Extra-articular Rheumatoid Arthritis Research Articles

Deteriorating Pulmonary Functions in Patients with Rheumatoid Arthritis- A Pilot Study from South India

Background and Objective: Pulmonary involvement is a common extra-articular manifestation of rheumatoid arthritis (RA). The present study attempts to highlight the extent of involvement by assessing lung function using pulmonary function tests (PFTs) in patients with RA. Methods: This pilot study involved 30 patients with RA and an equal number of age- and sexmatched healthy controls. All the study participants were subjected to spirometry and in RA patients, the test was repeated after 30 minutes of administering 400 mcg of salbutamol. PFT values of the controls and the pre and post-values of cases like forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), Percentage of forced expiratory volume in the first second (FEV1%), forced expiratory flow at 25% to 75% of the lung volume (FEF25-75%) and peak expiratory flow rate (PEFR) were recorded. Independent sample t-test or Mann-Whitney U test were used for comparisons. The pre- and post-values of PFT were compared using paired t-test, Welsch’s test, or Wilcoxon tests. (p ≤ 0.05 implied statistical significance). Results: PFT variables were significantly lower among patients with RA compared with controls (p<0.05). A significant negative correlation of FEF25%-75% and PEFR with BMI in obese patients (BMI >23) and FVC, FEV1, and PEFR significantly lower in post-menopausal women (p < 0.05) was seen. Conclusion: Based on the pilot study findings, patients in south India with RA could manifest decreased pulmonary functions. Obese patients and post-menopausal females with RA could be at a higher risk, and the administration of nebulized salbutamol could improve pulmonary functions.

Взаємозв’язок остеопорозу і вегетативної дисфункції при ревматоїдному артриті

Актуальність. Ревматоїдний артрит (РА) належить до найбільш частих запальних хвороб суглобів, і кількість хворих із цією патологією всюди збільшується, що пов’язано з величезними медико-соціальними й економічними збитками. Важлива роль в патогенезі РА відводиться порушенням функції вегетативної нервової системи (ВНС), стан якої тісно пов’язаний з кістковим метаболізмом та мінеральною щільністю кістки. Мета і задачі: оцінити частоту остеопорозу при різному «вегетативному паспорті» хворих на РА, вивчити взаємозв’язки ознак вегетативної дисфункції (ВД) з характером щільності кістки. Матеріал і методи. Обстежено 173 хворих на РА віком від 18 до 79 років (середній вік 46 років), серед яких було 21 % чоловіків і 79 % жінок. Тривалість маніфестації захворювання становила 10 років, серопозитивний за ревматоїдним фактором та протицитруліновими антитілами варіант РА встановлено в 3/4 випадків, позасуглобову (системну) форму хвороби діагностовано в 37 % спостережень. Результати. Остеопороз розвивається у 2/3 від числа хворих на РА, а патогенетичні побудови його пов’язані з наявністю ВД, тяжкість перебігу якої корелює з показниками щільності кістки, причому ті, у свою чергу, — з параметрами варіаційної пульсометрії, активністю й кістково-деструктивними складовими артикулярного синдрому, залежать від вегетативного типу пацієнтів (для хворих з остеопорозом більшою мірою характерна ваготонія, а для інших пацієнтів — симпатотонія). Дисбаланс маркерів кісткового метаболізму у хворих на РА посилює існуючі порушення ВНС, а рівень магнемії має прогностичну значущість відносно ВД. Тяжкість останньої взаємопов’язана з вираженістю остеопорозу, при цьому прогностично несприятливими є показники в крові кальцію більше 80 мг/л і активності лужної фосфатази більше 180 О/л. Висновок. Розвиток остеопорозу взаємопов’язаний не лише з особливостями перебігу суглобового синдрому та екстраартикулярних ознак РА, а й із станом ВНС, яка бере участь в патогенетичних побудовах зменшення щільності кістки і дисбалансі маркерів кісткового метаболізму. У майбутньому буде корисним активне виявлення ВД для подальших своєчасних реабілітаційних заходів.

Зв’язок реологічних властивостей сироватки крові зі станом вегетативної нервової системи при ревматоїдному артриті

Актуальність. Ревматоїдний артрит (РА) належить до найбільш частих запальних хвороб суглобів, і численність таких пацієнтів всюди збільшується, завдаючи величезного медико-соціального й економічного збитку. Важлива роль у патогенезі РА відводиться порушенням функції вегетативної нервової системи (ВНС), стан якої тісно пов’язаний із реологічними властивостями сироватки крові (РВСК). Мета дослідження: оцінити співвідношення «вегетативного паспорта» хворих на РА і вегетативної дисфункції з РВСК при різних варіантах перебігу хвороби. Матеріали та методи. Обстежено 173 хворих на РА у віці від 18 до 79 років (в середньому 46 років), серед яких було 21 % чоловіків та 79 % жінок. Тривалість маніфестації захворювання становила 10 років, серопозитивний за ревматоїдним фактором і антицитруліновими антитілами варіант РА встановлено в 3/4 випадків, позасуглобову (системну) форму хвороби діагностовано в 37 % спостережень. З використанням комп’ютерного тензіометру «PAT2-Sinterface» (Німеччина) визначали поверхневі показники сироватки крові — в’язкість, пружність, натяг, релаксацію й модуль в’язкоеластичності. Результати. «Вегетативний паспорт» визначав інтегральні клініко-лабораторні та інструментальні ознаки РА, при цьому тяжкість вегетативної дисфункції прямо корелювала з темпами прогресування патології суглобів, а у симпатотоніків — з початковими параметрами ревматоїдного фактора в крові й ступенем активності РА. Зміни РВСК супроводжувались збільшенням рівноважного (статичного) поверхневого натягу, що реєструвалося в 70 % випадків. Інтегральний стан міжфазної активності, релаксаційних та в’язкоеластичних характеристик крові визначав тип ВНС і наявність у хворих вегетативної дисфункції (ваготонікам властиві підвищення модуля в’язкоеластичності й зниження поверхневого натягу, симпатотонікам — підвищення поверхневого натягу та зниження поверхневої в’язкості). Параметри РВСК пов’язані з вираженістю вегетативних розладів, а показник поверхневої в’язкості має прогностичну значущість. Висновки. Розвиток вегетативної дисфункції пов’язаний не лише з особливостями перебігу суглобового синдрому і екстраартикулярних ознак РА, а й зі станом ВНС, що бере участь в порушеннях РВСК. У майбутньому буде корисною оцінка стану ВНС для подальших своєчасних реабілітаційних заходів щодо захворювання.

Depression and severity of articular destruction in patients with rheumatoid arthritis

To assess the influence of anxiety and depressive disorders on joint destruction in patients with rheumatoid arthritis (RA). 128 RA-patients were included, 87% were women with a mean age of 47.411.3 years and a median of RA duration 96 [48; 228] months. At the inclusion most patients had moderate (n=56, 43.7%) and severe (n=48, 37.5%) disease activity according to DAS28. Joint destruction was classified as maximal in patients with radiographic stage III, IV and/or osteonecrosis) and minimal in patients with stage I, II and no osteonecrosis. Pain intensity was measured with the BPI (Brief Pain Inventory) scale, severity of fatigue with fatigue severity scale (FSS), clinically important fatigue was diagnosed in patients with FSS4. Anxiety and depressive disorders (ADD) were diagnosed by a licensed psychiatrist in 123 (96.1%) of RA-patients in accordance with ICD-10 in semi-structured interview. Severity of depression and anxiety was evaluated with Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A). RA-patients with ADD were divided into the following treatment groups: 1 сDMARDs (n=39), 2 сDMARDs+PPT (sertraline or mianserine), n=43, 3 сDMARDs+bDMARDs (n=32), 4 сDMARDs+bDMARDs+PPT (sertraline or mianserine), n=9. Biologics treatment duration varied from 1 to 6 years, antidepressants from 6 to 96 weeks. 83 (67.5%) RA patients were assessed at five-years follow-up. Linear regression analysis was conducted to determine factors associated with maximal join destruction. According to linear regression analysis, maximal joint destruction at 5 years follow-up was associated with higher baseline BPImax, longer RA and ADD duration, clinically important fatigue at baseline, baseline extraarticular RA manifestations, recurrent depressive disorder at 5-years follow-up and treatment with cDMARDs only. Recurrent depressive disorder without antidepressant treatment is an important predictor of progression of joint destruction in patients with rheumatoid arthritis.

Infectious Triggers in Periodontitis and the Gut in Rheumatoid Arthritis (RA): A Complex Story About Association and Causality.

Rheumatoid arthritis (RA) is a systemic immune mediated inflammatory disease of unknown origin, which is predominantly affecting the joints. Antibodies against citrullinated peptides are a rather specific immunological hallmark of this heterogeneous entity. Furthermore, certain sequences of the third hypervariable region of human leukocyte antigen (HLA)-DR class II major histocompatibility (MHC) molecules, the so called “shared epitope” sequences, appear to promote autoantibody positive types of RA. However, MHC-II molecule and other genetic associations with RA could not be linked to immune responses against specific citrullinated peptides, nor do genetic factors fully explain the origin of RA. Consequently, non-genetic factors must play an important role in the complex interaction of endogenous and exogenous disease factors. Tobacco smoking was the first environmental factor that was associated with onset and severity of RA. Notably, smoking is also an established risk factor for oral diseases. Furthermore, smoking is associated with extra-articular RA manifestations such as interstitial lung disease in anatomical proximity to the airway mucosa, but also with subcutaneous rheumatoid nodules. In the mouth, Porphyromonas gingivalis is a periodontal pathogen with unique citrullinating capacity of foreign microbial antigens as well as candidate RA autoantigens. Although the original hypothesis that this single pathogen is causative for RA remained unproven, epidemiological as well as experimental evidence linking periodontitis (PD) with RA is rapidly accumulating. Other periopathogens such as Aggregatibacter actinomycetemcomitans and Prevotella intermedia were also proposed to play a specific immunodominant role in context of RA. However, demonstration of T cell reactivity against citrullinated, MHC-II presented autoantigens from RA synovium coinciding with immunity against Prevotella copri (Pc.), a gut microbe attracted attention to another mucosal site, the intestine. Pc. was accumulated in the feces of clinically healthy subjects with citrulline directed immune responses and was correlated with RA onset. In conclusion, we retrieved more than one line of evidence for mucosal sites and different microbial taxa to be potentially involved in the development of RA. This review gives an overview of infectious agents and mucosal pathologies, and discusses the current evidence for causality between different exogenous or mucosal factors and systemic inflammation in RA.

The impact of age and gut microbiota on Th17 and Tfh cells in K/BxN autoimmune arthritis

BackgroundAge is an important risk factor for rheumatoid arthritis (RA), which often develops in middle age. However, how age-associated changes in immunity impact RA is poorly understood. Gut microbiota are known to be involved in the pathogenesis of RA, but the effects of microbiota in older subjects remain mostly unknown.MethodsWe used segmented filamentous bacteria (SFB), a gut commensal species with immunomodulatory effects, and K/BxN mice, a T cell receptor (TCR) transgenic model, to study the effect of age and microbiota on autoimmune arthritis. Comparing young and middle-aged K/BxN T cells of the same TCR specificity allows us to study T cells with an age focus eliminating a key variable: TCR repertoire alteration with age. In addition to joints, we also studied pathological changes in the lung, an important extra-articular RA manifestation. We used flow cytometry to evaluate T follicular helper (Tfh) and T helper 17 (Th17) cells, as they both contribute to autoantibody production, a key disease index in both RA and K/BxN arthritis.ResultsMiddle-aged K/BxN mice had aggravated arthritis and pathological changes in the lung compared to young mice. Middle-aged mice displayed a strong accumulation of Tfh but not Th17 cells, and had defective Th17 differentiation and low expression of interleukin-23, a critical cytokine for Th17 maintenance. Although a soaring Tfh cell population accompanied by robust germinal center B cell responses were found in middle-aged mice, there was decreased cycling of Tfh cells, and SFB only induced the non-Tfh cells to upregulate Bcl-6, the Tfh master transcription factor, in the young but not the middle-aged group. Finally, the accumulated Tfh cells in middle-aged mice had an effector phenotype (CD62LloCD44hi).ConclusionAge-dependent Tfh cell accumulation may play a crucial role in the increased autoimmune disease phenotype in middle-age. SFB, a potent stimulus for inducing Tfh differentiation, fails to promote Tfh differentiation in middle-aged K/BxN mice, suggesting that most of the middle-aged Tfh cells with an effector phenotype are Tfh effector memory cells induced at an earlier age. Our results also indicate that exposure to immunomodulatory commensals may allow the young host to develop an overactive immune system reminiscent of that found in the middle-aged host.

Severe Extraarticular Manifestations in a Community-based Cohort of Patients with Rheumatoid Arthritis: Risk Factors and Incidence in Relation to Treatment with Tumor Necrosis Factor Inhibitors.

The aims of this study were to evaluate whether treatment with tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) affects the risk of developing severe extraarticular rheumatoid arthritis (ExRA) manifestations and to investigate potential predictors for developing ExRA. A dynamic community-based cohort of patients with RA was studied (n = 1977). Clinical records were reviewed and cases of severe ExRA were identified. Information on exposure to TNF inhibitors was obtained from a regional register. Exposure to TNF inhibitors was analyzed in a time-dependent fashion and the incidence of severe ExRA in exposed patients was compared with the incidence in unexposed patients. Cox regression models were used to assess potential predictors of severe ExRA. During treatment with TNF inhibitors, there were 17 patients with new onset of severe ExRA in 2400 person-years at risk (PY; 0.71/100 PY, 95% CI 0.41-1.13) compared with 104 in 15,599 PY (0.67/100 PY, 95% CI 0.54-0.81) in patients without TNF inhibitors. This corresponded to an incidence rate ratio of 1.06 (95% CI 0.60-1.78). The age- and sex-adjusted HR for ExRA in anti-TNF-treated patients was 1.21 (95% CI 1.02-1.43), with similar findings in models adjusted for time-dependent Health Assessment Questionnaire and propensity for anti-TNF treatment. Male sex, positive rheumatoid factor (RF), long disease duration, and greater disability were predictors for ExRA. This study suggests that patients treated with TNF inhibitors are at a slightly increased risk of developing severe ExRA. RF-positive patients with disabling disease of long duration were more likely to develop severe ExRA.

Factors influencing the choice of first- and second-line biologic therapy for the treatment of rheumatoid arthritis: real-life data from the Italian LORHEN Registry

According to international recommendations, the selection of the biologic disease modifying anti-rheumatic drug (bDMARD) for rheumatoid arthritis (RA) is mainly left to the clinician’s preference. We analyzed the real-life factors influencing the first-line choice or the switching strategy, focusing on the prescription of abatacept (ABA) or tocilizumab (TCZ) compared to TNFα inhibitors (TNFi). Patients enrolled in the Lombardy Rheumatology Network (LORHEN) Registry after January 1, 2010, when all considered bDMARD agents were available, were included. The population was divided into “first-” and “second-line” bDMARD. We included 1910 patients (first line n = 1264, second line n = 646). Age was higher in ABA or TCZ vs TNFi treated patients (p < 0.0001). Positive latent tuberculosis screening was associated with first-line ABA (p = 0.002). Methotrexate (MTX) combination therapy was lower in the TCZ group (p = 0.02). The type (dyslipidemia, hypertension, pulmonary disease) and the number of comorbidities influenced the choice towards ABA (p = 0.01). Multinomial logistic regression demonstrated that a second-line treatment, higher age, dyslipidemia, pulmonary disease, other comorbidities, and extra-articular RA manifestations were associated with ABA compared to TNFi. TCZ was associated with a second-line treatment, higher age, and more severe disease activity. Stopping the first bDMARD due to adverse events (AE) influenced the choice towards ABA. In real life, higher age and comorbidities influence the choice towards ABA and TCZ compared to TNFi. ABA was preferred in case of suspension of previous treatments due to AE. After failing a first-line TNFi, swapping to a different mechanism of action is more common.

Co-morbidity in patients with early rheumatoid arthritis - inflammation matters.

BackgroundPatients with rheumatoid arthritis (RA) suffer from co-morbidities that contribute to a shortened lifespan. Inflammation is important for the development of cardiovascular disease, but little is known on its relationship with other co-morbidities. We investigated the role of inflammation for the development of new comorbidities in early RA.MethodsSince 1995, all patients with early RA in Northern Sweden are included in a prospective study on co-morbidities, with a total of 950 patients being included. At the time for this study, 726 had been ill for ≥5 years. Data on co-morbidities, clinical and laboratory disease activity and pharmacological therapy were collected from patient records and further validated using a questionnaire at RA onset (T0) and after 5 years (T5).ResultsOf the patients, 53.2 % of the patients had one or more co-morbidity at onset, the commonest being: hypertension (27.3 %), obstructive pulmonary disease (13.9 %), diabetes (8.0 %), hypothyroidism (6.3 %) and malignancy (5.0 %). After 5 years, 41.0 % had developed at least one new co-morbidity, the most common being: hypertension (15.1 %), malignancy (7.6 %), stroke/transient ischemic accident (5.1 %), myocardial infarction (4.3 %) and osteoporosis (3.7 %). Age at disease onset, a raised erythrocyte sedimentation rate (ESR) at inclusion, previous treatment with glucocorticoids (GC; p < 0.001 for all), extra-articular RA (Ex-RA; p < 0.01), DAS28 (area under the curve) at 24 months (p < 0.05), previous smoking at inclusion (p = 0.058) and male gender (p < 0.01) were associated with a new co-morbidity overall at T5. Treatment with biologics (p < 0.05) reduced the risk. In multiple logistic regression modelling, ESR (p = 0.036) at inclusion was associated with a new co-morbidity after 5 years, adjusted for age, sex, smoking and GC treatment. In a similar model, Ex-RA (p < 0.05) was associated with a new co-morbidity at T5. In a third model, adjusted for age and sex, a new pulmonary co-morbidity was associated with a smoking history at inclusion (p < 0.01), but not with ESR.ConclusionThere was substantial co-morbidity among early RA patients already at disease onset, with considerable new co-morbidity being added during the first five years. Measures of disease activity were associated with the occurrence of a new co-morbidity indicating that the inflammation is of importance in this context.

Cerebral vasculitis as a major manifestation of rheumatoid arthritis

Objective and Importance:Cerebral vasculitis (CV) is a rare described complication of rheumatoid arthritis (RA). Although the most frequent neurological manifestations of RA are peripheral neuropathy and cervical spinal cord compression due to subluxation of the cervical vertebrae, CV can be seen especially in patients with seropositive and long-standing RA.Clinical presentation: We report two cases of CV associated with RA. Both patients had no extraarticular manifestations and RA clinics were under control. Our first case is a 30-years-old woman with seropositive RA for 15 years who had suddenly onset left facial and upper extremity weakness. In magnetic resonance imaging (MRI) DWI, hyperintensity in frontotemporal region due to acute ischaemia was detected. The new lacuner acute ischaemic lesions in right precentral gyrus, bilateral frontoparietal and corpus callosal region were detected in the control MRI. The cerebral MR angiography and transcranial doppler findings were consistent with CV. The patient responded favourably to pulse methylprednisolone and oral azathiopurine treatments. The second patient is a 52-year-old man who had been RA for 29 years. He admitted to our neurology clinic with speech difficulty and right upper extremity minimal weakness. Magnetic resonance imaging DWI showed left parietooccipital acute ischaemia which was progressed within a week and a new right parietooccipital ischaemia was added. His cerebral MR angiography and cerebral angiography were concordant with CV. The cyclophosphamide therapy was started since the cerebral ischaemia was progressed during pulse methylprednisolone and he responded well to this therapy.Conclusion: CV due to RA is an uncommon serious complication which can be life-threatening. Therefore clinicians should be aware of the possibility of CV especially in progressive strokes in RA.

FRI0069 Comorbidity in Early Rheumatoid Arthritis - Which is the Role of Inflammation?

BackgroundPatients with rheumatoid arthritis (RA) suffer from comorbidities that contribute to a shortened lifespan. Inflammation is of importance for the development of cardiovascular disease, but little is known on its...

THU0120 Is Early DMARD Use Associated with Less Joint Replacement Surgery? an Analysis of 5,199 Incident Rheumatoid Arthritis (RA) Patients

BackgroundEarly DMARD use in RA may prevent damage and possibly, need for joint replacement.ObjectivesTo assess joint replacements within incident RA patients in Quebec, Canada, and potential associations with early DMARD...

COMP-C3b Complexes in Rheumatoid Arthritis with Severe Extraarticular Manifestations

To investigate biomarker patterns in rheumatoid arthritis (RA) with extraarticular manifestations. Cartilage oligomeric matrix protein (COMP), COMP-C3b, and soluble terminal complement complexes (sTCC) were measured by ELISA. COMP-C3b levels were higher in patients with RA than in healthy controls and lower in extraarticular RA (ExRA) than in RA controls. In patients with ExRA, sTCC levels were higher than in RA controls, and correlated inversely with serum COMP-C3b levels in the ExRA group. Patients with ExRA had lower levels of COMP-C3b. This may be a consequence of complement consumption or a lower potential for COMP from these patients to activate complement.

THU0048 Radius 1: Correlation between serious infection events (SIES) and rheumatoid arthritis (RA) disease activity in patients requiring a change in therapy

BackgroundThe RA Disease-Modifying Anti-Rheumatic Drug (DMARD) Intervention and Utilization Study–1 (RADIUS 1) was a real-world, prospective, 5-year, observational study of 4968 patients (aged ≥18 y) with RA (per 1987 American...

AB0217 Relationship between anti-ccp positivity, results of pulmonary function tests and high resolution computed tomography of the lung in patients with rheumatoid arthritis

BackgroundInterstitial lung disease (ILD) represents a severe manifestation in connective tissue diseases, and is it still a challenge for clinicians evaluation and management. ILD is the most common manifestations of...

Extra-articular rheumatoid arthritis

To discuss recent findings on the epidemiology and pathogenesis of extra-articular manifestations in rheumatoid arthritis (RA), and provide an update on the literature on treatment of patients with extra-articular RA (ExRA) manifestations. ExRA is associated with increased comorbidity and mortality. Several surveys suggest that some ExRA manifestations, in particular vasculitis, occur less frequently than previously reported. This is probably due to improved overall control of disease activity. Active RA with high disease activity is associated with increased risk of severe ExRA manifestations. Studies on the impact of treatment with biologics on the occurrence of ExRA are inconclusive. Circulating immune complexes and T cells have been implicated in the pathogenesis of ExRA. The genetic background and related disease mechanisms may be somewhat different in manifestations such as vasculitis and interstitial lung disease. Limited data support a benefit from treatment with cyclophosphamide, TNF-inhibitors or rituximab in patients with severe ExRA. ExRA remains a major diagnostic and therapeutic challenge in some patients. Further studies of the pathogenesis of systemic involvement and on the effect of treatment on such mechanisms may be helpful for further improvement of the management of RA.

Extra-articular manifestations in a community-based sample of patients with rheumatoid arthritis: incidence and relationship to treatment with TNF inhibitors

Objectives: To determine the incidence of severe extra-articular rheumatoid arthritis (ExRA) in a community-based cohort of RA patients, and to evaluate whether treatment with tumour necrosis factor (TNF) inhibitors has any effect on the risk of ExRA.Methods: In a review of clinical records from 1 July 1997 to 31 December 2004, severe ExRA manifestations were classified according to predefined criteria. Patients were censored at the development of ExRA, death, emigration, or 31 December 2004. Exposure to anti-TNF treatment has continuously and independently been recorded as part of a regional follow-up system.Results: During treatment with TNF inhibitors, there were two patients with new onset of ExRA in 408 person-years at risk (pyr) [0.49/100 pyr, 95% confidence interval (CI) 0.06–1.77]. Among those without anti-TNF treatment there were 63 patients with ExRA in 5425 pyr (1.16/100 pyr, 95% CI 0.89–1.49). The relative risk comparing those treated to those not treated with TNF inhibitors was 0.42 (95% CI 0.10–1.73).Conclusion: Our data show a lower incidence of ExRA in patients treated with TNF inhibitors but further studies with a larger sample size are needed for a more accurate estimate of the size of the effect.

Incidence of Extraarticular Rheumatoid Arthritis in Olmsted County, Minnesota, in 1995–2007 Versus 1985–1994: A Population-based Study

To assess incidence and mortality effects of extraarticular rheumatoid arthritis (ExRA) in patients with incident RA in 1995-2007 compared to 1985-1994, in Olmsted County, Minnesota, USA. Data on incident ExRA were abstracted from medical records of patients with RA - Olmsted County residents who first met the 1987 American College of Rheumatology criteria for RA between January 1, 1995, and December 31, 2007. Patients were followed until death, migration from Olmsted County, or December 31, 2008. ExRA were classified using the predefined criteria and compared to the corresponding 1985-1994 inception RA cohort (n = 147). The 1995-2007 cohort included 463 patients with RA followed for a mean of 6.3 years; mean age was 55.6 years, 69% were women, 67% were positive for rheumatoid factor (RF). The 10-year cumulative incidence of any ExRA (50.1%) and severe ExRA (6.7%) in the 1995-2007 cohort was similar to the 1985-1994 cohort (46.2% and 9.7%, respectively). The 10-year cumulative incidence of vasculitis, but not other features of ExRA, was significantly lower in the 1995-2007 cohort (0.6%) compared to the 1985-1994 cohort (3.6%). RF positivity, erosions/destructive changes, and use of methotrexate, other disease-modifying antirheumatic drugs and systemic corticosteroids were significantly associated with ExRA in the 1995-2007 cohort. ExRA was associated with mortality risk (HR 2.1, 95% CI 1.2, 3.7) in the 1995-2007 cohort. The decrease in mortality following ExRA in the 1995-2007 cohort versus the 1985-1994 cohort did not reach statistical significance (HR 0.6, 95% CI 0.3, 1.2, p = 0.16). ExRA remains a common complication associated with increased mortality in RA. The occurrence of vasculitis appears to be decreasing in recent years.

Cardiovascular disease is associated with extra-articular manifestations in patients with rheumatoid arthritis

The objective of this study was to examine the clinical and genetic variables associated with extra-articular rheumatoid arthritis (ExRA). This was a cross-sectional study in which 538 Northwestern Colombian patients with rheumatoid arthritis (RA) were included. Information about demographics and clinical characteristics including disease activity, inflammatory markers, co-morbidities, cardiovascular (CV) risk factors, history of familial autoimmunity and therapy was recorded. The presence of HLA "shared epitope" (SE) alleles and TNF gene polymorphism was assessed. A multivariate statistical analysis was performed. ExRA was found in 32% of the patients, of which nodulosis, Sjögren's syndrome, and lung involvement were registered in 21%, 9%, and 4% of patients, respectively. Patients with ExRA were older than patients without it and they presented longer disease duration as well. Thus, an association between disease duration and ExRA manifestations was also observed. Patients with ExRA presented significant higher titers of anti-CCP antibodies as compared to patients without ExRA. Hypertension and thrombosis were significantly associated with ExRA. Never having smoked constituted a protective factor against ExRA onset. Associations between ExRA and the presence of traditional CV risk factors were also found. Our results show that duration of RA, CV disease and high titers of anti-CCP antibodies are associated with ExRA in Colombian patients with RA, and highlight the importance of preventing smoking in those who are prone to develop autoimmune diseases including RA.

Patterns of psychosocial risk and long-term outcomes in rheumatoid arthritis

This study examined the extent to which patterns of psychosocial risk were uniquely associated with long-term outcomes of rheumatoid arthritis (RA), after demographic factors and self-reported symptom severity over time were accounted for. Data were collected over an 8‐year period from 561 individuals with RA who were participants in the ongoing UCSF RA Panel Study in 1995. Panel members were interviewed annually, using a comprehensive structured telephone interview. Psychosocial factors assessed included mastery, perceptions about adequacy of social support, the impact of RA and self-assessed ability to cope with RA and satisfaction with health and function. Cluster analysis of psychosocial factors identified three distinctive patterns/levels of psychosocial risk (high, medium and low risk). The unique effects of psychosocial risk status on changes in depressive symptoms, basic functional limitations, global pain ratings and average annual doctor visits over an 8‐year period were estimated, using growth curve analyses. Analyses controlled for demographic factors (gender, marital/partner status, education, age and ethnicity), disease duration and year in the panel and time-varying self-reported symptom severity (morning stiffness, swollen joint counts, co-morbid medical conditions, extra-articular RA symptoms and changes in joint appearance), as well as self-reported medications taken over time (disease-modifying antirheumatic drugs [DMARDS], and prednisone). Overall, 32.4% of total variance in depressive symptoms was accounted for by the fully-estimated model, with 12.9% uniquely associated with psychosocial risk status. Half of the total variance (50.0%) in basic functional limitations was explained, with 12.1% of variance uniquely predicted by psychosocial risk status. Psychosocial risk status accounted for comparatively little total explained variance in global pain ratings (total = 38.6%, incremental = 3.2%), and average annual total doctor visits (total = 10.9%, incremental = 1.5%). Thus, psychosocial risk factors are more closely linked to depressive symptoms and function over time. Global pain and utilization appear to be more closely related to disease factors.