What is the appropriate work‑up and initial management for a patient presenting with a painful tongue?

Painful Tongue: Diagnostic Work-Up and Initial Management

Begin with a targeted laboratory evaluation to exclude secondary causes, followed by a thorough oral examination to differentiate between inflammatory, infectious, neuropathic, and neoplastic etiologies, with biopsy reserved for persistent lesions beyond 2 weeks or those with concerning features.

Initial Clinical Assessment

History and Physical Examination

• Document pain characteristics: burning, sharp, aching, or tingling quality; continuous versus intermittent; location (tip, lateral borders, diffuse); and aggravating factors (eating, touch, temperature) 1
• Examine the tongue appearance: Look for beefy red smooth appearance (atrophic glossitis), white patches (leukoplakia, candidiasis), ulceration, masses, or normal-appearing mucosa (burning mouth syndrome) 2, 3
• Assess for visible lesions: Any ulcer, mass, or induration warrants immediate concern for malignancy 1, 4
• Check for systemic signs: Fever, weight loss, lymphadenopathy, or constitutional symptoms suggest serious underlying disease 1, 4

Key Clinical Patterns

• Normal-appearing mucosa with bilateral burning: Strongly suggests primary burning mouth syndrome, especially in peri/post-menopausal women 1, 5, 6
• Beefy red smooth tongue: Pathognomonic for atrophic glossitis from nutritional deficiency (B12, folate, iron) 2, 7, 3
• Localized ulcer or mass: Requires biopsy to exclude squamous cell carcinoma 1, 4
• History of recent dental work or trauma: Consider post-traumatic trigeminal neuropathic pain 1, 5

Mandatory Laboratory Work-Up

Order these tests before proceeding to biopsy:

• Complete blood count with differential: Rules out anemia, leukemia, neutropenia 1, 4, 7
• Vitamin B12 level: Deficiency causes atrophic glossitis and glossodynia 2, 7, 3
• Iron studies (serum iron, ferritin): Iron deficiency commonly presents with burning tongue 5, 7
• Folate level: Deficiency produces glossodynia and papillary atrophy 7
• Fasting blood glucose and HbA1c: Diabetes predisposes to fungal infections and neuropathy 1, 4
• Thyroid function tests (TSH, free T4): Hyperthyroidism can cause tongue burning 5
• HIV antibody: Excludes immunodeficiency-related lesions 1, 4
• Syphilis serology: Rules out infectious causes 1, 4

If bullous disease suspected: Add serum antibodies for Dsg1, Dsg3, BP180, BP230 before biopsy 1

Indications for Immediate Biopsy

Proceed with biopsy if ANY of the following are present:

• Any lesion persisting beyond 2 weeks 4
• Ulcer with indurated or rolled borders 4
• Mass or growth on the tongue 1, 4
• Constitutional symptoms (fever, weight loss, malaise) 1, 4
• Risk factors: tobacco use, alcohol use, immunosuppression 4
• Multiple sites with different morphological characteristics (perform multiple biopsies) 1, 4

Check coagulation studies before biopsy to exclude surgical contraindications 1, 4

Initial Management Based on Diagnosis

If Nutritional Deficiency Identified

• Vitamin B12 deficiency: Oral B12 supplementation leads to symptom improvement within 3 months 2
• Iron or folate deficiency: Replacement therapy is curative and prevents irreversible neurologic damage 7
• Monitor response: Symptoms should improve as nutritional status normalizes 2, 7, 3

If Oral Candidiasis Suspected

• Perform oral swab with KOH preparation or culture 5, 6
• Treat with antifungals: Symptomatic median rhomboid glossitis improves with antifungal therapy 3
• Consider underlying immunosuppression or hyperglycemia 1

If Primary Burning Mouth Syndrome Diagnosed

Diagnosis requires normal-appearing mucosa and exclusion of all secondary causes 1, 5, 6

First-line management:

• Reassurance that condition will not worsen: This is crucial and often therapeutic by itself 1, 6
• Cognitive behavioral therapy (CBT): Primary intervention addressing psychological components 1, 6, 3
• Gabapentin: First-line pharmacological option, reduces burning in 50% of patients 6, 3

If inadequate response after 4-6 weeks:

• Add alpha-lipoic acid to gabapentin: Combination therapy outperforms monotherapy 6
• Alternative: Topical clonazepam: Has shown efficacy in studies 6, 3
• Consider amitriptyline: If gabapentin ineffective or not tolerated 6

Symptomatic measures:

• Avoid irritating foods (tomatoes, citrus, spicy, hot, crusty foods) 1, 8
• Avoid alcohol and smoking 1
• Use alcohol-free mouthwash 1
• Maintain adequate hydration 1

If Post-Traumatic Trigeminal Neuropathic Pain

• History of dental procedure or facial trauma within 3-6 months 1, 5
• Treat as neuropathic pain: Gabapentin or other anticonvulsants 1
• Qualitative sensory testing may confirm diagnosis 1

Critical Pitfalls to Avoid

• Do not delay biopsy for persistent lesions: Any lesion beyond 2 weeks requires tissue diagnosis 4
• Do not diagnose primary BMS without excluding secondary causes: Laboratory screening is mandatory 5, 6, 2
• Do not miss vitamin B12 deficiency: Can cause irreversible neurologic damage if untreated 2, 7
• Do not ignore hyperglycemia: Predisposes to invasive fungal infections that mimic benign conditions 1, 4
• Do not use chronic vaseline on lips: Promotes mucosal dehydration and infection risk 1

When to Refer

• Immediate referral to oral maxillofacial surgery or ENT: If biopsy confirms squamous cell carcinoma 4
• Hematology-oncology referral: If biopsy reveals lymphoma 4
• Pain specialist or neurologist: For refractory burning mouth syndrome after 4-6 weeks of treatment 6
• Superior pathologist consultation: If initial biopsy shows only "nonspecific inflammation" but clinical suspicion remains high 1

Prognosis Counseling

• Burning mouth syndrome: Poor prognosis with only small percentage achieving complete resolution, but condition does not worsen 1, 6
• Nutritional deficiency glossodynia: Excellent prognosis with replacement therapy 7, 3
• Spontaneous remission of BMS: Not definitively demonstrated; treatments are palliative only 8