Does high-dose steroid (corticosteroid) therapy affect Purified Protein Derivative (PPD) skin test readings?

High-Dose Steroids Significantly Affect PPD Skin Test Readings

High-dose corticosteroid therapy can suppress the immune response to tuberculin skin tests (PPD), potentially leading to false-negative results. 1, 2

Effect of Corticosteroids on PPD Testing

• Systemic corticosteroids can suppress delayed-type hypersensitivity reactions, which are the basis of the PPD skin test, leading to false-negative results 1
• The FDA drug label for prednisone specifically lists "suppression of reactions to skin tests" as a known adverse effect 2
• Corticosteroid therapy may mask tuberculosis infection by reducing the inflammatory response needed for a positive PPD test reading 3

Dose-Dependent Effects

• Doses of prednisolone higher than 10-20 mg per day are more likely to cause significant suppression of PPD skin test reactions 1
• Clinical experience suggests that if the daily dose is no higher than 10 mg prednisolone, suppression of positive patch tests is unlikely 1
• A study investigating the effects of prednisolone on cutaneous tuberculin response found that it significantly suppressed skin induration in corticosteroid-sensitive individuals 3

Clinical Implications and Recommendations

• Tuberculin skin testing should ideally be performed before initiating high-dose corticosteroid therapy whenever possible 1
• For patients already on high-dose steroids, consider the increased risk of false-negative results when interpreting PPD tests 1
• Alternative testing methods such as interferon-gamma release assays (IGRAs) may be less affected by steroid therapy and should be considered in patients on high-dose steroids 1
• Two-step testing may help identify individuals with waning hypersensitivity reactions who might otherwise have false-negative results 1

Special Considerations

• Patients with HIV infection may have both anergy due to their immunocompromised state and further suppression from corticosteroid therapy, making PPD interpretation particularly challenging 4
• Current corticosteroid use has been identified as an independent risk factor for anergy in hospitalized patients 4
• For patients requiring long-term corticosteroid therapy at doses exceeding 15 mg of prednisone daily for more than 3 weeks, preventive therapy for tuberculosis should be considered if they have a positive tuberculin test or are at high risk 1

Alternative Testing Approaches

• In patients on high-dose steroids, consider using IGRAs such as QuantiFERON-TB Gold, which may be less affected by steroid therapy 1
• When PPD testing must be done in patients on steroids, consider using anergy testing with companion antigens (e.g., Candida antigen and tetanus toxoid) to help interpret negative PPD results 1
• The most commonly reactive control tests for anergy panels include Candida, mumps, and tetanus or histoplasmin 5

Remember that false-negative PPD results in patients on high-dose steroids could lead to missed opportunities for preventive therapy in those with latent tuberculosis infection, potentially increasing the risk of progression to active disease when immunosuppression is present.