Occurrence of extraarticular disease manifestations is associated with excess mortality in a community based cohort of patients with rheumatoid arthritis

Department of Rheumatology, Malmö University Hospital, Sweden.
The Journal of Rheumatology (Impact Factor: 3.19). 01/2002; 29(1):62-7.
Source: PubMed


To investigate the occurrence of extraarticular manifestations (ExRA) in a well defined community based cohort of patients with rheumatoid arthritis (RA), and to examine their effect on mortality.
Using the resources of the Rochester Epidemiology Project, a retrospective medical record review was conducted of a cohort of 424 cases of RA in Olmsted County, MN, USA, diagnosed during the period 1955-1985. These cases had been classified using the American College of Rheumatology 1987 criteria for RA. Patients were followed 1955-1998 (median followup 14.8 yrs; range 0.2-42.8 yrs), and incident ExRA manifestations were recorded according to predefined criteria. Data on comorbidities were extracted using the definitions of the Charlson comorbidity index. Survival was compared to the general population using Kaplan-Meier estimates.
ExRA occurred in 169 patients, corresponding to an incidence rate of 3.67/100 person-yrs. Compared to the general population, survival among patients with RA was decreased. Survival among patients with ExRA was markedly decreased compared to the general population and to patients without ExRA (p < 0.001). A particularly poor prognosis was noted in a subgroup of 63 patients (incidence rate 1.04/100 person-yrs) who fulfilled predefined criteria for severe ExRA (i.e., vasculitis, pericarditis, pleuritis, and/or Felty's syndrome). For RA patients who did not fulfill these criteria, there was no significant increase of mortality (p = 0.09). In a multivariate model of mortality, including age, sex, and the presence of known comorbidities, the presence of one or more of these ExRA was the strongest predictor of mortality.
In this first community based study of extraarticular manifestations in RA, virtually all the excess mortality occurred in a subgroup of patients with severe extraarticular disease, suggesting that extraarticular disease is the major predictor of mortality in patients with RA.

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    • "Patients were invited to participate and after signing an informed consent they were assessed by one researcher through a structured interview about epidemiological characteristics (such as age at the time of the study) and disease antecedents; disease duration was defined as the time from the onset of first symptoms of RA until the inclusion in the present study and was assessed through DAS- 28 for disease activity, HAQ-DI for functioning, and other clinical measures. All the included patients were systematically assessed during the evolution of the disease and at the time of the study for presence of eExRA (Table 1), using a structured protocol based on a modification of the criteria described by Turesson et al. [11] to identify patients with ExRA. Briefly, all the patients were systematically assessed by two researchers (both rheumatologists) with a structured interrogatory, physical examination, and chart review; if an ExRA was suspected, this patient was sent for confirmation to an specialist of the organ being involved (for example, ophthalmologist, cardiologist, pulmonologist, dermatologist, and nephrologist). "
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    ABSTRACT: We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) with the presence of extra-articular (ExRA) manifestations in 225 patients with rheumatoid arthritis (RA). Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P = 0.40 and P = 0.91, resp.). Making an analysis of individual manifestations, rheumatoid nodules were associated with positivity for rheumatoid factor (RF); (P = 0.01), anti-CCP (P = 0.048), and anti-MCV (P = 0.02). Instead, RF, anti-CCP, or anti-MCV were not associated with SS, chronic anemia, or peripheral neuropathy. Levels of anti-CCP correlated with the score of the Health Assessment Questionnaire-Disability Index (HAQ-Di) (r = 0.154, P = 0.03), erythrocyte sedimentation rate (ESR); (r = 0.155, P = 0.03), and RF (P = 0.254, P < 0.001), whereas anti-MCV titres only correlated with RF (r = 0.169, P = 0.02). On adjusted analysis, ExRA was associated with longer age (P = 0.015), longer disease duration (P = 0.007), higher DAS-28 score (P = 0.002), and higher HAQ-DI score (P = 0.007), but serum levels of anti-CCP and anti-MCV were not associated. These findings show the need to strengthen the evaluation of the pathogenic mechanisms implied in each specific ExRA manifestation.
    Journal of Immunology Research 04/2014; 2014:536050. DOI:10.1155/2014/536050 · 2.93 Impact Factor
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    • "Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the joints [1]. Although the main manifestations involve the joints, previous studies have reported that extra-articular manifestations occur in 10%-20% of RA patients and that these symptoms correlate with increased mortality [2]. Clinical neuropathy occurs in 0.5% to 85% of RA patients [3,4,5,6], and presents in the form of mononeuritis multiplex, sensorimotor neuropathy, and entrapment neuropathy [5]. "
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    ABSTRACT: Objective To assess the prevalence of peripheral neuropathy in patients with rheumatoid arthritis (RA) having neuropathic symptoms, and to investigate the relationship between electrophysiological findings of peripheral neuropathy and clinical findings of RA. Methods Patients with a clinical diagnosis of RA and who had tingling or burning sensation in any extremity were electrophysiologically examined for evidence of peripheral neuropathy. Study parameters, including age, gender, laboratory parameters, duration of RA, and medication, were recorded. The symptoms and signs of neuropathy were quantified with the neuropathy symptom score, and the functional statuses of these patients were assessed. Results Out of a total of 30 RA patients, 10 (33%) had peripheral neuropathy: 2 had bilateral carpal tunnel syndrome (CTS), 5 had unilateral CTS, 1 had sensory polyneuropathy, and 2 had motor-sensory polyneuropathy. The mean ages of the patients with and without peripheral neuropathy were 69.4 and 56.5 years, respectively (p<0.05). A significant relationship was found between peripheral neuropathy and anti-cyclic citrullinated peptide (anti-CCP) antibody. However, no relationship was found between peripheral neuropathy and the type of medication, RA duration, the patients' functional status, neuropathic symptoms, erythrocyte sedimentation rate, and C-reactive protein values. Conclusion Neuropathic symptoms are common in RA patients, and it is difficult to distinguish peripheral neuropathy symptoms from those of arthritis. Patients with RA, particularly elderly patients and anti-CCP antibody positive patients who complain of neuropathic symptoms should undergo electrophysiological examination.
    Annals of Rehabilitation Medicine 04/2014; 38(2):249-55. DOI:10.5535/arm.2014.38.2.249
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    • "As a result of this observation, it has been suggested that risk as calculated by conventional risk stratification methods should incorporate a multiplier [22]. In particular, the European League Against Rheumatism (EULAR) task force have suggested that the cardiovascular risk estimate should be multiplied by 1.5 if at least two of the following criteria are present: disease duration of more than 10 years, rheumatoid factor or anti-cyclic citrullinated peptide positivity, presence of severe extra-articular manifestations [22] [23]. A recent study have reported that 2–26% of patients with RA without cardiovascular disease in secondary care are at sufficient high risk of developing cardiovascular disease, as calculated by different algorithms, to require primary prevention therapy with lipid-lowering agents [24]. "
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    ABSTRACT: The clinical benefits of statins are strongly related to their low density lipoprotein cholesterol (LDL-C) lowering properties. However, considering that the pharmacological target of statins, the 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase, is one of the upstream enzyme of the mevalonate pathway, its inhibition may determine a substantial impoverishment of additional lipid moieties required for a proper cellular function. From this hypothesis, several experimental and clinical evidence have been reported indicating additional effects of statins beyond the LDL-C lowering, in particular anti-inflammatory and immunomodulatory effects. Thus statin therapy, indicated for hyperlipidemic patients for primary and secondary prevention of coronary heart disease (CHD) have begun to be considered effective in other diseases not necessarily linked to altered lipid profile. In the present review we summarized the current clinical evidence of the efficacy and safety profile of statins in a variety of diseases, such as rheumatoid arthritis, venous thromboembolism, liver diseases, polycystic ovary syndrome, and age-related macular degeneration. As discussed in the review, pending large, well designed, randomized trials, it is reasonable to conclude that there is no definitive evidence for the use of statins in the aforementioned diseases.
    Pharmacological Research 02/2014; 88. DOI:10.1016/j.phrs.2014.02.003 · 4.41 Impact Factor
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