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To the Editors: Treatment of multidrug-resistant (MDR) tuberculosis (TB) (defined as in vitro resistance to at least isoniazid and rifampicin, the two most potent first-line drugs for TB treatment) and extensively drug-resistant (XDR)-TB (defined as in vitro resistance to isoniazid and rifampicin plus any fluoroquinolone and at least one of the injectable drugs: amikacin, capreomycin or kanamycin) is still a major problem from both a clinical and a public health perspective [1–5]. Treatment outcomes for complicated MDR-TB cases (those with additional resistance beyond isoniazid and rifampicin) and XDR-TB cases being still poor, the need for information on the safety, tolerability and efficacy of other antibiotics that are potentially useful in their treatment is urgent [6–9]. In vitro and pharmacological data suggest that linezolid, an oxazolidinone antibiotic, could be useful in treating mycobacterial infections, including MDR-TB [9–11]. However, clinical experience with the off-label use of linezolid is still limited to case reports and small case series involving nontuberculous mycobacterial diseases [12] and TB, the four largest cohorts including 10 [13], 12 [14], 30 [15] and 85 cases (but only 45 with information on efficacy) [9], respectively. The aim of this study was to evaluate the safety, tolerability and efficacy of linezolid in a cohort of patients with MDR/XDR-TB from Portugal. Clinical information necessary to study safety, tolerability and efficacy was prospectively collected on all MDR-TB cases treated with linezolid in Portugal between 2004 and 2009, with the exception of one case who started the treatment in 2003 (whose information was …

Resumo: A tuberculose é uma doença bem conhecida e para a qual há fármacos de reconhecida eficácia. Em Portugal, a incidência da tuberculose tem vindo a diminuir de forma consistente nos últimos anos, mantendo contudo valores acima da média europeia. Uma nova dificuldade surge, associada à resistência aos antibacilares reconhecidamente relacionada com a não adesão ao tratamento e/ou a uma incorrecta escolha do regime terapêutico. Assim, é importante focar a atenção na abordagem inicial do caso de tuberculose, sendo esse o objectivo desta revisão.Rev Port Pneumol 2010; XVI (4): 559-572 Abstract: Tuberculosis is a well-known illness for which there is treatment of recognized effectiveness. In Portugal, tuberculosis incidence has been diminishing although keeping values higher than the rest of the Western Europe. A new challenge is associated with resistance to drugs, admittedly related to treatment noncompliance or incorrect treatment choice. The purpose of this review to focus our attention on the importante of the first approach to the tuberculosis case.Rev Port Pneumol 2010; XVI (4): 559-572 Palavras-chave: Tuberculose, tratamento, efeitos colaterais, Key-words: Tuberculosis, treatment, side effects

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 (TNFα). 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-TNFα. 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-TNFα. No caso da actividade da DIA o exigir, o anti-TNFα 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

Resumo: A Sociedade Portuguesa de Reumatologia (SPR) e a Sociedade Portuguesa de Pneumologia (SPP) elaboraram recomendações para o diagnóstico e terapêutica da tuberculose latente (TL) e activa (TD) em doentes com doenças inflamatórias articulares (DIA), nomeadamente artrite reumatóide, artrite psoriática e espondilite anquilosante, tratadas com antagonistas do factor de necrose tumoral alfa (TNF-α).Devido ao elevado risco de tuberculose (TB) em doentes com DIA deverá proceder-se ao rastreio de TD e TL tão precocemente quanto possível, preferencialmente no momento do diagnóstico da doença reumática. No entanto, e mesmo que o rastreio já tenha sido efectuado no início da doença, a avaliação deverá ser repetida antes do início da terapêutica anti-TNFα. Sempre que houver indicação para terapêutica de tuberculose (TL ou TD), esta deverá ser, de preferência, cumprida integralmente antes de se iniciar o anti-TNF-α. No caso da actividade da DIA o exigir, o anti-TNF-α poderá ser iniciado ao fim de dois meses de terapêutica antibacilar, no caso de TD, ou ao fim de 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 em actividade e se se detectar história anterior de TB não tratada ou tratada de forma incorrecta ou incompleta, esta deverá ser tratada como TL. Se se suspeitar de lesões em actividade, o diagnóstico de TD deve ser confirmado 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 inferior a 5 mm, a prova deve ser repetida 1 a 2 semanas depois, no antebraço oposto, e considerada negativa se o segundo resultado for igualmente inferior a 5 mm. As PT positivas obrigam a tratamento de TL. Se a PT é realizada em fase de imunodepressão, o doente deve ser submetido a tratamento de TL antes de iniciar terapêutica anti-TNF-α, mesmo que a prova seja negativa. Abstract: The Portuguese Society of Rheumatology (SPR) and the Portuguese Society of Pulmonology (SPP) have developed guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (AT) in patients with inflammatory joint diseases (IJD), namely rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with tumour necrosis factor alpha (TNF-α) antagonists.Due to the high risk of tuberculosis (TB) in patients with IJD, LTBI and AT screening should be performed as soon as possible, ideally at the moment of IJD diagnosis. Even if TB screening was performed at the beginning of the disease, the evaluation should be repeated before starting anti-TNF-α therapy. When TB (LTBI or AT) treatment is indicated, it should be performed before the beginning of anti-TNF-α therapy. If the IJD activity requires urgent anti-TNF-α therapy, these drugs can be started after two months of antituberculosis therapy in AT cases, or after one month in LTBI cases. Chest X-ray is mandatory for all patients. If abnormal, e.g. Gohn complex, the patient should be treated as LTBI; residual lesions require the exclusion of AT and patients with history of untreated or incomplete TB treatment should be treated as LTBI. In cases of suspected active lesions, AT diagnosis should be confirmed and adequate therapy initiated. Tuberculin skin test (TST), with two units of RT23, should be performed in all patients. If induration is less than 5 mm, the test should be repeated after 1 to 2 weeks, on the opposite forearm, and should be considered negative if the result is again inferior to 5 mm. Positive TST implicates LTBI treatment. If TST is performed in immunosupressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFα therapy, even in the presence of a negative test. Palavras-Chave: Recomendações, Sociedade Portuguesa de Reumatologia, Sociedade Portuguesa de Pneumologia, tuberculose, terapêutica anti-TNFα, Keywords: Guidelines, Portuguese Society of Rheumatology, Portuguese Society of Pulmonology, tuberculosis, anti-TNFα drugs

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 (TNFalpha) 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-TNFalpha 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-TNFalpha therapy. If the IJD activity justifies the need for immediate treatment, anti-TNFalpha 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; 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 duration is5 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 again5 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-TNFalpha therapy, even in the presence of a negative test, after risk/benefit assessment.

The Portuguese Society of Rheumatology (SPR) and the Portuguese Society of Pulmonology (SPP) have developed guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (AT) in patients with inflammatory joint diseases (IJD), namely rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with tumour necrosis factor alpha (TNF-a) antagonists. Due to the high risk of tuberculosis (TB) in patients with IJD, LTBI and AT screening should be performed as soon as possible, ideally at the moment of IJD diagnosis. Even if TB screening was performed at the beginning of the disease, the evaluation should be repeated before starting anti-TNF-a therapy. When TB (LTBI or AT) treatment is indicated, it should be performed before the beginning of anti-TNF-a therapy. If the IJD activity requires urgent anti-TNF-a therapy, these drugs can be started after two months of antituberculosis therapy in AT cases, or after one month in LTBI cases. Chest X-ray is mandatory for all patients. If abnormal, e.g. Gohn complex, the patient should be treated as LTBI; residual lesions require the exclusion of AT and patients with history of untreated or incomplete TB treatment should be treated as LTBI. In cases of suspected active lesions, AT diagnosis should be confirmed and adequate therapy initiated. Tuberculin skin test (TST), with two units of RT23, should be performed in all patients. If induration is less than 5 mm, the test should be repeated after 1 to 2 weeks, on the opposite forearm, and should be considered negative if the result is again inferior to 5 mm. Positive TST implicates LTBI treatment. If TST is performed in immunosuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNF-a therapy, even in the presence of a negative test.

The Portuguese Society of Rheumatology (SPR) and the Portuguese Society of Pulmonology (SPP) have developed guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (AT) in patients with inflammatory joint diseases (IJD), namely rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with tumour necrosis factor alpha (TNF-alpha) antagonists. Due to the high risk of tuberculosis (TB) in patients with IJD, LTBI and AT screening should be performed as soon as possible, ideally at the moment of IJD diagnosis. Even if TB screening was performed at the beginning of the disease, the evaluation should be repeated before starting anti-TNF-alpha therapy. When TB (LTBI orAT) treatment is indicated, it should be performed before the beginning of anti-TNF-alpha therapy. If the IJD activity requires urgent anti-TNF-alpha therapy, these drugs can be started after two months of antituberculosis therapy in AT cases, or after one month in LTBI cases. Chest X-ray is mandatory for all patients. If abnormal, e.g. Gohn complex, the patient should be treated as LTBI; residual lesions require the exclusion of AT and patients with history of untreated or incomplete TB treatment should be treated as LTBI. In cases of suspected active lesions, AT diagnosis should be confirmed and adequate therapy initiated. Tuberculin skin test (TST), with two units of RT23, should be performed in all patients. If induration is less than 5 mm, the test should be repeated after 1 to 2 weeks, on the opposite forearm, and should be considered negative if the result is again inferior to 5 mm. Positive TST implicates LTBI treatment. IfTST is performed in immunosupressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFalpha therapy, even in the presence of a negative test.