What are the etiologies of oral ulceration?

Causes of Oral Ulcers

Oral ulcers arise from traumatic, infectious, allergic, autoimmune, neoplastic, and systemic disease etiologies, with some cases remaining idiopathic despite thorough evaluation. 1

Etiologic Categories

Traumatic Causes

• Mechanical trauma from sharp teeth, dental appliances, accidental biting, or sharp foods creates ulcers whose location and shape directly correspond to the inciting factor 1, 2
• Thermal burns from hot foods or beverages commonly affect the palate 3
• Chemical injury from strong acids, alkalis, or caustic substances 3

Infectious Causes

• Herpes simplex virus causes "cold sores" or "fever blisters," typically on keratinized mucosa (lips, hard palate, gingiva) 4
• Tuberculosis produces stellate ulcers with undermined edges and clear boundaries 1, 3
• Syphilis can manifest as oral ulceration at any stage, requiring serology testing 2, 3
• Deep fungal infections, particularly in patients with hyperglycemia or immunosuppression 2, 5
• HIV infection causes ulcers through direct viral effects and opportunistic infections 2
• Acute necrotizing ulcerative gingivitis presents as rapid-onset bacterial infection 6, 4

Recurrent Aphthous Stomatitis (RAS)

• Recurrent aphthous ulcers ("canker sores") appear as well-demarcated, oval or round ulcers with white/yellow pseudomembrane and erythematous halo 1, 2
• Potential triggers include immune dysregulation, genetic predisposition, nutrient deficiency (iron, folate, vitamin B12), oral trauma, anxiety, or stress, though none are definitively confirmed 1, 2
• Minor aphthous ulcers are the most common form 6
• Major aphthous ulcers and herpetiform aphthous ulcers represent more severe variants 6

Autoimmune and Mucocutaneous Diseases

• Pemphigus vulgaris requires evaluation for serum antibodies (Dsg1, Dsg3) 2, 3
• Mucous membrane pemphigoid requires testing for BP180 and BP230 antibodies 2, 3
• Erosive lichen planus represents chronic immune-mediated ulceration 4
• Behçet's disease characterized by recurrent bipolar aphthosis (oral and genital ulcers) 3, 6

Systemic Disease Associations

• Inflammatory bowel disease (Crohn's disease, ulcerative colitis) manifests with oral ulcers 2, 3, 6
• Anemia from iron, folate, or vitamin B12 deficiency contributes to ulceration 2, 5
• Leukemia, especially acute monocytic leukemia, presents with widespread necrotic ulcers when neutrophil counts are severely decreased 2, 3
• Neutropenia from any cause predisposes to oral ulceration 3, 6
• Celiac disease can be associated with recurrent aphthous stomatitis 6

Medication-Related Ulceration

• Drug-induced ulcers can occur from various medications and should be considered in the differential diagnosis 7, 6

Allergic Causes

• Erythema multiforme presents as rapid-onset ulcers, often postherpetic 6, 4
• Allergic reactions to foods, medications, or dental materials 1, 4

Neoplastic Causes

• Squamous cell carcinoma typically presents as a solitary chronic ulcer and must be excluded by biopsy in any ulcer persisting >2 weeks 2, 6
• Lymphoma or other hematologic malignancies can present as persistent oral ulcers 2

Diagnostic Algorithm by Duration

Acute Ulcers (<2 weeks)

• Consider trauma, bacterial infections, deep fungal infections, or systemic disease flares 2, 6
• Primary care physicians or general dentists can manage initially 2

Recurrent Ulcers (≥4 episodes/year)

• Most commonly recurrent aphthous stomatitis or herpes simplex virus 2, 6
• Evaluate for underlying systemic diseases (inflammatory bowel disease, nutritional deficiencies, immune disorders) 2, 6

Chronic Ulcers (>2 weeks)

• Mandatory specialist referral to oral medicine specialist 2, 5
• Biopsy is essential to exclude malignancy and establish definitive diagnosis 1, 2, 5

Critical Diagnostic Considerations

Morphologic Clues

• Well-demarcated oval/round with pseudomembrane and erythematous halo: recurrent aphthous ulcers 1, 2
• Stellate with undermined edges: tuberculosis 1, 5
• Location/shape corresponding to trauma source: traumatic ulceration 1, 2
• Solitary chronic ulcer: squamous cell carcinoma until proven otherwise 2, 6

Laboratory Evaluation Required Before Biopsy

• Full blood count to detect anemia, leukemia, or neutropenia 2, 5
• Coagulation studies to exclude biopsy contraindications 2, 5
• Fasting blood glucose (hyperglycemia predisposes to invasive fungal infections) 2, 5
• HIV antibody testing in persistent cases 2, 5
• Syphilis serology 2, 5
• Serum antibodies (Dsg1, Dsg3, BP180, BP230) if bullous disease suspected 2, 5

Common Pitfalls to Avoid

• Never rely solely on topical treatments for persistent ulcers without establishing definitive diagnosis, as this delays identification of malignancy or systemic disease that directly impacts mortality and morbidity 2, 3, 5
• Inadequate biopsy technique (too small or superficial) misses diagnostic features, particularly for deep infections or malignancy 2, 3
• Overlooking systemic causes leads to delayed diagnosis and inappropriate management 2, 3
• Neoplastic ulcers mimic benign lesions, making biopsy essential for any atypical or persistent ulcer 8