Mechanism of Corticosteroids Causing Thrush
Corticosteroids cause thrush primarily through local and systemic immunosuppression that impairs host defense mechanisms against Candida species, combined with direct effects that may enhance fungal growth and colonization. 1, 2
Primary Immunosuppressive Mechanisms
Corticosteroids suppress both cellular and humoral immunity through multiple pathways that create an environment permissive for Candida overgrowth:
Inhibition of cytokine production: Corticosteroids block production of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor (TNF), and gamma interferon, which are essential for mounting effective antifungal immune responses 2
Suppression of T-cell and B-cell responses: They block cellular proliferation after antigen stimulation and inhibit cytokine production necessary for immune activation, directly impairing the adaptive immune response needed to control fungal infections 2
Impaired inflammatory response: Corticosteroids profoundly affect the inflammatory response through vasoconstriction, decreased chemotaxis, and interference with macrophage function—all critical components of antifungal defense 3
Molecular-Level Actions
At the cellular level, corticosteroids work through specific protein synthesis modifications:
After passing through cell membranes, corticosteroids bind to cytoplasmic receptor proteins forming a steroid-receptor complex that moves into the nucleus and binds to DNA 4
This binding changes messenger RNA (mRNA) transcription, either stimulating or inhibiting synthesis of specific proteins that regulate immune and inflammatory responses 4
Corticosteroids stimulate production of lipocortin, a glycoprotein that inhibits phospholipase A2 activity, thereby reducing arachidonic acid release and subsequent production of inflammatory mediators 4
Clinical Risk Factors
The risk of developing Candida infections is dose-dependent and influenced by duration of therapy:
Systemic corticosteroids: Doses equivalent to ≥20 mg prednisolone daily for ≥2 weeks are associated with increased risk of fungal (Candida spp.) infections 1
Topical/inhaled corticosteroids: Local immunosuppression in the oral cavity or oropharynx creates favorable conditions for Candida colonization and infection 5, 6, 7
Corticosteroid use was more commonly associated with fungal (Candida spp.) infections compared to other immunomodulators in large observational studies 1
Direct Effects on Fungal Pathogens
Beyond immunosuppression, corticosteroids may have direct effects that favor fungal growth:
Corticosteroids can increase viral replication through direct effects on replication mechanisms, and similar mechanisms may apply to fungal pathogens 2
The anti-inflammatory and immunosuppressive effects create a local environment that reduces the host's ability to control normal commensal Candida, allowing overgrowth and symptomatic infection 5
Important Clinical Caveats
Prophylaxis should be considered in high-risk scenarios:
The National Comprehensive Cancer Network recommends fungal prophylaxis with fluconazole for patients receiving prednisone equivalent of ≥20 mg/day for 6 or more weeks 8
For inhaled corticosteroids, simple mouthwash procedures after use can reduce (though not eliminate) the risk of oral candidiasis 7
The cumulative immunosuppressive effect is particularly important when corticosteroids are combined with other immunomodulators, substantially increasing infection risk 1
The mechanism is fundamentally different from direct antimicrobial resistance—corticosteroids don't make Candida more virulent, but rather disable the host defenses that normally keep this commensal organism in check, allowing opportunistic infection to develop.