What are the differential diagnoses for thrush?

Differential Diagnoses for Thrush (Oral Candidiasis)

When evaluating white oral lesions suspected to be thrush, consider infectious mimics (herpes simplex, hairy leukoplakia), inflammatory conditions (lichen planus, erythema migrans), and underlying systemic diseases that predispose to or present similarly to candidiasis.

Primary Infectious Differentials

Oral Hairy Leukoplakia

• Presents as white, corrugated lesions on lateral tongue borders that cannot be scraped off, unlike thrush 1
• Strongly associated with HIV infection and Epstein-Barr virus 1
• Distinguishing feature: lesions are fixed and non-removable, whereas thrush plaques can be wiped away leaving erythematous base 2

Herpes Simplex Virus (Recurrent Herpes Labialis)

• Manifests as painful vesicles that rupture into ulcers, typically on keratinized mucosa (lips, hard palate) 2
• Unlike thrush, HSV lesions are acutely painful and have a vesicular stage before ulceration 2

Inflammatory and Autoimmune Conditions

Oral Lichen Planus

• Chronic inflammatory condition presenting in two forms: reticular (white lacy Wickham's striae) or erosive (painful erythematous areas) 2
• Reticular form can mimic thrush but has characteristic lacy pattern and cannot be scraped off 2
• More common in middle-aged adults and may be associated with hepatitis C 2

Erythema Migrans (Geographic Tongue)

• Waxing and waning disorder of unknown etiology with irregular red patches surrounded by white borders 2
• Distinguishing feature: lesions migrate over days to weeks, unlike stable thrush plaques 2

Recurrent Aphthous Stomatitis

• Presents as painful, round ulcers with erythematous halos, not white plaques 2
• Severe cases may indicate nutritional deficiencies, autoimmune disorders, or HIV infection 2

Conditions Predisposing to or Associated with Thrush

HIV/AIDS and Immunodeficiency States

• Persistent or recurrent thrush is a clinical category B condition indicating HIV-related immunosuppression 1
• HIV-infected patients with CD4 <200 cells/µL or those with unexplained fever, weight loss, or thrush should be evaluated for opportunistic infections including Pneumocystis pneumonia and tuberculosis 1
• Idiopathic CD4 lymphocytopenia should be considered in patients with opportunistic infections and CD4 <300 cells/µL without HIV 3

Laryngeal Candidiasis

• Isolated laryngeal thrush presents with hoarseness without oral manifestations, often misdiagnosed 4
• Strongly associated with inhaled corticosteroid use, systemic steroids, diabetes, or smoking 4
• Critical pitfall: may lead to unnecessary surgical intervention if not recognized 4

Diagnostic Approach Algorithm

Step 1: Clinical Examination Features

• Removability test: Attempt to scrape lesions; thrush plaques remove leaving erythema, while lichen planus and leukoplakia do not 2, 5
• Location: Thrush affects buccal mucosa, tongue, and palate; hairy leukoplakia is lateral tongue-specific 1, 2
• Pain pattern: Thrush causes burning sensation; aphthous ulcers cause sharp pain; lichen planus erosive form is painful 2, 5

Step 2: Risk Factor Assessment

• Immunosuppression: HIV status, chemotherapy, immunosuppressive medications 1, 3, 2
• Medication history: Inhaled corticosteroids, broad-spectrum antibiotics, systemic steroids 4, 2
• Systemic conditions: Diabetes, poor oral hygiene, ill-fitting dentures 2, 5

Step 3: HIV and Immunodeficiency Evaluation

• All patients with persistent or recurrent thrush require HIV testing, even with previous negative results 3
• If HIV-positive: Check CD4 count to stratify risk for other opportunistic infections 1, 3
• If HIV-negative with recurrent thrush: Consider idiopathic CD4 lymphocytopenia, autoimmune disorders, or occult malignancy 3

Step 4: Microbiological Confirmation When Needed

• Culture and sensitivity if treatment-resistant or atypical presentation 6, 5
• Biopsy for lesions that don't respond to antifungal therapy or have atypical features 1, 5

Critical Pitfalls to Avoid

• Do not dismiss treatment-resistant thrush as simple non-compliance; it may indicate underlying immunodeficiency requiring investigation 6
• Laryngeal thrush is frequently missed because clinicians don't examine beyond the oropharynx in patients with isolated hoarseness 4
• Necrotizing granulomas on biopsy can occur in sarcoidosis variants, not exclusively infections, when evaluating systemic disease 7
• In immunocompromised patients, multiple concurrent conditions are possible; thrush may coexist with other opportunistic infections 1, 3
• Geographic exposure history is essential: endemic fungi (histoplasmosis) and tuberculosis can present with oral manifestations in disseminated disease 8, 7