Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study

Mayo Clinic, Rochester, Minnesota 55905, USA.
Arthritis & Rheumatology (Impact Factor: 7.76). 09/2002; 46(9):2287-93. DOI: 10.1002/art.10524
Source: PubMed


A high frequency of infections complicating rheumatoid arthritis (RA) has been described in reports of case series. This retrospective longitudinal cohort study was undertaken to compare the frequency of infections in a population-based incidence cohort of RA patients with that in a group of individuals without RA from the same population.
RA patients included all members of an incidence cohort of Rochester, Minnesota residents ages >or=18 years who were first diagnosed as having RA between 1955 and 1994. One age- and sex-matched subject without RA was selected for each patient with RA. Study subjects were followed up by review of their entire medical record until death, migration from the area, or study end (January 1, 2000), and details of all documented infections, along with information on potential risk factors for infection, were recorded. Hazard ratios for infections were estimated using stratified Andersen-Gill proportional hazards models, with adjustment for potential confounders.
The 609 RA patients and 609 non-RA study subjects (mean age 58.0 years; 73.1% female) were followed up for a mean of 12.7 years and 15.0 years, respectively, reflecting higher mortality among the group with RA. Hazards ratios for objectively confirmed infections, infections requiring hospitalization, and any documented infection in patients with RA were 1.70 (95% confidence interval [95% CI] 1.42-2.03), 1.83 (95% CI 1.52-2.21), and 1.45 (95% CI 1.29-1.64), respectively, after adjustment for age, sex, smoking status, leukopenia, corticosteroid use, and diabetes mellitus. Sites of infection with the highest risk ratios were bone, joints, skin, soft tissues, and the respiratory tract.
In this study, patients with RA were at increased risk of developing infections compared with non-RA subjects. This may be due to immunomodulatory effects of RA, or to agents with immunosuppressive effects used in its treatment.

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    • "Patients with rheumatoid arthritis (RA) are reported to have an increased susceptibility to infection [1]. Studies of a specific * Corresponding author. "
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    ABSTRACT: Patients with rheumatoid arthritis (RA) have increased susceptibility to infection. The risk of acquiring infection including tuberculosis (TB) in RA may be increased in patients receiving any immuno-suppressive medication including anti-TNF therapy, which is used successfully for treating patients with rheumatoid arthritis. The aim of this work was to assess the risk of TB in RA patients on anti-TNF therapy compared to conventional disease modifying anti rheumatic drugs when screening for latent TB and TB chemoprophylaxis was applied.
    12/2014; 46(1). DOI:10.1016/j.ejcdt.2014.11.027
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    • "The higher rate of infectious events may result from an increased risk of infection inherent to RA (Doran et al., 2002a) (though this appears to have reduced over the last 50 years (Ni Mhuircheartaigh et al., 2013), which is thought to be secondary to immune disturbance associated with disease pathogenesis and the use of immune-modulators to control the condition (Doran et al., 2002a,b). An inherent risk of infection makes establishing a causal link between biologic DMARDs and infections more difficult. "
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    ABSTRACT: Rheumatoid arthritis (RA) is considered to be, in many respects, an archetypal autoimmune disease that causes activation of pro-inflammatory pathways resulting in joint and systemic inflammation. RA remains a major clinical problem with the development of several new therapies targeted at cytokine inhibition in recent years. In RA, biologic therapies targeted at inhibition of tumor necrosis factor alpha (TNFα) have been shown to reduce joint inflammation, limit erosive change, reduce disability and improve quality of life. The cytokine TNFα has a central role in systemic RA inflammation and has also been shown to have pro-inflammatory effects in the brain. Emerging data suggests there is an important bidirectional communication between the brain and immune system in inflammatory conditions like RA. Recent work has shown how TNF inhibitor therapy in people with RA is protective for Alzheimer's disease. Functional MRI studies to measure brain activation in people with RA to stimulus by finger joint compression, have also shown that those who responded to TNF inhibition showed a significantly greater activation volume in thalamic, limbic, and associative areas of the brain than non-responders. Infections are the main risk of therapies with biologic drugs and infections have been shown to be related to disease flares in RA. Recent basic science data has also emerged suggesting that bacterial components including lipopolysaccharide induce pain by directly activating sensory neurons that modulate inflammation, a previously unsuspected role for the nervous system in host-pathogen interactions. In this review, we discuss the current evidence for neuro-inflammation as an important factor that impacts on disease persistence and pain in RA.
    Frontiers in Neuroscience 11/2014; 8(357):1-11. DOI:10.3389/fnins.2014.00357 · 3.66 Impact Factor
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    • "Nevertheless, the potential aetiological roles of such bacteria are unknown. Furthermore, data from longitudinal cohort studies have demonstrated that patients with RA are at increased risk of developing infections compared to non-RA subjects [10], and that higher disease activity is associated with a higher probability of developing infections [11]. Moreover, elevated levels of calprotectin (a peptide with antimicrobial and pro-apoptotic effects that is predominantly produced by neutrophils) has been observed in RA serum [12] and atherosclerotic lesions [13]. "
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    ABSTRACT: The incidence of atherosclerosis is significantly increased in rheumatoid arthritis (RA). Infection is one factor that may be involved in the pathogenesis of both diseases. The cause of RA and atherosclerosis is unknown, and infection is one of the factors that may be involved in the pathogenesis of both diseases. The aims of this study were to identify bacteria in the aortic adventitia of patients with cardiovascular disease (CVD) in the presence and absence of RA, and to determine the effect of identified candidate pathogens on Toll-like receptor (TLR)-dependent signalling and the proinflammatory response. The aortic adventitia of 11 CVD patients with RA (RA+CVD) and 11 CVD patients without RA (CVD) were collected during coronary artery bypass graft surgery. Bacteria were detected in four samples from CVD patients and three samples from RA+CVD patients and identified by 16S rRNA gene sequencing. Methylobacterium oryzae was identified in all three RA+CVD samples, representing 44.1% of the bacterial flora. The effect of M. oryzae on TLR-dependent signalling was determined by transfection of HEK-293 cells. Although mild TLR2 signalling was observed, TLR4 was insensitive to M. oryzae. Human primary macrophages were infected with M. oryzae, and a TLDA qPCR array targeting 90 genes involved in inflammation and immune regulation was used to profile the transcriptional response. A significant proinflammatory response was observed, with many of the up-regulated genes encoding proinflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α) and chemokines (CCR7, IL-8). The aortic adventitia of CVD patients contains a wide range of bacterial species, and the bacterial flora is significantly less diverse in RA+CVD than CVD patients. M. oryzae may stimulate an proinflammatory response that may aggravate and perpetuate the pathological processes underlying atherosclerosis in RA patients.
    PLoS ONE 05/2014; 9(5):e98627. DOI:10.1371/journal.pone.0098627 · 3.23 Impact Factor
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