Prebiologic Therapy Tuberculosis Screening Experience in a Pediatric Rheumatology Center: TST and IGRA Are Both Necessary

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We read with interest the article by Lowenthal and the recent related reply letter by Tebruegge. Lowenthal et al1 compared the results of tuberculosis (TB) screening tools [tuberculin skin test (TST) and interferon-gamma release assay (IGRA)] in immigrant children before and after their arrival in California, USA. Because of the high number of TST+/IGRA− patients, the authors suggest for preimmigration screening IGRA instead of TST. More recently, Tebruegge et al2 reported that a substantial proportion of TST+/IGRA− discordant children are likely to be TB-infected on the basis of their cytokine biomarker profiles,3 thus, suggesting the usefulness of using both tests.
We also would like to provide our experience of a tertiary pediatric rheumatology center in screening our patients with juvenile idiopathic arthritis (JIA) for TB infection before starting anti–tumor necrosis factor-alpha (TNFα) treatment. Current rheumatologic treatment guidelines recommend screening for latent TB infection (LTBI) before starting anti-TNFα treatment; however, the most appropriate screening test remains debatable.4
Among 120 JIA patients screened between January 2013 and April 2016, using TST and IGRA (QuantiFERON-TB GOLD) combined, 6 patients (5%, 3 female and 3 male) had at least 1 positive TB screening methods, and they were diagnosed to have LTBI (Table, Supplemental Digital Content 1, http://links.lww.com/INF/C626, which illustrates epidemiology data and features of 6 children with LTBI among 120 JIA children screened before starting anti-TNFα treatment); thus, they received 3 months of treatment with isoniazid and rifampicin. All of them had negative chest radiographs. The median age was 8.5 years (range 2–17.5 years). A possible Mycobacterium tuberculosis exposure history has been detected in 2 cases. The biologic therapy was deferred 1 month after anti-TB chemoprophylaxis onset, and LTBI treatment was well tolerated. The median follow-up was 28 months, and during this period, no children developed active TB disease.
TST was positive in 5/6 patients; 3 of them were IGRA negative. IGRA was positive in 3/6 patients, 1 of them (TST negative) remaining IGRA positive when retested after 2 months. Therefore, only 2 patients had both TB tests positive. All patients with positive IGRA became negative after 3 months of anti-TB chemoprophylaxis.
The total concordance between TST and IGRA was 0.933; the Cohen kappa coefficient was 0.299, indicating only a modest agreement.
Although just 13% (16 subjects) of the entire cohort were not of Italian origin, almost all LTBI patients (5/6) were foreign (Fischer exact test, χ2 26.7, P < 0001).
In addition, 4 other patients had indeterminate IGRA with negative TST, but interferon-gamma release assay repeated after 1 month resulted negative. As previously reported in literature, the median age of these patients showed a lower age trend than that in children with positive IGRA (median age 5.4 years; range 2.17–7.5 vs 13 years; range 11.08–14.75); this was not unexpected because performance of IGRAs shows a lower efficiency in young children.5
Given the lack of evidence and in agreement with Tebruegge et al and other authors,6,7 we suggest performing both TST and IGRA before starting a biologic treatment to minimize the risk of developing an active TB infection while receiving biologic treatment. Particular attention should be paid to immigrants because in our data set, 31% (5/16) of them presented with LTBI.

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