Causes of Aphthous Ulcers
Aphthous ulcers are multifactorial in origin, with the exact pathophysiology remaining obscure, but key contributing factors include nutritional deficiencies (particularly vitamin B12, iron, and folate), immunological dysfunction, local trauma, genetic predisposition, and systemic diseases. 1, 2, 3
Primary Etiological Categories
Nutritional Deficiencies
- Vitamin B12 deficiency shows a clear relationship with recurrent aphthous ulceration and should be considered in all patients with recurrent lesions 2
- Iron and folate deficiencies are strongly associated with aphthous ulcers, with haematinic deficiencies found in 56.2% of recurrent aphthosis patients versus only 7% in controls 4, 5
- Routine haematological screening for serum iron, folic acid, and vitamin B12 should be performed in all patients with recurrent aphthosis 5
Genetic and Familial Factors
- Family history is significantly associated with recurrent aphthosis (P < 0.01) and represents the strongest independent predictor in logistic regression models 5
- Patients with positive family history show reduced response to replacement therapy compared to those without familial predisposition 5
Local Traumatic Factors
- Mechanical, physical, or chemical trauma can trigger ulcers in susceptible individuals 6, 3
- Local physical trauma may be the precipitating factor even when underlying susceptibility exists 7
Immunological and Inflammatory Factors
- Immune dysregulation plays a central role, though specific mechanisms remain incompletely understood 2, 3
- Neutropenia may present with widespread necrotic ulcers with yellowish-white pseudomembrane 4
Associated Systemic Conditions
Gastrointestinal Diseases
- Inflammatory bowel diseases (Crohn's disease, ulcerative colitis) can manifest with oral aphthous ulcers 4, 3
- Celiac disease is associated with recurrent aphthous stomatitis 3
Hematological Disorders
- Anemia and leukemia can present with oral ulcers, requiring full blood count and bone marrow evaluation 4
- Blood system diseases necessitate comprehensive hematological workup including immunotyping 4
Infectious Causes
- HIV infection can manifest with oral ulcers in persistent cases 4, 3
- Syphilis can present with oral ulceration 4
- Tuberculosis may cause stellate ulcers with undermined edges 4
- Deep fungal infections, particularly in hyperglycemic patients, can cause persistent oral ulcers 4, 3
- Bacterial infections including acute necrotizing ulcerative gingivitis 3
Autoimmune and Dermatological Conditions
- Bullous diseases (pemphigus, pemphigoid) require evaluation for serum-specific antibodies (Dsg1, Dsg3, BP180, BP230) 4
- Behçet's syndrome presents with recurrent bipolar aphthosis as its main clinical feature 1, 3
Environmental and Lifestyle Triggers
Dietary Factors
- Hard, acidic, and salty foods should be avoided 8
- Alcohol and carbonated drinks can trigger ulceration 8
- Food hypersensitivity may contribute to pathogenesis 2
Oral Hygiene Products
- Toothpastes containing sodium lauryl sulfate should be avoided 8
Other Contributing Factors
- Stress is recognized as a contributing factor 2
- Hormonal state may influence ulcer development 2
- Smoking (or smoking cessation) can be associated with aphthous ulcers 2
Clinical Pearls and Diagnostic Approach
When evaluating aphthous ulcers, distinguish between idiopathic recurrent aphthous stomatitis and "aphthous-like ulcers" (ALU) linked to systemic diseases—the frequency of ALU is unexpectedly higher than previously recognized 5. For ulcers persisting beyond 2 weeks or not responding to 1-2 weeks of treatment, comprehensive blood testing (full blood count, coagulation, fasting glucose, HIV antibody, syphilis serology) and specialist referral are indicated 1, 4. Patients with ALU and negative family history show complete remission after replacement therapy, while those with positive family history only achieve reduction in frequency and severity 5.