Osaki T. Serum cytokines, interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in oral disorders. Oral Surg Oral Med Oral Pathol. 1994;78(6):727–35.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Giovanni Lodi
    • 1
    Email author
  • Elena Varoni
    • 1
  • Jairo Robledo-Sierra
    • 2
  • Alessandro Villa
    • 3
    • 4
  • Mats Jontell
    • 2
  1. 1.Dipartimento di Scienze Biomediche, Chirurgiche e OdontoiatricheUniversità degli Studi di MilanoMilanItaly
  2. 2.Department of Oral Medicine and Pathology, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
  3. 3.Department of Oral Medicine, Infection and ImmunityHarvard School of Dental MedicineBostonUSA
  4. 4.Division of Oral Medicine and DentistryBrigham and Women’s HospitalBostonUSA

Personalised recommendations