Extra-articular Manifestation Of Rheumatoid Arthritis Research Articles

Rheumatoid meningitis in the absence of rheumatoid arthritis: 2 cases

Rheumatoid meningitis (RM) is a rare extra-articular manifestation of rheumatoid arthritis (RA) that has been increasingly recognized by neurologists. However, the diversity of its clinical manifestations makes its diagnosis difficult. RM does not have a unified diagnostic standard, and its link with RA needs to be studied further. Here we report two cases of RM without a history of RA. The first patient, an 80-year-old woman, presented with sudden unilateral limb weakness, with brain MR showing abnormal signals in the leptomeningeal of the right frontal parietal. Subarachnoid hemorrhage was excluded after imaging examination, and infectious meningitis was ruled out after cerebrospinal fluid (CSF) examination. The patient was diagnosed as having RM, she had increased levels of CCP and AKA, the markers of RA, but no history of the disease or other clinical manifestations of it. Another case, a 65-year-old man, was hospitalized with Bell’s palsy. We found that he had intracranial imaging changes highly consistent with those characteristic of RM during his routine examination. Except for the left peripheral facial palsy, the patient had no other neurological signs or symptoms and no RA history. After a careful physical examination, we found no joint or other manifestations or serological abnormalities consistent with RA (RF, CCP, AKA, etc.). However, after excluding infection meningitis and considering the patient’s unique imaging results, we diagnosed him as having RM. We report these two cases as references for clinical diagnosis and treatment of RM, providing a discussion of our rationale.

Design of ANCHOR-RA: a multi-national cross-sectional study on screening for interstitial lung disease in patients with rheumatoid arthritis

BackgroundPatients with rheumatoid arthritis (RA) are at risk of developing interstitial lung disease (ILD), which is associated with high mortality. Screening tools based on risk factors are needed to decide which patients with RA should be screened for ILD using high-resolution computed tomography (HRCT). The ANCHOR-RA study is a multi-national cross-sectional study that will develop a multivariable model for prediction of RA-ILD, which can be used to inform screening for RA-ILD in clinical practice.MethodsInvestigators will enrol consecutive patients with RA who have ≥ 2 of the following risk factors for RA-ILD: male; current or previous smoker; age ≥ 60 years at RA diagnosis; high-positive rheumatoid factor and/or anti-cyclic citrullinated peptide (titre > 3 x upper limit of normal); presence or history of certain extra-articular manifestations of RA (vasculitis, Felty’s syndrome, secondary Sjögren’s syndrome, cutaneous rheumatoid nodules, serositis, and/or scleritis/uveitis); high RA disease activity in the prior 12 months. Patients previously identified as having ILD, or who have had a CT scan in the prior 2 years, will not be eligible. Participants will undergo an HRCT scan at their local site, which will be assessed centrally by two expert radiologists. Data will be collected prospectively on demographic and RA-related characteristics, patient-reported outcomes, comorbidities and pulmonary function. The primary outcomes will be the development of a probability score for RA-ILD, based on a multivariable model incorporating potential risk factors commonly assessed in clinical practice, and an estimate of the prevalence of RA-ILD in the study population. It is planned that 1200 participants will be enrolled at approximately 30 sites in the USA, UK, Germany, France, Italy, Spain.DiscussionData from the ANCHOR-RA study will add to the body of evidence to support recommendations for screening for RA-ILD to improve detection of this important complication of RA and enable early intervention.Trial registrationclinicaltrials.gov NCT05855109 (submission date: 3 May 2023).

Risk factors for interstitial lung disease in rheumatoid arthritis: a cohort study from the KOBIO registry

Background: Interstitial lung disease (ILD) is a critical extra-articular manifestation of rheumatoid arthritis (RA). However, little is known about the risk factors of RA-ILD. Objectives: Here, we examined the effect of demographic, clinical, therapeutic, and environmental factors on the incidence of ILD in RA patients using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Design: We used data from the KOBIO registry, a multi-center, prospective, observational cohort that included RA patients in South Korea. Methods: RA patients who used biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) or conventional synthetic (cs)DMARDs, and were enrolled in the KOBIO registry, were examined. Demographic, clinical, and radiographic characteristics, as well as medications, were recorded at baseline and annually thereafter. Kaplan–Meier curves and the log-rank test were used to compare the incidence of ILD between RA patients taking different b/tsDMARDs. Hazard ratios (HRs) were calculated by Cox regression analyses. Results: In total, 2492 patients (1967 in the b/tsDMARDs group and 525 in the csDMARDs group) were analyzed. The b/tsDMARDs group showed longer disease duration, higher erythrocyte sedimentation rate/C-reactive protein, and higher disease activity score-28 (DAS28) than the csDMARDs group. The incidence of ILD was significantly higher in those taking tumor necrosis factor inhibitors and abatacept than in those taking csDMARDs (log ranked p < 0.001). Multivariate Cox regression analysis identified older age (HR = 1.057, p = 0.001), male sex (HR = 2.824, p = 0.007), time-averaged DAS28 (HR = 2.241, p < 0.001), and rheumatoid factor titer (HR = 1.009, p = 0.007) as having a significantly increased HR for ILD occurrence. Conclusion: ILD is a rare but critical extra-articular symptom of RA patients. Therefore, RA patients with the above risk factors should be monitored carefully for ILD development.

Rheumatoid interstitial lung disease in Canterbury, Aotearoa New Zealand – A retrospective cohort study

BackgroundRheumatoid arthritis associated interstitial lung disease (RA-ILD), is an important extra-articular manifestation of rheumatoid arthritis (RA). The frequency, risk factors, and prognosis of RA-ILD are incompletely understood. AimsTo determine the prevalence and incidence, clinical characteristics and risk factors for development, and outcomes of persons with RA-ILD in the population of the Canterbury District Health Board (CDHB) catchment area. MethodsIndividuals aged ≥ 18 years with RA, resident in the CDHB catchment area between 1 January 2006 and 31 December 2008 (Period One), and 1 January 2011 to 31 December 2013 (Period Two) were identified by medical record review and followed until 30 June 2019. Individuals with RA-ILD as defined by pre-specified criteria were identified. The association between demographic and clinical characteristics and RA-ILD development and mortality was examined using Cox-proportional hazards models. ResultsThe prevalence of RA-ILD per 100,000 was 10.97 (95 % CI 7.53,14.42) for Period One, and 14.74 (95 % CI 10.84,18.63) for Period Two. Among individuals evaluated for risk factors for RA-ILD development, the estimated cumulative incidence of ILD at 10 years was 4.47 % (95 % CI 3.14, 6.14). After adjusting for age, rheumatoid factor positivity (HR 3.73, 95 % CI, 1.32,10.56), extra-articular manifestations other than RA-ILD (HR 4.48, 95 % CI 2.36,8.48), and subcutaneous rheumatoid nodules (HR 4.66, 95 % CI 2.34, 9.26) were associated with increased risk of developing RA-ILD. The standardised mortality ratio for RA-ILD was 3.90 (95 % CI 2.55,5.72) compared to the general population. Extent of ILD on CT chest was associated with mortality (HR for >20% vs. < 20 % 4.47, 95 % CI 1.67,11.96). ConclusionsClinically evident RA-ILD occurred in approximately 5 % of individuals with RA. Mortality was increased almost fourfold compared to the general population. Radiologic extent was the most important prognostic factor.

Decline in Incidence of Extra-Articular Manifestations of Rheumatoid Arthritis: A Population-Based Cohort Study.

The focus of this study was to assess changes in the cumulative incidence of extra-articular manifestations of rheumatoid arthritis (ExRAs) and associated mortality risk. This study evaluated trends in occurrence of ExRAs using a population-based inception cohort that included all adult patients with incident rheumatoid arthritis (RA) from 1985 through 2014 meeting the 1987 American College of Rheumatology criteria. Patients were divided into two cohorts based on the incidence date of RA, 1985 to 1999 and 2000 to 2014. The occurrence of ExRAs was determined by manual chart review, and the 10-year cumulative incidence was estimated for each ExRA in both cohorts. Cox proportional hazard models were used to determine associations between specific demographic and RA disease characteristics and ExRAs and between ExRAs and mortality. There were 907 patients included, 296 in the 1985 to 1999 cohort and 611 in the 2000 to 2014 cohort. The 10-year cumulative incidence of any ExRA decreased significantly between the earlier and later cohorts (45.1% vs 31.6%, P < 0.001). This was largely driven by significant declines in subcutaneous rheumatoid nodules (30.9% vs 15.8%, P < 0.001) and nonsevere ExRAs (41.4% vs 28.8%, P = 0.001). Identified risk factors for the development of any ExRAs include rheumatoid factor positivity (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.43-2.86) and current smoking (HR 1.61, 95% CI 1.10-2.34). Mortality was increased in patients with either nonsevere (HR 1.83, 95% CI 1.18-2.85) or severe ExRAs (HR 3.05, 95% CI 1.44-6.49). The incidence of ExRAs has decreased over time. Mortality remains increased in patients with ExRAs.

Increased mortality in patients with RA-associated interstitial lung disease: data from a French administrative healthcare database

ObjectivesInterstitial lung disease (ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). The objectives of this study were to estimate mortality rate in patients with RA-ILD and identify factors...

Symposium 4

Interstitial lung disease (ILD) is a fibrotic disease of the lung parenchyma. It can occur in different connective tissue diseases, including rheumatoid arthritis (RA). Smoking, male gender and longstanding RA are possible risk factors for developing ILD 1 . Being a common extra-articular manifestation of RA, it can contribute to decreased quality of life, chronic disability, high utilization of healthcare resources, and may also lead to substantial morbidity and mortality for affected patients1. Hence, early identification and management is of paramount importance to improve patient outcomes. Clinical presentation, chest X-ray, pulmonary function testing and high-resolution computed tomography are common tools for investigation and they also allows assessment of subtype and disease extent 2 . The histopathologic and radiographic features of RA-ILD are heterogeneous. The most frequent patterns of RA-ILD are usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). Distinguishing the patterns is useful in predicting prognosis and would also affect subsequent management approach 2 . Traditionally treatment initiated for RA-ILD was generally empirical. Corticosteroids were often used as first-line agents and immunosuppressants maybe added2. However, these treatments are not specific and mainly target inflammation instead of fibrosis. With the advance in medicine, antifibrotic is now indicated for treating fibrosing ILD with progressive phenotype. FVC decline can be slowed in patients with connective tissue disease associated progressive ILD 3 . In this lecture, Prof. Vanessa Smith will share the current knowledge and evidence in RA-ILD. The approach on identifying and screening ILD in RA patients would be presented. The management strategy and options would also be reviewed.

Rheumatoid Vasculitis and Blepharitis Caused By Rheumatoid Arthritis In 6 Years Old Boy: A Case Report

Link of Video Abstract: https://youtu.be/4Guk_6foSxw Introduction: Rheumatoid Vasculitis (RV) is a rare complication affecting approximately 1% of patients with severe rheumatoid arthritis. This condition is an extra-articular manifestation of rheumatoid arthritis that affects the small and medium arteries in the body. Vasculitis is an inflammatory necrotizing vascular wall disease that can occur in autoimmune disease. This inflammation leads to damage in blood vessels due to stenosis or occlusion and thrombosis, resulting in pain, necrosis, and aneurysm. Inflammation can be primary or secondary. Skin, fingers, peripheral nerves, eyes and the heart are the most commonly affected areas. Case description: We report a case of a 6-year-old boy who presented RV and blepharitis. The patient subsequently experienced nail fold infarcts and gangrene of his left finger. He was found to fulfill Jones Criteria, and treatment with aspirin and corticosteroids significantly improved his symptoms. This rare case describes the early onset of rheumatoid vasculitis in a patient with rheumatoid arthritis. Rheumatoid vasculitis is a systemic disease that develops from rheumatoid arthritis with rheumatoid autoantibodies and extra-articular manifestations characterized by tissue damage or ischemia involving the skin and peripheral nerves. The incidence of rheumatoid vasculitis in children is less than 1%, with 12 to 53 cases per 100,000 children under 17 years old. Conclusion: Rheumatoid vasculitis is a rare complication of rheumatoid. This condition occurs in patients who have rheumatoid arthritis for a long period. The patient will prevent further complications with early diagnostic and proper treatment.

P27 A case of unilateral scleritis and biopsy proven retinal vasculitis in an elderly woman with rheumatoid arthritis and previous retinal detachment surgery with silicone oil band

P27 A case of unilateral scleritis and biopsy proven retinal vasculitis in an elderly woman with rheumatoid arthritis and previous retinal detachment surgery with silicone oil band

Carpal Tunnel Syndrome in Rheumatoid Arthritis Patients

Abstract Background Carpal tunnel syndrome (CTS) is one of the most frequent extra-articular manifestations of rheumatoid arthritis (RA). Aim and objectives to assess the presence and severity of Carpal tunnel syndrome in rheumatoid arthritis patients and its relation to disease activity. Patients and Methods This is observational cross sectional study, was carried out 30 rheumatoid arthritis patients recruited from Ain Shams University Hospital)inpatient internal medicine department and rheumotology outpatient clinic) in the period from November (2018) till November (2020). Result Only ultrasound assesment of CTS by measuring Of CSA&amp;gt;10 at wrist showed significant positive correlation with RA Patients ages, RA disease duration, CTS symptoms duration, CRP, RF and anti ccp positivity and negative correlation with HB% indicating association with disease compare to others activity. Conclusion CTS frequency in RA is found higher than normal population, especially in patients with additional risk factors of CTS. There was no relationship between CTS and disease activity, and CTS group had long disease duration and worse functional status. CTS could be a result of the chronic course in RA.

Serum CHI3L1 as a biomarker of interstitial lung disease in rheumatoid arthritis.

Interstitial lung disease (ILD) is a relatively prevalent extra-articular manifestation of rheumatoid arthritis (RA) and contributes to significant morbidity and mortality. This study aimed to analyze the association between chitinase-3 like-protein-1(CHI3L1) and the presence of RA-ILD. A total of 239 RA patients fulfilling the American Rheumatism Association (ACR) 1987 revised criteria were enrolled and subclassified as RA-ILD and RA-nILD based on the results of high-resolution computed tomography scans (HRCT) of the chest. The disease activity of RA was assessed by Disease Activity Score for 28 joints (DAS28) and categorized as high, moderate, low, and remission. Chemiluminescence immunoassays were applied to determine the serum levels of CHI3L1. Univariate analysis was performed and the receiver operating characteristics (ROC) curves were plotted to evaluate the correlation between RA-ILD and CHI3L1. Among the eligible RA patients studied, 60 (25.1%) patients were diagnosed with RA-ILD. Compared with RA-nILD, RA patients with ILD had significantly higher median age (median [IQR], 68.00 [62.00-71.75] vs 53.00 [40.00-63.00], p<0.001) and a higher proportion of males (21 (35.0%) vs 30 (16.8%), p=0.003). Notably, differences in DAS28 scores between the two groups were not observed. The serum level of CHI3L1 was significantly higher in RA-ILD patients (median [IQR], 69.69 [44.51-128.66] ng/ml vs 32.19 [21.63-56.99] ng/ml, p<0.001). Furthermore, the areas under the curve (AUC) of CHI3L1 attained 0.74 (95% confidence interval [CI], 0.68-0.81, p<0.001) in terms of identifying patients with RA-ILD from those without ILD. Similar trends were seen across the spectrum of disease activity based on DAS28-ESR. Our findings of elevated serum CHI3L1 levels in RA-ILD patients suggest its possible role as a biomarker to detect RA-ILD noninvasively.

Extra-articular manifestations of rheumatoid arthritis remain a major challenge: data from a large, multi-centric cohort

IntroductionAlthough Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients.ObjectiveTo determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables.MethodCross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann–Whitney U-test, and Fisher’s exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05).Results1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) (‘p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group.ConclusionsExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development.

Renal function in patients with rheumatoid arthritis in Rafsanjan city in 2021

Renal involvement is one of the extra-articular manifestations of rheumatoid arthritis (RA). The current study aims to investigate renal function and its associated factors in RA patients. This cross-sectional study included 443 RA patients who were referred to Rafsanjan's only rheumatology clinic in 2021. Disease Activity Score 28 (DAS28) index was used to determine disease activity. Blood levels of creatinine, C-Reactive Protein test (CRP), Erythrocyte Sedimentation Rate (ESR), and urine analysis were also determined. Renal failure was classified based on Estimated Glomerular Filtration Rate (eGFR). SPSS.20 one-way ANOVA, Kruskal-Wallis test, the Mann-Whitney U test, and Chi-square were used to analyze the data. Patiens' mean age was 53.99 ± 12.34, and 85.8% (380 people) of the participants were female. Ther were 147 (33.2%) patients without renal failure, 260 (58.7%) with mild renal failure, and 36 (8.1%) with moderate/severe failure. Men had a 3.059 higher risk of renal failure than women (P = 0.001). The probability of developing renal failure in patients increased by 1.047 times with each year of age (P &lt; 0.001). As a chronic disease, RA can directly or through the use of disease medications and other risk factors, adversely affect other organs of the body, including the kidney. The current study's findings revealed a high prevalence of mild renal failure in these patients.

Comorbidities and extra-articular manifestations of Rheumatoid arthritis in sub-Saharian Africa

Rheumatoid arthritis is a systemic auto-immune disorder that preferentially affects the joints. Extra-articular manifestations and comorbidities observed during rheumatoid arthritis are multiple and frequent. They are the cause of high morbidity and mortality in this population and make rheumatoid arthritis serious. Systematic screening for the extra-articular manifestations and comorbidities is therefore necessary in order to optimize its management in affected subjects. The various studies carried out on rheumatoid arthritis in developing countries have explored less the extra-articular manifestations as well as the comorbidities. This work reviews the literature on the extra-articular manifestations as well as the comorbidities encountered in subjects with rheumatoid arthritis in Sub saharia Africa in order to draw the attention of the nursing medical staff to their extent in order with a view to systematic screening and treatment.

P111 Exploratory Analysis of Filgotinib Safety Data in Patients With Moderately to Severely Active Rheumatoid arthritis and an Increased Risk of Cardiovascular Events: Data From Phase 2 and 3 Clinical Trials

Abstract Background/Aims The safety profile of filgotinib (FIL), a second-generation oral Janus kinase (JAK) 1 preferential inhibitor approved in Europe, Japan, and the UK for treatment of rheumatoid arthritis (RA) has been reported. In patients (pts) with active RA aged ≥50y with ≥1 cardiovascular (CV) risk factor, treated with the pan-JAK inhibitor tofacitinib, data from an interventional post-marketing study (NCT02092467) suggested a higher risk of major adverse cardiovascular events (MACE) and malignancies compared with TNF inhibitors. No data are available from a similar prospective study with FIL. This post hoc exploratory analysis aimed to describe the incidence of MACE and malignancies in a subgroup of pts with RA from the FINCH and DARWIN clinical trials, receiving FIL 200 mg (FIL200) and FIL 100 mg (FIL100). Methods Exploratory analysis of adverse events of special interest are reported using integrated FIL RA data from phase 2 (NCT01668641, NCT01894516), phase 3 (NCT02889796, NCT02873936, NCT02886728), and the long-term extension (LTE) studies DARWIN 3 (NCT02065700) and FINCH 4 (NCT03025308), in a pt population at higher risk of CV events similar to ORAL-SURVEILLANCE,1 namely, aged ≥50y with ≥1 CV risk factor (history of dyslipidemia, diabetes or CV disease; hypertension, ischemic vascular conditions, peripheral vascular disease, extra-articular manifestations of RA; or current smokers). All pts met ACR criteria for functional class I-III. Censored exposure-adjusted incidence rates (EAIRs)/100 pt-years of exposure for MACE, venous thromboembolism (VTE), malignancies excluding nonmelanoma skin cancer (NMSC), NMSC, (serious) infections, and deaths were determined. Data were as of Jan 11, 2022 (DARWIN 3) and Jan 31, 2022 (FINCH 4). Analyses were performed on an ad hoc interim analysis data set without additional cleaning. Results The higher-risk population included 1484 pts: mean age 62.1y (536 [36.1%] aged ≥65y), 291 (22.5%) current smokers, and 904 (60.9%) received background MTX; baseline (BL) MTX use was higher in the FIL100 vs FIL200 group (66.6% vs 54.6%); other BL demographics were balanced. Numerically higher EAIRs for malignancies (excluding NMSC), NMSC, serious infections, and deaths were observed for pts receiving FIL200 vs FIL100; 95% confidence intervals overlapped. For MACE and VTE, incidence is considered similar for both doses. The risk of experiencing MACE, malignancies excluding NMSC, and NMSC over time with FIL100 or FIL200 will be described. Conclusion In this RA population at higher risk of CV events, the incidence of MACE and VTE was similar for both doses. A numerically higher incidence of malignancies (excluding NMSC), NMSC, serious infections, and deaths was observed in the high- vs low-dose group. Limitations included population selection bias, low event numbers, and the post hoc nature of the analysis. The ongoing LTE and real-world studies in RA will continue to investigate the safety of FIL in these populations. Disclosure M.H. Buch: Honoraria; MHB has recieved funding (Paid to her host institution) fromAbbVie, Galapagos, Gilead, Pfizer, Eli Lilly, Merck-Serono, Roche, UCB. G.R. Burmester: Honoraria; AbbVie, Galapagos, Lilly, MSD, Pfizer, Roche, UCB, Janssen, Gilead Sciences, Inc. X. Mariette: Honoraria; AstraZeneca, Bristol Myers Squibb, Galapagos, GSK, Novartis, Pfizer. C. Charles-Schoeman: Honoraria; AbbVie, Bristol Myers Squibb (BMS), Pfizer, Regeneron-Sanofi, Gilead. V. Rajendran: Other; Employee of Galapagos NV. P. Stiers: Other; Employee of Galapagos NV. A. Cerani: Other; Employee of Galapagos NV. P. Van Hoek: Other; Employee of Galapagos NV. K. Van Beneden: Other; Employee of Galapagos NV. Y. Tanaka: Honoraria; Lilly, AbbVie, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Pfizer, Mitsubishi Tanabe, GlaxoSmithKline, Asahi Kasei, Takeda, Astellas, Janssen, Novartis, Sanofi, UCB, YL Biologics, MSD, Ono, T. H. Schulze-Koops: Honoraria; AbbVie, Galapagos, Lilly, Pfizer. R. Westhovens: Honoraria; Celltrion, Galapagos, Gilead. E. Favalli: Honoraria; AbbVie, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB.

E023 Rheumatoid vasculitis presenting in the absence of rheumatoid arthritis

Abstract Background/Aims Rheumatoid vasculitis (RV) is an extra-articular manifestation of rheumatoid arthritis (RA) which is usually seen in long-standing severe disease, affecting approximately 1-5% of the patient population. It involves small- to medium-sized arteries and has a high mortality rate of 40% at 5 years post-diagnosis. Methods In this report we describe a case of a 58-year-old male with no significant past medical history other than previous heavy smoking, who presented with a several week history of weakness, paraesthesia, numbness and pain affecting both hands and feet. He had also experienced weight loss of 12lbs in a short period, night sweats, and arthralgia in his hands, along with a six-week history of Raynaud’s phenomenon. Results Examination revealed nailfold infarcts but there was no evidence of synovitis and this was subsequently confirmed to be absent on ultrasound of the small joints of the hands and feet. Investigations showed: CRP 79, ESR 52, rheumatoid factor &amp;gt;130 and anti-CCP &amp;gt;733. Cryoglobulins were not detected, complement was normal and neuropathy screen bloods including viral and autoantibody screens were otherwise unremarkable. During admission he developed nodular lesions over the extensor aspect of his forearms bilaterally, consistent with rheumatoid nodules. These evolved over a period of four days. He also developed a vasculitic rash over the medial malleolus of his left foot. Nerve conduction studies demonstrated mononeuritis multiplex and PET CT showed evidence of small vessel vasculitis. CT chest, abdomen and pelvis identified a 3cm hypodense lesion within the tail of the pancreas, subsequently found to be a benign lymphoepithelial cyst on biopsy. Treatment with intravenous methylprednisolone for three days resulted in a rapid improvement in both motor and sensory function of his limbs. On discharge, he was commenced on oral methotrexate and a reducing course of prednisolone, starting at 30mg daily. The clinical picture was highly suggestive of RV in the absence of an established inflammatory arthritis. When reviewed three months post-discharge he reported continuing improvement of his symptoms; the nodules had regressed in size and almost disappeared. Conclusion To our knowledge, only seven cases have been reported in the literature of a patient with RV at initial diagnosis of RA and two cases in which a diagnosis of RV preceded the diagnosis of RA. Due to its high mortality and morbidity we would like to increase awareness amongst clinicians of this unusual vasculitic form of clinical presentation of RA. Disclosure D.A.J. Cromie: None. S.K. Stewart: None. G.D. Wright: None.

Rheumatoid nodules: a narrative review of histopathological progression and diagnostic consideration.

Rheumatoid nodules (RNs) are the most common extra-articular manifestation of rheumatoid arthritis and are also seen in patients with other autoimmune and inflammatory diseases. The development of RNs includes histopathological stages of acute unspecified inflammation, granulomatous inflammation with no or minimal necrosis, necrobiotic granulomas typically with central fibrinoid necrosis surrounded by palisading epithelioid macrophages and other cells, and likely an advanced stage of "ghost" lesions containing cystic or calcifying/calcified areas. In this article, we review RN pathogenesis, histopathological features in different stages, diagnostically related clinical manifestations, as well as diagnosis and differential diagnosis of RNs with an in-depth discussion about challenges in distinguishing RNs from their mimics. While the pathogenesis of RN formation remains elusive, it is hypothesized that some RNs with dystrophic calcification may be in transition and may be in coexistence or collision with another lesion in patients with RA or other soft tissue diseases and comorbidities. The diagnosis of typical or mature RNs in usual locations can be readily made by clinical findings often with classic RN histopathology, but in many cases, particularly with atypical or immature RNs and/or unusual locations, the clinical and histopathological diagnosis can be challenging requiring extensive examination of the lesional tissue with histological and immunohistochemical markers to identify unusual RNs in the clinical context or other lesions that may be coexisting with classic RNs. Proper diagnosis of RNs is critical for appropriate treatment of patients with RA or other autoimmune and inflammatory diseases.

Implementation of automated behavior metrics to evaluate voluntary wheel running effects on inflammatory-erosive arthritis and interstitial lung disease in TNF-Tg mice

BackgroundAlthough treatment options and algorithms for rheumatoid arthritis (RA) have improved remarkably in recent decades, there continues to be no definitive cure or pharmacologic intervention with reliable long-term efficacy. For this reason, the combination of medications and healthy lifestyle modifications are essential for controlling joint disease, and extra-articular manifestations of RA, such as interstitial lung disease (ILD) and other lung pathologies, which greatly impact morbidity and mortality. Generally, exercise has been deemed beneficial in RA patients, and both patients and clinicians are motivated to incorporate effective non-pharmacologic interventions. However, there are limited evidence-based and specific exercise regimens available to support engagement in such activities for RA patients. Here, we provided the continuous opportunity for exercise to mice and implemented automated recording and quantification of wheel running behavior. This allowed us to describe the associated effects on the progression of inflammatory-erosive arthritis and ILD in the tumor necrosis factor transgenic (TNF-Tg) mouse model of RA.MethodsWild-type (WT; males, n=9; females, n=9) and TNF-Tg (males, n=12; females, n=14) mice were singly housed with free access to a running wheel starting at 2 months until 5 to 5.5 months of age. Measures of running included distance, rate, length, and number of run bouts, which were derived from continuously recorded data streams collected automatically and in real-time. In vivo lung, ankle, and knee micro-computed tomography (micro-CT), along with terminal micro-CT and histology were performed to examine the association of running behaviors and disease progression relative to sedentary controls.ResultsTNF-Tg males and females exhibited significantly reduced running distance, rate, length, and number of run bouts compared to WT counterparts by 5 months of age (p<0.0001). Compared to sedentary controls, running males and females showed increased aerated lung volumes (p<0.05) that were positively correlated with running distance and rate in female mice (WT: Distance, ρ=0.705/rate, ρ=0.693 (p<0.01); TNF-Tg: ρ=0.380 (p=0.06)/ρ=0.403 (p<0.05)). Talus bone volumes were significantly reduced in running versus sedentary males and negatively correlated with running distance and rate in TNF-Tg mice (male: ρ=−903/ρ=−0.865; female: ρ=−0.614/ρ=−0.594 (p<0.001)). Histopathology validated the lung and ankle micro-CT findings.ConclusionsImplementation of automated wheel running behavior metrics allows for evaluation of longitudinal activity modifications hands-off and in real-time to relate with biomarkers of disease severity. Through such analysis, we determined that wheel running activity increases aerated lung volumes, but exacerbates inflammatory-erosive arthritis in TNF-Tg mice. To the end of a clinically relevant model, additional functional assessment of these outcomes and studies of pain behavior are warranted.

Scleritis in rheumatoid arthritis: Before and during biologic era.

Scleritis represents a severe extra-articular manifestation of rheumatoid arthritis (RA). Recent clinical observations suggest a decreasing incidence of scleritis in RA, attributed to improved treatment options. Our study reports on the incidence and clinical characteristics of scleritis in RA observed in the biological era and reflects on our results in a historical perspective. We performed a retrospective evaluation of all 1623 consecutive patients with RA diagnosed at the department of rheumatology between 2011 and 2021 at the Erasmus Medical Center to investigate the incidence of scleritis. We also reviewed clinical and laboratory data of all patients with scleritis and RA from the department of ophthalmology at our center. In addition, we reviewed the literature on this topic and discuss our results in view of changes over time. The incidence of scleritis within recent series of patients with a diagnosis of RA in our tertiary center was 0,25% in 10 years (4 out of 1623; 2011-2021).The cumulative incidence of scleritis in RA based on literature review from the pre-biologic era varied from 0.7% per 8 years to 0,8% per 30 years. Manifestations and complications of scleritis remained unchanged over time, with scleral necrosis developing in more than 80% of cases and mortality of RA patients with scleritis remained similar to pre-biologic era (30% in 9 years after the onset of scleritis). The RA patients with scleritis often exhibited autoantibodies (rheumatoid factor and/or anti-citrullinated protein antibody) and erosive disease. Although our recent series is characterized by a slightly lower incidence of scleritis in RA compared to the pre-biologic era, clinical presentation remained severe and similar to the pre-biologic era. Ophthalmologists and rheumatologists should be aware of scleritis as a severe extra-articular manifestation of RA.

Tomographic pleuropulmonary manifestations in rheumatoid arthritis: a pictorial essay.

Rheumatoid arthritis (RA) is an autoimmune inflammatory and heterogeneous disease that affects several systems, especially the joints. Among the extra-articular manifestations of RA, pleuropulmonary involvement occurs frequently, with different presentations, potentially in all anatomic thoracic compartments, and may determine high morbidity and mortality. The most common pleuropulmonary manifestations in patients with RA include interstitial lung disease (ILD), pleural disease, pulmonary arterial hypertension, rheumatoid lung nodules, airway disease (bronchiectasis and bronchiolitis), and lymphadenopathy. Pulmonary hypertension and ILD are the manifestations with the greatest negative impact in prognosis. HRCT of the chest is essential in the evaluation of patients with RA with respiratory symptoms, especially those with higher risk factors for ILD, such as male gender, smoking, older age, high levels of rheumatoid factor, or positive anti-cyclic citrullinated peptide antibody results. Additionally, other etiologies that may determine tomographic pleuropulmonary manifestations in patients with RA are infections, neoplasms, and drug-induced lung disease. In these scenarios, clinical presentation is heterogeneous, varying from being asymptomatic to having progressive respiratory failure. Knowledge on the potential etiologies causing tomographic pleuropulmonary manifestations in patients with RA coupled with proper clinical reasoning is crucial to diagnose and treat these patients.