Anti-TNF tedavisi uygulanan romatoloji hastalarında Tüberkülin deri testi seviyelerinin değişimi

Yıl 2019, , 254 - 257, 15.03.2019

Tayfun Özdemir Serpil Tuna , Özlem Karataş , Mehmet İhsan Arman

https://doi.org/10.28982/josam.537201

Öz

Giriş: Günümüzde Latent tüberküloz tanısında kullanılan en ucuz ve kolay uygulanan test PPD’dir. Öneriler doğrultusunda anti TNF ajanlarla tedavi öncesi izoniazid (İNH) profilaksisi verilmektedir.

Amaç: Çalışmamızda anti TNF-α tedavisi alan enflamatuvar romatizmal hastalığı olan hastalarda tedavi öncesi tüberkülin deri testi (PPD) düzeyleri ve anti TNF-α tedavisi sırasındaki kontrollerde tekrarlanan PPD düzeyindeki değişimleri değerlendirilmesi amaçladık.

Yöntemler: Çalışamaya anti-TNF tedavisi alan enflamutuvar romatizmal hastalığı olan toplam 117 hasta dahil edilmiştir. Anti TNF ilaç kullanan hastaların tedavi öncesi rutin olarak bakılan PPD düzeyleri, kontrollerde tekrarlanan PPD değişimleri, başlangıç ve kontrol PPD sonuçlarına göre İNH profilaksisi başlanma oranları değerlendirildi.

Bulgular: Çalışmamızda anti TNF ilaç kullanan 117 hastanın yaş ortalaması (81 erkek, 36 kadın) 40.4±12.90. Anti TNF ilaç kullanımı sonrası kontrol PPD ortalamasında başlangıç PPD seviyeleri ortalamasına göre istatistiksel olarak anlamlı bir artış saptandı. (p=0,001) Çalışmamıza alınan 117 hastanın 99’una (%84,6) İNH profilaksisi verilmiş, İNH profilaksisi verilen 99 hastanın 63’üne (%53) başlangıç PPD sonucuna göre, kalan 54 hastanın ise 36’sına (%30) daha kontrol PPD sonucuna göre İNH profilaksisi verildiği görüldü. Kontrol PPD sonucuna göre İNH profilaksisi başlanması ile hastalık tanısı ve kullanılan anti TNF ilaç çeşidi arasında anlamlı bir ilişki saptanmadı. (p=0,18)

Sonuç: Anti-TNF ilaç tedavisi alan romatizmal hastalarda, tedavi sürecinde immun cevabın düzenlenmesi ile PPD düzeyini değiştirip yalancı negatiflik oranını azaltabilir. Bu yüzden proflaksi alması gereken hastaları belirlemek için tedavinin ileri dönemlerinde de belli aralıklarla PPD testi tekrarlanması ve hastaların profilaksi açısından tekrar değerlendirilmesi önerilebilir.

Anahtar Kelimeler

Tumor nekroz faktör inhibitörü, Romatolojik hastalık, Tüberkülin deri testi, tüberküloz, Yan etki

Variations of tuberculin skin test in patients with rheumatologic disorders and under anti-TNF treatment

Öz

Aim: Nowadays PPD is the most inexpensive and easy to apply modality of test in identification of latent tuberculosis infection. Isoniazid (INH) prophylaxis must be given before usage of anti-TNF-α agents for patients. We aimed to investigate the change in Tuberculin skin test (TST) levels and Isoniazid (INH) prophylaxis rates in patients with inflammatory rheumatic diseases treated with anti-tumor necrosis factor alpha (TNF-α) agents. 

Methods: A cross-sectional study was planned. Patients with inflammatory rheumatic diseases treated with anti-TNF agents were included in the study. Demographic data, initial TST level and INH prophylaxis had obtained from patient’s files. Control TST tests had done at tuberculosis dispensaries in different time periods such as 1-2 / 2-3 / 3-4 / ≥4 years of anti TNF treatment. INH prophylaxis rates according to initial and control TST tests were compared. The relationship between INH prophylaxis and duration of anti-TNF therapy were examined.

Results: A total of 117 patients were included in the study. The mean age of the patients (81 male, 36 female) was 40.4±12.90. The control TST levels was significantly higher than initial TST (p=0.001). INH prophylaxis was given to total 99 (84.6%) of 117 patients (to 63 (53.8%) according to initial and to 36 (30.8%) according to control TST tests). There was no relationship between duration of anti TNF therapy and INH prophylaxis initiation (p=0.180). 

Conclusion: Anti-TNF treatments may reduce the rates of false-negative TST in patients with rheumatic diseases and latent tuberculosis (LTBI) at any stage of the treatment. Therefore, LTBI, which is not determined with initial TST tests, may be determined with TST test applied in the later stages of anti-TNF treatment, and the risk of active tuberculosis can be reduced by INH prophylaxis in this patients.

Anahtar Kelimeler

Tumor necrosis factor inhibitors, Tuberculin skin test, Rheumatic diseases, Tuberculosis, Minor side effect

Kaynakça

• 1. Keystone EC, Ware CF. Tumor necrosis factor and anti-tumor necrosis factor therapies. J Rheumatol Suppl. 2010;85:27-39.
• 2. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117(2):244-79.
• 3. Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001;345(15):1098-104.
• 4. Shim TS. Diagnosis and Treatment of Latent Tuberculosis Infection in Patients with Inflammatory Bowel Diseases due to Initiation of Anti-Tumor Necrosis Factor Therapy. Intest Res. 2014;12(1):12-9.
• 5. Hazlewood GS, Naimark D, Gardam M, Bykerk V, Bombardier C. Prophylaxis for latent tuberculosis infection prior to anti-tumor necrosis factor therapy in low-risk elderly patients with rheumatoid arthritis: a decision analysis. Arthritis Care Res (Hoboken). 2013;65(11):1722-31.
• 6. Yun JW, Lim SY, Suh GY, Chung MP, Kim H, Kwon OJ, et al. Diagnosis and treatment of latent tuberculosis infection in arthritis patients treated with tumor necrosis factor antagonists in Korea. Journal of Korean Medical Science. 2007;22(5):779-83.
• 7. Campbell JR, Krot J, Elwood K, Cook V, Marra F. A Systematic Review on TST and IGRA Tests Used for Diagnosis of LTBI in Immigrants. Mol Diagn Ther. 2015;19(1):9-24.
• 8. Menzies D, Pai M, Comstock G. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. Ann Intern Med. 2007;146(5):340-54.
• 9. Cagatay T, Kilicaslan Z, Cagatay P, Mertsoylu M, Gulbaran Z, Yildiz R, et al. TNF-alpha antagonist therapy modify the tuberculin skin test response. Rheumatol Int. 2011;31(9):1147-51.
• 10. Gomez-Reino JJ, Carmona L, Valverde VR, Mola EM, Montero MD. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum. 2003;48(8):2122-7.
• 11. Mohan AK, Cote TR, Block JA, Manadan AM, Siegel JN, Braun MM. Tuberculosis following the use of etanercept, a tumor necrosis factor inhibitor. Clin Infect Dis. 2004;39(3):295-9.
• 12. Yamada T, Nakajima A, Inoue E, Tanaka E, Hara M, Tomatsu T, et al. Increased risk of tuberculosis in patients with rheumatoid arthritis in Japan. Ann Rheum Dis. 2006;65(12):1661-3.
• 13. Carmona L, Hernandez-Garcia C, Vadillo C, Pato E, Balsa A, Gonzalez-Alvaro I, et al. Increased risk of tuberculosis in patients with rheumatoid arthritis. J Rheumatol. 2003;30(7):1436-9.
• 14. Hochberg MC, Lebwohl MG, Plevy SE, Hobbs KF, Yocum DE. The benefit/risk profile of TNF-blocking agents: findings of a consensus panel. Semin Arthritis Rheum. 2005;34(6):819-36..
• 15. Mutlu GM, Mutlu EA, Bellmeyer A, Rubinstein I. Pulmonary adverse events of anti-tumor necrosis factor-alpha antibody therapy. Am J Med. 2006;119(8):639-46
• 16. Hamdi H, Mariette X, Godot V, Weldingh K, Hamid AM, Prejean MV, et al. Inhibition of anti-tuberculosis T-lymphocyte function with tumour necrosis factor antagonists. Arthritis Res Ther. 2006;8(4):R114.
• 17. Society AT, Control CfD, Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161:S221-S47.
• 18. Smith BM, Menzies D. Treatment of latent TB: first do no harm. Expert Review of Anti-Infective Therapy. 2011;9(5):491-3.
• 19. Chee CB, KhinMar KW, Gan SH, Barkham TM, Pushparani M, Wang YT. Latent tuberculosis infection treatment and T-cell responses to Mycobacterium tuberculosis-specific antigens. Am J Respir Crit Care Med. 2007;175(3):282-7.
• 20. Vukmanovic-Stejic M, Reed JR, Lacy KE, Rustin MH, Akbar AN. Mantoux Test as a model for a secondary immune response in humans. Immunol Lett. 2006;107(2):93-101.
• 21. Ponce de Leon D, Acevedo-Vasquez E, Sanchez-Torres A, Cucho M, Alfaro J, Perich R, et al. Attenuated response to purified protein derivative in patients with rheumatoid arthritis: study in a population with a high prevalence of tuberculosis. Ann Rheum Dis. 2005;64(9):1360-1.
• 22. Joven BE, Almodovar R, Galindo M, Mateo I, Pablos JL. Does anti-tumour necrosis factor alpha treatment modify the tuberculin PPD response? Ann Rheum Dis. 2006;65(5):699.
• 23. Sezer I, Kocabas H, Melikoglu MA, Arman M. Positiveness of purified protein derivatives in rheumatoid arthritis patients who are not receiving immunosuppressive therapy. Clin Rheumatol. 2009;28(1):53-7.
• 24. Bonfiglioli K, Ribeiro A, Moraes J, Saad C, Souza F, Calich A, et al. LTBI screening in rheumatoid arthritis patients prior to anti-TNF treatment in an endemic area. The International Journal of Tuberculosis and Lung Disease. 2014;18(8):905-11.