Positive Conversion of Tuberculin Skin Test and Performance of Interferon Release Assay to Detect Hidden Tuberculosis Infection During Anti-Tumor Necrosis Factor Agent Trial

Abstract

Objectives. To evaluate tuberculin skin tests (TST) and interferon-γ (IFN-γ) assay in the detection of latent tuberculosis (TB) infection during tumor necrosis factor (TNF) antagonist treatment in Korean patients with initial negative TST result.

Methods. Eighty-six patients with rheumatic diseases who had received anti-TNF agents for over one year were investigated. Clinical data were obtained from medical records. All patients received followup TST, and IFN-γ assay was performed in 64.

Results. The study population consisted of 40 rheumatoid arthritis (RA), 34 ankylosing spondylitis (AS), 9 juvenile rheumatoid arthritis (JRA), and 3 other patients. The TST converted to positive in 28 (32.6%) patients. There was no significant variation between TST conversion rate and all risk factors. Although there was no statistical significance, the odds of the TST conversion rate tended to increase with the duration of TNF antagonist administration. Nine (14.1%) of 64 patients who performed an IFN-γ assay had positive results. Among 28 TST positive conversion cases, 4 patients with AS and 1 with psoriatic arthritis had positive IFN-γ assay results, and one of them developed miliary TB. However, none of the 4 RA patients with positive IFN-γ assay showed TST conversion. There was 68.6% agreement (kappa = 0.29, p = 0.02) between TST and IFN-γ assay results.

Conclusion. Serial TST with IFN-γ assay may be useful to identify false-negative response to cases of latent Mycobacterium tuberculosis infection and new TB infections in patients with immune mediated inflammatory diseases during longterm anti-TNF therapy, especially in areas with intermediate TB burden.