What is the differential diagnosis and management of recurrent aphthous ulcers on the tongue in a 35-year-old female?

Management of Recurrent Aphthous Ulcers on the Tongue in a 35-Year-Old Female

Begin with topical clobetasol gel 0.05% applied directly to the dried ulcer 2-4 times daily, combined with viscous lidocaine 2% before meals for pain control. 1

Differential Diagnosis

The primary diagnosis is recurrent aphthous stomatitis (RAS), but several conditions must be excluded, particularly if ulcers persist beyond 2 weeks or fail to respond to initial treatment 2, 1:

Common Causes to Consider:

• Recurrent aphthous ulcers (most likely): Well-demarcated, oval or round ulcers with white/yellow pseudomembrane and surrounding erythematous halo 2, 3
• Nutritional deficiencies: Iron, folate, or vitamin B12 deficiency 2, 3
• Behçet's syndrome: Recurrent bipolar aphthosis (oral and genital ulcers) 3, 4
• Inflammatory bowel disease: Crohn's disease or ulcerative colitis 2, 3
• Autoimmune bullous diseases: Pemphigus vulgaris or mucous membrane pemphigoid 2, 4
• Traumatic ulceration: Location and shape correspond to mechanical irritation 2, 3

Red Flags Requiring Immediate Investigation:

• Malignancy: Any solitary chronic ulcer requires biopsy to exclude squamous cell carcinoma 4, 5
• Blood disorders: Anemia, leukemia, or neutropenia presenting with widespread necrotic ulcers 3, 4
• Infections: Tuberculosis (stellate ulcers with undermined edges), deep fungal infections, syphilis, or HIV 2, 3, 4

Initial Management Approach

First-Line Topical Therapy:

For localized tongue ulcers (which is typical in this case):

• Apply clobetasol gel or ointment 0.05% directly to the dried ulcer 2-4 times daily 1
• Alternative: Triamcinolone acetonide 0.1% paste applied to dried ulcer 2-4 times daily 1

For pain control:

• Viscous lidocaine 2% applied before meals 1
• Benzydamine hydrochloride rinse or spray every 3 hours, particularly before eating 1

For mucosal protection:

• Barrier preparations such as Gelclair applied three times daily 1
• White soft paraffin ointment to affected areas 1

Oral Hygiene Measures:

• Warm saline mouthwashes daily 1
• Antiseptic oral rinses twice daily (0.2% chlorhexidine digluconate or 1.5% hydrogen peroxide) 1, 6

Lifestyle Modifications:

• Avoid hard, acidic, salty foods 6
• Avoid toothpastes containing sodium lauryl sulfate 6
• Avoid alcohol and carbonated drinks 6

When to Escalate Treatment

Indications for Further Workup:

Order blood tests if 2, 3, 4:

• Ulcers persist beyond 2 weeks
• No response to 1-2 weeks of topical treatment
• Recurrent episodes (≥4 times per year)

Required blood tests 2, 4:

• Full blood count (to detect anemia, leukemia, blood disorders)
• Serum iron, folate, vitamin B12 levels
• Fasting blood glucose
• HIV antibody testing
• Syphilis serology
• Coagulation studies (if biopsy planned)
• Serum antibodies (Dsg1, Dsg3, BP180, BP230) if bullous disease suspected

Second-Line Systemic Therapy:

For recurrent aphthous stomatitis (≥4 episodes per year) 1, 5:

• Colchicine as first-line systemic therapy, especially if erythema nodosum or genital ulcers present 1
• This is more effective than other systemic options for preventing recurrences 1, 5

For highly symptomatic or severe cases not responding to topical therapy 1:

• Intralesional triamcinolone injections weekly (total dose 28 mg) 1
• Systemic corticosteroids: Prednisone/prednisolone 30-60 mg or 1 mg/kg for 1 week with tapering over the second week 1

For refractory cases 1:

• Consider azathioprine, interferon-alpha, TNF-alpha inhibitors, or apremilast 1
• Thalidomide is most effective but reserved for severe refractory cases due to toxicity 5, 7

Critical 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 3
• Do not taper corticosteroids prematurely before disease control is established 1
• Always biopsy solitary chronic ulcers lasting over 2 weeks to exclude squamous cell carcinoma 4, 5
• Do not overlook systemic causes such as inflammatory bowel disease, nutritional deficiencies, or blood disorders 3

Specialist Referral Criteria

Refer to oral medicine specialist for 3, 4:

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