A variety of opportunistic pathogens have been reported to infect patients receiving tumor necrosis factor (TNF) antagonists for the treatment of autoimmune diseases. These pathogens are numerous, and include coccidioides, histoplasma, nontuberculous mycobacteria, Mycobacteria tuberculosis, and others of public health concern. Accordingly, TNF antagonists should be used with caution in patients at risk for tuberculosis, and screening for latent tuberculosis infection should be undertaken before anti-TNF therapy is initiated. Although screening and prevention efforts have decreased the risk of tuberculosis in this setting, optimal screening methods represent an area of evolving controversy. This article discusses the latest developments in screening methodologies for latent tuberculosis infection, as well as potential preventive and therapeutic considerations for opportunistic infections associated with anti-TNF agents and other biologic therapies.
"A pivotal cohort study evaluating RA patient data for up to 15 years found a twofold greater risk of infection in patients with RA compared to those without RA, in particular serious infections of the lung, skin, bone, and joint . Specific causes for the high rate of infections remain indistinct but having compromised immune systems may put this cohort at substantial risk for severe complications . "
[Show abstract][Hide abstract] ABSTRACT: Anti-tumor necrosis factor alpha (anti-TNF) drugs are very effective for the treatment of rheumatoid arthritis but may increase the risk of serious bacterial infections. We assessed the association between the risk of serious skin and soft tissue infections (SSSTI) and the use of these agents in rheumatoid arthritis patients (RA).
We conducted a nested case-control study among rheumatoid arthritis patients in the Veterans Integrated Service Network 20 from 2000-2008. We identified rheumatoid arthritis patients with SSSTI, matched them to three sets of RA controls and used conditional logistic regression to compare the risk of SSSTI between patients treated and those not treated with an anti-TNF drug, after adjusting for known confounders and important covariates. Limited by the design, we could not assess (absolute) risk but only relative risk in terms of association.
Among the 97 cases and 291 controls, 90 percent were male, 62 percent white, with a mean age of 63 years. Twenty percent received anti-TNF drugs during the study period. Thirty-nine percent of cases and 15 percent of controls died, (OR 3.5, 95% CI: 2.033, 6.11, p <0.01). Diabetes mellitus (37%), kidney disease (16%) and a history of skin infections (27%) were common among cases. Based on conditional logistic regression, anti-TNF use was not significantly associated with skin and soft tissue infections (OR 1.1, 95% CI: 0.61-2.03, p = 0.92). However, patients with diabetes mellitus (OR 2.5, 95% CI: 1.53-4.13, p = 0.01) or a prior history of skin infection (OR 5.7, 95% CI: 2.87-11.43, p <0.01) were more likely to have skin and soft tissue infections.
Use of anti-TNF therapy among RA patients was not associated with an increased risk of SSSTI, but patients with diabetes mellitus and those with a history of prior skin infection were significantly more likely to have SSSTI and mortality was higher among cases than controls in this veteran cohort.
"Animal studies have shown that TNF is critical in host immune response in controlling a wide variety of bacterial, fungal, parasitic, and mycobacterial infection. Studies have shown that individuals are at increased risk for many of these infections, in particular for TB in areas with a high background prevalence of TB [75, 76]. Therefore screening for LTBI has been recommended before TNF-alpha inhibitor therapy is initiated. "
[Show abstract][Hide abstract] ABSTRACT: The risk of progression from exposure to the tuberculosis bacilli to the development of active disease is a two-stage process governed by both exogenous and endogenous risk factors. Exogenous factors play a key role in accentuating the progression from exposure to infection among which the bacillary load in the sputum and the proximity of an individual to an infectious TB case are key factors. Similarly endogenous factors lead in progression from infection to active TB disease. Along with well-established risk factors (such as human immunodeficiency virus (HIV), malnutrition, and young age), emerging variables such as diabetes, indoor air pollution, alcohol, use of immunosuppressive drugs, and tobacco smoke play a significant role at both the individual and population level. Socioeconomic and behavioral factors are also shown to increase the susceptibility to infection. Specific groups such as health care workers and indigenous population are also at an increased risk of TB infection and disease. This paper summarizes these factors along with health system issues such as the effects of delay in diagnosis of TB in the transmission of the bacilli.
Pulmonary Medicine 02/2013; 2013(9):828939. DOI:10.1155/2013/828939
"Screening for TB exposure with PPD skin testing or newer interferon-based serum tests (although their optimal use in this setting is not yet clear) should be performed before beginning therapy with anti-TNF agents (Winthrop and Chiller 2009). Anergy is known to occur in patients with RA or Crohn's disease, and the possibility of false-negative skin tests should be taken into consideration. "
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