Inflammatory Arthritis Patients Research Articles

O11 Lymphocyte DNA methylation mediates genetic risk at RA risk loci that are shared with other immune mediated diseases

Abstract Background The aetiology of rheumatoid arthritis (RA) is complex. In particular, the vast majority of disease-associated variants implicated by genome-wide association studies are non-coding, leaving genetic mechanisms of adaptive immune dysregulation unresolved. The contribution to this process of epigenetic factors, including the addition of methyl groups to DNA, also remains uncertain. To address these issues and prioritise causal genes for downstream study, genome-wide data incorporating DNA methylation and gene expression measurements from lymphocyte subsets in an early arthritis inception cohort, were available. Methods Whole genome methylation and transcription data from isolated CD4+ T cells and B cells of > 100 well-characterised inflammatory arthritis patients, all of whom were naïve to immunomodulatory treatments and of Northern European ancestry, were obtained (Illumina HumanHT-12 v4 Expression BeadChip and Infinium MethylationEPIC BeadChip arrays, respectively). Genotyping was undertaken using the Illumina Human CoreExome-24 version 1-0 array. After independent pre-processing, normalisation and quality control of paired CD4+ and B lymphocyte data, methylation quantitative trait loci (meQTLs) were first modelled using the MatrixEQTL package in each cell type. Next, at RA risk-associated cis-CpGs, correlations between site-specific methylation and the expression of genes within ±500Kb identified quantitative trait methylations (eQTMs). To infer directionality of SNP-CpG-transcript associations a causal inference test (CIT) was applied. Multiple testing was accounted for, and in vitro assays were used to validate meQTLs at loci of interest and confirm regulatory mechanisms. Further analysis integrated GWAS data from other immune mediated diseases (IMDs) and additional publically available resources. Results We found strong evidence that disease-associated DNA variants regulate cis-CpG methylation of DNA in CD4+ T and/or B cells at 37% RA loci. In general we observed these variants to preferentially modify methylation at sites mapping to lymphocyte enhancers and regions flanking transcription start sites, and at positions bound by the NFκB transcription factor. Using paired, cell-specific transcriptomic data and a statistical approach to infer causality, we then identified examples where site-specific DNA methylation in turn mediates gene expression, including ORMDL3/GSDMB, IL6ST/ANKRD55, FCRL3 and JAZF1 in CD4+ lymphocytes. Leveraging GWAS data we noted that a number of genes regulated in this way highlight mechanisms common to RA, multiple sclerosis and asthma, distinguishing these IMDs from osteoarthritis which is considered a primarily degenerative disease. To validate our findings, cis-meQTL effects at sentinel loci were replicated by pyrosequencing in an independent cohort of genotyped early arthritis patients, and methylation-mediated regulation of FCRL3 expression downstream of the regulatory SNP was confirmed experimentally using a luciferase reporter assay in Jurkat T-cells. Conclusion Our observations highlight important mechanisms of genetic risk in RA and the wider context of autoimmunity. They confirm the utility of DNA methylation profiling as a tool for causal gene prioritisation and, potentially, therapeutic targeting in complex IMD. Disclosures A.D. Clark None. N. Nair None. A.E. Anderson None. N. Thalayasingam None. N. Naamane None. A.J. Skelton None. J. Diboll None. A. Barton None. S. Eyre None. J.D. Isaacs None. L.N. Reynard None. A.G. Pratt Grants/research support; I am a recipient of an unrestricted, investigator initiated research grant from Pfizer, paid to Newcastle University.

Appropriating and asserting power on inflammatory arthritis teams: A social network perspective.

BackgroundTherapeutic interventions for people with inflammatory arthritis (IA) increasingly involve multidisciplinary teams and strive to foster patient‐centred care and shared decision making. Participation in health‐care decisions requires patients to assert themselves and negotiate power in encounters with clinicians; however, clinical contexts often afford less authority for patients than clinicians. This disadvantage may inhibit patients' involvement in their own health care.ObjectiveTo identify communication attributes, IA patients use to influence and negotiate their treatment with members of their health‐care network.MethodA qualitative social network approach was used to analyse data from a larger study that investigated IA patients' overall experiences of multidisciplinary care. Fourteen patients with IA attended individual semi‐structured interviews. Researchers used thematic analysis to identify patterns of assertiveness and influence in the data.ResultsParticipants experienced loss of identity, control and agency in addition to the physical symptoms of IA. However, they had a sense of personal responsibility for managing their health care. Perceptions of health‐care team support enhanced patients' influence in treatment negotiations. Notably, there appeared to be an underlying tension between being empowered or disempowered.Discussion and conclusionsThe findings have significant implications for treatment decision communication approaches to IA care. A social network perspective may provide a pathway for clinicians to better understand the complexities of communication with their patients. This approach may reduce unequal power dynamics that occur within clinician/patient interactions and afford people with IA agency, control and affirmation of identity within their health‐care network.

T-cell subset abnormalities predict progression along the Inflammatory Arthritis disease continuum:\xa0implications for management

The presence of a disease continuum in inflammatory arthritis (IA) is a recognised concept, with distinct stages from at-risk stage (presence of anti citrullinated-peptide autoantibody) to diagnosis of rheumatoid arthritis (RA), including therapy-induced remission. Despite T-cell dysregulation being a key feature of RA, there are few reports of T-cell phenotyping along the IA-continuum. We investigated the disturbances of naïve, regulatory and inflammation related cell (IRC) CD4+ T-cell subsets in 705 individuals across the IA-continuum, developing a simple risk-score (summing presence/absence of a risk-associated with a subset) to predict progression from one stage to the next. In 158 at-risk individuals, the 3 subsets had individual association with progression to IA and the risk-score was highly predictive (p < 0.0001). In evolving IA patients, 219/294 developed RA; the risk-score included naïve and/or Treg and predicted progression (p < 0.0001). In 120 untreated RA patients, the risk-score for predicting treatment-induced remission using naïve T-cells had an odds ratio of 15.4 (p < 0.0001). In RA patients in treatment-induced remission, a score using naïve T-cells predicted disease flare (p < 0.0001). Evaluating the risk of progression using naïve CD4+ T-cells was predictive of progression along the whole IA-continuum. This should allow identification of individuals at high-risk of progression, permitting targeted therapy for improved outcomes.

Introduction: Evolution of inflammatory arthritis from innate to adaptive immune mechanisms.

Introduction: Evolution of inflammatory arthritis from innate to adaptive immune mechanisms.

Keeping Stable Inflammatory Arthritis Patients in Their Communities With the Advanced Clinician Practitioner in Arthritis Care

Keeping Stable Inflammatory Arthritis Patients in Their Communities With the Advanced Clinician Practitioner in Arthritis Care

Amplified prevalence and incidence of cardiovascular disease in patients with inflammatory arthritis and coexistent autoimmune disorders.

This study aims to assess the prevalence proportion and incidence rate of cardiovascular morbidity in patients with inflammatory arthritis compared with that in controls, and to determine whether the co-existence of multiple autoimmune disorders is associated with an amplified risk of cardiovascular disease. Data from the Nivel Primary Care Database were used to assess prevalence proportion and incidence rate of cardiovascular disease in patients with inflammatory arthritis only, patients with inflammatory arthritis coexistent with another autoimmune disorder, and controls. Hazard ratios were calculated using Cox regression models. The prevalence proportions in inflammatory arthritis patients were increased for type 1 diabetes [odds ratio (OR) 1.80, 95% CI: 1.27, 2.55], hypothyroidism (OR 1.49, 95% CI: 1.37, 1.61), psoriasis (OR 2.72, 95% CI: 2.49, 2.97) and IBD (OR 2.64, 95% CI: 2.28, 3.07) compared with that in controls. Cardiovascular disease prevalence (OR 1.34, 95% CI: 1.28, 1.41) and incidence rates (incidence rate ratio 1.3, 95% CI: 1.23, 1.41) were higher in inflammatory arthritis patients compared with that in controls, and were further increased in the presence of a second autoimmune disorder. The hazard ratio for cardiovascular disease was 1.32 (95% CI: 1.23, 1.41) for patients with inflammatory arthritis only, and 1.49 (95% CI: 1.31, 1.68) for patients with inflammatory arthritis co-existent with another autoimmune disorder. The amplification of cardiovascular disease risk in inflammatory arthritis patients with multiple autoimmune disorders warrants greater awareness, and since autoimmune disorders often co-exist, the need for cardiovascular risk management in these patients is once again emphasized.

Immune checkpoint inhibitor-induced inflammatory arthritis as a model of autoimmune arthritis.

The development of inflammatory arthritis in patients receiving immune checkpoint inhibitor therapy is increasingly recognized due to the growing use of these drugs for the treatment of cancer. This represents an important opportunity not only to define the mechanisms responsible for the development of this immune-related adverse event andto ultimately predict or prevent its development, but also to provide a unique window into early events in the development of inflammatory arthritis. Knowledge gained through the study of this patient population, for which the inciting event is known, could shed light into the pathogenesis of autoimmune arthritis. This review will highlight the clinical and immunologic features of these entities to define common elements for future study.

Influence of inflammatory arthritis on leukocyte esterase strip results in the diagnosis of periprosthetic joint infection

BackgroundThe leukocyte esterase (LE) strip is considered as a helpful method to detect infection, which might be influenced by other inflammatory diseases. This study aims to explore whether the centrifugation of synovial fluid could influence the positive result of LE strip caused by inflammatory arthritis during the diagnosis of periprosthetic joint infection (PJI).MethodsFrom March 2016 to December 2018, 64 patients who were diagnosed as PJI or aseptic arthritis and another 20 patients with inflammatory arthritis were enrolled in our study. After synovial fluid samples were obtained, the LE strip test was performed with and without centrifugation. Then clinicians read the color changes 3 min after the samples were dropped and classify the results based on the instruction of strip. The differences between septic and aseptic arthritis patients and septic and inflammatory arthritis patients were analyzed.ResultsAmong the included 21 PJI samples, 19 of them showed positive results (++) of LE strip before centrifugation. After centrifugation, two samples changed from two-positive (++) to one-positive (+), which is also considered as positive. Before centrifugation, 29 of the LE strip tests in the aseptic arthritis group (43 samples included) were ++ or +. After centrifugation, 16 of the samples yielded negative results. Among 20 samples with inflammatory arthritis, LE strip of 18 samples were positive (++ or +) before centrifugation, among which only 3 samples remained as positive after centrifugation.ConclusionLE strip test results could be influenced by inflammatory arthritis during the diagnosis of PJI. Centrifugation should be performed for LE strip tests to determine whether the result is a true positive or a false positive influenced by inflammatory arthritis.

A Study Protocol on the Evaluation of Referral Strategies for Inflammatory Arthritis in Primary Care Patients at the Level of Healthcare Organization, Patient Relevant Outcomes and Costs

Background: Considering the importance of getting the right patient at the right location to maintain and optimize quality of life of inflammatory arthritis patients, appropriate referral by general practitioners is essential. This study aims to assess the effect and cost effectiveness of different referral strategies for inflammatory arthritis in primary care patients. Methods: This study follows a cluster randomized controlled trial design. General practitioners from primary care centers in Southwest-The Netherlands are randomly assigned to either one of the two strategic interventions for referring adult patients who are in the opinion of the general practitioner suspected of inflammatory arthritis: 1) Standardized digital referral algorithm based on existing referral models PEST, CaFaSpA and CARE; 2) Triage by a rheumatologist in the local primary care center. These interventions will be compared to a control group, e.g. usual care. The primary outcome is the percentage of patients diagnosed with inflammatory arthritis by the rheumatologist. Secondary outcomes are quality of life as a patient reported outcome, work participation and healthcare costs. These data, including demographic and clinical parameters, are prospectively collected at baseline, three, six, and twelve months. Discussion: If this study can demonstrate improvements in appropriate referrals to the rheumatologist, thereby improving cost-effectiveness, there is sufficient supporting evidence to implement one of the referral strategies as a standard of care. Finally, with these optimization strategies a higher quality of care can be achieved, that might be of value for all patients with arthralgia. Trial Registration: NCT03454438, date of registration: March 5, 2018. Retrospectively registered: https://clinicaltrials.gov/ct2/show/NCT03454438?term=NCT03454438&draw=1&rank=1.

A quality improvement intervention failed to significantly increase pneumococcal and influenza vaccination rates in immunosuppressed inflammatory arthritis patients.

Pneumococcal and influenza vaccination rates have been suboptimal in studies of immunosuppressed patients. We aimed to assess barriers to and increase rates of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and influenza vaccination in this group. The primary endpoint was a statistically significant increase in adequate PPSV23 and influenza vaccination. In 2017, rheumatology outpatients completed an anonymous questionnaire recording vaccination knowledge, status, and barriers. Simultaneously, a low-cost multifaceted quality improvement (QI) intervention was performed. All outpatients on oral steroids, immunosuppressant conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologics disease-modifying antirheumatic drugs (bDMARDs) were included in the study. In 2018, post-intervention, the clinic was re-assessed. Demographics, diagnosis, medications, smart phone access, and willingness to use this for vaccination reminders were assessed for independent vaccination predictors using binary logistic regression analysis. Four hundred twenty-five patients were included (72.6% rheumatoid arthritis, 74% women, 45.6% ≥60years old). From 2017 to 2018, PPSV23 vaccination rates changed from 41.0 to 47.2% (P = 0.29) and influenza from 61.8 to 62.1% (P = 0.95). The most common reason for non-vaccination was lack of awareness. Following the intervention, this changed for influenza (36.7 to 34.2%) and PPSV23 (82.1 to 76.4%). General practitioners performed most vaccinations, only 3.6% were delivered in the hospital. Significant predictors of PPSV23 vaccination were older age {≥ 80years had an OR 41.66 (95% CI 3.69-469.8, P = 0.003), compared with ≤ 39years}, bDMARD use (OR 2.80, 95% CI 1.24-6.32, P = 0.013), and adequate influenza vaccination (OR 9.01, 95% CI 4.40-18.42, P < 0.001). Up-to-date PPSV23 vaccination (OR 8.93, 95% CI 4.39-18.17, P < 0.001) predicted influenza vaccination. PPSV23 and influenza vaccination rates were suboptimal. The intervention did not cause a statistically significant change in vaccination rates. Point-of-care vaccination may be more effective.Key Points• Low vaccination rates amongst immunosuppressed inflammatory arthritis outpatients• Less than 5% of vaccinations occurred in hospital• There was no statistically significant difference in the rates of adequate PPSV23 (41.0 to 47.2%) or influenza (61.8 to 62.1%) vaccination following our intervention.

Targeting of tolerogenic dendritic cells to heat-shock proteins in inflammatory arthritis

BackgroundAutologous tolerogenic dendritic cells (tolDC) are a promising therapeutic strategy for inflammatory arthritis (IA) as they can regulate autoantigen-specific T cell responses. Here, we investigated two outstanding priorities for clinical development: (i) the suitability of using heat-shock proteins (HSP), abundant in inflamed synovia, as surrogate autoantigens to be presented by tolDC and (ii) identification of functional biomarkers that confirm tolDC regulatory activity.MethodsCell proliferation dye-labelled human peripheral blood mononuclear cells of IA (rheumatoid arthritis (RA) and psoriatic arthritis (PsA)) patients or healthy donors were cultured with HSP40-, HSP60- and HSP70-derived peptides or recall antigens (e.g. tuberculin purified protein derivative (PPD)) in the presence or absence of tolDC or control DC for 9 days. Functional characteristics of proliferated antigen-specific T-cells were measured using flow cytometry, gene expression profiling and cytokine secretion immunoassays. Repeated measures analysis of variance (ANOVA) with Bonferroni correction for comparisons between multiple groups and paired Student t test for comparisons between two groups were used to determine significance.ResultsAll groups showed robust CD4+ T-cell responses towards one or more HSP-derived peptide(s) as assessed by a stimulation index > 2 (healthy donors: 78%, RA: 73%, PsA: 90%) and production of the cytokines IFNγ, IL-17A and GM-CSF. Addition of tolDC but not control DC induced a type 1 regulatory (Tr1) phenotype in the antigen-specific CD4+ T-cell population, as identified by high expression of LAG3, CD49b and secretion of IL-10. Furthermore, tolDC inhibited bystander natural killer (NK) cell activation in a TGFβ dependent manner.ConclusionsHSP-specific CD4+ T-cells are detectable in the majority of RA and PsA patients and can be converted into Tr1 cells by tolDC. HSP-loaded tolDC may therefore be suitable for directing T regulatory responses to antigens in inflamed synovia of IA patients. Tr1 markers LAG3, CD49b and IL-10 are suitable biomarkers for future tolDC clinical trials.

Reverse shoulder arthroplasty for rheumatoid arthritis since the introduction of disease-modifying drugs.

Rheumatoid arthritis has been associated with poor clinical outcomes in hemiarthroplasty and unconstrained total shoulder arthroplasty. The reverse shoulder arthroplasty can be utilized to address the shortcomings of hemiarthroplasty and unconstrained total shoulder arthroplasty in the inflammatory arthritis patient population. The objective of the present study was to retrospectively review clinical and radiographic outcomes of patients who underwent reverse shoulder arthroplasty for rheumatoid arthritis and other inflammatory arthropathies and provide a comprehensive analysis to identify factors that may alter patient outcomes. We identified 91 primary reverse shoulder arthroplasties performed between 2006 and 2013 in patients with inflammatory arthritis. Seventy-five had at least two years of follow up with an average follow-up of 4.0years. The average age at the time of surgery was 70years old. Peri-operative use of steroids, biologics, and methotrexate were reviewed. Outcomes evaluated included revision and reoperation rates, complications, American Shoulder and Elbow Surgeons (ASES) scores, simple shoulder test (SST) scores, component loosening, and scapular notching. The two and five year implant revision-free survival was 99%. The two and five year re-operation-free survival was 97%. Eighteen (24%) glenoid components required augmentation with corticocancellous autograft from the humeral head. There were two cases of glenoid loosening with gross changes in position. Patients experienced significant pain relief with a 92% satisfaction rate. Shoulder elevation and external rotation improved from 65 and 21 degrees pre-operatively to 138 and 45 degrees post-operatively, respectively (p < .01). Average ASES and SST scores were 72 and 7.0, respectively. The use of prednisone, DMARDs, or biologic medications had no significant impact on outcomes.

Detecting inflammation in rheumatoid arthritis using Fourier transform analysis of dorsal optical transmission images from a pilot study.

.A clinical need exists for low-cost and noninvasive imaging tools capable of detecting inflammation in the joints of inflammatory arthritis patients. Previous studies have reported an optical contrast between inflamed and noninflamed joints resulting from distinct absorption and scattering properties. Accurate classification using nonocclusion-based continuous wave, transillumination imaging was limited to patient-specific changes during follow-up examination as opposed to single time-point examination, which was attributed to high intersubject variability. In distinction from previous work, optical images were acquired from the dorsal side with illumination on the palmar side and features about the spatial distribution of transmitted light along the joint were assessed using a normalized Fourier transform method. Results using this approach demonstrated an area under receiver operator curve of up to 0.888 for detecting inflammation in a pilot study involving single time-point examination of 144 joints from 21 rheumatology patients. This workflow may enable future development of clinically viable, low-cost devices for assessing inflammation in arthritis patients, without the need for cuff occlusion or comparison to baseline.

APRIL Induces a Novel Subset of IgA+ Regulatory B Cells That Suppress Inflammation via Expression of IL-10 and PD-L1.

Regulatory B cells (Bregs) are immunosuppressive cells that modulate immune responses through multiple mechanisms. The signals required for the differentiation and activation of these cells remain still poorly understood. We have already shown that overexpression of A PRoliferation-Inducing Ligand (APRIL) reduces the incidence and severity of collagen-induced arthritis (CIA) in mice. Furthermore, we have described that APRIL, but not BAFF, promoted IL-10 production and regulatory functions in human B cells. Therefore, we hypothesized that APRIL, but not BAFF, may be involved in the induction and/or activation of IL-10 producing Bregs that suppress inflammatory responses in vitro and in vivo. Here, we describe that APRIL promotes the differentiation of naïve human B cells to IL-10-producing IgA+ B cells. These APRIL-induced IgA+ B cells display a Breg phenotype and inhibit T cell and macrophage responses through IL-10 and PD-L1. Moreover, APRIL-induced IL-10 producing Bregs suppress inflammation in vivo in experimental autoimmune encephalitis (EAE) and contact hypersensitivity (CHS) models. Finally, we showed a strong correlation between APRIL and IL-10 in the inflamed synovial tissue of inflammatory arthritis patients. Collectively, these observations indicate the potential relevance of this novel APRIL-induced IgA+ Breg population for immune homeostasis and immunopathology.

Association of rs2910164 Polymorphism in miRNA-146 and rs3746444 Polymorphism in miRNA-499 with Inflammatory Arthritis: A Meta-Analysis.

Objectives The purpose of this study was to explore the association of miRNA-146 and miRNA-499 polymorphisms with inflammatory arthritis. Methods A systematic search of studies on the association of miRNA-146 and miRNA-499 polymorphisms with inflammatory arthritis susceptibility was conducted in PubMed, Web of science, Elsevier ScienceDirect, and Cochrane Library. Eventually, 18 published studies were included. The strength of association between miRNA-146/499 polymorphisms and inflammatory arthritis susceptibility was assessed by odds ratios (ORs) with its 95% confidence intervals (CIs). Results A total of 18 case-control studies, consisting of 3385 inflammatory arthritis patients and 4584 controls, were included in the meta-analysis. This meta-analysis showed significant association between miRNA-499 rs3746444 polymorphism and inflammatory arthritis susceptibility in overall population (C vs T, OR: 1.422, 95% CI= 1.159-1.745, P=0.001). Similar results were found in subgroup analysis by region. But we did not find association between miRNA-146 rs2910164 polymorphism and inflammatory arthritis susceptibility in overall population (C vs T, OR: 1.061, 95% CI= 0.933-1.207, P=0.365). Conclusions The present study indicates that miRNA-499 rs3746444 polymorphism is associated with inflammatory arthritis susceptibility. However, there is lack of association between miRNA-146 rs2910164 polymorphism and inflammatory arthritis susceptibility. But, we also find miRNA-146 rs2910164 and miRNA-499 rs3746444 polymorphism are associated with inflammatory arthritis in Middle East. Therefore, more large-scale studies are warranted to replicate our findings.

Quantifying circulating Th17 cells by qPCR: potential as diagnostic biomarker for rheumatoid arthritis.

The diagnosis of RA patients remains a challenge, especially in ACPA-negative disease. Novel T-cell subsets, particularly Th17 may be useful, although data on Th17 frequency using flow cytometry in RA are conflicting. We investigated whether a novel epigenetic qPCR assay for the quantification of Th17 could differentiate patients with RA from those with symptoms evolving towards an alternative diagnosis. We used a qPCR assay measuring the extent of the methylation at a key position in the IL-17 and CD4 genes. Assays were performed on whole blood from 49 healthy controls (HC) and 165 early arthritis clinic patients. Flow cytometry was further used to detect the expression of CXCR4 on Th17 cells. In 75 inflammatory arthritis patients who progressed to RA, the qPCR assays showed significantly fewer Th17 cells compared with 90 patients who did not (P<0.0001). Regression models demonstrated a high predictive value for RA development (75.8% correct prediction), and particularly for the ACPA-negative group (n = 125) where Th17 and swollen joint count (SJC) were the only predictors (73% correct prediction). The chemokine receptor CXCR4 had significantly higher expression on Th17 from early RA patients (n = 11) compared with HC (n = 15). The results of the epigenetic qPCR assay showed that low levels of Th17 cells were predictive of developing RA, particularly in the ACPA-negative patients. This could have value for insights into pathogenesis and management. The results suggest the recruitment of Th17 to the inflammatory disease site, consistent with high CXCR4 expression.

E007 Etanercept (ETN) biosimilar (Benapali - SB4) switches in inflammatory arthritis patients at Wrightington Hospital

E007 Etanercept (ETN) biosimilar (Benapali - SB4) switches in inflammatory arthritis patients at Wrightington Hospital

197 Outcome of education with regards to influenza and pneumococcal vaccinations in inflammatory arthritis patients on DMARDs

197 Outcome of education with regards to influenza and pneumococcal vaccinations in inflammatory arthritis patients on DMARDs

Rheumatic associations of autoimmune thyroid disease: a systematic review.

To investigate specific disease patterns in the rheumatic manifestations associated with autoimmune thyroid disease (AITD) through a systematic literature review. We performed a systematic review using the Medline OVID, PubMed, EMBASE, and Web of Science databases through May 2018 for experimental and observational studies that explored the association of AITD with degenerative joint disease (DJD), osteoarthritis (OA), chronic widespread pain (CWP) and fibromyalgia syndrome (FMS), and seronegative inflammatory arthritis (IA). A total of 2132 articles were identified. After title and abstract screening and removal of duplicates, 66 articles were retrieved for full text review. Eighteen studies were deemed eligible for inclusion. Six observational studies reported up to 45% prevalence of DJD in AITD. Hand and spinal DJD were reportedly associated with higher odds of AITD. Twelve observational studies were retrieved reporting up to 62% prevalence of FMS in AITD patients. Four studies described the occurrence of seronegative IA in AITD patients. The rheumatic associations of AITD may manifest specific patterns of disease distinct from those of other well-defined autoimmune syndromes and contribute significantly to disease burden.

Association of Arthritis Onset with Influenza: Analysis of the Canadian Early Inflammatory Arthritis Cohort.

ObjectiveTo evaluate seasonal patterns of early inflammatory arthritis (IA) onset and potential associations with IA symptom onset.MethodsThe Canadian Early Arthritis Cohort (CATCH) is an inception cohort study of adults with early (12 months or less) IA. We used patient reports of symptom onset as a proxy of IA onset and examined the seasonal distribution of IA onset over 10 years. Influenza time series was based on laboratory‐confirmed influenza A and B from the Canadian FluWatch surveillance from 2010‐2016. Bivariate analysis of influenza and IA was performed using cross‐correlations with different time lags and Poisson regression. IA and influenza were recorded as monthly total frequencies.ResultsOf 2519 IA patients, 88% had confirmed rheumatoid arthritis (RA). Significantly, more IA onsets occurred in winter compared with other seasons (P = 0.03); although IA onset was more frequent in January, the difference between months was not statistically significant. Compared to months with the lowest influenza rates, months with the highest influenza rates had a statistically significant, but trivial, increase of 0.003% in the incidence of IA (incidence rate ratio (95% confidence interval): 1.00003 (1.00005; 1.000053), P = 0.02).ConclusionAlthough IA symptom onset occurs more frequently in winter, we found that flu outbreaks were not associated with a meaningful increase in IA symptom onset in a large, well‐characterized cohort of Canadian adults over 6 years.