High rates of tuberculin skin test positivity due to methotrexate therapy: False positive results?

Miguel Arias-Guillén, Marta M. Sánchez Menéndez, Mercedes Alperi, Sabino Riestra, María Teresa González Budiño, Marta María García-Clemente, Susana Martínez-González, Ana Isabel Enríquez, Rebeca Alonso-Arias, Juan José Palacios Gutiérrez, Miguel Santibáñez, Pablo Coto-Segura, Pablo Martínez Camblor, Lucía García-Alfonso, Isla Morante, Patricio Escalante

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Rationale: The tuberculin skin test (TST) and interferon ? release assays (IGRAs) are commonly used for latent tuberculosis infection (LTBI) screening. Unexpectedly high TST positivity rates have been reported in patients with rheumatic diseases, and methotrexate is frequently used in this population. We hypothesized that methotrexate use could be associated with false-positive TST results. Objectives: To investigate whether treatment with methotrexate and other factors are associated with false-positive TST results in patients with rheumatic diseases. Methods: Prospective single-center study conducted between April 2013 and March 2016. Adult patients with rheumatic diseases were evaluated with a TST and two IGRAs for LTBI screening. We compared TST and IGRA results in patients treated and not treated with methotrexate and analyzed for factors associated with positive TST results. Conclusions: Our data suggest false-positive TST results associated with methotrexate therapy. Thus, we recommend against using the TST for LTBI screening in patients receiving methotrexate and the preferential use of IGRAs in such patients. Measurements and Main Results: We studied 393 patients with rheumatic diseases, including ankylosing spondylitis (ASP, n = 90), rheumatoid arthritis (RA; n = 120), psoriatic arthritis (PA, n = 126), and other disorders (n = 57). The rate of TST positivity varied across the groups: ASP 22.2%, RA 25%, PA 35.7%, and other disorders (22.8%). Positivity rates were lower with IGRAs. Methotrexate use was associated with a statistically significant two-fold increase in the risk of a positive TST and a dose\x96 response relationship was observed. We found no statistically significant associations between methotrexate use and IGRA test positivity.

Original languageEnglish (US)
Pages (from-to)538-546
Number of pages9
JournalSeminars in Arthritis and Rheumatism
Issue number3
StatePublished - Dec 2018


  • Tuberculin Skin Test
  • interferon ? release assays
  • latent tuberculosis infection
  • methotrexate
  • rheumatic disease

ASJC Scopus subject areas

  • Rheumatology
  • Anesthesiology and Pain Medicine


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