Do anti-malaria drugs, corticosteroids, immunosuppressants, and biologics cause thrush?

Immunosuppressive Medications and Risk of Thrush (Oral Candidiasis)

Yes, corticosteroids, immunosuppressants, and biologics can cause thrush, with corticosteroids posing the highest risk among these medication classes. 1, 2

Risk by Medication Class

Corticosteroids

• Highest risk: Corticosteroids are most commonly associated with fungal infections, particularly Candida species 3, 1
• Risk increases with:
  • Higher doses (≥20 mg prednisolone equivalent for ≥2 weeks) 3, 1
  • Longer duration of therapy
  • Inhaled corticosteroids (direct exposure to oral mucosa) 4, 5
• Mechanism: Anti-inflammatory and immunosuppressive effects compromise local and systemic immune responses 5

Immunosuppressants

• Moderate risk: Traditional disease-modifying antirheumatic drugs (DMARDs) like methotrexate and azathioprine increase infection risk but less specifically for thrush 3
• Risk increases when combined with corticosteroids 3
• Mechanism: Impair cell-mediated immunity needed to control fungal overgrowth

Biologics

• Variable risk: Biologics, particularly TNF inhibitors, may increase risk of fungal infections 3
• Higher risk observed with:
  • Anti-TNF agents compared to traditional DMARDs 3
  • Combination therapy with other immunosuppressants 3
• Mechanism: Disruption of cytokine pathways important for antifungal immunity

Anti-malarial Drugs

• Lowest risk: Limited evidence for direct association with thrush
• Generally better safety profile regarding opportunistic infections compared to other immunosuppressants 3

Clinical Implications

High-Risk Scenarios

• Patients receiving multiple immunosuppressive agents 3
• Corticosteroid doses ≥20 mg prednisolone for ≥2 weeks 3, 1
• Inhaled corticosteroids without proper oral hygiene measures 4, 5
• Pre-existing conditions that increase risk:
  • Diabetes
  • Advanced age
  • Malnutrition 3
  • Prior colonization with Candida species 3

Prevention Strategies

• For inhaled corticosteroids:
  • Rinse mouth after each use
  • Use spacer devices when possible 5
• Monitor high-risk patients regularly for signs of oral candidiasis
• Consider prophylactic antifungal therapy in very high-risk patients

Management When Thrush Occurs

• For mild cases: Topical antifungal therapy (nystatin, clotrimazole)
• For moderate-severe cases: Systemic antifungals (fluconazole)
• Consider temporarily reducing immunosuppressive dose if clinically feasible 2
• Do not discontinue immunosuppressants in patients with autoimmune conditions unless absolutely necessary 3

Special Considerations

COVID-19 and Corticosteroids

• A marked increase (10-fold) in candidemia has been observed in COVID-19 patients receiving high-dose corticosteroids 6
• Higher mortality (72.7%) reported in these cases despite antifungal therapy 6

Inflammatory Bowel Disease

• Patients with IBD on immunosuppressive therapy have increased risk of opportunistic infections including thrush 3
• Corticosteroid use specifically associated with fungal (Candida) infections in IBD patients 3

In summary, while all immunosuppressive medications can potentially increase the risk of thrush, corticosteroids pose the highest risk, followed by combination immunosuppressive therapy. Anti-malarial drugs appear to have the lowest association with thrush development.