Comparison of Tuberculin Skin Test and Interferon Gamma Release Test in Latent Tuberculosis Screening Before Anti-TNF Alpha Treatment in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

Öz

Objective: We aimed to compare the tuberculin skin test (TST) and the interferon gamma release test (IGRT) for latent tuberculosis (LTBI) screening in patient with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) that have two different pathophysiological pathways and the immunosuppressive therapies used.Material-Method: 85 AS and 75 RA patients were included in the study. TST and IGRT for LTBI were performed in patients who were planned biological therapy due to disease activation. TST was applied using the Mantoux method. QuantiFERON-TB Gold PLUS (QFT-GP) was used for IGRT, a fourth version and a ELISA-based test. Results: In the RA group, TST was positive in 27 (36%) patients and negative in 48 (64%) patients. In the QuantiFERON-TB gold test of 27 patients who were found to be positive with TST, 1 (3.7%) was uncertain, 15 (55.5%) patients were negative, and 11 (40.7%) patients were positive. The kappa value of both tests in RA patients was determined to be 0.440 and was considered to be moderate. In the AS group, TST was positive in 44 (51.8) patients and negative in 41 (48.2%) patients. In this group, 34 (77.3%) patients who were found to be positive by TST were evaluated as negative by the QuantiFERON-TB gold test. Agreement of the two tests in AS patients (kappa) was found to be low (0.184).Conclusion: TST and IGRT are not tests with high agreement with each other. Therefore, although TST is recommended primarily in LTBI screening, IGST may be preferred in selected patient groups such as rheumatologic patients.

Romatoid Artrit ve Ankilozan Spondilit Hastalarında Anti-TNF Alfa Tedavi Öncesi Latent Tüberküloz Taramasında Tüberkülin Deri Testi ve İnterferon Gama Salınım Testinin Karşılaştırılması

Öz

Amaç: Ankilozan spondilit (AS) ve romatoid artrit (RA) gibi iki farklı patofizyolojik yolağa sahip ve kullanılan immünsupresif tedavilerin farklı olduğu hastalıkta latent tüberküloz taramasında tüberkülin deri testi (TDT) ve interferon gama salınım testini (İGST) karşılaştırmayı amaçladık. Materyal-Metod: Çalışmaya 85 AS ve 75 RA hastası dahil edildi. Hastalık aktivasyonu nedeniyle biyolojik tedavi planlanan hastalara LTBE amaçlı TDT ve IGST yapıldı. TDT, Mantoux yöntemi kullanılarak uygulandı. IGST için dördüncü sürüm ve elisa temelli bir test olan QuantiFERON-TB Gold PLUS (QFT-GP) kullanıldı. Bulgular: RA grubunda TDT 27 (%36) hastada pozitif, 48 (%64) hastada negatif olarak saptandı. TDT ile pozitif saptanan 27 hastanın QuantiFERON-TB gold testi ile 1 (%3,7) hasta belirsiz, 15 (%55,5) hasta negatif, 11 (%40,7) hasta pozitif olarak tespit edildi. Her iki testin RA hastalarında kappa değeri 0,440 tespit edildi ve orta uyumlu olarak değerlendirildi. AS grubunda ise TDT 44 (51,8) hastada pozitif, 41 (%48,2) hastada negatif olarak hesaplandı. TDT ile pozitif olarak tespit edilen 34 (%77,3) hasta QuantiFERON-TB gold testi ile negatif olarak değerlendirildi. İki testin AS hastalarında uyumu (kappa testi) düşük (0,184) olarak saptandı. Sonuç: TDT ve IGST’ i birbiri ile uyumu yüksek olan testler değildir. Bu nedenle her ne kadar LTBE taramasında TDT öncelikli olarak önerilse de romatolojik hastalar gibi seçilmiş hasta gruplarında IGST öncelikli tercih edilebilir.

Anahtar Kelimeler

• İnterferon Gama Salınım testi
• Tüberkülin Deri Testi
• Tüberküloz

Kaynakça

1. 1. A.J. Silman, J.E. Pearson. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res 2002;4(3):265-72.
2. 2. Sieper, J, Poddubnyy D. Axial spondyloarthritis. The Lancet 2017; 390(10089): 73–84.
3. 3. Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA, et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2019;71(10):1599-613.
4. 4. Godfrey M, Friedman L. Tuberculosis and Biologic Therapies: Anti-Tumor Necrosis Factor-α and Beyond. Clin Chest Med 2019;40(4):721-39.
5. 5. Kara F, editör. Tüberküloz Tanı ve Tedavi Rehberi, 2. Baskı Ankara, Mayıs 2019.
6. 6. Er AG, Gül A, Süer Aİ, Yurteri AŞ, Babalık A, Yıldırım A, et al. Anti-TNF kullanan hastalarda tüberküloz rehberi, Ankara, 2016.
7. 7. Cagatay T, Aydin M, Sunmez S, Cagatay P, Gulbaran Z, Gul A, et al. Follow-up results of 702 patients receiving tumor necrosis factor-α antagonists and evaluation of risk of tuberculosis. Rheumatol Int 2010;30(11):1459-63.
8. 8. Hasan T, Au E, Chen S, Tong A, Wong G. Screening and prevention for latent tuberculosis in immunosuppressed patients at risk for tuberculosis: a systematic review of clinical practice guidelines. BMJ Open 2018;12:8(9):e022445.

9. 9. Rudwaleit M, Landewé R, van der Heijde D, Listing J, Brandt J, Braun J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal. Ann Rheum Dis 2009;68:770–6.
10. 10. Aletaha D, Neogi T, Silman A, Funovits J, Felson D, Bingham CA 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62(9):2569-81.
11. 11. Zhou G, Luo Q, Luo S, et al. Interferon-γ release assays or tuberculin skin test for detection and management of latent tuberculosis infection: a systematic review and meta-analysis. Lancet Infect Dis 2020; 20(12):1457-69.
12. 12. Mayanja-Kizza H, Katamba A. Interferon-γ release assays or tuberculin skin test for latent tuberculosis infection?. Lancet Infect Dis 2020;20(12):1359-60.
13. 13. Kim JH, Won S, Choi CB, Sung YK, Song GG, Bae SC. Evaluation of the usefulness of interferon-gamma release assays and the tuberculin skin test for the detection of latent Mycobacterium tuberculosis infections in Korean rheumatic patients who are candidates for biologic agents. Int J Rheum Dis 2015;18(3):315-22.
14. 14. Kılınc O. Tüberkülin deri testi (TDT), yorumu ve son gelişmeler. 21. Yüzyılda Tüberküloz Sempozyumu ve II. Tüberküloz Laboratuvar Tanı Yöntemleri Kursu, Samsun.
15. 15. Arias-Guillén M, Sánchez Menéndez, MM, Alperi M, Riestra-Menéndez S, González Budiño MT, GArcia-Clemente MM, et al. High rates of tuberculin skin test positivity due to methotrexate therapy: False positive results? Semin Arthritis Rheum 2018;48(3):538-46.
16. 16. Agarwal S, Kumar Das S, Agarwal GG, Srivastava R. Steroids Decrease Prevalence of Positive Tuberculin Skin Test in Rheumatoid Arthritis: Implications on Anti-TNF Therapies. Interdiscip Perspect Infect Dis 2014;2014:430134.
17. 17. Yilmaz N, Aydin SZ, Inanc N, Karakurt S, Direskeneli H, Yavuz S. Comparison of QuantiFERON-TB Gold test and tuberculin skin test for the identification of latent Mycobacterium tuberculosis infection in lupus patients. Lupus 2012;21(5):491-5.
18. 18. Shalabi NM, Houssen ME. Discrepancy between the tuberculin skin test and the levels of serum interferon-gamma in the diagnosis of tubercular infection in contacts. Clin Biochem 2009;42:1596-601.
19. 19. H So, C Sw Yuen, R Ml Yip. Comparison of a commercial interferon-gamma release assay and tuberculin skin test for the detection of latent tuberculosis infection in Hong Kong arthritis patients who are candidates for biologic agents. Hong Kong Med J 2017;23(3):246-50.
20. 20. Gualano G, Mencarini P, Lauria FN, Palmieri F, Mfinanga S, Mwaba P, et al. Tuberculin skin test - Outdated or still useful for Latent TB infection screening?. Int J Infect Dis 2019;80S:20-2.
21. 21. Barut K, Şahin S, Adrovic A, Köşker M, Kılıç Ö, Camcıoğlu Y, et al. Tuberculin skin test response in patients with juvenile idiopathic arthritis on anti-TNF therapy. Turk J Med Sci 2018;48(6):1109-14.
22. 22. Brouqui P, Delaigue S, Parola P, Drancourt M. Interferon-gamma release assay: use and misuse. Clin Microbiol Infect 2012;18(11):1053-4.
23. 23. Madhukar P, Marcel B. Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays. Microbiol Spectr 2016;4(5).