Recomendações para o diagnóstico e tratamento das tuberculoses latente e activa nas doenças inflamatórias articulares candidatas a terapêutica com fármacos inibidores do factor de necrose tumoral alfa. Revisão de Março de 2008*

 

Recommendations for the diagnosis and treatment of latent and active tuberculosis in inflammatory joint diseases candidates for therapy with tumor necrosis factor alpha inhibitors – March 2008 update*

 

João Eurico Fonseca¹

Helena Lucas²

Helena Canhão¹

Raquel Duarte²

Maria José Santos¹

Miguel Villar²

Augusto Faustino¹

Elena Raymundo²

 

Resumo

A Sociedade Portuguesa de Reumatologia e a Sociedade Portuguesa de Pneumologia actualizaram as recomendações para o diagnóstico e a terapêutica das tuberculoses latente (TL) e activa (TD) em doentes com doenças inflamatórias articulares (DIA), candidatos a tratamento com antagonistas do factor de necrose tumoral alfa (TNFá).

Com o objectivo de reduzir o risco de reactivação da tuberculose (TB) ou nova infecção, recomenda-se o rastreio de TD e TL tão precocemente quanto possível, preferencialmente no momento do diagnóstico da DIA, e repetir a avaliação do doente antes de iníciar terapêutica anti-TNFá. O tratamento da TD e TL deve ser sempre supervisionado por um especialista em TB. Quando houver indicação para terapêutica de TB, esta deverá ser cumprida integralmente antes de se iniciar o anti -TNFá.

No caso da actividade da DIA o exigir, o anti –TNFá poderá ser iniciado após dois meses de terapêutica antibacilar, no caso de TD, ou após um mês, no caso de TL.

Todos os doentes devem realizar radiografia do tórax. Alterações compatíveis com complexo de Gohn devem ser tratadas como TL. Lesões residuais obrigam a excluir TB activa. Se se suspeitar de lesões em actividade, o diagnóstico de TD deve ser excluido e o tratamento adequado instituído.

A prova tuberculínica (PT), com 2 unidades de tuberculina RT23, deverá ser efectuada em todos os doentes. Se a induração for <5 mm, a prova deve ser repetida dentro de 1 a 2 semanas no antebraço oposto, e considerada negativa apenas se o segundo resultado for igualmente <5 mm. As PT positivas obrigam a tratamento de TL, excepto se o doente tiver sido previamente tratado de forma adequada. Se a PT é realizada apenas em fase de imunodepressão, mesmo que seja negativa, deve ser equacionado o tratamento de TL antes de iniciar terapêutica anti-TNFá, após ponderar a relação risco/benefício.

Palavras-chave: Guidelines, Sociedade Portuguesa de Reumatologia, Sociedade Portuguesa de Pneumologia, tuberculose, anti -TNFá.

 

Abstract

The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology have updated the guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with inflammatory joint diseases (IJD) that are candidates to therapy with tumour necrosis factor alpha (TNFá) antagonists. In order to reduce the risk of tuberculosis (TB) reactivation and the incidence of new infections, TB screening is recommended to be done as soon as possible, ideally at the moment of IJD diagnosis, and patient assessment repeated before starting anti -TNFá therapy. Treatment for ATB and LTBI must be done under the care of a TB specialist. When TB treatment is indicated, it should be completed prior to starting anti-TNFá therapy. If the IJD activity justifies the need for immediate treatment, anti-TNFá therapy can be started two months after antituberculous therapy has been initiated, in the case of ATB, and one month after in the case of LTBI. Chest X -ray is mandatory for all patients. If Gohn’s complex is present, the patient should be treated for LTBI; healed lesions require the exclusion of ATB. In cases of suspected active lesions, ATB should be excluded/confirmed and adequate therapy initiated.

Tuberculin skin test, with two units of RT23, should be performed in all patients. If the induration is <5 mm, the test should be repeated within 1 to 2 weeks, on the opposite forearm, and will be considered negative only if the result is again <5 mm. Positive TST implicates LTBI treatment, unless previous proper treatment was provided. If TST is performed in immunossuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNF -á therapy, even in the presence of a negative test, after risk / benefit assessment.

Key-words: Guidelines, Portuguese Society of Rheumatology, Portuguese Society of Pulmonology, Tuberculosis, Anti -TNFá drugs.

 

Texto completo disponível apenas em PDF.

Full text only available in PDF format.

 

Bibliography

1. Gomez-Reino JJ, Carmona L, Valverde VR, Mola EM, Montero MD; BIOBADASER Group. 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; 48:2122 -7.        [ Links ]

2. Vidal CG, Fernandez SR, Lacasa JM, et al. Paradoxical response to antituberculous therapy in infliximab-treated patients with disseminated tuberculosis. Clin Infect Dis 2005; 40:756 -9.

3. Mohan VP, Scanga CA, Yu K, et al. Effects of tumornecrosis factor alpha on host immune response in chronic persistent tuberculosis: possible role for limiting pathology. Infect Immun 2001; 69:1847 -55.

4. Choy EH, Panayi GS. Citokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001; 344:907 -16.

5. Olsen N Stein M. New Drugs for rheumatoid arthritis. N Engl J Med 2004; 350:2167 -79.

6. Yelin E, Callahan LF. The economic cost and social and psychological impact of musculoskeletal conditions. National Arthritis Data Work Groups. Arthritis Rheum 1995; 38:1351-62.

7. Wolfe F, Mitchell DM, Sibley JT, et al. The mortality of rheumatoid arthritis. Arthritis Rheum 1994; 37: 481-94.

8. Furst DE, Breedveld FC, Kalden JR, et al. Updated consensus statement on biological agents, specifically tumour necrosis factor á (TNF -á) blocking agents and interleukin -1 receptor antagonist (IL -1ra), for the treatment of rheumatic diseases, 2004. Ann Rheum Dis 2004; 63:ii2 -ii12.

9. Grupo de Estudos de Artrite Reumatóide da Sociedade Portuguesa de Reumatologia. Consensos para a utilização de terapêutica biológica na Artrite Reumatóide – actualização de Dezembro de 2005. Acta Reumatol Port 2005; 30:349 -53.

10. Grupo de Estudo de Artrite Reumatóide da Sociedade Portuguesa de Reumatologia. Análise de 376 doentes com artrite reumatóide submetidos a terapêutica biológica registados na base de dados de agentes biológicos da Sociedade Portuguesa de Reumatologia. Acta Reumatol Port 2005; 30:63-71.

11. Grupo de Consensos para as Terapêuticas Biológicas na Espondilite Anquilosante da Sociedade Portuguesa de Reumatologia. Consensos sobre a utilização de antagonistas do TNF -alfa na terapêutica da espondilite anquilosante. Acta Reumatol Port 2005; 30:155 -9.

12. Grupo de Consensos para as Terapêuticas Biológicas na Espondilite Anquilosante da Sociedade Portuguesa de Reumatologia. Análise de doentes com espondilite anquilosante submetidos a terapêutica biológica registados na base de dados de agentes biológicos da Sociedade Portuguesa de Reumatologia. Acta Reumatol Port 2005; 30: 253 -60.

13. Klareskog L, van der Heijde D, de Jager JP, et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind ran–domised controlled trial. Lancet 2004; 363: 675-81.

14. http://www.emea.eu.int/humandocs/PDFs/EPAR/Enbrel/014600en6.pdf

15. Ehlers S. Tumor necrosis factor and its blockade in granulomatous infections: differential modes of action of infliximab and etanercept? Clin Infect Dis 2005; 41(Suppl 3):S199-203.

16. Dinarello CA. Differences between anti –tumor necrosis factor -alpha monoclonal antibodies and soluble TNF receptors in host defense impairment. J Rheumatol 2005; 74(Suppl): 40-7.

17. http://www.emea.eu.int/pdfs/.human/opinion/22027005en.pdf

18. http://www.emea.eu.int/pdfs/human/opinion/20715105en.pdf

19. Breedveld FC, Weisman MH, Kavanaugh AF, et al. The PREMIER Study. A multicenter, randomized, doubleblind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate therapy. Arthritis Rheum 2006; 54:26-37.

20. Wallis RS, Broder MS, Wong JY, Beenhouwer D. Granulomatosus infections due to tumor necrosis factor blockade: Correction. Clin Infect Dis 2004; 39:1254 -5.

21. Keane J. TNF-blocking agents and tuberculosis: new drugs illuminate an old topic. Rheumatology (Oxford) 2005; 44:714 -20.

22. Fonseca JE, Canhão H, Silva C, e al. Tuberculose em doentes reumáticos tratados com antagonistas do factor de necrose tumoral alfa: a experiência portuguesa. Acta Reumatol Port 2006; 31:247 -53.

23. Programa nacional de luta contra a tuberculose, Direcção-Geral da Saúde. Tuberculose: ponto da situação em Portugal em 2006, dados preliminares em Março de 2007. http://www.dgs.pt/upload/membro.id/ficheiros/i009162.pdf

24. Duarte R, Amado J, Lucas H, Sapage M, Comissão de Trabalho de Tuberculose da Sociedade Portuguesa de Pneumologia. Tratamento da tuberculose latente – revisão das normas. Rev Port Pneumol 2006 (in press).

25. Ledingham J, Deighton C. British Society for Rheumatology Standards (SGAWG). Update on the British Society for Rheumatology guidelines for prescribing TNF_ blockers in adults with rheumatoid arthritis (update of previous guidelines of April 2001). Rheumatology 2005; 44:157 -63.

26. Carmona L, Gómez-Reino JJ, Rodríguez –Valverde V, et al. Effectiveness of recommendations to prevent reactivation of latent tuberculosis in patients treated with tumour necrosis factor antagonists. Arthritis Rheum 2005; 48:1766 -72.

27. Mariette X, Salmon D. French guidelines for diagnosis and treating latent and active tuberculosis in patients with RA treated with TNF blockers. Ann Rheum Dis. 2003;62:791.

28. Bieber J, Kavanough A. Consideration of the risk and treatment of tuberculosis in patients who have rheumatoid arthritis and receive biologic treatments. Rheum Dis Clin North Am 2004;30:257 -70.

29. Fonseca J E, Lucas H, Canhão H e tal. Recomendações para diagnóstico e tratamento da tuberculose latente e activa nas doenças inflamatórias articulares candidatas a tratamento com fármacos inibidores do factor de necrose alfa. Acta Reumatol Port 2006; 31:237 -45.

30. Fonseca J E, Lucas H, Canhão H e tal. Recomendações para diagnóstico e tratamento da tuberculose latente e activa nas doenças inflamatórias articulares candidatas a tratamento com fármacos inibidores do factor de necrose alfa. Rev Port Pneumol 2006;12:603 -13.

31. British Thoracic Society Standards of Care Committee. BTS recommendations for assessing risk and for managing Mycobacterium tubeculosis infection and disease in patients due to start anti– TNF -á treatment. Thorax 2005; 60: 800 -5.

32. Gardam MA, Keystone EC, Menzies R, et al. Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. The Lancet Infectious Diseases 2003; 3:148 -55.

33. Rampton DS. Preventing TB in patients with Crohn’s disease needing infliximab or other anti –TNF therapy. Gut 2005; 54: 1360 -2.

34. Pamplona P, Carvalho JM. Normas para a quimioprofilaxia da tuberculose. Boletim da Sociedade Portuguesa de Pneumologia 2000; 35:35 -41.

35. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of Tuberculosis. Am J Respir Crit Care Med 2003; 167:603 -62.

36. Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Thorax 1998; 53:536 -48.

37. Vanhoof J, Landewe S, Van Wijngaerden E, Geusens P. High incidence of hepatotoxicity of isoniazid treatment for tuberculosis chemoprophylaxis in patients with rheumatoid arthritis treated with methotrexate or sulfasalazine and anti -tumour necrosis factor inhibitors. Ann Rheum Dis 2003; 62:1241 -2.

38. Mor A, Bingham CO 3rd, Kishimoto M, et al. Methotrexate combined with isoniazid therapy for latent tuberculosis is well tolerated in rheumatoid arthritis patients: experience from an urban arthritis clinic. Ann Rheum Dis published online 29 Aug 2007.

39. In A tuberculose na viragem do milénio. Jaime Pina,Ed. Lidel 2000

40. Hsu KH. Thirty years after isoniazid. Its impact on tuberculosis in children and adolescents. JAMA 1984; 251:1283 -5.

41. JB Bass Jr, LS Farer, PC Hopewell et al. Treatment of latent tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention. Am J Respir Crit Care Med 1994; 149:1359 -74

 

¹ Rheumatoid Arthritis Study Group (Grupo de Estudos de Artrite Reumatóide -GEAR) of the Portuguese Society of Rheumatology (Sociedade Portuguesa de Reumatologia – SPR)

² Tuberculosis Committee of the Portuguese Society of Pulmonology (Sociedade Portuguesa de Pneumologia – SPP)

* O presente artigo foi publicado simultaneamente in Acta Reumatol Port 2008;33:77-85

This article has been copublished in Acta Reumatol Port 2008; 33: 77-85

Correspondência/Correspondence:

Sociedade Portuguesa de Reumatologia

Rua D. Estefânia, 177-1.D, 1000-154 Lisbon

E-mail: info@spreumatologia.pt

 

Recebido para publicação/Received for publication: 08.02.21

Aceite para publicação/accepted for publication: 08.02.22