Extra-articular Manifestation Of Rheumatoid Arthritis Research Articles

Epicardial Fat Thickness: A Cardiometabolic Risk Marker in Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder of unknown etiology which mainly involves synovial joints. However, the corresponding systemic inflammation may result in disorders of multiple other organ systems. Several organs and organ systems are potentially involved in RA, particularly in severe diseases. The organs most involved are the lung, heart, eyes, and nervous system. Extra-articular manifestations of RA may develop even before the onset of arthritis. Emerging epidemiological evidence shows that cardiovascular disease (CVD) accounts for near about 50% of RA-associated death. Epicardial fat thickness (EFT) has recently emerged as a new marker of cardiometabolic risk. Although Epicardial fat (EF) is needed for heart muscle function, given its intrinsic inflammatory status, EFT displays the potential to serve as a therapeutic target in patients with RA.Objectives: To evaluate EFT using echocardiography in RA patients compared to age and sex-matched control and to find the factors associated with EFT in RA patients.Materials and methods: This current study was conducted in the Department of Medicine, Postgraduate Institute of Medical Education & Research. The study was conducted from November 2016 to March 2018. Patients with BMI ≥ 30 kg/m2, diabetes mellitus, primary hyperlipidemia, and uncontrolled hypertension were particularly excluded. Thirty patients of age and sex-matched controls were also taken for the study. All the patients and controls selected for the study were subjected to detailed history taking and clinical examination. They were subjected to lab investigations and echocardiography. The 30 RA patients included in the study were diagnosed according to the 2010 ACR-EULAR criteria. Disease activity was measured by the disease activity score (DAS28) index.Results: Group 1 included 30 patients with RA and group 2 included 30 age and sex-matched controls. Pearson correlation analysis was done between EFT and other variables. Only HDL, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hS-CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), DAS28, and disease duration were found to have a significant correlation with EFT.Conclusion: In patients with RA, EFT, left ventricular mass, and diastolic dysfunction are increased in RA patients compared to healthy controls. Out of the conventional CVD risk factors, only HDL was associated with increased EFT in RA patients. In RA patients, DAS28, disease duration, RF, anti-CCP, and markers of inflammation (ESR, hs-CRP) were also associated with increased EFT.

Airway Disease in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common condition affecting approximately 1% of the general population. RA is a multisystem disorder that causes progressive articular destruction through synovial inflammation. One of the most common extraarticular manifestations of RA is pulmonary involvement, where all compartments of the pulmonary system can be impacted (e.g., pulmonary vasculature, pleura, parenchyma, and the airways). Although it has been known for decades that a portion of patients with RA develop interstitial lung disease, and recent advancements in understanding the genetic risk and treatment for RA-interstitial lung disease have drawn attention, more recent data have begun to highlight the significance of airway disease in patients with RA. Yet, little is known about the underlying pathogenesis, clinical impact, or optimal treatment strategies for airway disease in RA. This review will focus on airway disease involvement in patients with RA by highlighting areas of clinical inquiry for pulmonologists and rheumatologists and discuss areas for future research. Finally, we discuss a potential screening algorithm for providers when approaching patients with RA with respiratory complaints.

Screening for preclinical parenchymal lung disease in rheumatoid arthritis.

Pulmonary disease is a common extraarticular manifestation of RA associated with increased morbidity and mortality. No current strategies exist for screening this at-risk population for parenchymal lung disease, including emphysema and interstitial lung disease (ILD). RA patients without a diagnosis of ILD or chronic obstructive pulmonary disease underwent prospective and comprehensive clinical, laboratory, functional and radiological evaluations. High resolution CT (HRCT) scans were scored for preclinical emphysema and preclinical ILD and evaluated for other abnormalities. Pulmonary imaging and/or functional abnormalities were identified in 78 (74%) of 106 subjects; 45% had preclinical parenchymal lung disease. These individuals were older with lower diffusion capacity but had similar smoking histories compared with no disease. Preclinical emphysema (36%), the most commonly detected abnormality, was associated with older age, higher anti-cyclic citrullinated peptide antibody titres and diffusion abnormalities. A significant proportion of preclinical emphysema occurred among never smokers (47%) with a predominantly panlobular pattern. Preclinical ILD (15%) was not associated with clinical, laboratory or functional measures. We identified a high prevalence of undiagnosed preclinical parenchymal lung disease in RA driven primarily by isolated emphysema, suggesting that it may be a prevalent and previously unrecognized pulmonary manifestation of RA, even among never smokers. As clinical, laboratory and functional evaluations did not adequately identify preclinical parenchymal abnormalities, HRCT may be the most effective screening modality currently available for patients with RA.

Rheumatoid Meningitis as an Extra-articular Manifestation of Rheumatoid Arthritis.

Rheumatoid Meningitis as an Extra-articular Manifestation of Rheumatoid Arthritis.

MicroRNA146a gene polymorphism in patients with rheumatoid arthritis and the relevant value with disease activity and extra-articular manifestations

Aim of the workTo analyze the relationship between miRNA-146a rs2910164 and rheumatoid arthritis (RA) susceptibility and clarifying its association with disease activity and extra-articular involvement. Patients and methodsThe study enrolled 50 RA patients and 40 controls. DNA extraction from whole blood was done. Genotyping was performed by real-time polymerase chain reaction. The selected single nucleotide polymorphism was rs2910164 in the miRNA-146a gene. Genotyping was performed on genomic DNA samples by allelic discrimination assay. Disease activity score (DAS28) and health assessment questionnaire-disability index (HAQ-DI) were assessed. ResultsThe mean age of patients was 44.8 ± 9.9 years while age at onset was 37.2 ± 9.8 years. Female:male was 5.3 vs 1. Females had significantly higher DAS28, visual analogue scale and rheumatoid factor (RF) than males (p = 0.04, p = 0.009, p = 0.03). The frequency of GC genotype was more in both males and females (62.5 vs 47.6%). GC genotype and G allele were the most frequent in patients. No significant difference in the frequency distribution of genotypes and alleles was observed between patients and controls. There was a significant difference in the number of swollen joints (p = 0.04) and sicca symptoms (p = 0.01) being higher in those with CC genotype with a tendency of increased DAS28, HAQ-DI, deformities and rheumatoid nodules with CC genotype and interstitial pulmonary fibrosis and RF with GG genotype. ConclusionsCC genotype was associated with sicca symptoms and swollen joints, deformities, disease activity and functional disability. miRNA-146a may be a potential biomarker for extra-articular manifestations of RA that need more attention and warrant aggressive therapy.

INTERSTITIAL LUNG DISEASE AS THE ONLY MANIFESTATION OF RHEUMATOID ARTHRITIS: CAN LUNGS BE THE SITE OF ORIGIN FOR RHEUMATOID ARTHRITIS-RELATED INFLAMMATION?

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Rheumatoid Arthritis (RA) is a systemic inflammatory disease primarily involving joints. Extra-articular manifestations of RA without joint disease are extremely rare. Lung disease represents a second common cause of death in RA after cardiovascular events (1). RA related lung disease includes interstitial lung disease (ILD), bronchiectasis and pleural disease. We report a patient with severe progressive RA related ILD, usual interstitial pneumonia (UIP) phenotype without joint involvement and poor outcome. CASE PRESENTATION: A 67-year-old female with one-year history of seropositive rheumatoid arthritis without joint involvement, on methotrexate presented with worsening shortness of breath. The exertional dyspnea started two years ago, and a screening low dose CT chest showed mild fibrotic changes at lung bases prior to methotrexate initiation. This time HRCT revealed progressive interstitial lung disease-usual interstitial pneumonia pattern, bilateral honeycombing of the lung bases and traction bronchiectasis. Pulmonary function test revealed restrictive ventilatory and severe gas transfer defect. Rheumatoid factor (RF) and Cyclic Citrullinated Peptide antibody (IgG) were 99.6 and above 250 respectively. ANA titer was low at 1:40, speckled pattern with normal ANCA. Methotrexate was discontinued and prednisone was started. She was discharged home on oxygen therapy but continued to decompensate with progressive hypoxemic respiratory failure eventually requiring high flow nasal canula. Repeat HRCT showed new ground glass opacities on left along with baseline interstitial changes. Flexible bronchoscopy with bronchoalveolar lavage showed no evidence of infection or malignancy. Patient was started on pulse dose steroids for possible ILD flare. However, her oxygen requirement and symptoms continued to worsen, and she was started on Mycophenolate Mofetil. With no improvement patient eventually opted for home hospice. DISCUSSION: Risk factors associated with RA-related ILD include older age, male sex, smoking and seropositivity for RF or anti-CCP antibodies. In addition, women with seropositive RA have increased risk of lung involvement than women without RA (2). Our patient presented with rapidly progressive ILD-UIP type without any joint disease and poor outcome. Methotrexate was less likely a culprit given the interstitial fibrotic changes present before drug initiation and rapid progression of ILD despite drug cessation. In our case lungs seem to be the primary site of RA related inflammation in setting of smoking causing citrullination of proteins and autoimmune responses (2). CONCLUSIONS: Although data on identification, management staging or monitoring of RA-related ILD without joint disease is lacking, clinicians should remain vigilant of this complication. RA-related UIP is more frequent with progressive disease and poor outcome and warrants early recognition and treatment (3). REFERENCE #1: G. Cafaro, A. Alunno, V. Valentini, M.C. Leone, E. Marcucci, E. Bartoloni, R. Gerli. The onset of rheumatoid arthritis: the joints or the lung? Reumatismo, 2016; 68 (4): 167-175 REFERENCE #2: Paolo Spagnolo, Joyce S. Lee, Nicola Sverzellati, Giulio Rossi, Vincent Cottin. The lung in Rheumatoid Arthritis. Focus on Interstitial Lung Disease. ARTHRITIS & RHEUMATOLOGY Vol. 70, No. 10, October 2018, pp 1544-1554 DOI 10.1002/art.40574 American College of Rheumatology REFERENCE #3: Hyun-Kyung Lee, MD; Dong Soon Kim, MD; Bin Yoo, MD; Joon Beom Seo, MD; Jae-Yoon Rho, MD; Thomas V. Colby, MD; Masanori Kitaichi, MD. Histopathologic Pattern and Clinical Features of Rheumatoid Arthritis-Associated Interstitial Lung Disease (CHEST 2005; 127:2019-2027) DISCLOSURES: No relevant relationships by Maria Azhar, source=Web Response No relevant relationships by Fatima Halilu, source=Web Response No relevant relationships by Qasim Muhammad, source=Web Response No relevant relationships by Matthew Woodford, source=Web Response

CT Pulmonary Manifestations in Patients with Rheumatoid Arthritis: Visual scoring versus pulmonary function

Abstract Background Pulmonary involvement is the most common extra-articular manifestation of Rheumatoid arthritis. Aim of the Work To highlight the role of HRCT in detection and characterization of variable pulmonary manifestations that can be encountered in patients with Rheumatoid Arthritis trying to correlate the CT pulmonary manifestations with pulmonary functions using CT scoring system. Patients and Methods This was a retrospective study that included 32 patients who were diagnosed to have Rheumatoid Arthritis either outpatients or referred from the Rheumatology Department at Ain Shams University Hospitals to the Radiodiagnosis Department for HRCT chest examination. An acceptance from the ethical committee of Faculty of Medicine - Ain Shams University was obtained to use the data stored on PACs system with the patient’s consent was waived being a retrospective study. All patients underwent HRCT image analysis regarding the CT features and CT score for disease severity. Also, all patients did spirometery for pulmonary function assessment. Results Analyzing the data showed a female sex predominance (90.6%). 87% of the patients were diagnosed to have RA for more than 2 years duration. The most common respiratory symptom was dyspnea and the restrictive pattern was the commonest PFT finding. Ground glass pattern was the most common 78.1% followed by reticular pattern which was seen in 68.8% of patients. PFT and HRCT showed a positive correlation regarding the severity. Conclusion HRCT is a modality of choice for detection of pulmonary manifestation of rheumatoid arthritis patients with CT scoring can be used to assess the severity of disease and degree of lung involvement which is correlated with pulmonary function test.

SPECTRUM OF RHEUMATOID ARTHRITIS PATIENTS PRESENTING TO A TERTIARY CARE HOSPITAL IN PAKISTAN

Objective: To describe the demographic, clinical, serological and radiological scores in patients with rheumatoid arthritis (RA) presenting in a tertiary hospital in Pakistan.
 Study Design: Cross sectional study.
 Place and Duration of Study: Department of Rheumatology, Fauji Foundation Hospital (FFH), Rawalpindi, from Sep 2018 to Feb 2019.
 Methodology: The study included 52 female patients with RA between the ages of 18 and 80 years. Data were obtained from FFH Rawalpindi's outpatient department. Demographic details, reference data, and serological status were recorded. The joints involved in the onset of the disease, joint deformities, clinical disease activity index (CDAI) and overall functional status were evaluated. Extra-articular manifestations of rheumatoid arthritis have also been examined during a detailed physical examination. The patient's bone mineral density was calculated by the use of dual energy absorptiometry (DEXA scan). Radiological scores were evaluated using modified sharp score.
 Results: Mean age of the patient was 55.08 ± 8.79 and mean duration of disease 9 .73 ± 7.54. The most common co-morbidity in rheumatoid arthritis patients was hypertension 20 (38.5%). Twenty four (11.7%) patients had osteoporosis. Wrist was the first joint involved in 17 (32.7%) patients. Ulnar deviation was the most common deformity in 12 (23.1%) patients. Sharp score for joint space narrowing was 61.09 ± 36.90 and sharp score joint erosions were 36.90 ± 42.41. Most common extra articular manifestation was anemia.
 Conclusion: Rheumatoid arthritis as a variable spectrum of disease with different manifestations. Patients had radiological damage as demonstrated by high sharp score even before starting.................

Rheumatoid arthritis-interstitial lung disease: manifestations and current concepts in pathogenesis and management.

Rheumatoid arthritis (RA) is a systemic inflammatory disorder, with the most common extra-articular manifestation of RA being lung involvement. While essentially any of the lung compartments can be affected and manifest as interstitial lung disease (ILD), pleural effusion, cricoarytenoiditis, constrictive or follicular bronchiolitis, bronchiectasis, pulmonary vasculitis, and pulmonary hypertension, RA-ILD is a leading cause of death in patients with RA and is associated with significant morbidity and mortality. In this review, we focus on the common pulmonary manifestations of RA, RA-ILD and airway disease, and discuss evolving concepts in the pathogenesis of RA-associated pulmonary fibrosis, as well as therapeutic strategies, and have revised our previous review on the topic. A rational clinical approach for the diagnosis and management of RA-ILD, as well as an approach to patients with clinical worsening in the setting of treatment with disease-modifying agents, is included. Future directions for research and areas of unmet need in the realm of RA-associated lung disease are raised.

MRI brain findings in Rheumatoid Arthritis: a review of the literature

Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder that
 mainly attacks the joints and leads to early disability. Despite aggressive anti-inflammatory therapy, the risk of systemic complications remains high. Moreover, the rate of premature cardiovascular disease mortality in patients with active RA, as well as the risk for development of non-fatal cardiovascular and cerebrovascular complications is also high.
 Central nervous system (CNS) involvement is one of the main components of extra-articular manifestations of RA. Brain changes might be caused by systemic inflammatory response or by the drugs used for treatment.
 Assessment of brain involvement and its relationship to the characteristics of the disease in patients with RA are particularly useful. Early detection of changes without cerebral symptoms and rapid response in acute events are of particular importance.
 With the increasing use of more imaging modalities magnetic resonance imaging (MRI) has become highly specific, safe and non-invasive diagnostic tool for early detection and monitoring of different pathological processes involving the brain in patients with RA.
 Understanding MRI imaging findings in brain involvement is important for selecting appropriate treatment and control of disease progression.
 The aim of this review is to summarize literature data of brain changes in RA and their relationship with systemic inflammation as well as to demonstrate the role of MRI in their assessment.
 

POS0564 THE EFFECT OF ARTHRITIS TREATMENT ON THE COURSE OF RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE FOCUSING ON BIOLOGIC DMARDS: FROM A PROSPECTIVE COHORT STUDY (PART 5)

Background:Interstitial lung disease (ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). However, the effect of RA treatment on the course of ILD is not yet known.Objectives:To assess the effect of RA treatment on the course of lung physiology of RA-focusing on biologic DMARDs treatment.Methods:The Korean Rheumatoid Arthritis ILd (KORAIL) cohort is the prospective observational cohort and aims to investigate the natural course of RAILD. Based on either 1987 or 2020 ACR criteria, patients diagnosed with RA and ILD based on CT scan were recruited from six tertiary medical hospitals in Korea since January 2015. RA disease activity was assessed using disease activity (DAS)28-ESR and CRP, annually. Pulmonary function tests (PFT), including FVC and DLCO were conducted annually. In the current study, we analyzed patients who completed a 2-years follow-up or had died during those terms till October 2020. They classified patients into three groups: patients treated with abatacept ≥24 weeks ever (Group 1), those with other bDAMRDs ≥24 weeks ever (Group 2), and those without any bDMARDs or with bDMARDs <24 weeks (Group 3).Results:Of a total of 125 patients who completed 2-year follow-up, 21 patients were classified as Group 1, 26 for Group 2, and 78 for Group 3. The mean age or the number of patients with ≥ 65-year-old was comparable between groups(Table 1). The mean duration since RA diagnosis was shorter in Group 3, but that since ILD diagnosis was comparable. DAS28-ESR score was comparable between Group 1 and 2 at enrollment, so was in 1-year-follow-up (p=0.75) and 2-year-follow-up (p=1.00). FVC and % of the predicted value in FVC, FEV1, and DLco were also comparable among the three groups at enrollment. The numbers of patients with ≥10-point decline in % of FVC predicted was 2 (10.0%) for Group 1, 1 (3.8%) for Group 2, 3 (3.9%) for Group3 during the first 1-year follow-up, and 3 (15.8%), 3 (11.5%), 10 (14.1%) during the last 1-year follow up. The percent of FVC predicted was 81.6 ± 17.5 %, 87.4 ± 17.9 %, 85.2 ± 17.7 % for Group 1,2 and 3, respectively, at 1-year-follow-up, and 79.5 ± 18.8 %, 89.0 ± 16.8 %, 83.5 ± 17.3 % at 2-year-follow-up. (Figure 1A). The percent of DLco predicted was 75.5 ± 23.4 %, 66.7 ± 18.1 %, 67.5 ± 16.7 % for Group 1,2 and 3, respectively, at 1-year-follow-up, and 74.0 ± 23.7 %, 69.1 ± 18.9 %, 67.0 ± 18.5 % at 1-year-follow-up (Figure 1B).Conclusion:Treatment of bDMARDs did not exacerbate FVC than without bDMARDs treatment and mitigated the decline of DLCO compared to without bDMARDs treatment during 2-year-follow-up.Table 1.Clinical characteristics at enrollment (V1)TotalGroup 1.Group 2.Group 3.PN125212678Age at enrollment65.9±8.266.0±8.863.9±8.066.6±8.10.3465, n (%)72 (57.6)13 (61.9)11 (42.3)48 (61.5)0.21Female, n (%)89 (71.2)16 (76.2)17 (65.4)56 (71.8)0.71RA duration, years8.0±8.49.6±6.69.2±9.07.2±8.60.05ILD duration, years3.0±3.33.8±3.73.8±3.52.5±3.10.10BMI, kg/m224.1±3.123.8±3.724.8±2.923.9±3.00.39Ever-smoker1855180.57RF positive, n (%)111 (88.8)19 (90.5)22 (84.6)70 (89.7)0.72Anti-CCP positive, n (%)119 (95.2)20 (95.2)25 (96.2)74 (94.9)1.00Arthritis activityDAS28-ESR4.0 ± 1.44.1 ± 1.14.3 ± 1.83.8 ± 1.40.60*DAS28-CRP3.1 ± 1.43.2 ± 1.23.4 ± 1.63.0 ± 1.40.76*HAQ-DI0.70 ± 0.760.64 ± 0.490.82 ± 0.820.67 ± 0.800.28*Pulmonary function testFVC, ml2522.5 ± 765.42406.2 ± 772.62617.3 ± 965.22522.2 ± 692.30.65FVC, % of pred.84.6 ± 16.980.9 ± 17.786.12 ± 17.8285.08 ± 16.50.53FEV1, % of pred.92.4 ± 21.492.0 ± 24.890.6 ± 22.193.0 ± 20.40.88DLco, % of pred.71.5 ± 19.772.3 ± 26.769.1 ± 16.472.0 ± 18.70.80Figure 1.Acknowledgements:This research was supported by Bristol Myers Squibb Inc.Disclosure of Interests:Sung Hae Chang: None declared, Ji Sung Lee: None declared, Jeong Seok Lee: None declared, Chan Ho Park: None declared, Min Uk Kim: None declared, You-Jung Ha: None declared, Eun Ha Kang: None declared, Yeon Ah Lee: None declared, Yongbeom Park: None declared, Jung-Yoon Choe: None declared, Eun Young Lee Grant/research support from: Bristol Myers Squibb Inc.

POS0095 DEVELOPPING A SCORE TO PREDICT PRECLINICAL INTERSTITIAL LUNG DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS – A CROSS-SECTIONAL STUDY FROM THE ESPOIR COHORT

Background:Interstitial lung disease (ILD) is an extra-articular manifestation of rheumatoid arthritis (RA) detected in 20% to 60% of patients with RA on high-resolution computed-tomography (HRCT) chest scan and is clinically significant in near 10%. Despite a high morbi-mortality rate, a definite strategy for preclinical ILD screening in patients with RA remains to be determined. To date, several factors have been reported to increase the risk of RA-ILD occurrence (i.e. older age at RA onset, ACPA positivity, male sex, RA disease activity, the MUC5B rs35705950 promoter variant...). However, none of these risk factors has been validated in a prospective cohort of patients with RA. The ESPOIR prospective cohort includes patients aged 18 to 70 years with recent arthritis (less than 6 months) and a definite or probable diagnosis of RA.Objectives:To identify in the ESPOIR cohort factors associated with ILD after at least 10 years of RA duration in order to develop a predictive score to identify patients with preclinical RA-ILD.Methods:An ILD detection by chest HRCT scan was systematically offered to every patient with definite RA after at least 10 years-follow-up. Chest HRCT scans were centrally reviewed by an experienced radiologist. Potential predictors of ILD were prospectively collected from baseline to the date of the HRCT scan, and all included patients were genotyped for MUC5B rs35705950. To take into account repeated measures, trajectories were determined for disease activity, C reactive protein, smoking, treatment exposure (i.e. prednisone, methotrexate [MTX] and biological disease modifying anti-rheumatic drugs [bDMARDs]). A logistic model was used to identify independent predictors for the occurrence of ILD on HRCT scans. Confidence intervals were estimated using sampling methods. A predictive score for preclinical ILD occurrence was developed based on the identified predictors.Results:163 RA patients according to 2010 ACR/EULAR classification criteria, none of whom had pulmonary symptoms, were investigated with a chest HRCT scan (128 women (78.5%), mean RA duration 13.7 ± 1.1 years, age at inclusion 47.6 y/o ± 10.4, mean disease activity score [DAS]-28 during follow up was 3.1 ± 1.0). ILD was detected in 31 patients (19.0%). The MUC5B rs35705950 minor allele frequency (MAF) was 22.2% and 10.0% in the RA-ILD and RA-noILD populations, respectively (OR univariate=2.6 CI95% [1.2-5.5], P=0.01). After logistic regression, independent predictors for preclinical RA-ILD were male sex (OR=3.9 CI95% [1.4-11.4]), older age at RA onset (OR=1.1 per year CI95% [1.0-1.2]), mean DAS-28 score during the follow-up (OR=2.0 CI95% [1.2-3.4]) and MUC5B rs35705950 T risk allele (OR=3.7 CI95% [1.4-10.4]) (Figure 1). No influence of the use of RA-related drugs (prednisone, MTX or bDMARDs) was identified as risk factor. The logistic model could predict preclinical ILD occurrence after 13 years of RA duration with an AUC=0.82 CI95% (0.72-0.91). A predictive score for preclinical RA-ILD based on the 4 identified predictive risk factors was developed (Sensitivity 80%, Specificity 56%).Figure 1.Factors independently associated with preclinical ILD after 13 years of RA durationConclusion:In this cross-sectional study of the prospective ESPOIR cohort, we identified clinical and genetic predictors for ILD after 13 years of RA duration. We developed a predictive score that could improve risk stratification for preclinical RA-ILD and help physicians identify patients with RA in whom a HRCT scan should be performed.Disclosure of Interests:Pierre-Antoine Juge Consultant of: BMS, Benjamin Granger: None declared, Marie-Pierre Debray: None declared, Esther Ebstein: None declared, Fabienne Louis Sidney: None declared, Joanna KEDRA: None declared, Raphael Borie: None declared, Arnaud Constantin Consultant of: Bristol-Meyers Squibb, Chugai, Roche, Abbvie, MSD, Pfizer, and UCB, Bernard Combe Consultant of: Abbvie, Bristol-Meyers Squibb, Lilly, MSD, Janssen, Pfizer, Roche, Chigai, and Sanofi, Grant/research support from: Abbvie, Bristol-Meyers Squibb, Lilly, MSD, Janssen, Pfizer, Roche, Chugai, and Sanofi, René-Marc Flipo Consultant of: Bristol-Meyers Squibb, Roche, Chugai, Abbvie, and Pfizer, Grant/research support from: Roche, Chugai, Abbvie, and Pfizer, Xavier Mariette Consultant of: Bristol-Meyers Squibb, GSK, Janssen, Pfizer, and UCB, Olivier VITTECOQ Consultant of: Bristol Myers Squibb, Roche, Chugai, MSD, Novartis, Pfizer, Abbvie, and Lilly, Alain Saraux Consultant of: Roche, Chugai, and Bristol-Meyers Squibb, Grant/research support from: Roche, Chugai, and Bristol-Meyers Squibb, Guillermo CARVAJAL ALEGRIA: None declared, Jean Sibilia Consultant of: Roche, Chugai, Bristol-Meyers Squibb, UCB, GSK, LFB, Actelion, Pfizer, MSD, Novartis, Amgen, Hospira, AbbVie, Sandoz, Gilead, Lilly, Sanofi, Janssen, and Mylan, Francis Berenbaum Consultant of: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Elli Lilly, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma, Caroline Kannengiesser: None declared, Catherine Boileau: None declared, Bruno Crestani Consultant of: Boehringer Ingelheim, Roche, Sanofi, Apellis, Astra-Zeneca, Grant/research support from: MedImmune, Boehringer Ingelheim, Bruno Fautrel Consultant of: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, SOBI, UCB, Grant/research support from: AbbVie, MSD, Pfizer, Philippe Dieudé: None declared

OP0099 EPIDEMIOLOGY AND MORTALITY OF RA-ASSOCIATED INTERSTITIAL LUNG DISEASE: DATA FROM A FRENCH ADMINISTRATIVE HEALTHCARE DATABASE

Background:Interstitial lung disease (ILD) is a common extra-articular manifestation of RA and is associated with increased morbidity and mortality.1-3 Studies have shown variability in the prevalence and mortality rate of patients with RA-associated ILD (RA-ILD).4 Further studies are needed to better characterise the epidemiology of RA-ILD.Objectives:To estimate the prevalence and incidence of clinical RA-ILD in France and to compare mortality rates between patients with RA-ILD and patients with RA without clinical ILD (RA-noILD).Methods:A historical cohort study was conducted using data from the French national claims database (SNDS) between 1 January 2013 and 31 December 2018. Adults with an RA diagnosis (International Classification of Diseases, Tenth revision [ICD-10] codes M05, M06.0, M06.8 and M06.9) and ≥2 distinct dates of DMARD delivery were included. Onset of RA was defined as the first date of occurrence between RA codes and the first known DMARD reimbursement. ILD diagnosis was defined as having ICD-10 code J84 and ≥1 computed tomography scan after, but within 1 year of, the first date of ILD occurrence. All patients had ≥6 months’ reimbursement after RA-ILD onset. The prevalence and incidence (2014–2018) of RA-ILD were estimated. The mortality rate was calculated, comparing patients with RA-ILD and patients with RA-noILD, matched 1:1 for age, sex, age at RA-ILD onset, duration of RA and presence of diabetes, arterial disease, dyslipidaemia and cardiac disease. Mortality was compared between patients with RA with and without clinical ILD in the matched population using Cox proportional hazards regression.Results:The prevalence of RA-ILD was 6.52 per 100,000 inhabitants (incidence=1.04 per 100,000 person-years). Of the 173,138 patients with RA included in the overall population, 4330 (2.5%) had clinical ILD. Patients with RA-ILD were older at RA diagnosis (mean [SD] age: 63.3 [13.7] vs 56.9 [15.2] years) and were more likely to be male (39.8% vs 27.0%) compared with patients with RA-noILD. Patients with RA-ILD were more likely to have cardiac disease (84.9% vs 63.1%), arterial disease (38.0% vs 19.3%), diabetes (21.4% vs 12.5%) and dyslipidaemia (44.7% vs 32.9%) compared with those with RA-noILD. The mortality rate in patients with clinical RA-ILD was 1.71 per 100,000 inhabitants. The mortality rate increased according to age (0.28 per 100,000 inhabitants for patients aged <65 years, 4.60 per 100,000 inhabitants for patients aged 65–74 years and 11.4 per 100,000 inhabitants for patients aged ≥75 years). After matching, the adjusted mortality risk was three times higher (HR [95% CI]: 3.1 [3.1, 3.9]) in patients with RA-ILD than in those with RA-noILD (Figure 1).Conclusion:This is the largest epidemiological study of RA-ILD in France. The prevalence of clinical RA-ILD in this population was towards the lower end of previous estimates (1–58%),3 possibly due to under-reporting of claims data. However, the occurrence of clinical ILD was associated with a strong increase in mortality compared with patients with RA-noILD.

P129 Predictors of low bone mineral density in rheumatoid arthritis

Abstract Background/Aims Osteoporosis (OP) is an extra-articular manifestation of rheumatoid arthritis (RA) that leads to increased fracture susceptibility due to a variety of reasons including immobility and cytokine driven bone loss. Bone loss in other populations has well documented risk factors. It is unknown whether bone loss in RA predominantly affects the femoral neck or the spine. This study aimed to identify independent predictors of low bone mineral density (BMD) in patients RA at the lumbar spine and the femoral neck. Methods This was a retrospective observational cohort study using patients with Rheumatoid arthritis attending for a regional dual X-ray absorptiometry (DEXA) scan at the Royal Lancaster Infirmary between 2004 and 2014. BMD in L1-L4 in the spine and in the femoral neck were recorded. The risk factors investigated were steroid use, family history of osteoporosis, smoking, alcohol abuse, BMI, gender, previous fragility fracture, number of FRAX(tm) risk factors and age. Univariate and Multivariate regression analysis models were fitted to explore bone loss at these sites using BMD in g/cm2 as a dependant variable. . Results 1,527 patients were included in the analysis, 1,207 (79%) were female. Mean age was 64.34 years (SD11.6). mean BMI was 27.32kg/cm2 (SD 5.570) 858 (56.2%) had some steroid exposure . 169(11.1%) had family history of osteoporosis. fragility fracture history found in 406 (26.6%). 621 (40.7%) were current or ex smokers . There was a median of 3 OP risk factors (IQR 1,3) The performance of the models is shown in table one below. Different risk factors appeared to influence the BMD at different sites and the cumulative risk factors influenced BMD in the spine. None of the traditional risk factors predicted poor bone loss well in this cohort. P129 Table 1:result of the regression modelsCharacteristicB femoral neck95% CIpB spine95%CIpAge at scan-0.004-0.005,-0.003<0.01-0.0005-0.002,0.00050.292Sex-0.094-0.113,-0.075<0.01-0.101-0.129,-0.072<0.01BMI (mg/m2)0.0080.008,0.0101<0.010.01130.019,0.013<0.01Fragility fracture-0.024-0.055,0.0060.12-0.0138-0.060,0.0320.559Smoking0.007-0.022,0.0350.650.0286-0.015,0.0720.20Alcohol0.011-0.033,0.0 5560.620.0544-0.013,0.1120.11Family history of OP0.012-0.021,0.0450.470.0158-0.034,0.0650.53Number of risk factors-0.015-0.039,0.0080.21-0.039-0.075,-0.0030.03steroids0.004-0.023,0.0320.030.027-0.015,0.0690.21 Conclusion This study has shown that predictors of low BMD in the spine and hip are different and less influential than expected in this cohort with RA . As the FRAX(tm) tool only uses the femoral neck, this might underestimate the fracture risk in this population. Further work looking at individual areas is ongoing. Disclosure M.A. Swar: None. M. Bukhari: None.

Pulmonary abnormalities on high-resolution computed tomography in patients with long standing rheumatoid arthritis

Background. Rheumatoid arthritis (RA) is a systemic inflammatory disease, associated with a number of extra-articular organ manifestations. Pulmonary involvement is a frequent and severe extraarticular manifestations of rheumatoid arthritis. RA can affect lung parenchyma, airways and pleura. Objectives. To identify RA-related lung disease on chest computed tomography (CT). Material and methods. We performed high-resolution computed tomography (HRCT) on a total of 92 patients with longstanding RA. Results. The subjects were predominantely female (79.3%), the age at entry was 63.77 ±11.56 years, and 42.9% had a history of smoking. Disease duration was 15.00±11.55 years. Pulmonary CT abnormalities were found in 71 of the 92 patients (77.2%). The most common HRCT anomalies were: linear attenuation (reticulation) (52.11%), bronchiectasis andbronchial wall thickening (45%), nodular attenuation (39.43%) and pleural involvement (pleural effusion or thickening) (39.43%). Conclusions. We conclude that RA-related lung disease was commonly detected on chest CT imaging in longstanding RA patients.

Interstitial lung disease throughout the rheumatoid arthritis disease course.

To summarize the current understanding of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) throughout the rheumatoid arthritis (RA) disease course from preclinical to established disease. ILD is a serious extra-articular manifestation of RA. Multiple studies have demonstrated a high prevalence of both subclinical and clinical ILD throughout the RA disease course. Investigations of patients without RA have demonstrated an association between RA-related autoantibodies like anticitrullinated protein antibodies (ACPA) and interstitial abnormalities on lung imaging. A significant proportion of RA-ILD patients develop ILD prior to articular manifestations, suggesting that the lung plays a central role in RA development, perhaps through ACPA production. RA-ILD also occurs in early RA, when exuberant autoantibody production and systemic inflammation may propagate pulmonary disease activity. In patients with established RA, a high burden of subclinical and clinical ILD results in significant morbidity, mortality, and healthcare expenditure. Multiple epidemiologic and genetic risk factors, as well as serum biomarkers, have been associated with RA-ILD. Subclinical and clinical ILD occur frequently in preclinical, early, and established RA and may play a key role in RA-related autoantibody production and disease progression. Further studies are needed to better understand the risk factors, prognosis, and potential therapies for RA-ILD.

Unusual, but important, peri- and extra-articular manifestations of rheumatoid arthritis: a pictorial essay.

Ultrasonography is a useful technique to detect soft tissue changes of rheumatoid arthritisnot only synovitis, but also tenosynovitis, bursitis, and enthesitis-even at a subclinical stage. However, radiologists tend to focus on synovitis in daily practice, and unusual peri- or extra-articular manifestations of rheumatoid arthritis are difficult to detect at the initial presentation. This pictorial essay describes a broad spectrum of ultrasonographic findings in tendons, bursae, ligaments, subcutaneous tissues, bones, and nerves to assist in the accurate diagnosis of rheumatoid arthritis.

Mitral valvulitis as a severe extra-articular manifestation of rheumatoid arthritis: a case report.

BackgroundExtra-articular manifestations (EAMs) are common in patients with rheumatoid arthritis (RA). Cardiac EAMs are rare but may cause complete heart block and damage to the heart valves.Case summaryWe present the case of a middle-aged woman with long-standing RA and EAMs as the most prominent symptoms. The patient experienced complete atrioventricular heart block and developed nodular vegetations affecting the mitral valve, ultimately leading to severe mitral regurgitation and valve replacement.DiscussionThe diagnosis of cardiac EAMs in RA may be challenging for the clinicians. Symptoms and findings may mimic more common conditions such as malignancy and infectious endocarditis. A multidisciplinary approach is of paramount importance in order to make an early diagnosis and to provide optimal treatment to patients with RA and cardiac complications.

Endothelial Dysfunction and Extra-Articular Neurological Manifestations in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease that affects about 1% of the global population, with a female–male ratio of 3:1. RA preferably affects the joints, with consequent joint swelling and deformities followed by ankylosis. However, evidence has accumulated showing that patients suffering from RA can also develop extra-articular manifestations, including cardiovascular disease states, neuropathies, and multiorgan dysfunction. In particular, peripheral nerve disorders showed a consistent impact in the course of the disease (prevalence about 20%) mostly associated to vasculitis of the nerve vessels leading to vascular ischemia, axonal degeneration, and neuronal demyelination. The pathophysiological basis of this RA-associated microvascular disease, which leads to impairment of assonal functionality, is still to be better clarified. However, endothelial dysfunction and alterations of the so-called brain-nerve barrier (BNB) seem to play a fundamental role. This review aims to assess the potential mechanisms underlying the impairment of endothelial cell functionality in the development of RA and to identify the role of dysfunctional endothelium as a causative mechanism of extra-articular manifestation of RA. On the other hand, the potential impact of lifestyle and nutritional interventions targeting the maintenance of endothelial cell integrity in patients with RA will be discussed as a potential option when approaching therapeutic solutions in the course of the disease.

Assessment of auditory dysfunction as an extra-articular manifestation in rheumatoid arthritis using brainstem auditory-evoked potential

Assessment of auditory dysfunction as an extra-articular manifestation in rheumatoid arthritis using brainstem auditory-evoked potential