What causes recurrent aphthous ulcers?

Causes of Recurrent Aphthous Ulcers

Recurrent aphthous ulcers (RAU) are caused by a multifactorial combination of genetic predisposition, immune dysfunction, nutritional deficiencies, and environmental triggers, with no single definitive cause identified in most cases. 1

Classification and Presentation

• Minor aphthous ulcers: Most common (80-85%), <1cm in size, healing within 7-14 days 2
• Major aphthous ulcers: Larger, deeper, may leave scarring
• Herpetiform ulcers: Multiple small clustered ulcers

Primary Etiological Factors

1. Genetic Predisposition

• Strong genetic component with familial patterns 3
• Associated with specific interleukin genotypes 3
• Approximately 7% of cases may have familial tendencies 4

2. Immune System Dysfunction

• Disturbed immune response plays a central role 1
• Abnormal T-cell-mediated immune response 4
• Cytokine imbalances affecting mucosal integrity

3. Nutritional Deficiencies

• Vitamin B12 deficiency: Strong association with RAU recurrence 5
• Iron deficiency: May contribute to ulcer development
• Folate deficiency: Associated with persistent ulceration
• Zinc deficiency: May impair healing and increase susceptibility

4. Triggering Factors

Local Factors:

• Trauma: Mechanical injury to oral mucosa 1, 6
• Poor oral hygiene: Inadequate brushing time is a risk factor 7
• Dental appliances: Dentures or braces may trigger ulcers 7

Systemic Factors:

• Stress: Significant association with ulcer outbreaks 6, 7
• Hormonal changes: Menstruation may trigger episodes 6
• Food sensitivities: Certain foods may precipitate outbreaks 4
  • Acidic foods (citrus, tomatoes)
  • Spicy foods
  • Foods containing sodium lauryl sulfate

Associated Systemic Conditions

• Gastrointestinal disorders:
  • Celiac disease
  • Crohn's disease
  • Ulcerative colitis 4
• Behçet's disease: RAU with genital ulceration and eye disease 3
• Helicobacter pylori infection: Inverse association noted 1

Risk Factors Among University Students

• Academic grade level (higher grades = higher risk)
• Inadequate brushing time
• Poor exercise habits 7

Clinical Pearls and Pitfalls

Important Clinical Considerations:

• RAU may be the first sign of systemic diseases like Crohn's disease 1, 2
• Persistent ulcers lasting >2 weeks should prompt further investigation 1
• Biopsy may be necessary for atypical presentations 1

Common Pitfalls:

• Misdiagnosing RAU as herpes simplex virus infection
• Failing to investigate for underlying systemic conditions
• Overlooking nutritional deficiencies, especially vitamin B12 5
• Not recognizing stress as a significant trigger

Diagnostic Approach

1. Detailed history focusing on:

   • Pattern of recurrence
   • Duration of ulcers
   • Associated symptoms
   • Dietary habits
   • Stress levels
   • Family history

2. Laboratory investigations when indicated:

   • Complete blood count
   • Vitamin B12, folate, iron, and ferritin levels
   • Celiac disease screening
   • Inflammatory markers if systemic disease suspected

Remember that while multiple factors contribute to RAU development, the ultimate clinical presentation involves pain, recurrence, self-limitation, and epithelial destruction 6. Currently, no definitive laboratory test exists to confirm the diagnosis, which remains primarily clinical 6.