Tongue Ulcers: Differential Diagnosis, Evaluation, and Treatment
Direct Answer
For tongue ulcers lasting less than 2 weeks in an otherwise healthy patient, begin with topical corticosteroids or antiseptic agents after ruling out obvious trauma; however, any ulcer persisting beyond 2 weeks or failing to respond to 1-2 weeks of treatment mandates biopsy to exclude malignancy and systemic disease. 1, 2
Differential Diagnosis by Clinical Pattern
Acute Ulcers (< 2 weeks duration)
Traumatic causes (most common):
- Mechanical injury from sharp teeth, dental appliances, or accidental biting—ulcer location and shape match the inciting object 1, 2
- Thermal burns from hot foods/beverages 3
- Chemical injury from caustic substances 3
Recurrent aphthous stomatitis (RAS):
- Well-demarcated oval/round ulcers with white/yellow pseudomembrane surrounded by erythematous halo 1, 2
- Most common inflammatory oral ulcer (2-10% prevalence) 4
- Triggered by immune dysregulation, stress, nutrient deficiency, or oral trauma 1, 2
Infectious causes:
- Herpes simplex virus ("cold sores")—distinguished from aphthae by location on keratinized mucosa 5
- Acute necrotizing ulcerative gingivitis 6
Chronic Ulcers (> 2 weeks duration)
Malignancy (must exclude first):
- Every solitary chronic tongue ulcer requires biopsy to rule out squamous cell carcinoma 1, 2, 6
- Lymphoma can present as persistent ulceration 1
Chronic infections:
- Tuberculosis—produces stellate ulcers with undermined edges and clear boundaries 1, 2
- Syphilis—any stage can cause oral ulceration 1, 2
- Deep fungal infections—especially with hyperglycemia or immunosuppression 1, 2
Autoimmune/systemic diseases:
- Pemphigus vulgaris and mucous membrane pemphigoid 1, 3
- Behçet's syndrome—recurrent bipolar aphthosis 3, 6
- Inflammatory bowel disease (Crohn's, ulcerative colitis) 1, 3
Hematologic disorders:
- Anemia (iron, folate, B12 deficiency)—contributes to ulceration 1, 3
- Leukemia—widespread necrotic ulcers with yellowish-white pseudomembrane, especially with neutropenia 1, 3
Recommended Evaluation Algorithm
Step 1: Clinical Documentation
Document these specific characteristics 1, 2:
- Size, number, location, depth
- Presence of white/yellow pseudomembrane
- Surrounding erythema
- Duration and response to any prior treatment
- Identify corresponding traumatic factors if present
Step 2: Laboratory Workup (Before Biopsy)
Mandatory blood tests for ulcers > 2 weeks or atypical features 1, 2:
| Test | Purpose |
|---|---|
| Complete blood count | Detect anemia, leukemia, neutropenia [1,3] |
| Coagulation studies | Identify biopsy contraindications [1,3] |
| Fasting blood glucose | Exclude diabetes predisposing to fungal infection [1,3] |
| HIV antibody | Screen for HIV in persistent cases [1,3] |
| Syphilis serology | Rule out syphilitic ulceration [1,3] |
| Serum antibodies (Dsg1, Dsg3, BP180, BP230) | Evaluate for bullous autoimmune diseases [1,3] |
Step 3: Biopsy Indications (Critical)
- Any ulcer persisting > 2 weeks
- Ulcers failing to improve after 1-2 weeks of appropriate therapy
- Solitary chronic ulcers (to exclude squamous cell carcinoma)
- Atypical clinical features (unusual size, shape, induration)
Biopsy technique 1:
- Obtain adequate depth and size—superficial or small biopsies miss diagnostic features
- Multiple biopsies if lesions vary in appearance across sites
- Use adjunctive studies (direct immunofluorescence, immunohistochemistry, T-cell receptor profiling) based on initial histology
Step 4: Specialist Referral Criteria
Refer to oral medicine specialist for 1, 2:
- Ulcers lasting > 2 weeks
- Ulcers not responding to 1-2 weeks of treatment
- Recurrent, severe, or atypical presentations requiring biopsy
- Cases with systemic symptoms suggesting underlying disease
Treatment Approach
For Acute/Minor Ulcers (< 2 weeks)
First-line topical therapy 1, 4:
- Topical antiseptics (triclosan) or anti-inflammatory agents (diclofenac)
- Local anesthetics (lidocaine) for pain control
- Barrier preparations (Gengigel, Gelclair) for symptomatic relief 1
If ineffective, escalate to 4:
- Topical corticosteroids (betamethasone sodium phosphate, clobetasol 0.05%, fluticasone propionate) 1, 4
- Eliminate sources of trauma
- Avoid hard, acidic, salty foods; alcohol; carbonated drinks
- Avoid toothpastes containing sodium lauryl sulfate
- Maintain effective oral hygiene
For Recurrent Aphthous Stomatitis (≥ 4 episodes/year)
Systemic therapy for severe cases 6, 4:
- Colchicine combined with topical treatments (suitable for most RAS) 6
- Pentoxifylline or prednisolone for refractory cases 4
- Thalidomide is most effective but limited by adverse effects 6
For Autoimmune Diseases
Pemphigus vulgaris 1:
- Topical corticosteroids (betamethasone, fluticasone, clobetasol 0.05%)
- Systemic immunosuppression for refractory cases
Critical Pitfalls to Avoid
Never rely solely on topical treatments for persistent ulcers (> 2 weeks) without establishing definitive diagnosis—this delays identification of malignancy or systemic disease that directly impacts mortality 1, 2
Inadequate biopsy technique (too small or superficial) misses diagnostic features, particularly for deep infections or malignancy 1, 3
Overlooking systemic causes leads to delayed diagnosis and inappropriate management 1, 3
Accepting nonspecific pathology reports stating "inflammatory ulcer with lymphocytic infiltration"—these require consultation with superior pathologists or repeat biopsy 1
Missing hyperglycemia as a predisposing factor for invasive fungal infections 1
Follow-up Protocol
Close monitoring is essential 1:
- Regular follow-up with specialist until complete resolution
- If ulcer persists despite appropriate treatment, re-evaluation and possibly additional biopsies are necessary
- Any change in ulcer characteristics warrants immediate re-assessment