Turesson C, O’Fallon WM, Crowson CS, Gabriel SE, Matteson EL. Occurrence of extraarticular disease manifestations is associated with excess mortality in a community based cohort of patients with rheumatoid arthritis. J Rheumatol. 29: 62-67

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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    • "Occurrence of EAMs is usually accompanied with severe active disease and increased mortality (Turesson C et al. 2002, Gabriel SE et al. 2003, Carmona L et al. 2003, Young A and Koduri G 2013, Turesson C 2013). Thus, EAMs are serious, that should be aggressively treated and monitored (Young A and Koduri G 2013). "
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    ABSTRACT: Objectives: To assess the extra-articular manifestations (EAMs) in Saudi rheumatoid arthritis (RA) patients, and their association with serological markers [rheumatoid factor (RF) and anti-Cyclic Citrullinated Peptide (Anti-CCP)]. Methods: Retrospectively, we studied 205 Saudi RA patients at DR Dhia private center (Jeddah, SA) over three years (2/2011-2/2014). Positivity of RF and of anti-CCP, demographic and clinical features were recorded. Disease activity was scored for 28 joints (DAS28). Results: Prevalence of EAMs was 33%, and was higher in male (45%) than female (32%). EAMs included: Hypertension(HTN) [25 patient (12.5%)], Diabetes Melittus (DM) (22(11%)], Hypothyroidism [15(7.3%)],nodule [8(4%)], low WBC [5(2.4%)], ANA positivity [4(2%)], Gout [3(1.5%)], Sjögren's syndrome [2(1%)], and one case (0.5%) of each of lung affect, kidney atrophy, Sickle cell, high CK, high creatinin and epilepsy. EAMs showed no association with the serological markers, neither with RF nor with anti-CCP. Only hypertension showed significant correlation (P= 0.017) with DAS28. Conclusion: The low levels of nodules and EAMs in Saudi RA patients are different from European and North American populations. They are similar concerning the higher levels of EAMs in males than females. Only hypertension had correlation with disease activity. EAMs showed no association with the serological markers. Presence of discrepancies in rats of EAMs between centers in Saudi Arabia.
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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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