Extra-articular Manifestation Of Rheumatoid Arthritis Research Articles

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

Predictors of functional capacity as measured by the Glittre activities of daily living test in women with rheumatoid arthritis.

Although pulmonary involvement is the most common extra-articular manifestation of rheumatoid arthritis (RA), traditional pulmonary function tests (PFTs) do not show a good correlation with the field tests usually performed in these patients. In recent decades, measurement of ventilation distribution heterogeneity through the nitrogen single-breath washout (N2SBW) test and evaluation of functional capacity during exercise using the Glittre activities of daily living test (GA-T) have been increasingly used. Therefore, the objective of this study was to evaluate predictors of GA-T outcomes in women with RA considering demographic, anthropometric, clinical, functional variables, and chest computed tomography (CT) findings. Forty-three women with RA underwent the GA-T, the N2SBW test, spirometry, measurement of the diffusing capacity for carbon monoxide (DLco), measurement of respiratory muscle strength, and evaluation of physical function of the lower and upper limbs through the Health Assessment Questionnaire Disability Index (HAQ-DI). Chest CT scans were analyzed retrospectively. The GA-T time showed significant correlations with the DLco (rs=-0.397, P=0.008), forced vital capacity/DLco (rs=0.307, P=0.044), phase III slope of the N2SBW test (SIIIN2, rs=0.644, P<0.0001), and the HAQ-DI (rs=0.482, P=0.001). Disease extent as assessed by chest CT was associated with the GA-T time. On multiple regression analysis, the SIIIN2 and HAQ-DI were the only predictors of the GA-T time, explaining 40% of its variability. Thus, ventilation distribution heterogeneity and worse physical function substantially explain the variability in GA-T time in women with RA and varying extents of disease on chest CT.

Serum Metabolomic Profiling in Rheumatoid Arthritis Patients With Interstitial Lung Disease: A Case-Control Study.

Objectives: Interstitial lung disease (ILD) is an extra-articular manifestation in rheumatoid arthritis (RA), detected in 10.7% of patients, and causing a poor prognosis. Hence, biomarkers for ILD are urgently required in RA. Low molecular weight metabolites can be assessed by metabolomic analyses, and although these have been conducted in RA and in idiopathic pulmonary fibrosis, few have been carried out for ILD in the context of RA. Therefore, we analyzed serum metabolomic profiles of ILD in RA to identify novel biomarkers.Methods: Serum samples from 100 RA patients with ILD and 100 matched RA patients without chronic lung disease (CLD) were collected. These samples were subjected to metabolomic analyses using capillary electrophoresis time-of-flight mass spectrometry.Results: A total of 299 metabolites were detected in the metabolomic analysis. By univariate analysis, serum levels of decanoic acid and morpholine were lower in RA with ILD (false discovery rate Q = 1.87 × 10−11 and 7.09 × 10−6, respectively), and glycerol was higher (Q = 1.20 × 10−6), relative to RA without CLD. Serum levels of these metabolites in RA with usual interstitial pneumonia or RA with non-specific interstitial pneumonia were also altered. The partial least squares-discriminant analysis model generated from these three metabolites could successfully discriminate ILD in RA (area under the curve: 0.919, 95% confidence interval: 0.867–0.968, sensitivity 0.880, specificity 0.780).Conclusions: Serum levels of some metabolites were significantly different in RA with ILD compared with RA without CLD. It is concluded that metabolomic profiling will be useful for discovering candidate screening biomarkers for ILD in RA.

Rheumatoid arthritis-associated lung disease in black Africans: Descriptive study of 28 cases in Lomé.

Background Several studies have shown that lung disease is a common extra-articular manifestation of rheumatoid arthritis (RA). Objectives To describe the lung manifestations in the RA population in Lomé, Togo. Methods The study was conducted from October 2018 to July 2019 at the pulmonology unit of the Sylvanus Olympio University teaching hospital, in collaboration with rheumatology centres in Lomé, Togo. Patients meeting the American College of Rheumatology criteria for RA were prospectively enrolled. They underwent clinical examination, spirometry, a 6-minute walk test (6MWT) and a chest X-ray (CXR). All information collected and surveys gathered were subjected to statistical analysis. Results Twenty-four out of 28 patients were women (85.7%). The mean (standard deviation (SD)) duration of illness was 4.1 (2.8) years. Thirteen patients out of 28 (46.4%) had respiratory symptoms. On CXR, interstitial lung disease was the only pleuropulmonary lesion (17.8%). Spirometry was abnormal in 25% of cases, with a predominance of restrictive ventilatory disorder (21.4%). The 6MWT was abnormal in 25% of patients. A total of 20 patients (71.4%) had at least one lung manifestation. We noted that there were significantly more patients with respiratory symptoms and no radiographical abnormalities than those with both respiratory symptoms and radiographical abnormalities (p=0.013). Conclusion Lung changes affect a significant proportion of RA patients in Lomé. Studies conducted with appropriate respiratory investigations and combining cardiovascular explorations will bring us closer to an understanding of the effects of RA-associated lung disease.

Pancreatic manifestations in rheumatoid arthritis: a national population-based study.

RA is a systemic autoimmune disease characterized by persistent joint inflammation. Extra-articular manifestations of RA can involve different organs including the gastrointestinal (GI) system. Using a large database, we sought to describe the epidemiology of pancreas involvement in RA. We queried a multicentre database (Explorys Inc, Cleveland, OH, USA), an aggregate of electronic health record data from 26 major integrated US healthcare systems in the US from 1999 to 2019. After excluding patients younger than 18, a cohort of individuals with Systematized Nomenclature of Medicine - Clinical Terms (SNOMED-CT) diagnosis of RA was identified. Within this cohort, patients who developed a SNOMED-CT diagnosis of acute pancreatitis (AP), chronic pancreatitis (CP) and primary pancreatic cancer (PaCa) after at least 30 days of RA diagnosis were identified. Statistical analysis for multivariate model was performed using Statistical Package for Social Sciences (SPSS version 25, IBM Corp) to adjust for several factors. Of the 56183720 individuals in the database, 518280 patients had a diagnosis of RA (0.92%). Using a multivariate regression model, patients with RA were more likely to develop AP [odds ratio (OR): 2.51; 95% CI: 2.41, 2.60], CP (OR: 2.97; 95% CI: 2.70, 3.26) and PaC (OR: 1.79; 95% CI: 1.52, 2.10). In this large database, we found a modest increased risk of AP and CP among patients with RA after adjusting for the common causes of pancreatitis. Further studies are required to better understand this association and the effect of medications used for RA.

Case Report: Aortitis associated with rheumatoid arthritis: A challenging rheumatoid vasculitis presentation

Rheumatoid vasculitis (RV) is a rare but serious extra-articular manifestation of rheumatoid arthritis (RA). Its varied clinical presentation makes it hard to diagnose and treat. Hereby we describe a case of an aortitis revealing RV, which is a rare presentation of a rare complication of RA. A 56-year-old man with rheumatoid arthritis treated with methotrexate presented with fever, chest pain and arthritis. Blood tests revealed inflammatory syndrome associated with cholestasis. The diagnosis of pericarditis associated with aortitis was retained. Cholestasis was mostly due to methotrexate. The patient was treated with cyclophosphamide pulses and high doses of prednisolone. The patient was in complete remission of articular and extra-articular manifestations after two months of treatment.

Biological therapy in rheumatoid vasculitis: a systematic review.

Rheumatoid vasculitis (RV) is one of the most severe extra-articular manifestations of rheumatoid arthritis, with significant morbidity and mortality, requiring aggressive treatment with corticosteroids and/or immunosuppressants. Recently, biological drugs were included in its therapeutic armamentarium. The objective of this study was to perform a systematic review on the use of biological drugs in the treatment of RV. A systematic literature review was performed based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations and searching articles in MEDLINE/PubMed, Cochrane, SciELO, Scopus, and Virtual Health Library electronic databases. Secondary references were also evaluated. The methodological quality of the selected studies was evaluated by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria. Altogether, five articles, assessing the use of biological drugs, were included. Globally, 35 patients participated in the studies, of which 21 were treated with rituximab (RTX) in cycles of 1000 mg every 2 weeks; 9 used infliximab 5 mg/kg; 3 used infliximab 3 mg/kg; and 2 used etanercept 25 mg twice/week. In general, an improvement in clinical picture, reduction of the mean daily dose of corticosteroids, and improvement in the Birmingham Vasculitis Activity Score was achieved by the end of the treatment. Complete remission occurred in almost 70% of the cases. The adverse effect rate was 34%, mainly due to infections. There were two deaths, one due to sepsis and the other due to uncontrolled vasculitis, after the biological drug withdrawal, following the development of sepsis. Based on the results of the present review, we believe that the use of biological therapy such as RTX and anti-tumor necrosis factor α can be beneficial in treating this complication.

The effectiveness of combined pulse therapy in patients with rheumatoid arthritis

Objective. To study the efficacy of the tolerance of combined regimens of the therapy with high doses of methylprednisolone and methotrexate of the patients with rheumatoid arthritis (RA).&#x0D; Materials and methods. The study included 85 patients with RA who underwent inpatient treatment in the Rheumatologic Department of the Clinical Hospital of Dushanbe city for the period 2018-2019. From them, women – 83.2 %, men – 26.8 %; the average duration of the disease is 7.4 years. Extra-articular manifestations of RA were determined in 74.3 % of patients. Against the background of the standard therapy, a regimen of bolus pulse therapy (methylprednisolone 500-1000 mg and methotrexate) was taken for 3 days, which has been followed for observation for a year. The effectiveness of the treatment was assessed according to the American College of Rheumatology (ACR) 20/50/70 criteria. The number of the swollen joints and painful joints (NPV), ESR, C-reactive protein level, and the overall disease activity were determined.&#x0D; Results and discussion. After 1 month of therapy, significant positive dynamics were recorded in the all estimated parameters of the RA activity. There was a significant decrease in NPV, as well as the intensity of pain according to the visual analogue scale. During 3 months of observation, 78 % of the observed patients showed improvement and only 11 % of patients had side effects and have not been required of the discontinuation of the treatment.&#x0D; Conclusions. The combined pulse therapy of methylprednisolone and methotrexate was an effective and well-tolerated for systemic manifestations of RA and contributed to a significant decrease in RA activity in the shortest time.

SYMPTOMATIC PULMONARY AND INTRACRANIAL NODULES IN A PATIENT WITH LONGSTANDING, UNCONTROLLED RHEUMATOID ARTHRITIS

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary manifestations of rheumatoid arthritis (RA) are found in 60-80% of all RA patients and are responsible for 10-20% of RA-related mortality. RA nodules are observed in approximately 20% of RA patients with 20- 32% prevalence pulmonary RA nodules. Rarer intracranial RA nodules have been described in two case studies.1 Here we present a patient who demonstrates significant symptomatic pulmonary nodulosis along with intracranial nodules leading to intractable seizures and ventilator support. CASE PRESENTATION: Our patient was a 67-year-old woman with a 9-year history of RA, recurrent bilateral knee septic arthritis, and three months of focal seizures who presented to the emergency department for breakthrough focal seizures. Prior magnetic resonance imaging (MRI) showed contrast enhancing right temporal and right thalamic nodules up to 4mm consistent with electroencephalogram (EEG) localization of the seizures. Rheumatologically, the patient had RA flares multiple times per month despite maximal doses of hydroxychloroquine, leflunomide, and methrotrexate (MTX). 6 months prior, an outpatient Chest CT ordered for evaluation of dyspnea showed multiple solid and cavitary pulmonary lesions. Endobronchial ultrasound with biopsy of nodules showed necrotizing granulomatous inflammation consistent with RA nodules. During hospitalization, the patient presented with mildly elevated CRP, RF, and anti-CCP, and mildly decreased complement C3 but otherwise normal exam and negative serologic and cerebrospinal fluid tuberculosis, fungal, bacterial, viral, cancer and autoimmune workup. Repeat imaging showed multiple new bilateral pulmonary nodules up to 2.3 cm with stable intracranial nodules despite empiric acyclovir. The patient continued to have seizures in the unit despite maximal doses of intravenous seizure medication, six days later developing, ultimately fatal severe metabolic acidosis, bradycardia, and hypotension. DISCUSSION: This unique case of symptomatic intracranial and pulmonary nodules in the setting of RA does not have much literature accompaniment, but we hope to add our experience to a potential disease etiology. Several case reports, however, do show reduction in pulmonary nodule size with oral steroid courses. There is currently no strong consensus on treatment of RA nodules. While RA nodules are often considered relatively benign, in this patient the EEG and imaging finding suggest that the nodules may have significantly contributed to this patient’s breakthrough seizures. Unfortunately due to this patient’s comorbidities and tenuous medical status, pathologic review of the brain lesions was not obtained. CONCLUSIONS: This report highlights the need to consider RA as a potentially reversible cause when considering unexplained systemic findings, as well as the need for more research into treatment of extraarticular manifestations of RA. Reference #1: Esposito AJ, Chu SG, Madan R, Doyle TJ, Dellaripa PF. Thoracic Manifestations of Rheumatoid Arthritis. Clin Chest Med 2019;40(3):545–560. DISCLOSURES: No relevant relationships by Oleh Hnatiuk, source=Web Response No relevant relationships by adarsh vangala, source=Web Response No relevant relationships by Nicholas Villalobos, source=Web Response

Tocilizumab therapy in rheumatoid arthritis with interstitial lung disease: a multicentre retrospective study.

Interstitial lung disease (ILD) is the most severe extra-articular manifestation of rheumatoid arthritis (RA). Although it is responsible of 10-20% of all RA mortality, no controlled studies are available for the treatment of RA-ILD and its therapeutic approach is still debated. To analyse the evolution of ILD in a population of RA patients treated with tocilizumab (TCZ). In this national multicentre study, we retrospectively collected patients with RA-ILD treated with at least one dose of TCZ. For each patient, disease activity and serological data were evaluated. Moreover, we analysed the evolution of high-resolution computed tomography (HRCT) and pulmonary function tests, including forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO). Twenty-eight RA-ILD patients were identified (females/males 18/10, mean age 61.6 years), with a mean follow up for TCZ therapy of 30 months. At the end of follow up, FVC remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%). DLCO remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%), even though in 3 patients DLCO and FVC showed an opposite trend. HRCT remained stable in the majority (25) of cases, worsened in two patients with a usual interstitial pneumonia pattern and improved in only one case with a non-specific interstitial pneumonia pattern. The management of RA-ILD patients remains a critical unmet need. TCZ demonstrated a good safety profile in patients with RA-ILD and a potential effect on the stabilisation of lung involvement.

Incidence Rates of Interstitial Lung Disease Events in Tofacitinib-Treated Rheumatoid Arthritis Patients: Post Hoc Analysis From 21 Clinical Trials.

Background/ObjectiveTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Interstitial lung disease (ILD) is an extra-articular manifestation of RA. We investigated incidence rates of ILD in patients with RA, receiving tofacitinib 5 or 10 mg twice daily, and identified potential risk factors for ILD.MethodsThis post hoc analysis comprised a pooled analysis of patients receiving tofacitinib 5 or 10 mg twice daily or placebo from 2 phase (P)1, 10 P2, 6 P3, 1 P3b/4, and 2 long-term extension studies. Interstitial lung disease events were adjudicated as “probable” (supportive clinical evidence) or “possible” (no supportive clinical evidence) compatible adverse events. Incidence rates (patients with events per 100 patient-years) were calculated for ILD events.ResultsOf 7061 patients (patient-years of exposure = 23,393.7), 42 (0.6%) had an ILD event; median time to ILD event was 1144 days. Incidence rates for ILD with both tofacitinib doses were 0.18 per 100 patient-years. Incidence rates generally remained stable over time. There were 17 of 42 serious adverse events (40.5%) of ILD; for all ILD events (serious and nonserious), 35 of 42 events (83.3%) were mild to moderate in severity. A multivariable Cox regression analysis identified age 65 years or older (hazard ratio 2.43 [95% confidence interval, 1.13–5.21]), current smokers (2.89 [1.33–6.26]), and Disease Activity Score in 28 joints–erythrocyte sedimentation rate score (1.30 [1.04–1.61]) as significant risk factors for ILD events.ConclusionsAcross P1/2/3/4/long-term extension studies, incidence rates for ILD events were 0.18 following tofacitinib treatment, and ILD events were associated with known risk factors for ILD in RA.

Understanding the Role of Interleukin-6 (IL-6) in the Joint and Beyond: A Comprehensive Review of IL-6 Inhibition for the Management of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune disorder involving inflammation and progressive destruction of the joints, affecting up to 1% of the population. The majority of patients with RA have one or more comorbid conditions, the most common being cardiovascular disease, osteoporosis, and depression, the presence of which are associated with poorer clinical outcomes and lower health-related quality of life. RA pathogenesis is driven by a complex network of proinflammatory cells and cytokines, and of these, interleukin-6 (IL-6) plays a key role in the chronic inflammation associated with RA. Through cell signaling that can be initiated by both membrane-bound and soluble forms of its receptor, IL-6 acts both locally to promote joint inflammation and destruction, and in the circulation to mediate extra-articular manifestations of RA, including pain, fatigue, morning stiffness, anemia, and weight loss. This narrative review describes the role of IL-6 in the pathogenesis of RA, its comorbidities, and extra-articular systemic manifestations, and examines the effects of the IL-6 receptor inhibitors sarilumab and tocilizumab on clinical endpoints of RA, patient-reported outcomes, and common comorbidities and extra-articular manifestations.

Toenail abnormalities in rheumatoid arthritis patients are associated with radiographic damage and impact disability: a cross sectional study nested within a cohort

Cutaneous involvement is an extra-articular manifestation of rheumatoid arthritis (RA). This includes nail abnormalities, which are often overlooked. We described nail findings in RA patients currently attending an early arthritis cohort (n=145), and associated them with disease activity and/or damage, as well as patient-reported outcomes. A standardised nail examination was performed in 122 patients (84.1% of the cohort), concomitant to the rheumatic assessment. Disability, quality of life and perceived nail-related health were also assessed. Nail findings and their location were recorded and classified according to standardised definitions. Logistic and linear regression models were used to investigate predictors of nail findings and to identify the impact of toenail findings on disability, which was evaluated with the HAQ. Patients consented to participate. Patients were primarily middle-aged females, with median follow-up of 9 years, and had disease under control. Most patients (62.3%) had at least one nail finding and these patients scored lower their nail-related health. The median (IQR) of findings/abnormalities per patient was 3 (2-5) and the number of nails affected per patient was 10 (2-12). Age (OR: 1.04, 95%CI: 1.007-1.074) and erosive disease (OR: 2.26, 95%CI: 1.1-5.1) were associated with nail findings. Toenail involvement was consistently associated with HAQ score out of normal range (OR=3.4, 95%CI=1.24-9.35, p=0.02). There was a linear association between the number of toenails affected and the HAQ score. Nail abnormalities are common and heterogeneous findings in RA patients; they are associated with erosive damage and impact disability.

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.

Association of rheumatoid arthritis with hearing loss: a systematic review and meta-analysis

Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting up to 1% of the worldwide population. RA is associated with multiple extra-articular manifestations (EAMs). Middle ear, cochlea and the auditory nerve are suspected sites of RA activity and hearing loss is a possible novel EAM of RA. Objective was to investigate the association of RA with the different subtypes of hearing loss. This systematic review was performed according to the PRISMA guidelines. A random effects model meta-analysis was conducted and the I2 was used to assess heterogeneity. Twelve studies comprising 20,022 RA patients and 79,244 controls were included in this systematic review. All studies were observational and were rated to a moderate rate of bias. RA patients had nearly fourfold increased odds of sensorineural hearing loss (SNHL) compared with controls (OR 3.42; 95% CI 2.50-4.69; I2 = 13). RA patients also had a significantly increased risk of SNHL (RR 2.28; 95% CI 1.88-2.76; I2 = 0). RA patients did not have increased odds of conductive hearing loss (CHL) and mixed hearing loss (MHL) (OR 1.36; 95% CI 0.52-3.55; I2 = 22); (OR 2.73; 95% CI 0.78-9.58; I2 = 0%). RA is significantly associated with SNHL. RA is not associated with CHL and MHL. Early screening of RA patients with pure tone audiometry should be considered.

OP0035 EXAMINATION OF INTERSTITIAL LUNG DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS – PREVALENCE, TIME TO ONSET, AND CLINICAL CHARACTERISTICS

Background:Interstitial lung disease (ILD) is a known extraarticular manifestation of rheumatoid arthritis (RA). Previous studies have shown variability in the prevalence of RA-ILD, as well as clinical characteristics and risk factors of RA-ILD.Objectives:To evaluate the prevalence and time to onset of ILD and compare the clinical characteristics between RA patients (pts) with or without ILD using a large US electronic medical record (EMR)-based dataset.Methods:Pts with an initial RA diagnosis (ICD-9-CM code: 714.0; ICD-10-CM codes: M05 &amp; M06) during the study period (01JAN2009-20SEP2019) were included from the Discus Analytics JointMan database. The initial RA diagnosis date was defined as the index date. Pts with ILD were identified by ICD diagnosis codes or by provider indication in the JointMan record. Pts who developed ILD before RA were excluded from this analysis. The prevalence and time to onset of ILD were reported. Pt demographics, comorbidities, RA characteristics and disease activity scores were compared for 6 months prior to or on the index date (baseline period) for selected adult RA pts with available information.Results:Among 8,963 identified RA pts, 337 (3.8%) were diagnosed with ILD on or after RA diagnosis. The median time to ILD onset post-RA was 2.3 years, and 47% had ILD within 2 years after RA diagnosis. RA-ILD pts were significantly older than those without ILD (65.8 years vs. 59.1 years; p&lt;0.001; Table 1). At baseline, a higher percentage of RA-ILD pts had history of chronic obstructive pulmonary disease, positive rheumatoid factor, rheumatoid nodules, erosive joint disease, positive anti-cyclic citrullinated peptide antibody, and joint swelling compared to RA-only pts (Table 2). The mean ESR and RA disease activity scores were also significantly higher for RA-ILD pts.Table 1.Patient DemographicsPatient demographicsRA-ONLY COhort(N = 5,612)RA-ild coHORT(N = 205)P-valueAge, Mean ± SD, years59.1 ± 14.265.8 ± 11.8&lt;.001Male, N (%)1,375 (24.5%)72 (35.1%)0.001Race, N (%) White4,014 (71.5%)165 (80.5%)0.005 African American365 (6.5%)9 (4.4%)0.226 Other/Missing1,233 (22.0%)31 (15.1%)0.020Table 2.Baseline Clinical CharacteristicsClinical CharacteristicsRA-ONLY COhort(N = 3,846)RA-ild coHORT(N = 115)P-valueHistory of Chronic Obstructive Pulmonary Disease, N (%)102 (2.7%)8 (7.0%)0.006Hypertension, N (%)900 (23.4%)23 (20.0%)0.395Serious Infection, N (%)38 (1.0%)3 (2.6%)0.091Rheumatoid Factor Positive, N (%)1,388 (36.1%)69 (60.0%)&lt;.001Joint Stiffness, N (%)1,092 (28.4%)39 (33.9%)0.197Rheumatoid Nodules, N (%)153 (4.0%)17 (14.8%)&lt;.001Erosive Joint Disease, N (%)459 (11.9%)23 (20.0%)0.009Anti-CCP Antibody Positive, N (%)858 (22.3%)45 (39.1%)&lt;.001Joint Swelling*, N (%)2,861 (58.0%)123 (68.0%)0.008Joint Tenderness*, N (%)3,728 (75.6%)138 (76.2%)0.851ESR**, Mean ± SD, mm/hr22.0 ± 22.630.1 ± 25.5&lt;.001CRP**, Mean ± SD, mg/L22.5 ± 13.060.6 ± 25.00.086CDAI, Mean ± SD16.4 ± 12.318.9 ± 15.70.044DAS28-CRP, Mean ± SD2.6 ± 1.23.1 ± 1.4&lt;.001DAS28-ESR, Mean ± SD3.3 ± 1.43.9 ± 1.5&lt;.001SDAI, Mean ± SD20.2 ± 29.328.6 ± 40.20.048* A total of 4,929 non-ILD and 181 ILD patients had joint swelling and tenderness data.** Variables were calculated among patients who had available information.Conclusion:This large real-world RA population provides insight into the burden of ILD in RA pts. Pts with ILD had a higher proportion of comorbidities and RA-related conditions and higher RA activity. Further analysis is warranted to assess the risk factors of ILD and its prognosis.Disclosure of Interests:Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Qisu Zhang Consultant of: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company., Keith Knapp Consultant of: In the last year, I was a paid consultant to Bristol Myers-Squibb Company., Employee of: I am a paid employee of Discus Analytics., Yuexi Wang Consultant of: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company., Cynthia Gutierrez Consultant of: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company., Ding He Consultant of: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company., Lin Xie Consultant of: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company., Sonie Lama Shareholder of: I own shares of Bristol-Myers Squibb Company., Employee of: I am a paid employee of Bristol-Myers Squibb Company., Gary Craig Consultant of: I have served as a consultant to Bristol-Myers Squibb Company., Employee of: I am a paid employee of Arthritis Northwest and VP of Discus Analytics., Speakers bureau: I am a member of the speakers bureau for Bristol-Myers Squibb Company.

THU0150 INTERSTITIAL LUNG DISEASE RELATED TO RHEUMATOID ARTHRITIS. WHAT DO WE DON’T KNOW? THE LIRA STUDY (LUNG INVOLVEMENT IN RHEUMATOID ARTHRITIS).

Background:Interstitial lung disease (ILD) is one of the more frequent and potentially severe extra-articular manifestation of rheumatoid arthritis (RA). ILD significantly decreases the survival and quality of life of patients and influences the treatment approach to the patient.Despite its clinical relevance, the prevalence, incidence and survival of RA-ILD is unknown and supposed on the base of retrospective data or registry-based studies.Objectives:For the first time, the Lung Involvement in Rheumatoid Arthritis (LIRA) study aims to investigate epidemiology, features and prognosis of RA-ILD patients in a prospective international multicentre study.Methods:All RA patients referring to the involved centres will be evaluated every six months with a digital stethoscope and a software able to identify velcro crackles with a diagnostic accuracy of 83.9% (VECTOR). In fact, velcro crackles are virtually identified in all stages of fibrosing alveolitis like RA-ILD, and their search is as a simple and reliable method to screening patients to be undergone to high resolution computed tomography (HRCT).For each patient, clinical and serological data are recorded at baseline and every six months; when velcro crackles or other conditions suspicious for ILD, such as cough or dyspnoea, are detected, a HRCT is requested to confirm ILD. Patients with ILD periodically perform pulmonary function tests to monitor lung function evolution.Results:At now, 205 RA patients have been enrolled (female/male 161/44, mean age 64.8±12.9 years, mean disease duration 14.2±8.9 years), anti-citrullinated peptides antibodies (ACPA) and rheumatoid factor (RF) were positive in 77.1% and 78.1%, respectively. The prevalence of ILD was 21% (43 patients). In other 13 patients the HRCT is ongoing; therefore, we could suppose up to a prevalence of 27.3%. Patients with ILD were symptomatic in 53.5% of cases (23 patients), they are more frequently males and were older than patients without ILD (mean age 73.2±7.4 and 62.7±13.2; p&lt;0.0001, female/male ratio 139/23 vs 22/21; p&lt;0.0001) without significant differences regarding disease duration, positivity for ACPA or RF.Conclusion:The prevalence and the incidence of RA-ILD is still not well defined. Preliminary data of our study confirm a prevalence of ILD higher than 20%, patients are asymptomatic in almost the half of cases and more frequently males and elderly. Our study can help to define the clinical history of these patients, the possible association with clinical and serological features and the supposed role of some drugs.

Management issues in rheumatoid arthritis-associated interstitial lung disease.

Summarize recent evidence on the identification and management of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Clinical and subclinical interstitial lung disease (ILD) are frequent extra-articular manifestations of rheumatoid arthritis (RA). Better means of identifying and treating RA-ILD are needed to improve the prognosis, with a median survival of only 3-7 years after diagnosis. Several serum biomarkers are currently being evaluated for their ability to detect RA-ILD. Thorough evaluation and multidisciplinary discussion remains the gold standard for establishing the diagnosis of RA-ILD. Management is challenging with most RA disease-modifying antirheumatic drugs (DMARDs) linked to pneumonitis. Methotrexate is typically avoided in clinically significant ILD, although alternative therapies including leflunomide and biologic DMARDs also carry risks in RA-ILD. Antifibrotics appear to slow the progression of ILD, and a large phase II trial exclusively in RA-ILD is underway. In addition, smoking cessation, pulmonary rehabilitation, oxygen therapy, managing comorbidities, and lung transplantation evaluation are vital to improving patient outcomes in RA-ILD. With little high-quality evidence to guide the management of RA-ILD, multidisciplinary teams with expertise in RA-ILD are highly valuable for diagnosing and treating RA-ILD. Clinical and translational research in RA-ILD is needed to fill the many evidence gaps.