What are the differential diagnoses and recommended treatment for white patches on the tongue?

White Spots on the Tongue: Differential Diagnosis and Treatment

If the white patches scrape off easily revealing an erythematous base, treat immediately for oral candidiasis with fluconazole 100 mg daily for 7-14 days; if patches cannot be removed, biopsy is mandatory to exclude leukoplakia or malignancy. 1

Immediate Clinical Assessment

The first critical step is attempting to scrape the lesion with a tongue depressor:

• Scrapable white patches with underlying erythema indicate pseudomembranous candidiasis (oral thrush) 1, 2
• Non-scrapable white patches require consideration of leukoplakia, lichen planus, or oral hairy leukoplakia 1
• Any oral abnormality persisting >2 weeks must be reevaluated and considered for biopsy to exclude malignancy 1

Key Risk Factors to Document

Identify predisposing conditions that guide diagnosis:

• Immunosuppression: HIV/AIDS (especially CD4 <200 cells/μL), diabetes mellitus, corticosteroid use (including inhaled), chemotherapy 2, 3
• Medication history: Recent broad-spectrum antibiotics, chronic corticosteroid use 2
• Tobacco and alcohol use: Up to 75% of oral cancers are attributable to these exposures 1
• Denture wearing: Creates environment conducive to Candida growth 2

Primary Differential Diagnoses

1. Oral Candidiasis (Most Common if Scrapable)

Clinical presentation:

• Creamy white, plaque-like lesions on buccal mucosa, tongue, or oropharynx that scrape off, often revealing bleeding underneath 2
• Candida albicans accounts for the vast majority of cases 2, 3

Treatment algorithm:

• First-line: Fluconazole 100 mg orally daily for 7-14 days 4
• Alternative: Itraconazole solution 200 mg daily for 7-14 days (equivalent efficacy to fluconazole) 4
• Topical options (less effective): Clotrimazole troches 10 mg five times daily or nystatin suspension 4-6 mL four times daily for 7-14 days 4

Critical pitfall: Suspect esophageal involvement if patient reports dysphagia, retrosternal pain, or odynophagia (occurs in 10-20% of cases); these patients require systemic therapy, not topical 2

2. Oral Leukoplakia (If Non-Scrapable)

Clinical presentation:

• White patches that cannot be scraped off and cannot be characterized as another definable disorder 4
• Nonhomogeneous leukoplakia has higher malignant transformation risk than homogeneous type 4

Management:

• Pathological confirmation is mandatory via biopsy 4
• Photodynamic therapy with topical 5-aminolevulinic acid (ALA-PDT) is emerging as fourth-line therapeutic approach for confirmed leukoplakia 4
• Traditional options include surgical excision, CO2 laser ablation, or observation depending on dysplasia grade 4

Red flag: Immediate referral required if lesions show indurated borders, ulceration, or fixation to underlying tissue suggesting malignancy 1

3. Oral Lichen Planus

Clinical presentation:

• White, lacy, reticular patterns (Wickham's striae) on tongue and buccal mucosa 1
• May have erosive component with erythema and ulceration 1

Management:

• Refer to oral medicine specialist for definitive diagnosis and management 1
• Biopsy typically required to confirm diagnosis 1

4. Oral Hairy Leukoplakia

Clinical presentation:

• White, corrugated patches typically on lateral tongue borders 1, 5
• Does not respond to antifungal treatment 5
• Strongly associated with HIV infection; patients should be considered highly suspect for immunosuppression 1, 5

Management:

• Document HIV status; if unknown, recommend HIV testing 1
• Refer to infectious disease specialist if HIV-positive 1

Treatment-Refractory Candidiasis

If initial fluconazole therapy fails:

• Second-line: Itraconazole solution >200 mg daily (effective in approximately two-thirds of fluconazole-refractory cases) 4
• Third-line: Amphotericin B oral suspension 1 mL four times daily 4
• Last resort: IV amphotericin B 0.3 mg/kg/day for azole-refractory infections 4

Resistance patterns: Occurs in 10-20% of immunocompromised patients with prolonged fluconazole exposure, particularly with CD4 <50 cells/μL 2. Consider non-albicans Candida species (C. glabrata, C. krusei) which may have intrinsic azole resistance 2, 3.

When to Refer Immediately

• Lesions suggesting malignancy: indurated borders, ulceration, fixation to underlying tissue 1
• Diagnosis unclear after initial workup or biopsy shows atypical findings 1
• Immunocompromised patient with atypical presentation or treatment failure 1
• Any lesion persisting >2 weeks despite appropriate treatment 1

Common Pitfalls to Avoid

• Do not rely on oral fungal cultures for candidiasis diagnosis; many individuals have asymptomatic colonization 4
• Failure to identify underlying predisposing factors leads to treatment failure in 20-30% of cases 2
• Do not use suppressive antifungal therapy routinely; reserve only for frequent or disabling recurrences to reduce resistance development 4
• Do not assume all white patches are benign; biopsy is essential for non-scrapable lesions to exclude malignancy 1