Progress in research of prophylactic therapy in contacts of rifampicin-resistant tuberculosis patients / 中华流行病学杂志

Tuberculosis (TB) prophylactic therapy for latent infection, which can reduce the risk for the development of active TB, is an important measure in TB control. China recommends prophylactic therapy for latent tuberculosis infection (LTBI) in some key populations to reduce the risk for TB. Contacts of patients with multi-drug and rifampicin-resistant TB (MDR/RR-TB) are at high risk for the infection with drug-resistant pathogen, however, no unified prophylactic therapy regimen has been recommended for LTBI due to exposure to MDR/RR-TB patients. This paper summarizes the current MDR/RR-TB prophylactic therapy regimen and its protection effect based on the results of the retrieval of literature, guidelines, expert consensus and technical specifications to provide reference for the prevention and control of LTBI.

Desarrollo de infección tuberculosa latente y efectos adversos de la isoniazida durante tratamiento con biológico por enfermedad de Crohn / Development of latent tuberculosis and adverse effects with isoniazid during biologist therapy´s in Crohn´s disease / Desenvolvimento de tuberculose latente durante e efeitos adversos da isoniazida o tratamento com biológicos para a doença de Crohn

Los fármacos anti factor de necrosis tumoral alfa (TNF-α) bloquean una de las citoquinas implicadas en la patogénesis de la Enfermedad Inflamatoria intestinal (EII). Su uso se relaciona con aumento de tuberculosis (TB), por lo que el despistaje previo es obligatorio. En la infección tuberculosa latente (ITBL) se utiliza isoniazida como quimioprofilaxis, fármaco que no se encuentra libre de reacciones adversas. Se presenta y discute el caso de una paciente con reacción adversa en piel secundaria al uso de isoniazida.

Anti-tumor necrosis factor alfa drugs are responsible for blocking one of the cytoquines implicated on inflammatory bowel disease pathogenesis. Its use has been linked to an increase in tuberculosis cases which is why screening before starting treatment is mandatory. Latent tuberculosis is treated with isoniazid as chemoprophylaxis although its use may provoke adverse effects. A case is presented of a patient with skin adverse reaction due to the use of isoniazid.

Os medicamentos anti factor de necrose tumoral alfa (TNF-α ) bloqueiam uma das citocinas envolvidas na patogénese da doença inflamatória intestinal (DII). A sua utilização está associada com um aumento da tuberculose (TB), de modo que a despistagem anterior dessa doença é necessária. Na TB latente, frequentemente se utiliza a isoniazida é usado como quimioprofilaxia, uma droga que não está livre de reações adversas. Apresentamos e discutimos o caso de uma paciente com reação adversa na pele secundária ao uso da isoniazida.

The Risk of Tuberculosis in Korean Patients with Inflammatory Bowel Disease Receiving Tumor Necrosis Factor-alpha Blockers

The aims of this study were to assess the risk of tuberculosis (TB) and the status of latent tuberculosis infection (LTBI) in Korean patients with inflammatory bowel disease (IBD) receiving tumor necrosis factor (TNF)-alpha blockers. We reviewed medical records of 525 Korean IBD patients (365 TNF-alpha blocker naive and 160 TNF-alpha blocker exposed) between January 2001 and December 2013. The crude incidence of TB was significantly higher in IBD patients receiving TNF-alpha blockers compared to TNF-alpha-blocker-naive patients (3.1% vs. 0.3%, P=0.011). The mean incidence of TB per 1,000 patient-years was 1.84 for the overall IBD population, 4.89 for TNF-alpha blocker users, and 0.45 for TNF-alpha-blocker-naive patients. The adjusted risk ratio of TB in IBD patients receiving TNF-alpha blocker was 11.7 (95% confidence interval, 1.36-101.3). Pulmonary TB was prevalent in patients treated with TNF-alpha blockers (80.0%, 4/5). LTBI was diagnosed in 17 (10.6%) patients, and none of the 17 LTBI patients experienced reactivation of TB during treatment with TNF-alpha blockers. Treatment with TNF-alpha blockers significantly increased the risk of TB in IBD patients in Korea. De novo pulmonary TB infection was more prevalent than reactivation of LTBI, suggesting an urgent need for specific recommendations regarding TB monitoring during TNF-alpha blocker therapy.

The Risk of Tuberculosis in Korean Patients with Inflammatory Bowel Disease Receiving Tumor Necrosis Factor-alpha Blockers

The aims of this study were to assess the risk of tuberculosis (TB) and the status of latent tuberculosis infection (LTBI) in Korean patients with inflammatory bowel disease (IBD) receiving tumor necrosis factor (TNF)-alpha blockers. We reviewed medical records of 525 Korean IBD patients (365 TNF-alpha blocker naive and 160 TNF-alpha blocker exposed) between January 2001 and December 2013. The crude incidence of TB was significantly higher in IBD patients receiving TNF-alpha blockers compared to TNF-alpha-blocker-naive patients (3.1% vs. 0.3%, P=0.011). The mean incidence of TB per 1,000 patient-years was 1.84 for the overall IBD population, 4.89 for TNF-alpha blocker users, and 0.45 for TNF-alpha-blocker-naive patients. The adjusted risk ratio of TB in IBD patients receiving TNF-alpha blocker was 11.7 (95% confidence interval, 1.36-101.3). Pulmonary TB was prevalent in patients treated with TNF-alpha blockers (80.0%, 4/5). LTBI was diagnosed in 17 (10.6%) patients, and none of the 17 LTBI patients experienced reactivation of TB during treatment with TNF-alpha blockers. Treatment with TNF-alpha blockers significantly increased the risk of TB in IBD patients in Korea. De novo pulmonary TB infection was more prevalent than reactivation of LTBI, suggesting an urgent need for specific recommendations regarding TB monitoring during TNF-alpha blocker therapy.

Tumor necrosis factor-α antagonists: Side effects and their management.

As elevated levels of tumor necrosis factor-alpha (TNF-α) are associated with disease severity in psoriasis and psoriatic arthritis, TNF-α antagonists are being used to treat moderate to severe disease in patients who have contraindications, fail to respond or develop side effects to conventional systemic therapies. It is of utmost importance to be well versed with the possible adverse effects and contraindications of TNF-α antagonists so that they can be used effectively and safely. Many of their adverse effects have been well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) and may not be completely applicable in psoriasis. This is because patients with RA and IBD are on multiple immunosuppressants while those with psoriasis are mostly receiving single systemic therapy and often have comorbidities that distinguish them from those with RA or IBD. Also, some of the side effects are still controversial and debated. Long-term prospective randomized controlled studies are needed to better understand the associated risk in patients of psoriasis. Baseline screening and periodic monitoring during treatment can reduce and help in early identification and appropriate management of the adverse outcomes. This article reviews the side effects known to be associated with TNF-α antagonists, their pathomechanisms and management guidelines. Some of the common side effects include infusion and injection site reactions, infections particularly reactivation of tuberculosis, autoantibody formation and drug induced lupus erythematosus, liver function abnormalities, hematological, and solid organ malignancies.

Tumor necrosis factor-α antagonists: Side effects and their management.

As elevated levels of tumor necrosis factor-alpha (TNF-α) are associated with disease severity in psoriasis and psoriatic arthritis, TNF-α antagonists are being used to treat moderate to severe disease in patients who have contraindications, fail to respond or develop side effects to conventional systemic therapies. It is of utmost importance to be well versed with the possible adverse effects and contraindications of TNF-α antagonists so that they can be used effectively and safely. Many of their adverse effects have been well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) and may not be completely applicable in psoriasis. This is because patients with RA and IBD are on multiple immunosuppressants while those with psoriasis are mostly receiving single systemic therapy and often have comorbidities that distinguish them from those with RA or IBD. Also, some of the side effects are still controversial and debated. Long-term prospective randomized controlled studies are needed to better understand the associated risk in patients of psoriasis. Baseline screening and periodic monitoring during treatment can reduce and help in early identification and appropriate management of the adverse outcomes. This article reviews the side effects known to be associated with TNF-α antagonists, their pathomechanisms and management guidelines. Some of the common side effects include infusion and injection site reactions, infections particularly reactivation of tuberculosis, autoantibody formation and drug induced lupus erythematosus, liver function abnormalities, hematological, and solid organ malignancies.

Investigação de infecção tuberculosa latente em pacientes com psoríase candidatos ao uso de drogas imunobiológicas / Investigation of latent tuberculosis infection in patients with psoriasis who are candidate for receiving immunobiological drugs

O uso dos inibidores do fator de necrose tumoral no tratamento de pacientes com psoríase vem sendo relacionado a uma maior incidência de tuberculose, particularmente, nas suas formas extrapulmonar e disseminada. Apesar de sua indiscutível eficácia, essas drogas elevam o risco da reativação de infecção tuberculosa latente (ITBL), tornando obrigatório o diagnóstico da referida condição antes da sua administração. A investigação da infecção tuberculosa latente pelo teste cutâneo da tuberculina é falha, dada sua baixa especificidade, além de apresentar resultados duvidosos em pacientes com psoríase. Ensaios baseados na detecção da produção de interferon-gama in vitro por células monoclonais periféricas, estimuladas por antígenos específicos (Esat-6 e CFP-10), parecem oferecer maior acurácia quando comparados ao teste de Mantoux na identificação de infecção tuberculosa latente. Essa ferramenta diagnóstica tem oferecido maior especificidade, já que não apresenta correlação com medidas indiretas de exposição ao M. tuberculosis, como a vacinação por BCG, e com infecções por outras micobactérias.

The use of tumor necrosis factor inhibitors for the treatment of patients with psoriasis has been related to a higher incidence of tuberculosis, specially the disseminated and extrapulmonary forms. Despite their efficacy, these drugs increase the risk of reactivating latent tuberculosis infection, thus requiring diagnosis of the condition before their administration. Investigation of latent tuberculosis infection with tuberculin skin test is ineffective due to its low specificity and the dubious results that it generates in patients with psoriasis. Assays based on the detection of synthesis of gamma interferon in vitro by peripheral monoclonal cells, stimulated by specific antigens (ESAT-6 and CFP-10), seem to offer better accuracy when compared to the Mantoux test in identifying latent tuberculosis infection. This diagnosis tool has demonstrated higher specificity, since it has no correlation with indirect forms of exposure to M. tuberculosis such as BCG vaccination or with infections by other mycobacteria.

Tuberculose em pacientes com artrite reumatoide: a dificuldade no diagnóstico da forma latente / Tuberculosis in rheumatoid arthritis patients: the difficulty in making the diagnosis of latent infection

Desde o início do uso de drogas anti-TNF para o tratamento da artrite reumatoide e outras doenças inflamatórias, casos de tuberculose pulmonar e extrapulmonar vêm sendo notificados em pacientes submetidos a tal tratamento. Na maioria das vezes, a doença se desenvolve durante as seis primeiras infusões. Todo paciente deve ser avaliado para tuberculose latente antes do início do uso de um bloqueador de TNF; no entanto, o diagnóstico de tuberculose latente é um desafio. A prova tuberculínica, o único teste disponível para a detecção de tuberculose latente por quase um século, apresenta uma série de limitações. Testes baseados na detecção da produção de IFN-γ in vitro por células mononucleares ativadas por antígenos específicos parecem ser mais acurados e vêm sendo pesquisados em pacientes com artrite reumatoide.

Since the beginning of the use of anti-TNF in the treatment of rheumatoid arthritis and other inflammatory diseases, cases of pulmonary tuberculosis and extrapulmonary tuberculosis have been reported in patients receiving such treatment. In most cases, the disease develops by the time the patient has received the sixth infusion. Every patient should be evaluated for latent tuberculosis infection prior to the use of a TNF inhibitor. However, the diagnosis of latent tuberculosis infection is a challenge. The tuberculin test, which was the only test available to detect latent tuberculosis infection for nearly a century, presents a number of limitations. Tests based on the detection of the in-vitro production of IFN-γ by mononuclear cells activated by specific antigens appear to be more accurate and have been studied in patients with rheumatoid arthritis.