What are the causes of thrush on the tongue in adults, particularly those with a history of antibiotic use, corticosteroid therapy, diabetes, HIV/AIDS, or other immunocompromising diseases?

Causes of Oral Thrush in Adults

Oral thrush (oropharyngeal candidiasis) in adults is caused by overgrowth of Candida species—predominantly Candida albicans—triggered by disruption of normal oral flora or compromised host defenses, with the most important predisposing factors being immunosuppression (especially HIV/AIDS with CD4+ counts <200 cells/μL), antibiotic use, corticosteroid therapy (including inhaled steroids), diabetes mellitus, and denture wearing. 1, 2

Primary Causative Organisms

• Candida albicans accounts for the majority of oral thrush cases 1, 3
• Non-albicans species including C. glabrata, C. dubliniensis, and C. krusei can cause infection, particularly in patients with repeated azole exposure or fluconazole resistance 4, 1
• C. dubliniensis was first identified specifically in HIV-infected patients with oral candidiasis 4, 1

Major Predisposing Factors

Immunosuppression (Most Critical)

• HIV/AIDS is the single most important risk factor, with oral candidiasis occurring in over 90% of AIDS patients at some point during their illness 5
• The erythematous and pseudomembranous forms are predictive of progressive immunodeficiency in HIV patients 4
• CD4+ counts <200 cells/μL significantly increase risk 1
• Other immunosuppressive conditions and malignancies predispose to infection 6, 2

Medication-Related Causes

• Antibiotic use disrupts normal oral flora balance, allowing Candida overgrowth 6, 2
• Corticosteroid therapy, including inhaled corticosteroids for asthma/COPD, suppresses local immune defenses 1, 6
• The mechanism involves both systemic immunosuppression and local mucosal effects 2

Metabolic and Endocrine Factors

• Diabetes mellitus creates a favorable environment for Candida growth through elevated glucose levels in saliva 6, 2
• Cushing's syndrome increases susceptibility through cortisol-mediated immunosuppression 2

Local Oral Factors

• Denture wearing is a major local risk factor, particularly in elderly patients, with prevalence ranging from 13-47% in institutionalized elderly 6
• Impaired salivary gland function (xerostomia) removes the protective antimicrobial effects of saliva 6, 2
• Poor oral hygiene allows accumulation of organisms 6
• High carbohydrate diet provides substrate for Candida growth 2

Other Risk Factors

• Extremes of age (very young and elderly) have altered immune function 2
• Smoking damages oral mucosa and alters local immunity 2
• Malnutrition impairs immune function 6
• Radiation therapy to the head and neck damages mucosa and salivary glands 1

Pathophysiology

• Candida species normally exist as commensal organisms in the oral cavity 1
• Transition from commensal to pathogen occurs when the balance of oral microflora is disrupted or host defense mechanisms are compromised 1
• Repeated antifungal exposure, particularly fluconazole, can lead to emergence of non-albicans species with intrinsic reduced azole susceptibility 4, 1

Clinical Patterns

The American College of Physicians and ESCMID guidelines recognize three main clinical presentations 4, 7, 1:

• Pseudomembranous candidiasis: Creamy white, plaque-like lesions on buccal mucosa, oropharynx, or tongue that can be scraped off 4, 7
• Erythematous candidiasis: Red patches without white plaques, typically on the palate or diffusely on the tongue 4, 7
• Angular cheilitis: Inflammation and cracking at the corners of the mouth 7, 8

Important Clinical Considerations

• In HIV-infected patients, oral candidiasis can occur at any stage of infection (primary infection, chronic asymptomatic phase, or AIDS), but its presence often signals progressive immunodeficiency 4
• Clinical relapse is common and depends on the degree of immunosuppression 5
• The introduction of HAART has led to a dramatic decline in refractory disease and resistant Candida isolates in HIV patients 4