False-Positive Tuberculin Skin Test Results Linked to Methotrexate Therapy

Tuberculin syringe
Tuberculin syringe
High rates of false-positive results on the tuberculin skin test have been reported among patients treated with methotrexate.

High rates of false-positive results on the tuberculin skin test (TST) have been reported among patients treated with methotrexate, regardless of bacillus Calmette-Guerin vaccination status, according to the results of a prospective, single-center cohort study recently published in Seminars in Arthritis and Rheumatism.

The investigators sought to examine whether methotrexate therapy and other factors are linked to false-positive TST results among patients with rheumatic diseases. The study was conducted between April 2013 and March 2016. Adult patients were screened for latent tuberculosis infection (LTBI) using a TST and 2 interferon γ release assays (IGRAs). The results of TST and IGRA tests were compared among patients who were or were not treated with methotrexate and were studied for factors linked to positive TST test results.

A total of 393 patients with rheumatic diseases, including ankylosing spondylitis (AS; n=90), rheumatoid arthritis (RA; n=120), psoriatic arthritis (PsA; n=126), and other rheumatic or inflammatory conditions (n=57) were evaluated. The rate of TST positivity varied across the patient groups, with rates of 22.2% in the AS group, 25% in the RA group, 35.7% in the PsA group, and 22.8% among participants with other rheumatic conditions. Rates of positivity were lower with IGRA tests compared with TST tests.

The use of methotrexate was associated with a statistically significant 2-fold increased risk for a positive TST test result, with an observed dose-response relationship. No statistically significant association between methotrexate use and IGRA positivity was reported.

Related Articles

The investigators concluded that the results of this study suggest that false-positive TST test results are associated with the use of methotrexate therapy. Therefore, they recommend against the use of TST testing in methotrexate-treated patients, and suggest that these individuals be screened for LTBI with IGRA testing prior to initiation of biologic therapy. Longitudinal studies are warranted to assess various LTBI screening strategies and their utility for predicting TB reactivation in this population.

follow @RheumAdvisor


Arias-Guillén M, Sánchez Menéndez MM, Alperi M, et al. High rates of tuberculin skin test positivity due to methotrexate therapy: false positive results? [published online March 29, 2018]. Semin Arthritis Rheum. doi: 10.1016/j.semarthrit.2018.03.018