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Double Screening for Latent Tuberculosis Infection in Patients Treated With Anti –Tumor Necrosis Factor α

Double Screening for Latent Tuberculosis Infection in Patients Treated With Anti –Tumor Necrosis... The use of drugs that block the action of tumor necrosis factor α increases the risk of reactivation of latent tuberculosis infection (LTI).1 Screening before beginning treatment reduces the number of cases of tuberculosis by up to 78% to 85%.2 Report of Cases We describe 3 patients who were treated with anti –tumor necrosis factor α and in whom a combined tuberculin test (TT) and interferon gamma release assay (IGRA) (QuantiFERON-TB Gold; Cellestis Inc, Valencia, California) allowed the diagnosis of a recent contact or an LTI that would have not been detected with a TT alone (Table). Table. Summary of the Patients' Historya Table. Summary of the Patients' Historya View LargeDownload Comment At present, there is no criterion standard for the diagnosis of LTI. The classic screening test for the study of household contacts of tuberculosis is the TT, but it is well known that there have been false positives in persons who were vaccinated with BCG and false negatives in immunosuppressed patients. Recently, other techniques have been developed based on the detection of interferon gamma released by T lymphocytes sensitized against specific antigens of the Mycobacterium tuberculosis complex. These antigens are absent in the BCG vaccine and in nontuberculosis mycobacteria other than Mycobacterium kansaii, Mycobacterium marinum, and Mycobacterium szulgai. This characteristic allows discrimination between persons who are infected or have been vaccinated or exposed to nonpathogenic mycobacteria. The new interferon gamma tests are more specific and at least as sensitive as the TT,3 and they also incorporate a positive control that can detect the presence of anergy. However, IGRAs are not available in all hospitals because of cost and a lack of a properly equipped laboratory. Thus far, there are no uniform criteria on how to screen for LTI in patients who are scheduled to undergo biologic therapy; however, the use of the TT, the TT plus a booster, and the TT plus the IGRA in vaccinated and immnunodepressed patients has been proposed. Recently, the TT plus IGRA and the IGRA alone have been recommended for LTI screening in patients with psoriasis,4 but studies confirming double-screening advantages are lacking to date. Although IGRAs have not been validated for LTI diagnosis in patients who are receiving biologic treatment, in our experience the QuantiFERON-TB Gold has the following advantages: (1) it can detect cases of anergy, differentiating them from TT false negatives resulting from immunosuppression; (2) because it incorporates specific antigens present in M tuberculosis that are absent in the BCG vaccine, it can detect false TT positives due to vaccination; and (3) it turns positive more rapidly than the TT after recent contact with M tuberculosis,5 thus reducing the likelihood of underdiagnosed infection in patients who are receiving biologic therapy. A positive IGRA result should be considered as a cell-mediated immunologic memory to a true tuberculosis contact; therefore, isoniazid chemoprophylaxis will not change the positivity, thereby rendering repetition unnecessary after treatment is discontinued. However, a negative IGRA result must be interpreted with caution in patients who are receiving immunosuppressive treatment because it may be a false negative. Consequently, we believe that double screening (interferon gamma determination and TT) plus chest radiography and a guided medical history should be performed before biologic therapy is initiated. Furthermore, we recommend double screening every year thereafter because of the greater risk of tuberculosis in these patients. Back to top Article Information Correspondence: Dr Sempau, Department of Dermatology, Complejo Asistencial Universitario de Le ón, Altos de Nava SN, 24071 Le ón, Spain, (leticiasempau@gmail.com). Financial Disclosure: None reported. References 1. Elbek O, Uyar M, Aydin N, et al. Increased risk of tuberculosis in patients treated with antitumor necrosis factor alpha. Clin Rheumatol. 2009;28(4):421-42619052832PubMedGoogle ScholarCrossref 2. Carmona L, G ómez-Reino JJ, Rodr íguez-Valverde V, et al; BIOBADASER Group. Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum. 2005;52(6):1766-177215934089PubMedGoogle ScholarCrossref 3. Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med. 2008;149(3):177-18418593687PubMedGoogle Scholar 4. Perlmutter A, Mittal A, Menter A. Tuberculosis and tumour necrosis factor- α inhibitor therapy: a report of three cases in patients with psoriasis: comprehensive screening and therapeutic guidelines for clinicians. Br J Dermatol. 2009;160(1):8-1519016693PubMedGoogle ScholarCrossref 5. Diel R, Loddenkemper R, Meywald-Walter K, Gottschalk R, Nienhaus A. Comparative performance of tuberculin skin test, QuantiFERON-TB-Gold In Tube assay, and T-Spot.TB test in contact investigations for tuberculosis. Chest. 2009;135(4):1010-101819017873PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

Double Screening for Latent Tuberculosis Infection in Patients Treated With Anti –Tumor Necrosis Factor α

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Publisher
American Medical Association
Copyright
Copyright © 2011 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archdermatol.2011.270
Publisher site
See Article on Publisher Site

Abstract

The use of drugs that block the action of tumor necrosis factor α increases the risk of reactivation of latent tuberculosis infection (LTI).1 Screening before beginning treatment reduces the number of cases of tuberculosis by up to 78% to 85%.2 Report of Cases We describe 3 patients who were treated with anti –tumor necrosis factor α and in whom a combined tuberculin test (TT) and interferon gamma release assay (IGRA) (QuantiFERON-TB Gold; Cellestis Inc, Valencia, California) allowed the diagnosis of a recent contact or an LTI that would have not been detected with a TT alone (Table). Table. Summary of the Patients' Historya Table. Summary of the Patients' Historya View LargeDownload Comment At present, there is no criterion standard for the diagnosis of LTI. The classic screening test for the study of household contacts of tuberculosis is the TT, but it is well known that there have been false positives in persons who were vaccinated with BCG and false negatives in immunosuppressed patients. Recently, other techniques have been developed based on the detection of interferon gamma released by T lymphocytes sensitized against specific antigens of the Mycobacterium tuberculosis complex. These antigens are absent in the BCG vaccine and in nontuberculosis mycobacteria other than Mycobacterium kansaii, Mycobacterium marinum, and Mycobacterium szulgai. This characteristic allows discrimination between persons who are infected or have been vaccinated or exposed to nonpathogenic mycobacteria. The new interferon gamma tests are more specific and at least as sensitive as the TT,3 and they also incorporate a positive control that can detect the presence of anergy. However, IGRAs are not available in all hospitals because of cost and a lack of a properly equipped laboratory. Thus far, there are no uniform criteria on how to screen for LTI in patients who are scheduled to undergo biologic therapy; however, the use of the TT, the TT plus a booster, and the TT plus the IGRA in vaccinated and immnunodepressed patients has been proposed. Recently, the TT plus IGRA and the IGRA alone have been recommended for LTI screening in patients with psoriasis,4 but studies confirming double-screening advantages are lacking to date. Although IGRAs have not been validated for LTI diagnosis in patients who are receiving biologic treatment, in our experience the QuantiFERON-TB Gold has the following advantages: (1) it can detect cases of anergy, differentiating them from TT false negatives resulting from immunosuppression; (2) because it incorporates specific antigens present in M tuberculosis that are absent in the BCG vaccine, it can detect false TT positives due to vaccination; and (3) it turns positive more rapidly than the TT after recent contact with M tuberculosis,5 thus reducing the likelihood of underdiagnosed infection in patients who are receiving biologic therapy. A positive IGRA result should be considered as a cell-mediated immunologic memory to a true tuberculosis contact; therefore, isoniazid chemoprophylaxis will not change the positivity, thereby rendering repetition unnecessary after treatment is discontinued. However, a negative IGRA result must be interpreted with caution in patients who are receiving immunosuppressive treatment because it may be a false negative. Consequently, we believe that double screening (interferon gamma determination and TT) plus chest radiography and a guided medical history should be performed before biologic therapy is initiated. Furthermore, we recommend double screening every year thereafter because of the greater risk of tuberculosis in these patients. Back to top Article Information Correspondence: Dr Sempau, Department of Dermatology, Complejo Asistencial Universitario de Le ón, Altos de Nava SN, 24071 Le ón, Spain, (leticiasempau@gmail.com). Financial Disclosure: None reported. References 1. Elbek O, Uyar M, Aydin N, et al. Increased risk of tuberculosis in patients treated with antitumor necrosis factor alpha. Clin Rheumatol. 2009;28(4):421-42619052832PubMedGoogle ScholarCrossref 2. Carmona L, G ómez-Reino JJ, Rodr íguez-Valverde V, et al; BIOBADASER Group. Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum. 2005;52(6):1766-177215934089PubMedGoogle ScholarCrossref 3. Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med. 2008;149(3):177-18418593687PubMedGoogle Scholar 4. Perlmutter A, Mittal A, Menter A. Tuberculosis and tumour necrosis factor- α inhibitor therapy: a report of three cases in patients with psoriasis: comprehensive screening and therapeutic guidelines for clinicians. Br J Dermatol. 2009;160(1):8-1519016693PubMedGoogle ScholarCrossref 5. Diel R, Loddenkemper R, Meywald-Walter K, Gottschalk R, Nienhaus A. Comparative performance of tuberculin skin test, QuantiFERON-TB-Gold In Tube assay, and T-Spot.TB test in contact investigations for tuberculosis. Chest. 2009;135(4):1010-101819017873PubMedGoogle ScholarCrossref

Journal

Archives of DermatologyAmerican Medical Association

Published: Oct 1, 2011

Keywords: tumor necrosis factors,latent tuberculosis,screening

References

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