How does steroid use affect the Purified Protein Derivative (PPD) test for tuberculosis (TB)?

Impact of Steroid Use on PPD Testing for Tuberculosis

Corticosteroid therapy can cause false-negative PPD test results by suppressing the cell-mediated immune response required for tuberculin reactivity. 1

Mechanism of Interference

Steroids affect the PPD test through several mechanisms:

• Immunosuppression: Corticosteroids suppress T-cell function, which is essential for the delayed-type hypersensitivity reaction that produces induration in the PPD test 2
• Reduced inflammation: Steroids inhibit the inflammatory response needed to produce visible induration at the test site
• Impaired lymphocyte function: Steroids decrease the ability of lymphocytes to respond to tuberculin antigens 3

Clinical Significance by Steroid Type and Dose

Systemic Corticosteroids

• High-dose oral steroids (≥15 mg prednisone or equivalent daily for ≥1 month):
  • Most likely to cause false-negative PPD results
  • May suppress reactivity even in persons known to be infected with M. tuberculosis 2
  • Require special consideration when interpreting results (5 mm induration is considered positive) 2

Inhaled Corticosteroids

• Generally considered safer with less systemic effect
• Research suggests inhaled corticosteroids (e.g., budesonide) appear safe in PPD-positive asthmatic children without causing reactivation of latent TB 4

Timing Considerations

• PPD testing should ideally be performed before initiating corticosteroid therapy 2
• If not possible, be aware that:
  • False-negative results are more likely with ongoing steroid therapy
  • The suppressive effect may persist for weeks after discontinuation of steroids

Interpretation Guidelines for Steroid Users

The CDC and American Thoracic Society recommend the following cutoff points for PPD positivity in steroid users 2, 1:

• ≥5 mm induration: Consider positive in patients receiving immunosuppressive therapy (equivalent of ≥15 mg/day prednisone for >1 month)
• This lower threshold compensates for the potential suppressive effect of steroids on the immune response

Alternative Testing Options

For patients on corticosteroids who require TB screening:

• Interferon-Gamma Release Assays (IGRAs) may be less affected by steroid therapy than PPD, though they can still be impacted by severe immunosuppression 1
• Chest radiography should be considered in addition to skin testing for patients on corticosteroids, especially if high-dose or long-term therapy 2

Prophylaxis Considerations

• For PPD-positive patients requiring steroid therapy (≥15 mg prednisone daily for ≥1 month), isoniazid prophylaxis should be considered regardless of the size of PPD reaction 2, 5
• A case-control study showed 97% reduction in TB risk with complete isoniazid prophylaxis in steroid-treated patients with rheumatic diseases 5

Key Pitfalls to Avoid

1. Don't rely solely on PPD results in patients on steroids due to increased false-negative risk
2. Don't assume a negative PPD excludes TB infection in patients on corticosteroids
3. Don't delay TB screening until after starting steroids when possible
4. Don't overlook the need for TB prophylaxis in high-risk patients requiring long-term steroid therapy

In summary, clinicians should maintain a high index of suspicion for TB in steroid-treated patients regardless of PPD results, consider alternative testing methods, and implement appropriate prophylaxis for high-risk individuals.