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      The Challenging Evaluation of Patients with Severe Psoriasis for Latent Tuberculosis: An Important Indication for IGRA

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          Abstract

          It is well-established that tumour necrosis factor (TNF)-α-antagonist regimens are advisable for the control of moderate to severe psoriasis; however the application of these agents is associated with increased risk of TB reactivation. Screening for latent tuberculosis infection (LTBI) is indispensable prior to treatment inception in order to diminish the risk of active TB. Although tuberculin skin test (TST) still represents a useful tool for LTBI detection, it is difficult to be performed and read in patients with extensive psoriatic lesions. In this paper, we report the case of a 65-year-old male with severe psoriasis, who was evaluated by an interferon-gamma release assay (IGRA) for LTBI diagnosis prior to anti-TNF-α therapy. Furthermore, the physiological aspects of interferon-gamma release assays are discussed emphasizing the value of these novel immunodiagnostic tests (IGRAs) for presumable LTBI in all patients with extensive skin disorders.

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          Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update.

          Madhukar Pai, Alice Zwerling, Dick Menzies (2008)
          Interferon-gamma-release assays (IGRAs) are alternatives to the tuberculin skin test (TST). A recent meta-analysis showed that IGRAs have high specificity, even among populations that have received bacille Calmette-Guérin (BCG) vaccination. Sensitivity was suboptimal for TST and IGRAs. To incorporate newly reported evidence from 20 studies into an updated meta-analysis on the sensitivity and specificity of IGRAs. PubMed was searched through 31 March 2008, and citations of all original articles, guidelines, and reviews for studies published in English were reviewed. Studies that evaluated QuantiFERON-TB Gold, QuantiFERON-TB Gold In-Tube (both from Cellestis, Victoria, Australia), and T-SPOT.TB (Oxford Immunotec, Oxford, United Kingdom) or its precommercial ELISpot version, when data on the commercial version were lacking. For assessing sensitivity, the study sample had to have microbiologically confirmed active tuberculosis. For assessing specificity, the sample had to comprise healthy, low-risk individuals without known exposure to tuberculosis. Studies with fewer than 10 participants and those that included only immunocompromised participants were excluded. One reviewer abstracted data on participant characteristics, test characteristics, and test performance from 38 studies; these data were double-checked by a second reviewer. The original investigators were contacted for additional information when necessary. A fixed-effects meta-analysis with correction for overdispersion was done to pool data within prespecified subgroups. The pooled sensitivity was 78% (95% CI, 73% to 82%) for QuantiFERON-TB Gold, 70% (CI, 63% to 78%) for QuantiFERON-TB Gold In-Tube, and 90% (CI, 86% to 93%) for T-SPOT.TB. The pooled specificity for both QuantiFERON tests was 99% among non-BCG-vaccinated participants (CI, 98% to 100%) and 96% (CI, 94% to 98%) among BCG-vaccinated participants. The pooled specificity of T-SPOT.TB (including its precommercial ELISpot version) was 93% (CI, 86% to 100%). Tuberculin skin test results were heterogeneous, but specificity in non-BCG-vaccinated participants was consistently high (97% [CI, 95% to 99%]). Most studies were small and had limitations, including no gold standard for diagnosing latent tuberculosis and variable TST methods and cutoff values. Data on the specificity of the commercial T-SPOT.TB assay were limited. The IGRAs, especially QuantiFERON-TB Gold and QuantiFERON-TB Gold In-Tube, have excellent specificity that is unaffected by BCG vaccination. Tuberculin skin test specificity is high in non-BCG-vaccinated populations but low and variable in BCG-vaccinated populations. Sensitivity of IGRAs and TST is not consistent across tests and populations, but T-SPOT.TB appears to be more sensitive than both QuantiFERON tests and TST.
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            Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010.

            Gerald H. Mazurek, John Jereb, Andrew Vernon … (2010)
            n 2005, CDC published guidelines for using the QuantiFERON-TB Gold test (QFT-G) (Cellestis Limited, Carnegie, Victoria, Australia) (CDC. Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR;54[No. RR-15]:49-55). Subsequently, two new interferon gamma (IFN- gamma) release assays (IGRAs) were approved by the Food and Drug Administration (FDA) as aids in diagnosing M. tuberculosis infection, both latent infection and infection manifesting as active tuberculosis. These tests are the QuantiFERON-TB Gold In-Tube test (QFT-GIT) (Cellestis Limited, Carnegie, Victoria, Australia) and the T-SPOT.TB test (T-Spot) (Oxford Immunotec Limited, Abingdon, United Kingdom). The antigens, methods, and interpretation criteria for these assays differ from those for IGRAs approved previously by FDA. For assistance in developing recommendations related to IGRA use, CDC convened a group of experts to review the scientific evidence and provide opinions regarding use of IGRAs. Data submitted to FDA, published reports, and expert opinion related to IGRAs were used in preparing these guidelines. Results of studies examining sensitivity, specificity, and agreement for IGRAs and TST vary with respect to which test is better. Although data on the accuracy of IGRAs and their ability to predict subsequent active tuberculosis are limited, to date, no major deficiencies have been reported in studies involving various populations. This report provides guidance to U.S. public health officials, health-care providers, and laboratory workers for use of FDA-approved IGRAs in the diagnosis of M. tuberculosis infection in adults and children. In brief, TSTs and IGRAs (QFT-G, QFT-GIT, and T-Spot) may be used as aids in diagnosing M. tuberculosis infection. They may be used for surveillance purposes and to identify persons likely to benefit from treatment. Multiple additional recommendations are provided that address quality control, test selection, and medical management after testing. Although substantial progress has been made in documenting the utility of IGRAs, additional research is needed that focuses on the value and limitations of IGRAs in situations of importance to medical care or tuberculosis control. Specific areas needing additional research are listed.
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              T-cell assays for the diagnosis of latent tuberculosis infection: moving the research agenda forward.

              Jane Cunningham, Richard O'Brien, Keertan Dheda … (2007)
              For nearly a century, the tuberculin skin test was the only tool available for the detection of latent tuberculosis infection. A recent breakthrough has been the development of T-cell-based interferon-gamma release assays. Current evidence suggests interferon-gamma release assays have higher specificity than the tuberculin skin test, better correlation with surrogate markers of exposure to Mycobacterium tuberculosis in low-incidence settings, and less cross-reactivity as a result of BCG vaccination compared with the tuberculin skin test. The body of literature supporting the use of interferon-gamma release assays has rapidly expanded. However, several unresolved and unexplained issues remain. To address these issues, a group of experts met in Geneva, Switzerland, in March, 2006, to discuss the research evidence on T-cell-based assays, their clinical usefulness, limitations, and directions for future research, with a specific focus on resource-limited and high HIV prevalence settings. On the basis of 2 days of discussions, a comprehensive research agenda was generated, which will propel the field forward by stimulating focused high-impact research and encourage the investment of resources needed to tackle priority research questions, especially in resource-limited settings. Ultimately, if adequately financed, the research findings will inform appropriate use of novel latent tuberculosis infection diagnostics in global tuberculosis control.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Open Respir Med J
                Journal ID (publisher-id): TORMJ
                Title: The Open Respiratory Medicine Journal
                Publisher: Bentham Open
                ISSN (Electronic): 1874-3064
                Publication date (Electronic): 24 June 2011
                Publication date Collection: 2011
                Volume: 5
                Pages: 59-60
                Affiliations
                [1 ]Department of Pneumonology, University Hospital of Ioannina, Ioannina, Greece
                [2 ]Department of Skin and Venereal Diseases, University Hospital of Ioannina, Ioannina, Greece
                Author notes
                [* ]Address correspondence to this author at the University of Ioannina, Medical School, Department of Pneumonology, 45110, Ioannina, Greece; Tel: +30-26510-07535; Fax: +30-2651-07051; E-mail: skatsenos@ 123456yahoo.gr
                Article
                Publisher ID: TORMJ-5-59
                DOI: 10.2174/1874306401105010059
                PMC ID: 3132865
                PubMed ID: 21754976
                SO-VID: 0fe53d33-6183-40f6-9cfe-4783f35c1ab5
                Copyright © © Katsenos et al.; Licensee Bentham Open.
                License:

                This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                Date received : 10 February 2011
                Date revision received : 10 May 2011
                Date accepted : 27 May 2011
                Categories
                Subject: Article

                ScienceOpen disciplines: Respiratory medicine
                Keywords: latent tuberculosis infection,anti-tumour necrosis factor therapy.,interferon-gamma release assay,tuberculin skin test,psoriasis
                Data availability:
                ScienceOpen disciplines: Respiratory medicine
                Keywords: latent tuberculosis infection, anti-tumour necrosis factor therapy., interferon-gamma release assay, tuberculin skin test, psoriasis

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