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Aphthous Ulcers Clinical Presentation

  • Author: Crispian Scully, MD, MRCS, PhD, MDS, CBE, FDSRCS(Eng), FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FSB, DSc, DChD, DMed(HC), Dr(HC); Chief Editor: Arlen D Meyers, MD, MBA  more...
 
Updated: May 10, 2016
 

History

The 3 main clinical types of recurrent aphthous stomatitis (RAS) are as follows:

(1) Minor aphthous ulcers (MiAUs, 80% of all RAS)

(2) Major aphthous ulcers (MjAUs)

(3) Herpetiform ulcers.

However, any significance of these distinctions is unclear (ie, they could just be 3 distinct disorders). Diagnosis is based on history and clinical features.

Characteristics of MiAUs (ie, Mikulicz ulcers) include the following:

  • They occur mainly in persons 10-40 years of age.
  • They often cause minimal symptoms.
  • They are small round or ovoid ulcers 2-4 mm in diameter. (MiAUs are round or ovoid in most situations but are often more linear when in the buccal sulcus, a common site.)
  • They have an ulcer floor that is initially yellowish but assumes a gray hue as healing and epithelialization proceeds.
  • They are surrounded by an erythematous halo and some edema.
  • They are found mainly on the nonkeratinized mobile mucosa of the lips, cheeks, floor of the mouth, sulci, or ventrum of the tongue; they are uncommonly seen on the keratinized mucosa of the palate or dorsum of the tongue.
  • They occur in groups of only a few ulcers (ie, 1-6) at a time.
  • They heal in 7-10 days.
  • They recur at intervals of 1-4 months.
  • They leave little or no evidence of scarring.

Characteristics of MjAUs (ie, Sutton ulcers, periadenitis mucosa necrotica recurrens [PMNR]) include the following:

  • They are larger, of longer duration, of more frequent recurrence, and often more painful than MiAUs.
  • They are round or ovoid like MiAUs but are larger and associated with surrounding edema.
  • They reach a large size, usually about 1 cm in diameter or even larger.
  • They are found on any area of the oral mucosa, including the keratinized dorsum of the tongue or palate.
  • They occur in groups of only a few ulcers (ie, 1-6) at one time.
  • They heal slowly over 10-40 days.
  • They recur extremely frequently.
  • They may heal with scarring.
  • They occasionally are found with a raised erythrocyte sedimentation rate or plasma viscosity.

Characteristics of herpetiform ulceration (HU) include the following:

  • They are found in a slightly older age group than the other RAS.
  • They are mainly found in females.
  • They begins with vesiculation that passes rapidly into multiple, minute, pinhead-sized, discrete ulcers.
  • They involve any oral site, including the keratinized mucosa, increase in size, and coalesce to leave large round ragged ulcers.
  • They heal in 10 days or longer.
  • They are often extremely painful.
  • They recur so frequently that ulceration may be virtually continuous.

Most patients with RAS appear to be otherwise well, but a minority have etiologic/precipitating factors that can be identified by the history. These factors may include the following:

  • Dentifrices containing sodium lauryl sulfate
  • Trauma
  • Stress
  • Cessation of smoking
  • Menstrual cycle association
  • Food allergy

Aphthous-like ulcers may appear in the following diseases and states:

  • Hematinic deficiency (eg, iron, folate, vitamin B-12)
  • Celiac disease
  • Crohn disease
  • Behçet syndrome, which may include genital, cutaneous, ocular, or other lesions (The mouth ulcers in Behçet syndrome often mimic major aphthae, with frequent episodes and long duration to healing.)
  • Immunodeficiencies such as human immunodeficiency virus (HIV) infection, and neutropenia (Ulcers appearing on a regular 3-week cycle may indicate cyclic neutropenia.)
  • Auto-inflammatory syndromes, such as periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) in children
  • Malignancy (Ulcers appearing for the first time in an older individual may reflect underlying systemic disease [eg, colonic carcinoma with chronic hemorrhage].)
  • Drug use (eg, nicorandil, NSAIDs, others)
  • Sweet syndrome, a rare immunologically mediated condition that belongs to the group of neutrophilic dermatoses and must be differentiated, particularly from Behçet disease
    • Sweet syndrome is characterized by red-brown plaques and nodules that are frequently painful and occur primarily on the head, neck, and upper extremities.
    • Patients often also have neutrophilia and fever and may have oral ulceration.
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Physical

RAS ulcers are recurrent small, round, or ovoid ulcers with circumscribed margins, erythematous haloes, and yellow or gray floors. No specific investigations exist for RAS; the other causes of recurrent mouth ulceration noted above, should be excluded.

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Causes

Some RAS cases involve a familial and genetic basis; approximately 40% of patients with RAS have a familial history, but inheritance may be polygenic with penetrance dependent on other factors.

Most relevant studies have found hematinic (eg, iron, folic acid, vitamin B-12) deficiencies in as many as 20% of patients with recurrent ulcers. In addition, deficiencies of vitamins B-1, B-2, and B-6 have been noted in some patient cohorts.

The previously proposed association between recurrent ulcers and celiac disease (gluten-sensitive enteropathy [GSE]) is tenuous, despite some evidence that the haplotype of HLA-DRW 10 and DQW1 may predispose patients with GSE to RAS.

Hypersensitivity reactions to exogenous antigens other than gluten do not have a significant etiologic role in RAS, and associations with atopy are inconsistent. Moreover, a consistent association between aphthous ulceration and psychological illness, zinc deficiency, or sex hormone levels is unlikely.

Local physical trauma may initiate ulcers in susceptible people, and RAS is uncommon where mucosal keratinization is present or in patients who smoke tobacco.

Various microorganisms have been examined for a causal association. Latterly, Helicobacter pylori has been detected in lesional tissue of ill-defined oral ulcers, but the frequency of serum immunoglobin G (IgG) antibodies to H pylori is not increased in RAS. On the other hand, a study by Gülseren et al indicated that H pylori may play a role in the etiology of RAS. The rapid urease test was used to find the bacterium in dental plaque samples from 34 of 38 patients with RAS (89.5%), compared with 24 of 43 controls (55.8%).[4]

A study by Hijazi et al also suggested that the development of idiopathic RAS is associated with changes in the mucosal microbiome. The investigators found, for example, that species of the bacterial family Porphyromonadaceae related to periodontal disease were more abundant in ulcerated areas in the mucosae of patients with RAS than in the mucosae of healthy controls. In contrast, species of the bacterial family Streptococcaceae that are associated with oral health were more abundant in the healthy controls than in the ulcerated areas of RAS patients.[5]

Similarly, a study by Kim et al suggested that dysbiosis contributes to the development of RAS. In an analysis of the oral mucosa and saliva from RAS patients and controls, the investigators found that the patients with RAS had reductions in healthy core microbiota and increases in rare microbial species. These changes included decreases in Streptococcus salivarius and increases in Acinetobacter johnsonii.[6]

Little evidence suggests an etiologic association between viruses and RAS. Human herpesvirus (HHV)–6 and HHV-7 DNA has not been demonstrated in RAS, but HHV-8 DNA is present in HIV-related oral ulcers.

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Contributor Information and Disclosures
Author

Crispian Scully, MD, MRCS, PhD, MDS, CBE, FDSRCS(Eng), FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FSB, DSc, DChD, DMed(HC), Dr(HC) Emeritus Professor, University College London; Visiting Professor, Universities of Athens, BPP, Edinburgh, Granada, Helsinki and Plymouth

Crispian Scully, MD, MRCS, PhD, MDS, CBE, FDSRCS(Eng), FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FSB, DSc, DChD, DMed(HC), Dr(HC) is a member of the following medical societies: Academy of Medical Sciences, British Society for Oral Medicine, European Association for Oral Medicine, International Academy of Oral Oncology, International Association for Dental Research, International Association for Oral and Maxillofacial Pathology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Robert M Kellman, MD Professor and Chair, Department of Otolaryngology and Communication Sciences, State University of New York Upstate Medical University

Robert M Kellman, MD is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Head and Neck Society, American Rhinologic Society, Triological Society, American Neurotology Society, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Medical Association, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;SymbiaAllergySolutions<br/>Received income in an amount equal to or greater than $250 from: Symbia<br/>Received from Allergy Solutions, Inc for board membership; Received honoraria from RxRevu for chief medical editor; Received salary from Medvoy for founder and president; Received consulting fee from Corvectra for senior medical advisor; Received ownership interest from Cerescan for consulting; Received consulting fee from Essiahealth for advisor; Received consulting fee from Carespan for advisor; Received consulting fee from Covidien for consulting.

Additional Contributors

Hassan H Ramadan, MD, MSc Professor and Vice-Chair, Department of Otolaryngology-Head and Neck Surgery, Professor, Department of Pediatrics, West Virginia University School of Medicine

Hassan H Ramadan, MD, MSc is a member of the following medical societies: American Academy of Otolaryngic Allergy, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Rhinologic Society

Disclosure: Nothing to disclose.

References
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  2. Preeti L, Magesh K, Rajkumar K, Karthik R. Recurrent aphthous stomatitis. J Oral Maxillofac Pathol. 2011 Sep. 15(3):252-6. [Medline]. [Full Text].

  3. Shotts RH, Scully C, Avery CM, Porter SR. Nicorandil-induced severe oral ulceration: a newly recognized drug reaction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999 Jun. 87(6):706-7. [Medline].

  4. Gülseren D, Karaduman A, Kutsal D, Nohutcu RM. The relationship between recurrent aphthous stomatitis, and periodontal disease and Helicobacter Pylori infection. Clin Oral Investig. 2016 Jan 6. [Medline].

  5. Hijazi K, Lowe T, Meharg C, et al. Mucosal Microbiome in Patients with Recurrent Aphthous Stomatitis. J Dent Res. 2014 Dec 24. [Medline].

  6. Kim YJ, Choi YS, Baek KJ, Yoon SH, Park HK, Choi Y. Mucosal and salivary microbiota associated with recurrent aphthous stomatitis. BMC Microbiol. 2016 Apr 1. 16 Suppl 1:57. [Medline]. [Full Text].

  7. 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].

  8. 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].

  9. 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].

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  13. 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].

  14. Calderon PE, Valenzuela FA, Carreno LE, Madrid AM. A possible link between cow milk and recurrent aphtous stomatitis. J Eur Acad Dermatol Venereol. 2008 Jul. 22(7):898-9. [Medline].

  15. 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].

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

  17. Gulcan E, Toker S, Hatipoğlu H, Gulcan A, Toker A. Cyanocobalamin may bebeneficial in the treatment of recurrent aphthous ulcers even when vitamin B12levels are normal. Am J Med Sci. 2008. 336:379-82.

  18. Marakoglu K, Sezer RE, Toker HC, Marakoglu I. The recurrent aphthous stomatitis frequency in the smoking cessation people. Clin Oral Investig. 2007 Jun. 11(2):149-53. [Medline].

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  22. Porter S, Scully C. Aphthous ulcers (recurrent). Clin Evid. 2004. 12:360-361.

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  27. Volkov I, Rudoy I, Freud T, Sardal G, Naimer S, Peleg R, et al. Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: arandomized, double-blind, placebo-controlled trial. J Am Board Fam Med. 2009. 22:9-16.

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Traumatic ulcer on ventrum/lateral margin of tongue; these must be differentiated from aphthae.
Recurrent aphthae in floor of mouth, showing ovoid ulcer with inflammatory halo.
Typical aphthous ulcer in a common site, showing inflammatory halo surrounding a yellowish round ulcer.
 
 
 
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