Latent Infection and Tuberculosis Disease in Rheumatoid Arthritis Patients

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Epidemiology of latent tuberculosis infection and tuberculosis disease

The World Health Organization (WHO) estimates that approximately one third of the world's population, or approximately 2 billion people, are latently infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. In 2006 the WHO reported a global incidence of 139 per 100,000 population, indicating that more than 1 million people develop active tuberculosis disease every year and approximately 2 million die as a result. Approximately every 20 minutes, 64 people die of

The Life Cycle of Mycobacterium tuberculosis in Infected Individuals

The immune response mounted to the infection generally is successful in containing, although not eliminating, the pathogen; thus, the infection becomes latent. M tuberculosis becomes dormant, residing in granulomas; as a result, infected individuals are asymptomatic and noninfectious.6 This latency often extends throughout a lifetime. Reactivation of latent tuberculosis infections (LTBIs), however, can occur in response to perturbations of the immune response, with active tuberculosis ensuing.

Tuberculosis and rheumatoid arthritis

New drug classes have been developed over the past 10 years based on human or chimeric antibodies against cytokines or receptors with pivotal roles in the inflammatory pathways of immune-mediated inflammatory disease. These agents are collectively referred to as biologics. Anti–TNF-α agents carry the largest infection risk of all the biologics, predisposing patients to mycobacterial infections. This is not surprising, as TNF has an important role in granuloma formation and maintenance, which is

Aging, rheumatoid arthritis, and the response of the immune system to Mycobacterium tuberculosis infection

Aging is a physiologic process that occurs over time in every living being and that is characterized by structural and functional changes at the cellular, organ, and system levels. The aging of the immune system, a process known as immunosenescence, usually parallels chronologic age; however, in autoimmune diseases, such as RA, this process can accelerate, resulting in further dysregulation of the immune system.46 This dysregulation in turn contributes to an increase susceptibility to

Latent Tuberculosis Infection in Patients who have Rheumatoid Arthritis

The cases of tuberculosis that occur in patients who have RA and are receiving anti–TNF-α therapy are, for the most part, the result of the reactivation of LTBI,51 which makes its diagnostic and treatment compulsory. The diagnosis begins with an adequate clinical history to detect the presence of risk factors predisposing to the development of tuberculosis. Even though the radiologic findings of granulomatous diseases are not specific, and abnormalities in LTBI are detected in only 10% to 20%

Screening test for tuberculosis before the initiation of biologic therapy in patients who have rheumatoid arthritis: current recommendations

Several countries have generated national guidelines that address LTBI before TNF-α blocker therapy is initiated, and these should be consulted.58 There are some notable differences between countries, which probably reflect local prevalence and other conditions of care.

Similar to any other diagnostic test, the predictive value of the IGRAs results depends on the prevalence of M tuberculosis infection in the population being tested. Results should be interpreted in conjunction with other

Nontuberculosis mycobacterial disease in patients undergoing anti–tumor necrosis factor α therapy

NTM infections are caused a group of more than 100 species of bacteria that are ubiquitous in soil and water and which exhibit varied pathogenicity. NTM infections are opportunistic, requiring defects in local or systemic host immunity to cause disease in humans. Unlike tuberculosis, disease from NTM infection is due to exposure to environmental organisms; cases of human-to-human transmission have never been documented.65 Patients who have pre-existing structural lung disease are known to be at

Summary

Patients receiving biologic therapies are at higher risk for developing tuberculosis than patients who have similar diseases and are not receiving these treatments or the general population; a definite risk exists particularly with anti-TNF agents. All patients who are candidates for the use of biologic agents should be screened for latent and active tuberculosis before its initiation. Despite a considerable reduction in the incidence of tuberculosis after initiation of anti-TNF therapy

Acknowledgments

The authors are grateful to Graciela S. Alarcón, MD, MPH, for her comments and suggestions in an earlier version of this article and for her help editing the English version.

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      The greater association of active TB with anti-TNF antibody-treated patients caused by disruption of the granuloma is consistent with the lack of effectiveness of soluble TNF receptor etanercept in granulomatous diseases such as sarcoidosis or Crohn's disease [51,53]. Current biologic drugs that target CD4+T cells, B cells and IL-6, the main host mechanisms of protection against Mycobacterium tuberculosis, are likely to increase susceptibility to the reactivation of LTBI in patients [45]. An increased rate of reactivation of LTBI has been reported in RCTs with tocilizumab and abatacept, and to a much lesser extent with rituximab [54].

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