What is the differential diagnosis and management of tongue ulcers?

Differential Diagnosis of Tongue Ulcers

Tongue ulcers should be systematically categorized into acute (sudden onset, short duration) versus chronic (insidious onset, persistent beyond 2 weeks) presentations, with traumatic ulcers, recurrent aphthous stomatitis, and infections being most common, while any solitary chronic ulcer requires biopsy to exclude malignancy. 1, 2

Classification Framework

Tongue ulcers are best approached by temporal pattern and clinical morphology:

Acute Ulcers (Sudden Onset, Short Duration)

Traumatic causes:

• Mechanical injury from sharp food, dental appliances, or tooth edges—diagnosis is straightforward when ulcer location and shape correspond to the inciting factor 1, 3
• Thermal burns from hot foods or beverages 3
• Chemical injury from strong acids, alkalis, or caustic substances 3

Infectious etiologies:

• Viral infections (herpes simplex, varicella-zoster, coxsackievirus) 2, 4
• Bacterial infections including acute necrotizing ulcerative gingivitis 2, 4
• Deep fungal infections, particularly in patients with hyperglycemia or immunosuppression 3, 2

Recurrent aphthous ulcers (RAU):

• Present as well-demarcated, oval or round ulcers with white or yellow pseudomembrane and surrounding erythematous halo 1, 5
• May be triggered by immune dysregulation, genetic predisposition, nutrient deficiency, oral trauma, anxiety, or stress, though no single factor is confirmed 1

Systemic disease manifestations:

• Behçet's disease with recurrent bipolar aphthosis 3, 2
• Inflammatory bowel disease (Crohn's disease, ulcerative colitis) 3, 2
• Blood disorders (anemia, leukemia, neutropenia) presenting with widespread necrotic ulcers with yellowish-white pseudomembrane 3, 2

Chronic Ulcers (Insidious Onset, Persistent >2 Weeks)

Autoimmune bullous diseases:

• Pemphigus vulgaris and mucous membrane pemphigoid—require evaluation for serum antibodies (Dsg1, Dsg3, BP180, BP230) 1, 3
• Oral lichen planus 6, 7
• Lupus erythematosus 7

Infectious causes:

• Tuberculosis producing stellate ulcers with undermined edges and clear boundaries 1, 3
• Syphilis requiring serology testing 1, 3
• Chronic fungal or parasitic infections 7

Neoplastic:

• Squamous cell carcinoma—every solitary chronic tongue ulcer mandates biopsy to exclude malignancy 2, 6
• Benign tumors 2

Drug-induced ulceration 2, 6, 7

Diagnostic Algorithm

Initial assessment:

• Document ulcer size, number, location, depth, presence of white/yellow pseudomembrane, and surrounding erythema 3, 5
• Determine duration and response to any prior treatment 1, 3
• Identify corresponding traumatic factors if present (sharp tooth edges, ill-fitting dentures) 1, 3

For ulcers persisting beyond 2 weeks or not responding to 1-2 weeks of treatment, proceed with comprehensive workup: 1, 3

Mandatory blood tests before biopsy:

• Full blood count to detect anemia, leukemia, or other blood disorders 1, 3
• Coagulation studies and fasting blood glucose to exclude biopsy contraindications and identify hyperglycemia predisposing to fungal infection 1, 3
• HIV antibody and syphilis serology 1, 3
• Serum antibodies (Dsg1, Dsg3, BP180, BP230) if bullous disease suspected 1, 3
• Iron, folate, vitamin B12 levels if anemia or nutritional deficiency suspected 1, 3

Biopsy indications:

• Ulcers with atypical features or unclear etiology 1
• Any solitary chronic ulcer to rule out squamous cell carcinoma 2, 6
• Multiple biopsies if ulcers involve multiple sites with different morphological characteristics 1
• Direct immunofluorescence for suspected autoimmune conditions 1, 3

Critical Pitfalls to Avoid

Never rely solely on topical treatments for persistent ulcers without establishing definitive diagnosis—this delays identification of malignancy or systemic disease that directly impacts mortality and morbidity 3

Inadequate biopsy technique (too small or superficial) misses diagnostic features, particularly for deep infections or malignancy 3

Overlooking systemic causes leads to delayed diagnosis and inappropriate management—blood disorders, HIV, inflammatory bowel disease, and nutritional deficiencies require specific systemic treatment 3

Failing to biopsy solitary chronic ulcers risks missing squamous cell carcinoma, which has significant mortality implications if diagnosed late 2, 6

Specialist Referral Criteria

Refer to oral medicine specialist for: 3, 5

• Ulcers lasting more than 2 weeks
• Ulcers not responding to 1-2 weeks of treatment
• Recurrent, severe, or atypical presentations requiring biopsy or advanced diagnostic testing
• Cases with systemic symptoms suggesting underlying disease