Recurrent aphthous stomatitis

Last updated on: 06.02.2024

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Recurrent aphthous stomatitis (mouth ulcer) is characterized by painful mucosal ulcers in non-keratinized areas of the mouth and throat (Bijelić B et al. 2019).

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Although no single identifiable cause has been identified, the etiology of aphthous stomatitis is thought to be multifactorial (Ship II 1966)]. This disease is associated with autoimmune diseases such as Behcet's disease, inflammatory bowel disease, gluten sensitivity (CD) and SLE, as well as various dermatologic diseases, malnutrition (e.g. vitamin B12, folate and iron deficiencies), infections (e.g. HIV) and certain medications (e.g. methotrexate).

In a meta-analysis (Nieri M et al. 2017), the authors demonstrated a higher prevalence of recurrent aphthous stomatitis (RAS) in CD patients compared to healthy individuals (OR: 3.79, 95%CI: 2.67-5.3). This association has been demonstrated in pediatric populations.

Local trauma, e.g. an accidental bite on the tongue, is also a common trigger of the disease (Gasmi Benahmed A et al. 2021).

Furthermore, RAS characterizes Behçet's disease. Atypical severe RAS can occur as a monitoring sign of HIV infection (Plewa MC et al. 2024).

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T-cell-mediated immune disorders and the secretion of cytokines such as TNF-alpha play an important role in the development of aphthous ulcers (Albrektson M et al. 2014).

Clinical features
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Aphthous ulcers are characterized by their round to oval shape, with crater-like defects with a yellowish-grey base and erythematous margins. The ulcers can manifest in various forms, including smaller ulcers (the most common), larger ulcers and herpetiform ulcers (26Shakeri R et al. 2009).

Clinical studies: In a study by Shakeri et al. in Iran, 247 patients with recurrent aphthous ulcers were examined. In a subgroup of patients (2.83%), there was a significant improvement in symptoms within six months of the introduction of a strict GFD (gluten-free diet). This improvement was also observed in cases that did not respond to conventional anti-aphta treatment (Ferguson R et al. 1976).

In a further study by Ferguson et al. in Birmingham, similar results were obtained with the indication of a causative gluten sensitivity for aphthous ulcers. A study by Wray on 20 patients with recurrent aphthous stomatitis, all of whom were on a GFD, showed a favorable response in 25% of patients, suggesting gluten sensitivity even without enteropathy (28Wray D 1981). A meta-analysis showed that patients with CD were significantly more likely to develop aphthous stomatitis compared to healthy individuals (OR=3.79, 95% CI=2.67-5.39) [30]. In addition, Ferguson et al. recommended screening for folate, B12 and iron deficiency in patients with recurrent aphthous stomatitis, with jejunal biopsy only performed if there are signs of malabsorption.

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Treatment of aphthous stomatitis focuses on symptom relief and includes the use of topical corticosteroids, antimicrobials and anesthetics. The above studies suggest that screening for vitamin deficiencies and serologic markers may improve the evaluation and treatment of aphthous ulcers.

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  1. Akintoye SO et al (2014) Recurrent aphthous stomatitis. Dent Clin North Am 58:281-297.
  2. Albrektson M et al. (2014) Recurrent aphthous stomatitis and pain management with low-level laser therapy: a randomized controlled trial. Oral Surg Oral Med Oral Pathol Oral Radiol 117:590-594.
  3. Bijelić B et al. (2019) Celiac disease-specific and inflammatory bowel disease-related antibodies in patients with recurrent aphthous stomatitis. Immunobiology 224:75-79.
  4. Ferguson R et al. (1976) Jejunal mucosal abnormalities in patients with recurrent aphthous ulceration. Br Med J 1:11-13.
  5. Gasmi Benahmed A et al. (2021) Oral aphthous: pathophysiology, clinical aspects and medical treatment. Arch Razi Inst 76:1155-1163.
  6. Nieri M et al. (2017) Enamel defects and aphthous stomatitis in celiac and healthy subjects: systematic review and meta-analysis of controlled studies. J Dent 65:1-10.
  7. Plewa MC et al. (2024) Recurrent aphthous stomatitis. 2023 Nov 13. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. PMID: 28613713.

  8. Shakeri R et al. (2009) Gluten sensitivity enteropathy in patients with recurrent aphthous stomatitis. BMC Gastroenterol 9:44.
  9. Ship II (1966) Socioeconomic status and recurrent aphthous ulcers. J Am Dent Assoc73:120-123.
  10. Wray D (1981) Gluten-sensitive recurrent aphthous stomatitis. Dig Dis Sci 26:737-740.


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Last updated on: 06.02.2024