1986
The Journal of Rheumatology 2013; 40:12; doi:10.3899/jrheum.130303
Personal non-commercial use only. The Journal of Rheumatology Copyright © 2013. All rights reserved.
Screening for Latent Tuberculosis Infection in Patients
with Chronic Inflammatory Arthritis: Discrepancies
Between Tuberculin Skin Test and Interferon-γ Release
Assay Results
Félicie Costantino, Marcelo de Carvalho Bittencourt, Anne-Christine Rat, Damien Loeuille,
Hervé Dintinger, Marie C. Béné, Gilbert Faure, and Isabelle Chary-Valckenaere
ABSTRACT. Objective. Screening for latent tuberculosis infection (LTBI) is mandatory before initiating biologics
in patients with chronic inflammatory arthritis (CIA). However, few studies have evaluated the
discrepancies between the results of tuberculin skin test (TST) and interferon-γ release assays
(IGRA) in these patients. The purpose of our study was to investigate factors associated with TST
and IGRA results in a large cohort of patients with CIA before the introduction of biologics.
Methods. A total of 563 consecutive patients with CIA (293 rheumatoid arthritis, 270 spondy-
loarthritis) and eligible for biologics were prospectively enrolled. Demographic, clinical, and
biological data were recorded. Risk factors for LTBI were assessed. All patients underwent a TST, a
chest radiograph, and an IGRA test (T-SPOT.TB).
Results. Agreement between the 2 tests was low (κ = 0.16). The bacillus Calmette-Guerin (BCG)
status was significantly associated with discordance between the 2 tests (p = 0.004). The TST
positivity rate was 34.8%. Factors associated with a negative TST were female sex (p = 0.02) and
immunosuppressive treatment (p = 0.003). The only LTBI risk factor associated with TST positivity
was an abnormal chest radiograph (p = 0.02). T-SPOT.TB was positive in 21.7% of patients and
indeterminate in 15.6%. Previous active TB and chest radiograph abnormalities were associated with
IGRA positivity (p = 0.008 and p = 3.9 × 10
-5
, respectively). The BCG vaccination was associated
with negative IGRA (p = 3 × 10
-4
). Indeterminate IGRA results were associated with age, C-reactive
protein, and immunosuppressive treatment (p = 0.005, 0.007, and 0.004, respectively).
Conclusion. Our data support the combined use of T-SPOT.TB and TST in patients with CIA before
biologics introduction. However, despite these good diagnostic values, indeterminate results may
complicate the use of IGRA. (First Release Oct 1 2013; J Rheumatol 2013;40:1986–93; doi:10.3899/
jrheum.130303)
Key Indexing Terms:
TUBERCULOSIS BIOLOGICAL AGENTS INTERFERON-γ RELEASE TESTS
ANKYLOSING SPONDYLITIS RHEUMATOID ARTHRITIS
From the Rheumatology Department and the Immunology Department,
CHU Nancy, Nancy; Université de Lorraine, Lorraine, France.
F. Costantino, MD, Rheumatology Department, CHU Nancy; M. de
Carvalho Bittencourt, MD, PhD, Immunology Department, CHU Nancy,
and EA RHEM4369, Université de Lorraine; A.C. Rat, MD, PhD,
Rheumatology Department, and INSERM, CIC-EC CIE6, Epidémiologie
et Evaluation Cliniques, CHU Nancy; D. Loeuille, MD, PhD,
Rheumatology Department, CHU Nancy, and UMR 7365 (IMoPA) CNRS,
Université de Lorraine; H. Dintinger, MD, Rheumatology Department,
CHU Nancy; M.C. Béné, MD, PhD, Immunology Department, CHU
Nancy and EA RHEM4369, Université de Lorraine; G.C. Faure, MD,
PhD, Immunology Department, CHU Nancy; EA RHEM4369, Université
de Lorraine; I. Chary-Valckenaere, MD, PhD, Rheumatology Department,
CHU Nancy, and UMR 7365 (IMoPA) CNRS, Université de Lorraine.
Address correspondence to Dr. F. Costantino, Institut Cochin Bâtiment
Hardy A, 1e étage, 27 rue du Faubourg Saint Jacques, 75014 Paris,
France. E-mail: felicie.costantino@inserm.fr
Accepted for publication July 25, 2013.
Tumor necrosis factor (TNF) antagonists are very effective
treatments of many immune-mediated inflammatory
diseases including rheumatoid arthritis (RA) and spondy-
loarthritis (SpA). However, anti-TNF therapy is associated
with an increased risk of tuberculosis (TB)
1
most often
because of reactivation of a latent infection
2
. Therefore,
screening for latent TB infection (LTBI) has become
mandatory before the initiation of TNF antagonists.
National recommendations for LTBI screening based on
medical history, clinical examination, tuberculin skin test
(TST), and chest radiograph
3,4,5,6,7
have demonstrated their
effectiveness to reduce TB incidence
8
. However, despite
recommendations, the incidence of TB in patients treated
with anti-TNF therapy still remains higher than in the
general population
9,10
.
Use of the TST has been questioned. Indeed, TST has
well-known limitations: poor specificity owing to
cross-reactivity with environmental mycobacteria or
bacillus Calmette-Guerin (BCG)
11
, poor sensitivity in
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