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Semin Arthritis Rheum. 2018 Dec;48(3):538-546. doi: 10.1016/j.semarthrit.2018.03.018. Epub 2018 Mar 29.

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

Author information

1
Department of Respiratory Medicine, Instituto Nacional de Silicosis\x96Hospital Universitario Central de Asturias, University of Oviedo School of Medicine, Avda, Roma, s/n, 33011 Oviedo, Asturias, Spain. Electronic address: miguelariasguillen@gmail.com.
2
Department of Rheumatology, Centro Médico de Asturias, Avda, José María Richard, s/n, 33193 Oviedo, Asturias, Spain.
3
Department of Rheumatology, Hospital Universitario Central de Asturias, Avda, Roma, s/n, 33011 Oviedo, Asturias, Spain.
4
Department of Gastroenterology, Hospital Universitario Central de Asturias, Avda, Roma, s/n, 33011 Oviedo, Asturias, Spain.
5
Department of Respiratory Medicine, Instituto Nacional de Silicosis\x96Hospital Universitario Central de Asturias, University of Oviedo School of Medicine, Avda, Roma, s/n, 33011 Oviedo, Asturias, Spain.
6
Department of Respiratory Medicine, Hospital Carmen y Severo Ochoa, Calle Sienra 11, 33800 Cangas del Narcea, Asturias, Spain.
7
Department of Immunology Hospital Universitario Central de Asturias, Avda, Roma, s/n, 33011 Oviedo, Asturias, Spain.
8
Department of Microbiology, Mycobacterial Regional Reference Unit, Hospital Universitario Central de Asturias, Avda, Roma, s/n, 33011 Oviedo, Asturias, Spain.
9
Department of Nursery, Universidad de Cantabria-IDIVAL, Av. de Valdecilla, 25, 39008 Santander, Cantabria, Spain.
10
Department of Dermatology, Hospital Universitario Central de Asturias, Avda, Roma, s/n, 33011 Oviedo, Asturias, Spain.
11
Geisel School of Medicine, Dartmouth College, 1 Rope Ferry Rd, Hanover, NH 03755, EE.UU, Universidad Aut\xF3noma de Chile, Santiago, Chile.
12
Department of Rheumatology, Hospital de Sierrallana, Barrio de Ganzo, s/n, 39300 Torrelavega, Cantabria, Spain.
13
Division of Pulmonary and Critical Care Medicine, Department of Medicine, and Mayo Clinic Center for Tuberculosis, Mayo Clinic, 200 1st St SW, Rochester, MN 55905.

Abstract

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.

KEYWORDS:

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

[Indexed for MEDLINE]

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