Abstract Background: Rheumatic diseases are associated with an increase in overall risks of tuberculosis (TB). The aim of this study was to evaluate the frequency of TB and the frequency of latent TB infection (LTBI), in clinical practice, for juvenile idiopathic arthritis (JIA) patients from high and low risk of TB incidence endemic countries. Methods: This is an international, multicenter, cross-sectional, observational study of data collection from Brazil and Registry of Portugal at REUMA.PT. The inclusion criteria were patients with Juvenile Idiopathic Arthritis (JIA) with age ≤ 18 years who underwent screening for Mycobacterium tuberculosis infection [tuberculin skin test (TST) and/or interferon gamma release assay (IGRA)]. Chest X-rays and history of exposure to TB were also assessed. Results: 292 JIA patients were included; mean age 14.3 years, mean disease duration 7.5 years, 194 patients (66.4%) performed only TST, 14 (4.8%) only IGRA and 84 (28.8%) both. The frequency of LTBI (10.6%) and TB was similar between the two countries. The reasons for TB screening were different; in Brazil it was performed more often at JIA onset while in Portugal it was performed when starting Disease Modified Anti-Rheumatic Drugs (DMARD) treatment (p < 0.001). Isoniazid therapy was prescribed in 40 (13.7%) patients (31 with LTBI and 9 with epidemiologic risks and/or due to contact with sick people). Only three patients (1%) developed active TB. Conclusion: We found nearly 10% of patients with LTBI, a small percentage of patients with treatment due to epide-miologic risks and only 1% with active TB. Distinct reasons and screening methods for LTBI were observed between the two countries.

Abstract High-resolution musculoskeletal ultrasound (MSUS) has been increasingly employed in daily rheumatological practice and in clinical research. In rheumatoid arthritis (RA), MSUS can be now considered a complement to physical examination. This method evaluates synovitis through gray-scale and power Doppler and it is also able to identify bone erosions. The utilization of MSUS as a marker of RA activity has received attention in recent literature. Current data account for good correlation of MSUS with classical measures of clinical activity; in some instances, MSUS appears to perform even better. Diagnosis of subclinical synovitis by MSUS might help the physician in RA management. With some variation, interobserver MSUS agreement seems excellent for erosion and good for synovitis. However, lack of MSUS score standardization is still an unmet need. In this review, we describe several MSUS scores, as well as their correlation with clinical RA activity and response to therapy. Finally, we look at the relationship of MSUS with synovial tissue inflammation and discuss future perspectives for a better interpretation and integration of this imaging method into clinical practice.

A imunossupressão crónica é um reconhecido factor de risco para a tuberculose. O nosso objectivo foi o de obter um consenso para o rastreio e prevenção da tuberculose em portadores de doenças inflamatórias imunomediadas candidatos a terapêutica biológica. Métodos: Revisão crítica da literatura e opinião de peritos acerca das terapêuticas imunossupressoras e risco de tuberculose. Resultados e conclusão: O método actualmente recomendado para o rastreio é o teste cutâneo da tuberculina e o doseamento do interferão gama, após exclusão da tuberculose activa. Doentes com rastreio positivo devem receber tratamento para a tuberculose latente. Estes doentes podem iniciar a terapêutica biológica após 1 a 2 meses, desde que a sua adesão seja rigorosa e apresentem boa tolerância à terapêutica profilática.

Chronic immunosuppression is a known risk factor for tuberculosis. Our aim was to reach a consensus on screening and prevention of tuberculosis in patients with immune mediated inflammatory diseases who are candidates to biologic therapy. Methods: Critical appraisal of the literature and expert opinion on immunosuppressive therapies and risk of tuberculosis. Results and conclusion: The currently recommended method for screening is the tuberculin skin test and the interferon gamma assay, after exclusion of active tuberculosis. Positively screened patients should be treated for latent tuberculosis infection. Patients may start biological therapy after 1-2 months, as long as they are strictly adhering to and tolerating their preventive regimen.

A reactivação da infecção pelo vírus da hepatite B (VHB) é uma complicação potencialmente grave da imunossupressão, que pode ser identificada e prevenida de modo eficaz. Tem-se verificado um número crescente de casos de reactivação do VHB em doentes sob imunossupressão no contexto de doenças reumáticas, como a artrite reumatóide o u o lúpus eritematoso sistémico. As recomendações nesta área devem ser individualizadas, tendo em conta dois aspectos: os esquemas imunossupressores utilizados (alto ou baixo risco de reactivação) e as diferentes fases da infecção pelo VHB, como seja a hepatite B crónica, o portador inactivo do VHB, ou mesmo a infecção oculta (por exemplo AgHBs negativo com anti-HBc positivo). Nos doentes com doenças reumáticas que vão iniciar terapêutica imunossupressora de alto risco, propomos o rastreio universal com testes serológicos da hepatite B com o antigénio de superfície do VHB (AgHBs), anticorpo anti-HBs e anti-HBc. Os doentes com hepatite B crónica (AgHBs positivo, ADN VHB l 2000 UI/ml) devem iniciar terapêutica antivírica; os portadores inactivos do VHB (AgHBs positivo, ADN VHB < 2000 UI/ml, aminotransferases normais) expostos a terapêutica imunossupressora de alto risco devem realizar igualmente profilaxia da reactivação do VHB. A profilaxia deve ser iniciada 2 a 4 semanas antes do início da terapêutica imunossupressora e mantida pelo menos durante 6 a 12 meses após a sua suspensão. Recomenda-se a utilização do entecavir ou tenofovir como antivirícos de primeira linha. Nos portadores inactivos do VHB sob terapêutica imunossupressora de baixo risco nos doentes AgHBs negativo / anti-HBc positivo (infecção a VHB no passado ou infecção oculta), a estratégia deve ser monitorização da reactivação viral através da determinação das aminotransferases e do ADN-VHB a cada 6 meses).

Reactivation of infection with hepatitis B virus (HBV) is a potentially serious complication of immunosuppression, which should be identified and efficiently prevented. There have been an increasing number of cases of HBV reactivation in patients receiving immunosuppression in the context of rheumatic diseases such as rheumatoid arthritis or systemic lupus erythematosus. The recommendations in this area should be individualized taking into account two aspects: immunosuppressive regimens used (high or low risk of reactivation) and the different stages of HBV infection: chronic hepatitis B, inactive HBV carrier, occult hepatitis B infection defined by HB surface antigen (HBsAg) negative and antibody anti-HB core (anti-HBc) positive. In patients with rheumatic diseases that will start high risk immunosuppressive drugs, we propose a universal screening with serological tests for hepatitis B (HBsAg, anti-HBs and anti-HBc). Patients with chronic hepatitis B (HBsAg positive, HBV DNA l 2000 IU / ml) should initiate antiviral therapy. Inactive HBV carriers (HBsAg positive, HBV DNA < 2000 IU / ml, normal aminotransferases) exposed to high risk immunosuppressive therapy should undergo prophylaxis of HBV reactivation. Prophylaxis should be started 2 to 4 weeks before the beginning of immunosuppressive therapy and maintained for at least 6 to 12 months after its suspension. It is recommended to use entecavir or tenofovir as first line antiviral agents. In inactive HBsAg carriers under low-risk immunosuppressive therapy and patients with HBsAg negative / anti-HBc positive (HBV infection in the past or occult inspection), the strategy should be monitoring of viral reactivation with aminotransferases and HBV DNA determination in every 6 months.

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.

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.

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-á). 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-TNFá. 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-á. No caso da actividade da DIA o exigir, o anti-TNF-á 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-á, mesmo que a prova seja negativa.

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-á) 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-á therapy. When TB (LTBI or AT) treatment is indicated, it should be performed before the beginning of anti-TNF-á therapy. If the IJD activity requires urgent anti-TNF-á 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-TNFá therapy, even in the presence of a negative test.