What causes recurrent mouth ulcers?

Causes of Recurrent Mouth Ulcers

Recurrent mouth ulcers arise from a heterogeneous set of etiologies including traumatic injury, nutritional deficiencies (particularly B vitamins and iron), autoimmune conditions, systemic diseases (especially inflammatory bowel disease and Behçet's disease), infections, medications, and idiopathic recurrent aphthous stomatitis, though no single principal cause has been identified in most cases. 1, 2

Primary Etiologic Categories

Traumatic and Chemical Causes

• Mechanical trauma from sharp food, dental appliances, or accidental biting creates ulcers that correspond in location and shape to the inciting factor 3
• Thermal burns and chemical injury from caustic substances produce acute ulcerations 2, 4
• These typically resolve within 2 weeks once the trauma source is eliminated 5

Nutritional Deficiencies

• Vitamin B complex deficiencies (B1, B2, B6) occur in approximately 28% of patients with recurrent mouth ulcers 6
• Iron and folate deficiencies are established precipitating factors 4
• Replacement therapy in deficient patients produces significant sustained clinical improvement, whereas non-deficient patients show no benefit from supplementation 6

Recurrent Aphthous Stomatitis (RAS)

• Idiopathic RAS affects at least 1 in 5 individuals and is defined by ≥4 episodes per year 1, 4
• Precipitating factors include local trauma, stress, specific food intake, hormonal changes, and immune dysregulation 1, 2
• Genetic predisposition plays a role, though no principal causative mechanism has been discovered 1

Systemic Diseases

Gastrointestinal associations:

• Celiac disease presents with recurrent oral ulcers as a mucosal manifestation 4
• Inflammatory bowel disease (Crohn's disease and ulcerative colitis) commonly causes oral ulceration 7, 4
• These require specific investigation when ulcers are recurrent and unexplained 4

Autoimmune and immunologic conditions:

• Behçet's disease manifests as recurrent bipolar aphthosis (oral and genital ulcers) 8, 4
• HIV infection and neutropenia predispose to recurrent ulceration 4
• Pemphigus vulgaris and mucous membrane pemphigoid cause chronic erosive lesions 9

Infectious Causes

• Herpes simplex virus causes "cold sores" or "fever blisters," typically on keratinized mucosa (lips, hard palate) 9
• Deep fungal infections occur particularly in immunosuppressed or hyperglycemic patients 5, 3
• Tuberculosis and syphilis produce stellate ulcers with undermined edges requiring serology testing 3
• Acute necrotizing ulcerative gingivitis causes rapid-onset multiple ulcers 4, 9

Medication-Related Ulceration

• Drug-induced ulcers represent an important iatrogenic cause requiring medication review 2, 4
• NSAIDs can cause gastrointestinal complications including oral ulceration 7

Malignancy

• Squamous cell carcinoma typically presents as a solitary chronic ulcer 3, 4
• Lymphoma and hematologic malignancies can manifest as persistent oral ulcers 5

Critical Diagnostic Considerations

Red Flags Requiring Immediate Investigation

• Any solitary chronic ulcer >2 weeks must be biopsied to exclude malignancy 3, 4
• Ulcers not responding to 1-2 weeks of treatment require specialist referral 8, 5
• Atypical features (indurated borders, fixed to underlying tissue, progressive enlargement) suggest malignancy 3

Essential Workup for Recurrent Ulcers

• Blood tests should include full blood count, fasting glucose, HIV antibody, syphilis serology, and nutritional markers (B vitamins, iron, folate) 3, 6
• Coagulation studies must be performed before any biopsy 3
• Biopsy with histopathology is mandatory for persistent or atypical ulcers, with multiple biopsies if morphologically different sites exist 3

Common Pitfalls to Avoid

• Relying solely on topical treatments for persistent ulcers without establishing definitive diagnosis delays identification of malignancy or systemic disease 3
• Inadequate biopsy technique (small or superficial samples) misses diagnostic features, particularly for deep infections or malignancy 5
• Overlooking systemic causes leads to delayed diagnosis and inappropriate management 5
• Premature vitamin supplementation without documented deficiency provides no benefit and delays proper investigation 6