What is the differential diagnosis for a patient with white patches on the tongue for 2 weeks?

Differential Diagnosis of White Patches on Tongue for 2 Weeks

The most likely diagnosis is oral candidiasis (thrush), presenting as pseudomembranous candidiasis with white plaques that can be scraped off, but you must also consider leukoplakia, oral hairy leukoplakia, lichen planus, and less commonly, early oral malignancy or systemic conditions like immunosuppression-related lesions. 1, 2

Primary Differential Diagnoses

Oral Candidiasis (Most Common)

• Pseudomembranous candidiasis appears as creamy white, plaque-like lesions on the tongue, buccal mucosa, or oropharynx that can be scraped off, leaving an erythematous base 2
• Candida albicans is the causative organism in 80% of cases, existing as a commensal in 40-65% of healthy mouths but becoming pathogenic when host defenses are compromised 3, 4
• Key predisposing factors include immunosuppression (HIV with CD4+ <200), diabetes mellitus, corticosteroid use (including inhaled steroids), antibiotic therapy, poor oral hygiene, and denture wearing 1, 3
• The dorsal tongue surface is a favored reservoir site for Candida colonization 3

Leukoplakia and Premalignant Lesions

• Any oral abnormality lasting more than 2 weeks should be reevaluated and considered for biopsy, particularly to exclude malignancy 5
• Leukoplakia presents as white patches that cannot be scraped off, distinguishing it from candidiasis 5
• Tobacco and alcohol use are major risk factors, with up to 75% of oral cancers attributable to these exposures 5
• Hyperplastic candidiasis can mimic leukoplakia and requires biopsy for definitive diagnosis 6

Oral Hairy Leukoplakia

• Presents as white, corrugated patches typically on lateral tongue borders in immunocompromised patients, especially those with HIV 1
• Cannot be scraped off, unlike candidiasis 2

Lichen Planus

• Appears as white, lacy, reticular patterns (Wickham's striae) on the tongue and buccal mucosa
• May have erosive component with erythema and ulceration
• Bilateral presentation is common

Critical Diagnostic Algorithm

Step 1: Attempt to Scrape the Lesion

• If white patches scrape off easily revealing erythematous base: strongly suggests pseudomembranous candidiasis 2
• If patches cannot be removed: consider leukoplakia, lichen planus, or oral hairy leukoplakia 2

Step 2: Assess Risk Factors

• Document history of diabetes, immunosuppression, recent antibiotic or corticosteroid use, denture wearing, and tobacco/alcohol use 1, 3
• For lesions persisting >2 weeks, obtain blood tests: full blood count (to exclude anemia, leukemia), fasting glucose (diabetes screening), HIV antibody, and coagulation studies 5

Step 3: Empiric Treatment vs. Biopsy Decision

• If clinical presentation strongly suggests candidiasis with identifiable risk factors: initiate antifungal therapy (nystatin rinse or clotrimazole lozenges) and reassess in 1-2 weeks 3, 6
• If lesions persist despite 1-2 weeks of antifungal treatment or if candidiasis is unlikely: proceed to biopsy 5
• Biopsy is mandatory for any lesion >2 weeks that doesn't respond to treatment to exclude malignancy, tuberculosis, or systemic disease 5

Less Common but Critical Diagnoses to Consider

Oral Tuberculosis

• Presents as stellate ulcers with undermined edges, but can have atypical white patches 5
• Consider in patients with history of tuberculosis or systemic symptoms 5
• Requires Ziehl-Nielsen staining and chest imaging 5

Systemic Disease Manifestations

• Crohn's disease can present with oral lesions including white patches and ulceration 5
• Hematologic malignancies (leukemia, lymphoma) may present with oral white patches or ulceration with pseudomembrane 5
• Invasive fungal infections in diabetic or severely immunocompromised patients can present with white patches progressing to necrosis 5

Syphilis

• Secondary syphilis can cause white mucous patches on the tongue
• Obtain syphilis serology if risk factors present or diagnosis unclear 5

Common Pitfalls to Avoid

• Do not assume all white patches are benign candidiasis: failure to biopsy persistent lesions delays diagnosis of malignancy 5
• Do not overlook systemic predisposing factors: undiagnosed diabetes or HIV may be the underlying cause 1, 3
• Do not treat empirically beyond 2 weeks without tissue diagnosis: this risks missing serious pathology 5
• Do not forget to examine the entire oral cavity: multiple sites with different morphology may require multiple biopsies 5

When to Refer or Escalate

• Immediate referral if lesions suggest malignancy (indurated borders, ulceration, fixation to underlying tissue) 5
• Refer to oral medicine specialist if diagnosis remains unclear after initial workup or if biopsy shows atypical findings 5
• Consider infectious disease consultation if immunocompromised patient with atypical presentation or treatment failure 1