Diagnóstico de tuberculose latente em pessoas com artrite reumatóide, através dos testes tuberculínico e interferon - gamma release assays

Detalhes bibliográficos
Autor(a) principal: Pereira, Ana Maria
Data de Publicação: 2011
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
Texto Completo: http://repositorio.ufes.br/handle/10/5469
Resumo: The use of anti-TNF-α biologic agents to treat rheumatoid arthritis (RA) is implicated in the increase of tuberculosis (TB) incidence, requiring caution in its prescription. Thus, it is necessary to screen TB before beginning the anti-TNF-α treatment. RA patients show T lymphocyte dysfunction which may harm the late cutaneous response to tuberculin test skin (TST). More recently, other tests, ex vivo, have been used to diagnose latent TB (LTB), these tests are IGRAs (Interferon - Gamma Release Assays), which may be useful to diagnose LTB in RA patients. Thus, the author set out to undertake a comparative crosssectional analysis between RA patients and a healthy comparison group (without RA), in relation to the positivity of tests to diagnose LTB – PPD RT23 QuantiFeron-TB Gold In Tube (QTF-TB GIT) – as well as a comparison among tests. And make a systematic review of the positivity and agreement between TT and IGRAs in patients with RA, with the aim of identifying the results which used TT and IGRA inn populations with RA. The review used the LILACS, Scielo, Cochrane and Medline sources with pre-defined descriptors in Portuguese, English and Spanish, having accepted publications in these languages. The description of the methodological characteristics of the studies was made, the results of the tests in each study were presented with their respective statistical analyses. The analyses of statistical agreement among tests were also presented. The level of significance adopted was 0.05. After the exclusion of the articles which were not eligible, 19 publications were selected for analysis. No uniformity among the studies included in the review was found in relation to the methodological characteristics. The design was mostly comparative, 3 were cross-sectional and one was longitudinal coorte, the sample size in the RA group varied between 25 and 112 subjects. The composition of the comparison group also varied. Healthy subjects, subjects with other rheumatic diseases and even patients with tuberculosis were part of the groups. The tests used, both PPD and IGRAs, were of different types. No uniformity found in relation to the tests results, be it in the proportion of positivity in the RA group, which varied between 10,4% and 69,7% for the TT and 6,9% to 44,6% for the IGRAs or in the difference or similarity with comparison groups. The agreement between the TT and IGRAs was analyzed in a few studies which proved contradictory. Regarding the study conducted by the author in patients with RA in Espírito Santo (ES), the ≥ 5mm value was adopted for the reactor TT for the RA group and the ≥10mm value was adopted for the group without RA. Chi-Square tests were used for the qualitative variables and tStudent tests for the quantitative, to compare groups with and without RA. As for the RA group, it was stratified by conditions: activity of disease and immunosuppression by treatment, Fisher’s exact test was used for the activity of the disease and Chi-Square for immunosuppression. The Kappa test was used to statistically analyze the agreement between PPD RT23 and QTF-TB GIT and the McNemar test was used for disagreement. The value of significance for p was p ≤ 0.05, in all tests. The TT was reactive in 40.8% in the group with RA and 25% in the group without (p = 0.187) and the QTF-TB GIT was positive in 2 (4%) of the group with RA and 3 (7.1%) in the group without RA (p = 0.5078). No significant difference was found for reactivity to TT in RA when compared with strata with or without the disease in action (0,64). 11 However, a significant difference was found for the immunosuppressed and not immunosuppressed strata, with a better response to the not immunosuppressed group (p=0,032). The groups with and without RA did not show statistically significant agreement between the 2 tests (K = 0,116; p = 0,082 (RA); K = 0,217; p = 0,083 (without RA)). A statistically significant disagreement was found for both groups with McNemar test (p = 0,001 (RA); p = 0,039 (without RA). When the total sample was analyzed (with RA + without RA), a low but statistically significant agreement was found between tests (K = 0,146; p = 0,024), and also a significant disagreement (p = 0,001). Conclusion: The systematic review showed great heterogeneity among studies which does not enable conclusions regarding the performance of TT and IGRAs in people with RA, due to the lack of consensus among results. The study with patients with RA in ES did not show any difference between groups with and without RA in relation to reactivity to TT, as well as positivity of QTF-TB GIT. The activity of the disease did not interfere with the response to the TT, nevertheless the treatment immunosuppressor did. So as to better assess the usefulness of the tests studied in people with RA, more longitudinal and prospective studies are needed, in populations with different prevalence levels and vaccine coverage for TB, and with stratified sample for characteristics of RA such as: activity and severity of disease and level of immunosuppression by treatment.
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spelling Diagnóstico de tuberculose latente em pessoas com artrite reumatóide, através dos testes tuberculínico e interferon - gamma release assaysRheumatoid arthritisTuberculosis infectionTuberculin skin testArtrite reumatóideTuberculoseTeste tuberculínicoInterferonSaúde Coletiva614The use of anti-TNF-α biologic agents to treat rheumatoid arthritis (RA) is implicated in the increase of tuberculosis (TB) incidence, requiring caution in its prescription. Thus, it is necessary to screen TB before beginning the anti-TNF-α treatment. RA patients show T lymphocyte dysfunction which may harm the late cutaneous response to tuberculin test skin (TST). More recently, other tests, ex vivo, have been used to diagnose latent TB (LTB), these tests are IGRAs (Interferon - Gamma Release Assays), which may be useful to diagnose LTB in RA patients. Thus, the author set out to undertake a comparative crosssectional analysis between RA patients and a healthy comparison group (without RA), in relation to the positivity of tests to diagnose LTB – PPD RT23 QuantiFeron-TB Gold In Tube (QTF-TB GIT) – as well as a comparison among tests. And make a systematic review of the positivity and agreement between TT and IGRAs in patients with RA, with the aim of identifying the results which used TT and IGRA inn populations with RA. The review used the LILACS, Scielo, Cochrane and Medline sources with pre-defined descriptors in Portuguese, English and Spanish, having accepted publications in these languages. The description of the methodological characteristics of the studies was made, the results of the tests in each study were presented with their respective statistical analyses. The analyses of statistical agreement among tests were also presented. The level of significance adopted was 0.05. After the exclusion of the articles which were not eligible, 19 publications were selected for analysis. No uniformity among the studies included in the review was found in relation to the methodological characteristics. The design was mostly comparative, 3 were cross-sectional and one was longitudinal coorte, the sample size in the RA group varied between 25 and 112 subjects. The composition of the comparison group also varied. Healthy subjects, subjects with other rheumatic diseases and even patients with tuberculosis were part of the groups. The tests used, both PPD and IGRAs, were of different types. No uniformity found in relation to the tests results, be it in the proportion of positivity in the RA group, which varied between 10,4% and 69,7% for the TT and 6,9% to 44,6% for the IGRAs or in the difference or similarity with comparison groups. The agreement between the TT and IGRAs was analyzed in a few studies which proved contradictory. Regarding the study conducted by the author in patients with RA in Espírito Santo (ES), the ≥ 5mm value was adopted for the reactor TT for the RA group and the ≥10mm value was adopted for the group without RA. Chi-Square tests were used for the qualitative variables and tStudent tests for the quantitative, to compare groups with and without RA. As for the RA group, it was stratified by conditions: activity of disease and immunosuppression by treatment, Fisher’s exact test was used for the activity of the disease and Chi-Square for immunosuppression. The Kappa test was used to statistically analyze the agreement between PPD RT23 and QTF-TB GIT and the McNemar test was used for disagreement. The value of significance for p was p ≤ 0.05, in all tests. The TT was reactive in 40.8% in the group with RA and 25% in the group without (p = 0.187) and the QTF-TB GIT was positive in 2 (4%) of the group with RA and 3 (7.1%) in the group without RA (p = 0.5078). No significant difference was found for reactivity to TT in RA when compared with strata with or without the disease in action (0,64). 11 However, a significant difference was found for the immunosuppressed and not immunosuppressed strata, with a better response to the not immunosuppressed group (p=0,032). The groups with and without RA did not show statistically significant agreement between the 2 tests (K = 0,116; p = 0,082 (RA); K = 0,217; p = 0,083 (without RA)). A statistically significant disagreement was found for both groups with McNemar test (p = 0,001 (RA); p = 0,039 (without RA). When the total sample was analyzed (with RA + without RA), a low but statistically significant agreement was found between tests (K = 0,146; p = 0,024), and also a significant disagreement (p = 0,001). Conclusion: The systematic review showed great heterogeneity among studies which does not enable conclusions regarding the performance of TT and IGRAs in people with RA, due to the lack of consensus among results. The study with patients with RA in ES did not show any difference between groups with and without RA in relation to reactivity to TT, as well as positivity of QTF-TB GIT. The activity of the disease did not interfere with the response to the TT, nevertheless the treatment immunosuppressor did. So as to better assess the usefulness of the tests studied in people with RA, more longitudinal and prospective studies are needed, in populations with different prevalence levels and vaccine coverage for TB, and with stratified sample for characteristics of RA such as: activity and severity of disease and level of immunosuppression by treatment.O uso de agentes biológicos anti-TNF-α para tratamento de artrite reumatóide (AR) está implicado no aumento da incidência de tuberculose (TB), exigindo muita prudência na sua prescrição. Portanto, é indispensável rastrear TB antes do início do anti-TNF-α. Os pacientes com AR apresentam disfunção dos linfócitos T, o que pode prejudicar a resposta cutânea tardia ao teste tuberculínico (TT). Mais recentemente outros testes, ex-vivo, estão sendo usados para diagnosticar TB latente (TBL), são eles os IGRAs (Interferon - Gamma Release Assays). Talvez os IGRAs possam ser úteis no diagnóstico de TBL em pacientes com AR. Dessa forma, a autora se propôs a desenvolver um estudo transversal comparativo entre pacientes com AR do Espírito Santo e grupo de comparação saudável (sem AR), em relação à positividade dos testes TT (PPD RT23) e QuantiFeron-TB Gold In Tube (QTF-TB GIT) – assim como comparar os testes entre si. E realizar uma revisão sistemática sobre a positividade e concordância entre TT e IGRAs em pacientes com AR, com a finalidade de conhecer os resultados de estudos que utilizaram TT e IGRA em populações com AR. A revisão foi realizada nas fontes LILACS, Scielo, Cochrane e Medline, com os descritores pré-definidos, nos idiomas português, inglês e espanhol, e foram aceitas publicações nos mesmos idiomas. Foi realizada a descrição das características metodológicas dos estudos, apresentados os resultados dos testes realizados por cada um, com suas respectivas análises estatísticas. Foram ainda apresentadas as análises estatísticas de concordância entre os testes. O nível de significância adotado foi de 0,05. Após exclusão dos artigos que não foram elegíveis, 19 publicações foram selecionadas para análise. Não houve uniformidade em relação às características metodológicas dos estudos incluídos nesta revisão. O desenho, em sua maioria foi do tipo comparativo, 3 foram corte transversal e um foi coorte prospectiva. O tamanho da amostra, no grupo de AR, variou de 25 a 112 sujeitos. A composição do grupo de comparação também foi variável. Sujeitos saudáveis, sujeitos com outras doenças reumáticas e até mesmo pacientes com tuberculose compuseram os grupos. Os testes utilizados, tanto PPD, quanto IGRAs foram de tipos diferentes. Não houve uniformidade também em relação aos resultados dos testes, tanto nas proporções de positividade no grupo AR, que variou de 10,4% a 69,7% para o TT e 6,9% a 44,6% para os IGRAs, quanto na diferença ou semelhança com grupos de comparação. A concordância entre os TT e IGRAs foi analisada em poucos estudos, que se mostraram contraditórios. Em relação ao estudo realizado pela autora em pacientes com AR do Espírito Santo (ES), foi adotado o valor de ≥ 5mm para o grupo com AR e ≥10mm para o grupo sem AR como reator para TT. Para variáveis qualitativas, utilizaram-se os testes Qui-quadrado e para as quantitativas, o teste t - Student para comparação dos grupos com e sem AR. Quando o grupo AR foi estratificado pelas condições: atividade da doença e imunossupressão por tratamento, utilizou-se o teste exato de Fisher para atividade da doença e Qui-quadrado para imunossupressão. Para a análise estatística realizada para avaliar concordância entre o PPD RT23 e o QTF-TB GIT utilizaram-se o teste Kappa e para a discordância o teste de McNemar. Foi considerado significante o valor de p ≤ 0,05, em todos os testes. O TT foi reator em 40,8% do grupo com AR e em 25% do grupo sem AR (p = 0,187) e o QTF- 9 TB GIT foi positivo em 2 (4%) do grupo com AR e 3 (7,1%) do grupo sem AR (p = 0,5078). Também não foi encontrada diferença significativa em relação à reatividade ao TT em AR quando comparados os estratos estar ou não com doença em atividade (0,64). Porém houve diferença significativa entre os estratos estar ou não imunossuprimido, com melhor resposta nos não imunossuprimidos (p = 0,032). Os grupos com e sem AR não mostraram concordância estatisticamente significante entre os 2 testes (K = 0,116; p = 0,082 (AR); K = 0,217; p = 0,083 (sem AR)). A discordância foi estatisticamente significativa, em ambos os grupos pelo teste McNemar (p = 0,001 (AR); p = 0,039 (sem AR). Quando avaliado a amostra total (com AR + sem AR) foi encontrada concordância baixa, porém significativa entre os testes (K = 0,146; p = 0,024), e discordância também significativa (p = 0,001). Conclusão: A revisão sistemática mostrou grande heterogeneidade entre os estudos, não tendo sido possível tirar conclusões a cerca do desempenho dos testes TT e IGRAs em pessoas com AR, devido à falta de consenso entre os resultados. O estudo realizado em pacientes com AR do ES, não encontrou diferença entre os grupos com e sem AR em relação a reatividade ao TT, assim como a positividade do QTF-TB GIT. A atividade da doença não interferiu na resposta ao TT, entretanto o tratamento imunossupressor sim. Para melhor avaliar a utilidade dos testes estudados em pessoas com AR, serão necessários mais estudos longitudinais e prospectivos, em populações com diferentes prevalências e cobertura vacinal para TB, e com amostra estratificada por características da AR como: atividade e gravidade da doença e grau de imunossupressão pelo tratamento.Universidade Federal do Espírito SantoBRMestrado em Saúde ColetivaCentro de Ciências da SaúdeUFESPrograma de Pós-Graduação em Saúde ColetivaValim, ValériaZandonade, ElianaMaciel, Ethel Leonor NoiaPereira, Ana Maria2016-08-30T10:50:11Z2016-07-112016-08-30T10:50:11Z2011-11-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisTextapplication/pdfhttp://repositorio.ufes.br/handle/10/5469porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)instname:Universidade Federal do Espírito Santo (UFES)instacron:UFES2024-07-16T17:08:11Zoai:repositorio.ufes.br:10/5469Repositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestopendoar:21082024-07-16T17:08:11Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)false
dc.title.none.fl_str_mv Diagnóstico de tuberculose latente em pessoas com artrite reumatóide, através dos testes tuberculínico e interferon - gamma release assays
title Diagnóstico de tuberculose latente em pessoas com artrite reumatóide, através dos testes tuberculínico e interferon - gamma release assays
spellingShingle Diagnóstico de tuberculose latente em pessoas com artrite reumatóide, através dos testes tuberculínico e interferon - gamma release assays
Pereira, Ana Maria
Rheumatoid arthritis
Tuberculosis infection
Tuberculin skin test
Artrite reumatóide
Tuberculose
Teste tuberculínico
Interferon
Saúde Coletiva
614
title_short Diagnóstico de tuberculose latente em pessoas com artrite reumatóide, através dos testes tuberculínico e interferon - gamma release assays
title_full Diagnóstico de tuberculose latente em pessoas com artrite reumatóide, através dos testes tuberculínico e interferon - gamma release assays
title_fullStr Diagnóstico de tuberculose latente em pessoas com artrite reumatóide, através dos testes tuberculínico e interferon - gamma release assays
title_full_unstemmed Diagnóstico de tuberculose latente em pessoas com artrite reumatóide, através dos testes tuberculínico e interferon - gamma release assays
title_sort Diagnóstico de tuberculose latente em pessoas com artrite reumatóide, através dos testes tuberculínico e interferon - gamma release assays
author Pereira, Ana Maria
author_facet Pereira, Ana Maria
author_role author
dc.contributor.none.fl_str_mv Valim, Valéria
Zandonade, Eliana
Maciel, Ethel Leonor Noia
dc.contributor.author.fl_str_mv Pereira, Ana Maria
dc.subject.por.fl_str_mv Rheumatoid arthritis
Tuberculosis infection
Tuberculin skin test
Artrite reumatóide
Tuberculose
Teste tuberculínico
Interferon
Saúde Coletiva
614
topic Rheumatoid arthritis
Tuberculosis infection
Tuberculin skin test
Artrite reumatóide
Tuberculose
Teste tuberculínico
Interferon
Saúde Coletiva
614
description The use of anti-TNF-α biologic agents to treat rheumatoid arthritis (RA) is implicated in the increase of tuberculosis (TB) incidence, requiring caution in its prescription. Thus, it is necessary to screen TB before beginning the anti-TNF-α treatment. RA patients show T lymphocyte dysfunction which may harm the late cutaneous response to tuberculin test skin (TST). More recently, other tests, ex vivo, have been used to diagnose latent TB (LTB), these tests are IGRAs (Interferon - Gamma Release Assays), which may be useful to diagnose LTB in RA patients. Thus, the author set out to undertake a comparative crosssectional analysis between RA patients and a healthy comparison group (without RA), in relation to the positivity of tests to diagnose LTB – PPD RT23 QuantiFeron-TB Gold In Tube (QTF-TB GIT) – as well as a comparison among tests. And make a systematic review of the positivity and agreement between TT and IGRAs in patients with RA, with the aim of identifying the results which used TT and IGRA inn populations with RA. The review used the LILACS, Scielo, Cochrane and Medline sources with pre-defined descriptors in Portuguese, English and Spanish, having accepted publications in these languages. The description of the methodological characteristics of the studies was made, the results of the tests in each study were presented with their respective statistical analyses. The analyses of statistical agreement among tests were also presented. The level of significance adopted was 0.05. After the exclusion of the articles which were not eligible, 19 publications were selected for analysis. No uniformity among the studies included in the review was found in relation to the methodological characteristics. The design was mostly comparative, 3 were cross-sectional and one was longitudinal coorte, the sample size in the RA group varied between 25 and 112 subjects. The composition of the comparison group also varied. Healthy subjects, subjects with other rheumatic diseases and even patients with tuberculosis were part of the groups. The tests used, both PPD and IGRAs, were of different types. No uniformity found in relation to the tests results, be it in the proportion of positivity in the RA group, which varied between 10,4% and 69,7% for the TT and 6,9% to 44,6% for the IGRAs or in the difference or similarity with comparison groups. The agreement between the TT and IGRAs was analyzed in a few studies which proved contradictory. Regarding the study conducted by the author in patients with RA in Espírito Santo (ES), the ≥ 5mm value was adopted for the reactor TT for the RA group and the ≥10mm value was adopted for the group without RA. Chi-Square tests were used for the qualitative variables and tStudent tests for the quantitative, to compare groups with and without RA. As for the RA group, it was stratified by conditions: activity of disease and immunosuppression by treatment, Fisher’s exact test was used for the activity of the disease and Chi-Square for immunosuppression. The Kappa test was used to statistically analyze the agreement between PPD RT23 and QTF-TB GIT and the McNemar test was used for disagreement. The value of significance for p was p ≤ 0.05, in all tests. The TT was reactive in 40.8% in the group with RA and 25% in the group without (p = 0.187) and the QTF-TB GIT was positive in 2 (4%) of the group with RA and 3 (7.1%) in the group without RA (p = 0.5078). No significant difference was found for reactivity to TT in RA when compared with strata with or without the disease in action (0,64). 11 However, a significant difference was found for the immunosuppressed and not immunosuppressed strata, with a better response to the not immunosuppressed group (p=0,032). The groups with and without RA did not show statistically significant agreement between the 2 tests (K = 0,116; p = 0,082 (RA); K = 0,217; p = 0,083 (without RA)). A statistically significant disagreement was found for both groups with McNemar test (p = 0,001 (RA); p = 0,039 (without RA). When the total sample was analyzed (with RA + without RA), a low but statistically significant agreement was found between tests (K = 0,146; p = 0,024), and also a significant disagreement (p = 0,001). Conclusion: The systematic review showed great heterogeneity among studies which does not enable conclusions regarding the performance of TT and IGRAs in people with RA, due to the lack of consensus among results. The study with patients with RA in ES did not show any difference between groups with and without RA in relation to reactivity to TT, as well as positivity of QTF-TB GIT. The activity of the disease did not interfere with the response to the TT, nevertheless the treatment immunosuppressor did. So as to better assess the usefulness of the tests studied in people with RA, more longitudinal and prospective studies are needed, in populations with different prevalence levels and vaccine coverage for TB, and with stratified sample for characteristics of RA such as: activity and severity of disease and level of immunosuppression by treatment.
publishDate 2011
dc.date.none.fl_str_mv 2011-11-18
2016-08-30T10:50:11Z
2016-07-11
2016-08-30T10:50:11Z
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format masterThesis
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dc.publisher.none.fl_str_mv Universidade Federal do Espírito Santo
BR
Mestrado em Saúde Coletiva
Centro de Ciências da Saúde
UFES
Programa de Pós-Graduação em Saúde Coletiva
publisher.none.fl_str_mv Universidade Federal do Espírito Santo
BR
Mestrado em Saúde Coletiva
Centro de Ciências da Saúde
UFES
Programa de Pós-Graduação em Saúde Coletiva
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
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