title: A comparison of an interferon-gamma release assay and tuberculin skin test in refractory inflammatory disease patients screened for latent tuberculosis prior to the initiation of a first tumor necrosis factor α inhibitor.
abstract: Treatment with TNFα inhibitors increases risk of reactivating a latent tuberculosis\infection (LTBI). Therefore screening, prior to therapy with TNFα inhibitors, has been recommended, even in low-endemic areas such as well-developed Western Europe countries. We evaluated interferon-gamma release assay (IGRA), as opposed to tuberculin skin test (TST), for detection of LTBI in refractory inflammatory disease patients prior to the initiation of a first TNFα inhibitor. In addition, we evaluated the impact of impaired cellular immunity on IGRA. Patients starting on TNFα inhibition were screened for LTBI by TST and IGRA (Quantiferon-TB Gold). Data on tuberculosis exposure and Bacillus Calmette-Guérin (BCG) vaccination were obtained. Cellular immunity was assessed by CD4(+) T lymphocyte cell count. Nine out of 56 patients (16.1%) tested positive for LTBI. A concordant positive result was present in three patients with a medical history of tuberculosis exposure. Six patients with discordant test results had either: (1) a negative TST and positive IGRA in combination with a medical history of tuberculosis exposure (n = 1) or (2) a positive TST and negative IGRA in combination with BCG vaccination (n = 3) or a medical history of tuberculosis exposure (n = 2). CD4(+) T lymphocyte cell counts were within normal limits, and no indeterminate results of IGRA were present. IGRA appears reliable for confirming TST and excluding a false positive TST (due to prior BCG vaccination) in this Dutch serie of patients. In addition, IGRA may detect one additional case of LTBI out of 56 patients that would otherwise be missed using solely TST. Immune suppression appears not to result significantly in lower CD4(+) T lymphocyte cell counts and indeterminate results of IGRA, despite systemic corticosteroid treatment in half of the patients. Confirmation in larger studies, including assessment of cost-effectiveness, is required.
authors.affiliation: Department of Rheumatology, Medical Center Leeuwarden, P.O. Box 888, 8901 BR, Leeuwarden, The Netherlands.
authors.forename: Arjan J
authors.initials: AJ
authors.lastname: Kwakernaak
authors.forename: Pieternella M
authors.initials: PM
authors.lastname: Houtman
authors.forename: Jan F L
authors.initials: JF
authors.lastname: Weel
authors.forename: Johanna P L
authors.initials: JP
authors.lastname: Spoorenberg
authors.forename: Tim L T A
authors.initials: TL
authors.lastname: Jansen
mesh_terms: D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy; D001379:Azathioprine / Q000008:administration & dosage; D001681:Biological Assay; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000097:blood*; D007555:Isoxazoles / Q000008:administration & dosage; D055985:Latent Tuberculosis / Q000175:diagnosis*; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011446:Prospective Studies; D014374:Tuberculin Test; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D005938:Glucocorticoids; D007555:Isoxazoles; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000077339:Leflunomide; D001379:Azathioprine; D008727:Methotrexate